Moorestown, New Jersey, United States
biotecHOPE™ 2024
KAFTRIO® ivacaftor/tezacaftor/elexacaftor SYMKEVI® tezacaftor/ivacaftor ORKAMBI® lumacaftor/ivacafto
KAFTRIO® ivacaftor/tezacaftor/elexacaftor SYMKEVI® tezacaftor/ivacaftor ORKAMBI® lumacaftor/ivacafto
KAFTRIO® ivacaftor/tezacaftor/elexacaftor SYMKEVI® tezacaftor/ivacaftor ORKAMBI® lumacaftor/ivacafto
BUSINESS WIRE
20JUN 2024
Vertex Announces Extended Long-Term Reimbursement Agreement with NHS England for Access to Cystic Fibrosis Medicines KAFTRIO®, SYMKEVI® and ORKAMBI®
LONDON
Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced an extended long-term reimbursement agreement with NHS England providing access to KAFTRIO® (ivacaftor/tezacaftor/elexacaftor), SYMKEVI® (tezacaftor/ivacaftor) and ORKAMBI® (lumacaftor/ivacaftor) for all existing and future eligible cystic fibrosis (CF) patients in England.
The agreement, which also includes access to any future licence extensions of these medicines, comes as the National Institute for Health and Care Excellence (NICE) issues a positive recommendation for these CFTR modulators.
Vertex, NHS England and NICE have also committed to work together on a path towards rapid access for all eligible patients for the next in class triple combination treatment for CF, the investigational therapy vanzacaftor/tezacaftor/deutivacaftor, subject to authorisation by the Medicines and Healthcare products Regulatory Agency (MHRA).
Vertex is working with the NHS authorities in Scotland, Wales and Northern Ireland to finalise similar access agreements as soon as possible.
“We are delighted to have agreed extended long-term access to KAFTRIO® (ivacaftor/tezacaftor/elexacaftor), SYMKEVI® (tezacaftor/ivacaftor) and ORKAMBI® (lumacaftor/ivacaftor) for eligible CF patients in England,” said Ludovic Fenaux, Senior Vice President, Vertex International. ”I would like to acknowledge the collaboration of NHS England, NICE and the SMC, and also thank the CF community for their contribution in describing the value that these innovative medicines bring to patients.”
Vertex CF medicines are broadly available in over 60 countries worldwide including Australia, France, Italy, Germany, the Republic of Ireland, the Netherlands, Spain and the U.S.
About KAFTRIO® (ivacaftor/tezacaftor/elexacaftor) in Combination With Ivacaftor
In people with certain types of mutations in the CFTR gene, the CFTR protein is not processed or folded normally within the cell, and this can prevent the CFTR protein from reaching the cell surface and functioning properly. KAFTRIO® (ivacaftor/tezacaftor/elexacaftor) in combination with ivacaftor is an oral medicine designed to increase the quantity and function of the CFTR protein at the cell surface. Elexacaftor and tezacaftor work together to increase the amount of mature protein at the cell surface by binding to different sites on the CFTR protein. Ivacaftor, which is known as a CFTR potentiator, is designed to facilitate the ability of CFTR proteins to transport salt and water across the cell membrane. The combined actions of ivacaftor, tezacaftor and elexacaftor help hydrate and clear mucus from the airways.
KAFTRIO® (ivacaftor/tezacaftor/elexacaftor) in combination with Ivacaftor is a prescription medicine used for the treatment of cystic fibrosis (CF) in patients aged 2 years and older who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
For complete product information, please see the Summary of Product Characteristics that can be found on https://products.mhra.gov.uk/.
About SYMKEVI® (tezacaftor/ivacaftor) in Combination With Ivacaftor
In people with certain types of mutations in the CFTR gene, the CFTR protein is not processed or folded normally within the cell, and this can prevent the CFTR protein from reaching the cell surface. SYMKEVI® (tezacaftor/ivacaftor) in combination with ivacaftor is an oral medicine that is a combination of tezacaftor and ivacaftor. Tezacaftor is designed to increase the amount of mature protein at the cell surface by targeting the trafficking and processing defect of the CFTR protein to enable it to reach the cell surface. Ivacaftor, which is known as a CFTR potentiator, is designed to facilitate the ability of CFTR proteins to transport salt and water across the cell membrane. The combined actions of tezacaftor and ivacaftor help hydrate and clear mucus from the airways.
SYMKEVI® (tezacaftor/ivacaftor) in a combination regimen with KALYDECO® (ivacaftor) is a prescription medicine used for the treatment of cystic fibrosis (CF) in patients aged 6 years and older who have two copies of the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene or one copy of the F508del mutation and one copy of the following 14 mutations in the CFTR gene that result in residual CFTR activity: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A→G, S945L, S977F, R1070W, D1152H, 2789+5G→A, 3272-26A→G and 3849+10kbC→T.
For complete product information, please see the Summary of Product Characteristics that can be found on https://products.mhra.gov.uk/.
About ORKAMBI® (lumacaftor/ivacaftor)
In people with two copies of the F508del mutation, the CFTR protein is not processed and trafficked normally within the cell, resulting in little to no CFTR protein at the cell surface.
ORKAMBI® (lumacaftor/ivacaftor) is an oral medicine that is a combination of lumacaftor and ivacaftor. Lumacaftor is designed to increase the amount of mature protein at the cell surface by targeting the processing and trafficking defect of the F508del-CFTR protein. Ivacaftor, which is known as a CFTR potentiator, is designed to facilitate the ability of CFTR proteins to transport salt and water across the cell membrane. The combined actions of lumacaftor and ivacaftor help hydrate and clear mucus from the airways.
ORKAMBI® (lumacaftor/ivacaftor) is a prescription medicine used for the treatment of cystic fibrosis (CF) in patients aged 1 year and older who have two copies of the F508del mutation (F508del/F508del) in their CFTR gene.
For complete product information, please see the Summary of Product Characteristics that can be found on https://products.mhra.gov.uk/.
About Cystic Fibrosis
Cystic fibrosis (CF) is a rare, life-shortening genetic disease affecting more than 92,000 people globally. CF is a progressive, multi-organ disease that affects the lungs, liver, pancreas, GI tract, sinuses, sweat glands and reproductive tract. CF is caused by a defective and/or missing CFTR protein resulting from certain mutations in the CFTR gene. Children must inherit two defective CFTR genes — one from each parent — to have CF, and these mutations can be identified by a genetic test. While there are many different types of CFTR mutations that can cause the disease, the vast majority of people with CF have at least one F508del mutation. CFTR mutations lead to CF by causing CFTR protein to be defective or by leading to a shortage or absence of CFTR protein at the cell surface. The defective function and/or absence of CFTR protein results in poor flow of salt and water into and out of the cells in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus, chronic lung infections and progressive lung damage that eventually leads to death for many patients. The median age of death is in the 30s, but with treatment, projected survival is improving.
Diagnosis of CF is often made by genetic testing and is confirmed by testing sweat chloride (SwCl), which measures CFTR protein dysfunction. The diagnostic threshold for CF is SwCl ≥60 mmol/L, while levels between 30-59 indicate CF is possible and more testing may be needed to make the diagnosis of CF. A SwCl level of <30 mmol/L is seen in people who carry one copy of the CF gene but do not have any manifestation of disease (carriers). Higher levels of SwCl are associated with more severe disease. Restoring CFTR function leads to lower levels of SwCl.
About Vertex
Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has approved medicines that treat the underlying causes of multiple chronic, life-shortening genetic diseases — cystic fibrosis, sickle cell disease and transfusion-dependent beta thalassemia — and continues to advance clinical and research programs in these diseases. Vertex also has a robust clinical pipeline of investigational therapies across a range of modalities in other serious diseases where it has deep insight into causal human biology, including acute and neuropathic pain, APOL1-mediated kidney disease, IgA nephropathy, autosomal dominant polycystic kidney disease, type 1 diabetes, myotonic dystrophy type 1 and alpha-1 antitrypsin deficiency.
Vertex was founded in 1989 and has its global headquarters in Boston, with international headquarters in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia, Latin America and the Middle East. Vertex is consistently recognized as one of the industry's top places to work, including 14 consecutive years on Science magazine's Top Employers list and one of Fortune’s 100 Best Companies to Work For. For company updates and to learn more about Vertex’s history of innovation, visit www.vrtx.com/en-gb/
View source version on businesswire.com: https://www.businesswire.com/news/home/20240619004730/en/
Investors: InvestorInfo@vrtx.com or 617-961-7163
Media: mediainfo@vrtx.com or International: +44 20 3204 5275 or U.S.: 617-341-6992
© Business Wire, Inc.
Vertex inks a long-term coverage deal for cystic fibrosis drugs in England
Jun. 20, 2024 3:38 PM ET
Vertex Pharmaceuticals Incorporated (VRTX) Stock
By: Dulan Lokuwithana, SA News Editor
After months of uncertainty, Vertex Pharmaceuticals (NASDAQ:VRTX) on Thursday announced a long-term reimbursement agreement with England’s National Health Service (NHS) for its drugs targeted at a lung disorder called cystic fibrosis.
The agreement comes after the National Institute for Health and Care Excellence (NICE), which sets drug policy for the NHS, recommended its medicines Kaftrio, Symkevi, and Orkambi for all eligible patients with cystic fibrosis in England.
OPDIVO® (nivolumab)
KAFTRIO® ivacaftor/tezacaftor/elexacaftor SYMKEVI® tezacaftor/ivacaftor ORKAMBI® lumacaftor/ivacafto
KAFTRIO® ivacaftor/tezacaftor/elexacaftor SYMKEVI® tezacaftor/ivacaftor ORKAMBI® lumacaftor/ivacafto
European Medicines Agency Validates Bristol Myers Squibb’s Application for Subcutaneous Nivolumab
06/21/2024
CATEGORY:
Validation is based on results from CheckMate -67T, the first Phase 3 trial of the subcutaneous formulation of Opdivo to evaluate and demonstrate noninferior pharmacokinetics and efficacy vs. its intravenous formulation
Application seeks approval for subcutaneous nivolumab formulation to treat multiple Opdivo adult solid tumor indications in the European Union
PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced that the European Medicines Agency (EMA) has validated the extension application to introduce a new route of administration (subcutaneous use) for Opdivo ® (nivolumab) that includes a new pharmaceutical form (solution for injection) and a new strength (600 mg/vial) across multiple previously approved adult solid tumor indications as monotherapy, monotherapy maintenance following completion of nivolumab plus ipilimumab combination therapy, or in combination with chemotherapy or cabozantinib, based on the results from the Phase 3 CheckMate -67T study. Validation of the application confirms the submission is complete and begins the EMA’s centralized review procedure.
“Subcutaneous nivolumab has the potential to change the way patients living with cancer receive Opdivo treatment and to significantly reduce administration time by utilizing a single injection in three-to-five minutes. By providing patients the same quality of care as IV Opdivo in a fraction of the time, patients can focus on what is important to them rather than spending a longer wait time at the infusion center,” said Susan Parker, vice president, global program lead, product design & development, Bristol Myers Squibb. “We are committed to advancing medicines that improve the patient experience and are evaluating innovative formulations across our broad portfolio. We look forward to working with the EMA to advance this application with the goal of introducing the subcutaneous option of Opdivo.”
In the Phase 3 CheckMate -67T trial, subcutaneous nivolumab demonstrated noninferiority of Cavgd28 (time-averaged Opdivo serum concentration over 28 days) and Cminss (trough serum concentration at steady state), the study’s primary endpoints, vs. intravenous (IV) Opdivo in patients with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who have received no more than two prior lines of systemic therapy. Additionally, subcutaneous nivolumab showed noninferiority of the key secondary endpoint of objective response rate (ORR) as assessed by Blinded Independent Central Review (BICR) vs. IV Opdivo. The safety profile of subcutaneous nivolumab was consistent with the IV formulation. The pharmacokinetics, efficacy and safety results from CheckMate -67T were presented at the 2024 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium. Additional safety analyses and patient reported outcomes were recently presented at the 2024 ASCO Annual Meeting.
About CheckMate -67T
CheckMate -67T is a Phase 3 randomized, open-label trial evaluating subcutaneous administration of Opdivo co-formulated with Halozyme’s proprietary recombinant human hyaluronidase, rHuPH20, or subcutaneous nivolumab (nivolumab and hyaluronidase) compared to intravenous Opdivo, in patients with advanced or metastatic ccRCC who have received prior systemic therapy. This trial presents an opportunity to potentially bring a subcutaneous formulation of Opdivo to patients. A total of 495 patients were randomized to either subcutaneous nivolumab or intravenous Opdivo. The co-primary endpoints of the trial are time-averaged serum concentration over 28 days (Cavgd28) and trough serum concentration at steady-state (Cminss) of subcutaneous nivolumab vs. intravenous Opdivo. Objective response rate (ORR) is a key secondary endpoint.
Bristol Myers Squibb: Creating a Better Future for People with Cancer
Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine and, through innovative digital platforms, are turning data into insights that sharpen their focus. Deep understanding of causal human biology, cutting-edge capabilities and differentiated research platforms uniquely position the company to approach cancer from every angle.
Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. As a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.
About Opdivo
Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.
Opdivo’s leading global development program is based on Bristol Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has treated more than 35,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.
In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In September 2015, the Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.
INDICATIONS
OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult and pediatric patients 12 years and older with unresectable or metastatic melanoma.
OPDIVO® is indicated for the adjuvant treatment of adult and pediatric patients 12 years and older with completely resected Stage IIB, Stage IIC, Stage III, or Stage IV melanoma.
OPDIVO® (nivolumab), in combination with platinum-doublet chemotherapy, is indicated as neoadjuvant treatment of adult patients with resectable (tumors ≥4 cm or node positive) non-small cell lung cancer (NSCLC).
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (≥1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM).
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with intermediate or poor risk advanced renal cell carcinoma (RCC).
OPDIVO® (nivolumab), in combination with cabozantinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
OPDIVO® (nivolumab), as a single agent, is indicated for the adjuvant treatment of adult patients with urothelial carcinoma (UC) who are at high risk of recurrence after undergoing radical resection of UC.
OPDIVO® (nivolumab), in combination with cisplatin and gemcitabine, is indicated as first-line treatment for adult patients with unresectable or metastatic urothelial carcinoma.
OPDIVO® (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
OPDIVO® (nivolumab) is indicated for the treatment of adult patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.
OPDIVO® (nivolumab) is indicated for the adjuvant treatment of completely resected esophageal or gastroesophageal junction cancer with residual pathologic disease in adult patients who have received neoadjuvant chemoradiotherapy (CRT).
OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC).
OPDIVO® (nivolumab), in combination with fluoropyrimidine- and platinum- containing chemotherapy, is indicated for the treatment of adult patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.
Please see U.S. Full Prescribing Information for OPDIVO and YERVOY.
Clinical Trials and Patient Populations
Checkmate 227–previously untreated metastatic non-small cell lung cancer, in combination with YERVOY; Checkmate 9LA–previously untreated recurrent or metastatic non-small cell lung cancer in combination with YERVOY and 2 cycles of platinum-doublet chemotherapy by histology; Checkmate 649–previously untreated advanced or metastatic gastric cancer, gastroesophageal junction and esophageal adenocarcinoma; Checkmate 577–adjuvant treatment of esophageal or gastroesophageal junction cancer; Checkmate 238–adjuvant treatment of patients with completely resected Stage III or Stage IV melanoma; Checkmate 76K–adjuvant treatment of patients 12 years of age and older with completely resected Stage IIB or Stage IIC melanoma; Checkmate 274–adjuvant treatment of urothelial carcinoma; Checkmate 275–previously treated advanced or metastatic urothelial carcinoma; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Attraction-3–esophageal squamous cell carcinoma; Checkmate 648—previously untreated, unresectable advanced recurrent or metastatic esophageal squamous cell carcinoma; Checkmate 648–previously untreated, unresectable advanced recurrent or metastatic esophageal squamous cell carcinoma; Checkmate 040–hepatocellular carcinoma, in combination with YERVOY; Checkmate 743–previously untreated unresectable malignant pleural mesothelioma, in combination with YERVOY; Checkmate 037–previously treated metastatic melanoma; Checkmate 066–previously untreated metastatic melanoma; Checkmate 067–previously untreated metastatic melanoma, as a single agent or in combination with YERVOY; Checkmate 017–second-line treatment of metastatic squamous non-small cell lung cancer; Checkmate 057–second-line treatment of metastatic non-squamous non-small cell lung cancer; Checkmate 816–neoadjuvant non-small cell lung cancer, in combination with platinum-doublet chemotherapy; Checkmate 901–Adult patients with unresectable or metastatic urothelial carcinoma; Checkmate 141–recurrent or metastatic squamous cell carcinoma of the head and neck; Checkmate 025–previously treated renal cell carcinoma; Checkmate 214–previously untreated renal cell carcinoma, in combination with YERVOY; Checkmate 9ER–previously untreated renal cell carcinoma, in combination with cabozantinib; Checkmate 205/039–classical Hodgkin lymphoma
About the Bristol Myers Squibb and Ono Pharmaceutical Collaboration
In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, X (formerly Twitter), YouTube, Facebook and Instagram.
Bristol Myers Opdivo injectable accepted for EU review
Jun. 21, 2024 7:25 AM ET
Bristol-Myers Squibb Company (BMY) Stock, HALO Stock
By: Dulan Lokuwithana, SA News Editor1 Comment
Bristol Myers Squibb (NYSE:BMY) announced Friday that the EU drug regulator, the European Medicines Agency (EMA), validated its request to expand the approval for its cancer therapy Opdivo (nivolumab) to include a subcutaneous formulation.
The PD-1 immune checkpoint inhibitor is already approved in the region as an intravenous infusion for several forms of solid tumors as a single agent or in combination with other medications, such as BMY’s CTLA-4-blocking antibody, Yervoy.
ELEVIDYS (delandistrogene moxeparvovec-rokl)
KAFTRIO® ivacaftor/tezacaftor/elexacaftor SYMKEVI® tezacaftor/ivacaftor ORKAMBI® lumacaftor/ivacafto
ELEVIDYS (delandistrogene moxeparvovec-rokl)
Sarepta Therapeutics Announces Expanded US FDA Approval of ELEVIDYS to Duchenne Muscular Dystrophy Patients Ages 4 and Above
06/20/24 5:02 PM EDT
– FDA grants traditional approval to ELEVIDYS for ambulatory Duchenne patients
– FDA grants accelerated approval to ELEVIDYS for non-ambulatory Duchenne patients
– Sarepta will host an investor conference call on June 21, 2024, at 8:30 a.m. ET
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Jun. 20, 2024-- Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, today announced U.S. Food and Drug Administration (FDA) approval of an expansion to the labeled indication for ELEVIDYS (delandistrogene moxeparvovec-rokl) to include individuals with Duchenne muscular dystrophy (DMD) with a confirmed mutation in the DMD gene who are at least 4 years of age. Confirming the functional benefits, the FDA granted traditional approval for ambulatory patients. The FDA granted accelerated approval for non-ambulatory patients. Continued approval for non-ambulatory Duchenne patients may be contingent upon verification of clinical benefit in a confirmatory trial. ELEVIDYS is contraindicated in patients with any deletion in exon 8 and/or exon 9 in the DMD gene.
“Representing many years of dedicated research, development, investment and creative energy, the expansion of the ELEVIDYS label to treat Duchenne patients aged 4 and above, regardless of ambulatory status, is a defining moment for the Duchenne community. Today also stands as a watershed occasion for the promise of gene therapy and a win for science,” said Doug Ingram, president and chief executive officer, Sarepta. “At this pivotal moment, I want to give warm thanks to Drs. Jerry Mendell and Louise Rodino-Klapac for their dogged, 20-year pursuit of a gene therapy to treat this ruthless and life-robbing disease, to the FDA for following the scientific evidence to speed delivery of a therapy for a life-threatening rare disease to waiting patients, and to the many clinical investigators and courageous Duchenne families who have participated in the multiple studies that led to this important day.”
“Today’s expansion of the ELEVIDYS label represents the culmination of my 50-year pursuit of a treatment for Duchenne patients and, along with my colleague Dr. Louise Rodino-Klapac, a nearly 20-year effort to optimize and develop a gene therapy that could be safely and effectively delivered to muscle,” said Jerry Mendell, M.D., co-inventor of ELEVIDYS and senior advisor, Medical Affairs, Sarepta. “The initial approval of ELEVIDYS was a significant milestone, and the expanded indication means clinicians now have a treatment option for the great majority of boys and young men living with Duchenne. This expansion speaks to the success of the science, the evidence and the improvements in the trajectory of the disease we have seen to date across studies.”
Consistent with the accelerated approval pathway, Sarepta has committed to conduct and submit the results of a randomized, controlled trial to verify and confirm the clinical benefit of ELEVIDYS in patients with Duchenne muscular dystrophy who are non-ambulatory. ENVISION (Study SRP-9001-303), a global, randomized, double-blind, placebo-controlled Phase 3 study of ELEVIDYS in non-ambulatory and older ambulatory individuals with Duchenne, is underway and intended to serve as this postmarketing requirement.
As part of a collaboration agreement signed in 2019, Sarepta is working with Roche to transform the future for the Duchenne community, enabling those living with the disease to maintain and protect their muscle function. Sarepta is responsible for regulatory approval and commercialization of ELEVIDYS in the U.S., as well as manufacturing. Roche is responsible for regulatory approvals and bringing ELEVIDYS to patients across the rest of the world.
Patients and physicians can access more information about ELEVIDYS at www.SareptAssist.com or by calling 1-888-727-3782.
Conference call details
At 8:30 a.m. ET on June 21, 2024, Sarepta will host a conference call and webcast to discuss this update.
The event will be webcast live under the investor relations section of Sarepta’s website at https://investorrelations.sarepta.com/events-presentations and following the event a replay will be archived there for one year. Interested parties participating by phone will need to register using this online form. After registering for dial-in details, all phone participants will receive an auto-generated e-mail containing a link to the dial-in number along with a personal PIN number to use to access the event by phone.
About ELEVIDYS (delandistrogene moxeparvovec-rokl)
ELEVIDYS (delandistrogene moxeparvovec-rokl) is a single-dose, adeno-associated virus (AAV)-based gene transfer therapy for intravenous infusion designed to address the underlying genetic cause of Duchenne muscular dystrophy – mutations or changes in the DMD gene that result in the lack of dystrophin protein – through the delivery of a transgene that codes for the targeted production of ELEVIDYS micro-dystrophin in skeletal muscle.
ELEVIDYS is indicated for the treatment of Duchenne muscular dystrophy (DMD) in individuals at least 4 years of age.
- For patients who are ambulatory and have a confirmed mutation in the DMD gene.
- For patients who are non-ambulatory and have a confirmed mutation in the DMD gene.
The DMD indication in non-ambulatory patients is approved under accelerated approval based on expression of ELEVIDYS micro-dystrophin (noted hereafter as “micro-dystrophin”) in skeletal muscle. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Please see the full Prescribing Information for ELEVIDYS.
Sarepta surges 38% after hours on expanded Elevidys Duchenne approval (updated)
Jun. 20, 2024 5:31 PM ET
Sarepta Therapeutics, Inc. (SRPT) StockRHHBY
By: Jonathan Block, SA News Editor3 Comments
This article was updated at 545p ET to indicate surge in company's share price.
- Sarepta is up ~38% in post-market trading Thursday after the U.S. FDA granted accelerated approval for a label expansion of its Duchenne muscular dystrophy treatment Elevidys (delandistrogene moxeparvovec) to include patients who are non-ambulatory.
- Trading was halted around 454p ET for news pending and resumed at 535p.
- https://seekingalpha.com/news/4117773-sareptas-elevidys-now-approved-for-non-ambulatory-duchenne-muscular-dystrophy?source=content_type%3Areact%7Cfirst_level_url%3Amarket-news%7Csection_asset%3Amain%7Csection%3Abiotech-stocks
- Sarepta Therapeutics, Inc. (SRPT) Stock
- https://www.sarepta.com/
- https://www.elevidys.com/
KYV-101
SUNLENCA® (lenacapavir) injectable HIV-1 capsid inhibitor
ELEVIDYS (delandistrogene moxeparvovec-rokl)
Kyverna's KYV-101 Receives U.S. FDA IND Clearance for Treatment of Patients With Treatment-Refractory Stiff-Person Syndrome in the KYSA-8 Phase 2 Trial
June 20, 2024
This IND clearance expands the use of KYV-101 CAR T-cell therapy in a Phase 2, open-label KYSA-8 clinical trial targeting a devastating neuroimmunological autoimmune disease
KYV-101 is a fully human anti-CD19 CAR T-cell therapy designed for use in patients with B cell-driven autoimmune diseases
EMERYVILLE, Calif., June 20, 2024 /PRNewswire/ -- Kyverna Therapeutics, Inc. (Kyverna), a patient-centered, clinical-stage biopharmaceutical company focused on developing cell therapies for patients suffering from autoimmune diseases, announced today the clearance of its Investigational New Drug (IND) application by the U.S. Food and Drug Administration (FDA) for its autologous, fully human anti-CD19 chimeric antigen receptor (CAR) T-cell product candidate, KYV-101, to be used for the treatment of stiff-person syndrome (SPS) in Kyverna's trial, named KYSA-8.
"CAR T-cell therapy has already shown preliminary but promising results in patients with SPS treated outside of the US," said Marinos Dalakas, M.D., FAAN, Professor of Neurology, Director of the Neuromuscular Division at Thomas Jefferson University School of Medicine in Philadelphia, PA, and a leading physician and researcher on SPS. "I find the KYSA-8 trial of extraordinary importance as a promising novel therapy for patients with stiff person syndrome who do not respond to current therapies, with implications in providing potentially long-lasting benefits."
"The IND clearance gives us confidence in our dedication to bringing a potential paradigm shift in the treatment of patients suffering from SPS and reaffirms a target dose of 100 million cells for KYV-101," said Sham Dholakia, M.D., business unit head rare diseases at Kyverna. "We are also very grateful to the FDA for the collaborative approach and timely vetting of our clinical trial design."
About Stiff Person Syndrome (SPS)
SPS is a rare, progressive neurological autoimmune disorder causing debilitating muscle stiffness in the torso, arms, and legs, impacting the ability to walk or move. Patients typically present with muscle spasms and stiffness, resulting in difficulty turning and bending. When stiffness is severe, the patient's walking resembles a statue. Muscle spasms and stiffness can be precipitated by unexpected stimuli, including sounds, like a phone ring or a siren, sudden touches or conditions triggering anxiety and emotional upset which, when severe, are misdiagnosed as a primary anxiety disorder1.
There is no cure for SPS, but only treatments focused on treating the symptoms.
About KYV-101
KYV-101 is an autologous, fully human anti-CD19 CAR T-cell product candidate for use in B cell-driven autoimmune diseases. The CAR in KYV-101 was designed by the National Institutes of Health (NIH) to improve tolerability and tested in a 20-patient Phase 1 trial in oncology. Results were published by the NIH in Nature Medicine2.
KYV-101 is currently being evaluated in sponsored, open-label, Phase 1/2 and Phase 2 trials of KYV-101 in the United States and Germany across two broad areas of autoimmune disease: rheumatology and neurology.
With 50 patients treated so far with the CAR in KYV-101 in both oncological and autoimmune conditions at more than 15 locations in Europe and the U.S., we believe that the differentiated properties of KYV-101 are critical for the potential success of CAR T cells as autoimmune disease therapies.
KYV-101 is also being evaluated in investigator-initiated trials for multiple indications in multiple geographies.
About Kyverna Therapeutics
Kyverna Therapeutics, Inc. (Nasdaq: KYTX) is a patient-centered, clinical-stage biopharmaceutical company focused on developing cell therapies for patients suffering from autoimmune diseases.
Our lead CAR T-cell therapy candidate, KYV-101 is advancing through clinical development with sponsored clinical trials across two broad areas of autoimmune disease: rheumatology and neurology, including Phase 2 trials for stiff person syndrome, multiple sclerosis and myasthenia gravis, a Phase 1/2 trial for systemic sclerosis, and two ongoing multi-center, open-label Phase 1/2 trials in the United States and Germany for patients with lupus nephritis.
Kyverna's pipeline includes next-generation CAR T-cell therapies in both autologous and allogeneic formats with properties intended to be well suited for use in B cell-driven autoimmune diseases.
For more information, please visit https://kyvernatx.com.
Cision View original content to download multimedia:https://www.prnewswire.com/news-releases/kyvernas-kyv-101-receives-us-fda-ind-clearance-for-treatment-of-patients-with-treatment-refractory-stiff-person-syndrome-in-the-kysa-8-phase-2-trial-302177671.html
SOURCE Kyverna Therapeutics
Kyverna gains as FDA clears trial for lead therapy
Jun. 20, 2024 1:55 PM ET
Kyverna Therapeutics, Inc. (KYTX) Stock
By: Dulan Lokuwithana, SA News Editor
- Kyverna Therapeutics (NASDAQ:KYTX) traded higher on Monday after the U.S. FDA greenlighted a mid-stage clinical trial for its lead candidate, KYV-101, in patients with a rare disease called stiff-person syndrome (SPS).
- The FDA nod for its Investigational New Drug (IND) application paves the way for Kyverna (KYTX) to test the autologous CD19-targeting CAR T-cell therapy in KYSA-8, a Phase 2 open-label clinical trial.
- https://seekingalpha.com/news/4117645-kyverna-stock-gains-fda-clears-trial-lead-therapy?source=content_type%3Areact%7Cfirst_level_url%3Amarket-news%7Csection_asset%3Amain%7Csection%3Abiotech-stocks
- Kyverna Therapeutics, Inc. (KYTX) Stock
- https://kyvernatx.com/
- https://kyvernatx.com/platform-pipeline/pipeline/
ANKTIVA® (nogapendekin alfa inbakicept-pmln)
SUNLENCA® (lenacapavir) injectable HIV-1 capsid inhibitor
SUNLENCA® (lenacapavir) injectable HIV-1 capsid inhibitor
ImmunityBio Announces Insurance Coverage of ANKTIVA® Across Multiple States with First Commercial Doses Administered Just Weeks After FDA Approval—Opening New Era for Immunotherapy Beyond Checkpoint Inhibitors
Jun 20, 2024
- Multiple patients treated across the U.S. with ANKTIVA less than eight weeks after FDA approval of first-in-class cytokine immunotherapy for BCG unresponsive non-muscle invasive bladder cancer
- ANKTIVA launch initiates the next era of immunotherapy beyond checkpoint inhibitors that is based on cytokines and natural killer (NK) cells
- ANKTIVA’s novel mechanism of action activates the body’s immune system of natural killer and killer T cells to attack BCG resistant tumor cells and induce memory T cells resulting in a long duration of complete response exceeding 47 months1
- ANKTIVA reimbursement now covered by multiple healthcare plans
- Urologists treating eligible bladder cancer patients can learn more about the treatment option and access support program ImmunityBio CARE™ at Anktiva.com
CULVER CITY, Calif., June 20, 2024 — ImmunityBio, Inc. (NASDAQ: IBRX) today announced the initial treatment of multiple patients in the United States to receive therapy with ANKTIVA® (nogapendekin alfa inbakicept-pmln), ImmunityBio’s recently approved immunotherapy for Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) carcinoma in situ. ANKTIVA was approved by the U.S. Food and Drug Administration (FDA) on April 22, 2024 for the treatment of patients with BCG-unresponsive NMIBC CIS with or without papillary tumors.
The intravesical therapy employs a combination of ANKTIVA, an IL-15 agonist in combination with BCG. The combination is the first FDA-approved immunotherapy in NMIBC that functions by activating the body’s NK and killer T-cell immune system to attack tumor cells, while simultaneously activating memory T cells, leading to a prolonged duration of complete response exceeding 47 months for some patients.
“We are grateful to be able to offer this first-in-class immunotherapy to qualified bladder cancer patients less than two months after the therapeutic was approved by the FDA,” said Patrick Soon-Shiong, M.D., Executive Chairman and Global Chief Scientific and Medical Officer at ImmunityBio. “The interest in this next era of immunotherapy beyond checkpoint inhibitors—the era of cytokines—from urologists treating NMIBC patients has been strong and we look forward to offering more patients an alternative to bladder removal.”
The first patients to receive commercial doses are located throughout the U.S. and several are being treated by community urologists, as the therapy does not require any special handling or equipment that would limit its use to specialty medical centers.
“In addition to its unique mechanism of action, ANKTIVA can be readily administered by urologists in their own offices and clinics enabling more patients to receive it in familiar settings from their own providers,” said Richard Adcock, President and CEO of ImmunityBio. “We look forward to ANKTIVA reaching more and more eligible NMIBC patients and for our science to deliver even more therapies from our pipeline.”
ANKTIVA received Breakthrough Therapy Designation and approval from the FDA based on the safety and efficacy outcome of complete responses (CR) and duration of complete response (DOR) in BCG-unresponsive NMIBC CIS. The 77 evaluable patients in this single-arm, multicenter trial received ANKTIVA with BCG maintenance therapy for up to 37 months. The tumor status was assessed with cystoscopy and urine cytology and will continue for up to five years after each patient began their participation in the trial.
The CR rate for the 77 evaluable patients was 62% with the upper end of the confidence interval being 73%. The duration of complete response as of the November 2023 cut-off was more than 47 months and is ongoing to date. These prolonged duration of complete response results beyond 24 months with ANKTIVA and BCG exceed the benchmark for the magnitude of meaningful clinical results suggested by a panel of experts at the International Bladder Cancer Group.
In May, ImmunityBio announced it had drug substance sufficient for 170,000 doses of ANKTIVA for commercial and clinical trial use.
ImmunityBio CARE™
The ImmunityBio CARE™ program is designed to help patients access ImmunityBio’s innovative treatment for NMIBC CIS. The program offers services and resources for benefits investigation, prior authorization support and tracking, coding and billing assistance, claim denial guidance and payer specific appeal assistance. More information for patients and healthcare professionals is available on Anktiva.com.
How ANKTIVA Works
The cytokine interleukin-15 (IL-15) plays a crucial role in the immune system by affecting the development, maintenance, and function of key immune cells—NK and CD8+ killer T cells—that are involved in killing cancer cells. By activating NK cells, ANKTIVA overcomes the tumor escape phase of clones resistant to T cells and restores memory T cell activity with resultant prolonged duration of complete response.
ANKTIVA is a first-in-class IL-15 agonist IgG1 fusion complex, consisting of an IL-15 mutant (IL-15N72D) fused with an IL-15 receptor alpha, which binds with high affinity to IL-15 receptors on NK, CD4+, and CD8+ T cells. This fusion complex of ANKTIVA mimics the natural biological properties of the membrane-bound IL-15 receptor alpha, delivering IL-15 by dendritic cells and drives the activation and proliferation of NK cells with the generation of memory killer T cells that have retained immune memory against these tumor clones. The proliferation of the trifecta of these immune killing cells and the activation of trained immune memory results in immunogenic cell death, inducing a state of equilibrium with durable complete responses. ANKTIVA has improved pharmacokinetic properties, longer persistence in lymphoid tissues, and enhanced anti-tumor activity compared to native, non-complexed IL-15 in-vivo.
Selected Safety Information for ANKTIVA
The most common (≥15%) adverse reactions, including laboratory test abnormalities, are increased creatinine, dysuria, hematuria, urinary frequency, micturition urgency, urinary tract infection, increased potassium, musculoskeletal pain, chills, and pyrexia.
About ImmunityBio
ImmunityBio is a vertically-integrated biotechnology company developing next-generation therapies and vaccines that bolster the natural immune system to defeat cancers and infectious diseases. The company’s range of immunotherapy and cell therapy platforms, alone and together, act to drive and sustain an immune response with the goal of creating durable and safe protection against disease. Designated an FDA Breakthrough Therapy, ANKTIVA® is the first FDA-approved immunotherapy for non-muscle invasive bladder cancer that activates natural killer cells, T cells, and memory T cells for a long duration response. The company is applying its science and platforms to treating cancers, including the development of potential cancer vaccines, as well as developing immunotherapies and cell therapies that we believe sharply reduce or eliminate the need for standard high-dose chemotherapy. These platforms and their associated product candidates are designed to be more effective, accessible, and easily administered than current standards of care in oncology and infectious diseases.
For more information, please visit: www.immunitybio.com
- ANKTIVA Prescribing Information. ImmunityBio Inc.; 2024
ImmunityBio spikes after commercial update on lead drug Anktiva
Jun. 20, 2024 12:28 PM ET
ImmunityBio, Inc. (IBRX) Stock
By: Dulan Lokuwithana, SA News Editor
ImmunityBio (NASDAQ:IBRX) traded higher Thursday after the company said multiple payors across the U.S. have offered insurance coverage for its bladder cancer therapy, Anktiva, even though only weeks have passed since its FDA approval.
The stock has recorded its biggest intraday gain since April, albeit on below-average volumes. A little over 4.0M IBRX shares have changed hands compared to the 65-day average of ~6.9M.
In April, the FDA cleared Anktiva, an intravesically delivered immunotherapy in combination with the Bacillus Calmette-Guérin (BCG) vaccine, for patients with BCG-unresponsive non-muscle invasive bladder cancer. ImmunityBio (IBRX) launched the product in mid-May.
“We are grateful to be able to offer this first-in-class immunotherapy to qualified bladder cancer patients less than two months after the therapeutic was approved by the FDA,” said IBRX’s chief medical officer, Patrick Soon-Shiong.
SUNLENCA® (lenacapavir) injectable HIV-1 capsid inhibitor
SUNLENCA® (lenacapavir) injectable HIV-1 capsid inhibitor
SUNLENCA® (lenacapavir) injectable HIV-1 capsid inhibitor
June 20, 2024
Gilead’s Twice-Yearly Lenacapavir Demonstrated 100% Efficacy and Superiority to Daily Truvada® for HIV Prevention
– First Phase 3 HIV Prevention Trial Ever to Show Zero Infections –
– Independent Data Monitoring Committee Recommended That Gilead Stop the Blinded Phase of the PURPOSE 1 Trial at Interim Analysis and Offer Open-Label Lenacapavir to All Participants –
Foster City, Calif. – June 20, 2024 – Gilead Sciences, Inc. (Nasdaq: GILD) today announced topline results from an interim analysis of its pivotal, Phase 3 PURPOSE 1 trial indicating that the company’s twice-yearly injectable HIV-1 capsid inhibitor, lenacapavir, demonstrated 100% efficacy for the investigational use of HIV prevention in cisgender women.
PURPOSE 1 met its key efficacy endpoints of superiority of twice-yearly lenacapavir to once-daily oral Truvada® (emtricitabine 200mg and tenofovir disoproxil fumarate 300mg; F/TDF) and background HIV incidence (bHIV). Based on these results, the independent Data Monitoring Committee (DMC) recommended that Gilead stop the blinded phase of the trial and offer open-label lenacapavir to all participants.
“With zero infections and 100% efficacy, twice-yearly lenacapavir has demonstrated its potential as an important new tool to help prevent HIV infections,” said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. “We look forward to additional results from the ongoing PURPOSE clinical program and continuing toward our goal of helping to end the HIV epidemic for everyone, everywhere.”
These are the first data generated from Gilead’s landmark PURPOSE program, which is the most comprehensive and diverse HIV prevention trial program ever conducted. The PURPOSE program comprises five HIV prevention trials around the world that are focused on innovation in science, trial design, community engagement and health equity.
Topline PURPOSE 1 data
PURPOSE 1, a Phase 3, double-blind, randomized study, is evaluating the safety and efficacy of twice-yearly, subcutaneous lenacapavir for pre-exposure prophylaxis (PrEP) and once-daily oral Descovy® (emtricitabine 200mg and tenofovir alafenamide 25mg; F/TAF) in more than 5,300 cisgender women and adolescent girls aged 16-25 across 25 sites in South Africa and three sites in Uganda. The drugs are being tested in parallel, with one group receiving twice-yearly lenacapavir and one group taking once-daily oral Descovy. Additionally, a third group was assigned once-daily oral Truvada. Study participants were randomized in a 2:2:1 ratio to lenacapavir, Descovy and Truvada, respectively. Because effective PrEP options already exist, there is broad consensus in the PrEP field that a placebo group would be unethical; thus, the trial used bHIV as the primary comparator and Truvada as a secondary comparator.
There were 0 incident cases of HIV infection among 2,134 women in the lenacapavir group (incidence 0.00 per 100 person-years). There were 16 incident cases among 1,068 women in the Truvada group (incidence 1.69 per 100 person-years). The results demonstrated superiority of twice-yearly lenacapavir over bHIV (primary endpoint, incidence 2.41 per 100 person-years) and superiority of twice-yearly lenacapavir over once-daily Truvada (secondary endpoint), with p<0.0001 for both endpoints. In the trial, lenacapavir was generally well-tolerated and no significant or new safety concerns were identified.
HIV incidence in the Descovy group was numerically similar (39 incident cases among 2,136 women, incidence 2.02 per 100 person-years) to that in the Truvada group and was not statistically superior to bHIV. Previous clinical trials among cisgender women have commonly found challenges with adherence to daily oral pills for PrEP, and adherence analyses for Descovy and Truvada from PURPOSE 1 are ongoing. In the trial, both Descovy and Truvada were generally well-tolerated and no new safety concerns were identified.
More detailed data from PURPOSE 1 will be presented at a future conference.
“Twice-yearly lenacapavir for PrEP, if approved, could provide a critical new choice for HIV prevention that fits into the lives of many people who could benefit from PrEP around the world—especially cisgender women,” said Linda-Gail Bekker, MBChB, DTM&H, DCH, FCP(SA), PhD, Director of the Desmond Tutu HIV Center at the University of Cape Town, South Africa, and past President of the International AIDS Society. “While we know traditional HIV prevention options are highly effective when taken as prescribed, twice-yearly lenacapavir for PrEP could help address the stigma and discrimination some people may face when taking or storing oral PrEP pills, as well as potentially help increase PrEP adherence and persistence given its twice-yearly dosing schedule.”
The use of lenacapavir and the use of Descovy for the prevention of HIV in cisgender women are investigational and have not been determined to be safe or efficacious and are not approved anywhere globally.
Additional PURPOSE trials assessing twice-yearly lenacapavir for PrEP are ongoing
Gilead expects results in late 2024/early 2025 from the program’s other pivotal trial, PURPOSE 2, which is assessing twice-yearly lenacapavir for PrEP among cisgender men who have sex with men, transgender men, transgender women and gender non-binary individuals who have sex with partners assigned male at birth in Argentina, Brazil, Mexico, Peru, South Africa, Thailand and the United States. The regulatory filing for lenacapavir for PrEP will include the results of both PURPOSE 1 and PURPOSE 2, if positive, in order to ensure lenacapavir for PrEP can be approved for multiple populations and communities most in need of additional HIV prevention options.
Gilead is committed to partnering with communities that are disproportionately affected by HIV in their respective countries and regions, and community input on the PURPOSE trials has been instrumental in factors ranging from program design to participant recruitment strategies. This kind of collaborative approach will continue to help Gilead implement clinical trials with rigor, innovation and intentional inclusion of communities that have historically been underrepresented in HIV prevention research. It will also help bolster the post-implementation science activities that Gilead will conduct for PURPOSE 1 and future successful trials.
Gilead recognizes the importance of helping to enable access in order for twice-yearly lenacapavir for PrEP, if approved by regulatory authorities, to achieve the broadest impact. In light of today’s milestone and the company’s ongoing commitment to communities affected by HIV, Gilead intends to brief community partners and provide a public statement regarding its planned access approach for high-incidence, resource-limited countries, which are primarily low- and lower-middle-income countries.
More information about the PURPOSE program, including individual trial descriptions, populations and locations, can be found at www.purposestudies.com.
U.S. Indication for Descovy for PrEP ®
DESCOVY for PrEP is indicated in at-risk adults and adolescents (≥35 kg) to reduce the risk of sexually acquired HIV-1 infection, excluding individuals at risk from receptive vaginal sex. HIV-1–negative status must be confirmed immediately prior to initiation.
- Limitation of Use: DESCOVY FOR PrEP is not indicated in individuals at risk of HIV-1 from receptive vaginal sex because effectiveness in this population has not been evaluated by the U.S. FDA.
About Gilead HIV
Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California.
For more than 35 years, Gilead has been a leading innovator in the field of HIV, driving advances in treatment, prevention and cure research. Gilead researchers have developed 12 HIV medications, including the first single-tablet regimen to treat HIV, the first antiretroviral for pre-exposure prophylaxis (PrEP) to help reduce new HIV infections, and the first long-acting injectable HIV treatment medication administered twice-yearly. Our advances in medical research have helped to transform HIV into a treatable, preventable, chronic condition for millions of people.
Gilead is committed to continued scientific innovation to provide solutions for the evolving needs of people affected by HIV around the world. Through partnerships, collaborations and charitable giving, the company also aims to improve education, expand access and address barriers to care, with the goal of ending the HIV epidemic for everyone, everywhere. Gilead was recognized as the number one philanthropic funder of HIV-related programs in a report released by Funders Concerned About AIDS.
Learn more about Gilead’s unique collaborations worldwide and the work to help end the global HIV epidemic.
U.S. full Prescribing Information for Descovy and Truvada, including Boxed Warnings, is available at www.gilead.com
Descovy, Descovy for PrEP, Gilead, the Gilead logo, Truvada, and Truvada for PrEP are registered trademarks of Gilead Sciences, Inc., or its related companies.
For more information about Gilead, please visit the company’s website at www.gilead.com , follow Gilead on Twitter ( @Gilead Sciences ) and LinkedIn , or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
Source: Gilead Sciences, Inc.
Gilead gains on trial win for twice-yearly HIV PrEP therapy
Jun. 20, 2024 10:00 AM ET
Gilead Sciences, Inc. (GILD) Stock
By: Dulan Lokuwithana, SA News Editor9 Comments
Gilead Sciences (NASDAQ:GILD) traded higher in the morning hours Thursday after announcing that a Phase 3 trial for its experimental therapy lenacapavir succeeded when used as a twice-yearly option to prevent HIV infection (pre-exposure prophylaxis).
Citing interim data from its Phase 3 PURPOSE 1 trial, the Foster City, California-based biotech said lenacapavir as an injectable outperformed its once-daily oral PrEP therapy Truvada and background HIV incidence, meeting the trial’s key goals in cisgender women.
Gilead Sciences, Inc. (GILD) Stock
https://services.gileadhiv.com/content/pdf/sunlenca/Important_Facts.pdf
SKYRIZI® (risankizumab-rzaa)
CAPVAXIVE™ (Pneumococcal 21-valent Conjugate Vaccine)
CAPVAXIVE™ (Pneumococcal 21-valent Conjugate Vaccine)
June 18, 2024
U.S. FDA Approves SKYRIZI® (risankizumab-rzaa) for Ulcerative Colitis, Expanding AbbVie's Portfolio Across Inflammatory Bowel Disease
- Approval supported by two Phase 3 clinical trials that evaluated SKYRIZI® for the treatment of moderate to severe ulcerative colitis: a 12-week induction study, INSPIRE,1 and a 52-week maintenance study, COMMAND2
- Data showed that clinical remission, the primary endpoint in both the induction and maintenance studies, was achieved along with endoscopic improvement, a key secondary endpoint1,2
- SKYRIZI is the first IL-23 antagonist approved for both ulcerative colitis and Crohn's disease
NORTH CHICAGO, Ill., June 18, 2024 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced the U.S. Food and Drug Administration (FDA) has approved SKYRIZI® (risankizumab-rzaa) for adults with moderately to severely active ulcerative colitis, making it the first IL-23 specific inhibitor approved for both moderate to severe ulcerative colitis and moderate to severe Crohn's disease.3 SKYRIZI is now approved for four indications across immune-mediated inflammatory diseases.
Access the multimedia news release here: https://www.multivu.com/players/English/9251951-abbvie-fda-ulcerative-colitis/
"When treating patients with ulcerative colitis, it's important to prioritize both early and sustained clinical remission as well as endoscopic improvement," said Edward V. Loftus, Jr., M.D., Maxine and Jack Zarrow Family Professor of Gastroenterology in the division of gastroenterology and hepatology at Mayo Clinic in Rochester, Minnesota. "This approval for SKYRIZI is an important step toward addressing these treatment goals."
With over 1 million people living with ulcerative colitis, the United States has one of the largest populations affected by this disease and the numbers are continuing to rise.4 Ulcerative colitis is a form of inflammatory bowel disease (IBD) that causes inflammation in the digestive tract and can result in damage to the colon lining.5 Patients often experience a range of unpredictable symptoms that impact their daily lives, such as abdominal pain, bloody stool and urgency to use the bathroom.5,6 The disease course of ulcerative colitis varies between patients, and in some cases can lead to surgery or complications, including cancer or death.6,7
"Today's approval of SKYRIZI for ulcerative colitis expands our IBD portfolio and demonstrates our commitment to helping address ongoing needs of patients," said Roopal Thakkar, M.D., senior vice president, chief medical officer, global therapeutics, AbbVie. "We will continue to invest in transforming the treatment landscape and the lives of people suffering from lBD."
Dosing of SKYRIZI for this indication includes a 12-week induction period with three 1200 mg doses delivered every four weeks, followed by maintenance therapy of either 180 mg or 360 mg delivered every eight weeks.3 Following the induction period, SKYRIZI treatment can be maintained at home using an on-body injector (OBI).3 The OBI is a hands-free device designed with patients in mind that adheres to the body and takes about five minutes to deliver the medication following preparation steps.3
Do not use if you are allergic to SKYRIZI. SKYRIZI may cause serious side effects, including serious allergic reactions, an increased risk of infections, and liver problems. Stop using SKYRIZI and get emergency medical help right away if experiencing symptoms of a serious allergic reaction. Before starting treatment, your doctor should check for infections and tuberculosis. Tell your doctor right away about any infections or symptoms of infection and about planned or recent vaccines. Liver problems may happen while being treated for Crohn's disease or ulcerative colitis that can lead to hospitalization. Your doctor will do liver blood tests before and during treatment and may stop SKYRIZI if liver problems develop.
Risankizumab (SKYRIZI) is part of a collaboration between Boehringer Ingelheim and AbbVie, with AbbVie leading development and commercialization globally.
For more information about SKYRIZI, visit SKYRIZI.com.
Patient Access & Support
AbbVie is committed to helping people access SKYRIZI and other medicines, including offering a patient support program and co-pay card that may reduce out-of-pocket costs to as little as $0 per month for eligible, commercially insured patients. Financial support might also include reimbursement for out-of-pocket costs related to IV administration. For those with limited or no health insurance, AbbVie offers myAbbVie Assist, a patient assistance program that provides SKYRIZI at no charge to those who qualify. More information about this assistance program can be found at www.AbbVie.com/myAbbVieAssist.
About Ulcerative Colitis
Ulcerative colitis is a chronic, idiopathic, immune-mediated inflammatory bowel disease (IBD) of the large intestine that causes continuous mucosal inflammation extending, to a variable extent, from the rectum to the more proximal colon.5,8 The hallmark signs and symptoms of ulcerative colitis include rectal bleeding, abdominal pain, bloody diarrhea, tenesmus (a sense of pressure), urgency and fecal incontinence.5,6 The disease course of ulcerative colitis varies between patients and can range from quiescent disease to chronic refractory disease, which in some cases can lead to surgery or complications, including cancer or death.6,7 The severity of symptoms and unpredictability of disease course can lead to substantial burden and often disability among those living with the disease.9
About the INSPIRE Induction Study1
INSPIRE is a multicenter, randomized, double-blind, placebo-controlled Phase 3 study evaluating the efficacy and safety of risankizumab 1200 mg IV administered every four weeks as induction therapy in subjects with moderately to severely active ulcerative colitis.
The primary endpoint is clinical remission (per Adapted Mayo Score, defined as SFS ≤1 and not greater than baseline, RBS of 0 and endoscopic subscore ≤1 without friability) at week 12. Secondary endpoints include clinical response (decrease from baseline in the Adapted Mayo Score ≥2 points and ≥30% from baseline, plus a decrease in RBS ≥1 or an absolute RBS ≤1), endoscopic improvement (endoscopic subscore ≤1 without friability), and histologic and endoscopic mucosal improvement (HEMI) (endoscopic subscore of 0 or 1 without friability and Geboes score ≤3.1) at week 12. More information can be found on www.clinicaltrials.gov (NCT03398148).
About the COMMAND Maintenance Study2
The COMMAND study is a Phase 3, multicenter, randomized, double-blind, controlled, 52-week maintenance study designed to evaluate the efficacy and safety of risankizumab 180 mg or 360 mg SC in adults with moderately to severely active ulcerative colitis. This study followed a re-randomized withdrawal design in which all patients received risankizumab IV induction and those who responded to risankizumab were re-randomized to receive risankizumab 180 mg or 360 mg SC or withdrawal from risankizumab treatment (induction-only control group). For those randomized to withdraw from risankizumab treatment (induction-only control group), the rest of the study duration was a risankizumab washout. The objective of the Phase 3 study is to evaluate the efficacy and safety of risankizumab 180 mg or 360 mg as maintenance therapy versus withdrawal from risankizumab treatment (control) in patients with moderately to severely active ulcerative colitis who responded to risankizumab IV induction in the INSPIRE study.
The primary endpoint is clinical remission (per Adapted Mayo Score, defined as SFS ≤1 and not greater than baseline, RBS of 0 and endoscopic subscore ≤1 without evidence of friability) at week 52. Secondary endpoints include endoscopic improvement (endoscopic subscore ≤1 without evidence of friability), histologic and endoscopic mucosal improvement (HEMI) (endoscopic subscore of ≤1 without evidence of friability and Geboes score ≤3.1), and steroid-free clinical remission (defined as clinical remission per Adapted Mayo Score at week 52 and corticosteroid free for ≥90 days prior to week 52) at week 52. More information can be found on www.clinicaltrials.gov (NCT03398135).
About SKYRIZI® (risankizumab-rzaa)
SKYRIZI is an interleukin-23 (IL-23) inhibitor that selectively blocks IL-23 by binding to its p19 subunit.10 IL-23, a cytokine involved in inflammatory processes, is thought to be linked to a number of chronic immune-mediated diseases.11 SKYRIZI is approved by the U.S. Food and Drug Administration (FDA) for the treatment of moderately to severely active ulcerative colitis, plaque psoriasis, psoriatic arthritis and Crohn's disease.11,12,13
SKYRIZI® (risankizumab-rzaa) U.S. Uses and Important Safety Information3
SKYRIZI is a prescription medicine used to treat adults with:
- moderate to severe plaque psoriasis who may benefit from taking injections or pills (systemic therapy) or treatment using ultraviolet or UV light (phototherapy).
- active psoriatic arthritis.
- moderate to severe Crohn's disease.
- moderate to severe ulcerative colitis.
- https://www.skyrizi.com/
Please click here for the Full Prescribing Information and Medication Guide.
Globally, prescribing information varies; refer to the individual country product label for complete information.
About AbbVie in Gastroenterology
With a robust clinical trial program, AbbVie is committed to cutting-edge research to drive exciting developments in inflammatory bowel diseases (IBD), like ulcerative colitis and Crohn's disease. By innovating, learning and adapting, AbbVie aspires to eliminate the burden of IBD and make a positive long-term impact on the lives of people with IBD. For more information on AbbVie in gastroenterology, visit https://www.abbvie.com/our-science/therapeutic-focus-areas/immunology/immunology-focus-areas/gastroenterology.html.
About AbbVie
AbbVie's mission is to discover and deliver innovative medicines that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas – immunology, oncology, neuroscience, eye care – and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on LinkedIn, Facebook, Instagram, X (formerly Twitter) and YouTube.
Forward-Looking Statements
SOURCE AbbVie
https://www.nasdaq.com/market-activity/stocks/abbv/dividend-history
CAPVAXIVE™ (Pneumococcal 21-valent Conjugate Vaccine)
CAPVAXIVE™ (Pneumococcal 21-valent Conjugate Vaccine)
CAPVAXIVE™ (Pneumococcal 21-valent Conjugate Vaccine)
U.S. FDA Approves CAPVAXIVE™ (Pneumococcal 21-valent Conjugate Vaccine) for Prevention of Invasive Pneumococcal Disease and Pneumococcal Pneumonia in Adults
June 17, 2024 5:29 pm ET
CAPVAXIVE (V116) is specifically designed for adults and covers serotypes responsible for approximately 84% of invasive pneumococcal disease in adults 50 years of age and older
Across four Phase 3 studies, CAPVAXIVE demonstrated robust immune responses in both vaccine-naïve and vaccine-experienced adult populations
RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced today that the U.S. Food and Drug Administration (FDA) has approved CAPVAXIVE™ (Pneumococcal 21-valent Conjugate Vaccine) for:
- Active immunization for the prevention of invasive disease caused by Streptococcus pneumoniae serotypes 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15B, 15C, 16F, 17F, 19A, 20A, 22F, 23A, 23B, 24F, 31, 33F and 35B in individuals 18 years of age and older;
- Active immunization for the prevention of pneumonia caused by S. pneumoniae serotypes 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20A, 22F, 23A, 23B, 24F, 31, 33F and 35B in individuals 18 years of age and older.
CAPVAXIVE is specifically designed to help protect adults against the serotypes that cause the majority of invasive pneumococcal disease (IPD) cases. The approval follows the FDA’s Priority Review of Merck’s application. Do not administer CAPVAXIVE to individuals with a history of a severe allergic reaction (e.g., anaphylaxis) to any component of CAPVAXIVE or to diphtheria toxoid; see additional Select Safety Information below.
This indication for the prevention of pneumonia caused by S. pneumoniae serotypes 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20A, 22F, 23A, 23B, 24F, 31, 33F and 35B is approved under accelerated approval based on immune responses as measured by opsonophagocytic activity (OPA). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
The U.S. Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices is expected to meet later this month to discuss and make recommendations for the use of CAPVAXIVE in adults.
“Complications from invasive pneumococcal disease can lead to hospitalization, organ damage and even death. Many cases of adult disease are caused by serotypes not included in other approved pneumococcal conjugate vaccines,” said Dr. Walter Orenstein, professor emeritus of medicine, epidemiology, global health and pediatrics at Emory University and member of Merck’s Scientific Advisory Committee. “CAPVAXIVE is designed to include the serotypes that cause the majority of invasive pneumococcal disease in adults, helping to protect adults against invasive pneumococcal disease and pneumococcal pneumonia.”
Based on CDC data from 2018-2021, the serotypes covered by CAPVAXIVE are responsible for more cases of IPD in adults compared to PCV20 (pneumococcal 20-valent conjugate vaccine).
- In adults 50 years of age and older, CAPVAXIVE covers the serotypes responsible for approximately 84% of IPD cases, compared to approximately 52% covered by PCV20.
- In adults 65 years of age and older, CAPVAXIVE covers the serotypes responsible for approximately 85% of IPD cases, compared to approximately 51% covered by PCV20.
These values are based on CDC epidemiologic data and do not reflect the efficacy of the respective vaccines. There are currently no studies comparing the efficacy of CAPVAXIVE and PCV20.
CAPVAXIVE includes eight unique serotypes not covered by other currently approved pneumococcal vaccines; those serotypes were responsible for approximately 27% of IPD cases in adults 50 years of age and older and approximately 30% in adults 65 years of age and older, based on the same CDC data.
“Today’s approval is a testament to our population-specific strategy behind CAPVAXIVE, which demonstrated robust immunogenicity in a range of adult populations and is driven by a deep understanding of pneumococcal disease,” said Dr. Dean Y. Li, president, Merck Research Laboratories. “We are proud to provide CAPVAXIVE as a new option specifically designed to help protect against the majority of invasive pneumococcal disease-causing serotypes in adults.”
Among the clinical data supporting the approval are results from the pivotal Phase 3 STRIDE-3 trial (NCT05425732), which evaluated CAPVAXIVE compared to PCV20 in adults 18 years of age and older who had not previously received a pneumococcal vaccine. The approval is also supported by results from the Phase 3 STRIDE-5 (NCT05526716) and STRIDE-6 (NCT05420961) trials evaluating CAPVAXIVE in vaccine-naïve and vaccine-experienced adults (see “Clinical Data Supporting FDA Approval,” below, for additional details).
About CAPVAXIVE
CAPVAXIVE is Merck’s approved 21-valent pneumococcal conjugate vaccine indicated for active immunization for the prevention of invasive disease and pneumonia in adults 18 years of age and older. CAPVAXIVE is specifically designed to help address Streptococcus pneumoniae serotypes predominantly responsible for adult invasive pneumococcal disease (IPD), including eight unique serotypes, 15A, 15C, 16F, 23A, 23B, 24F, 31 and 35B compared to other pneumococcal vaccines. CAPVAXIVE is administered as a single dose.
Select Safety Information for CAPVAXIVE
Do not administer CAPVAXIVE to individuals with a history of a severe allergic reaction (eg, anaphylaxis) to any component of CAPVAXIVE or to diphtheria toxoid.
Individuals with altered immunocompetence, including those receiving immunosuppressive therapy, may have a reduced immune response to CAPVAXIVE.
The most commonly reported (>10%) solicited adverse reactions in individuals 18 through 49 years of age who received CAPVAXIVE were: injection-site pain (73.1%), fatigue (36.0%), headache (27.5%), myalgia (16.4%), injection-site erythema (13.8%), and injection-site swelling (13.3%).
The most commonly reported (>10%) solicited adverse reactions in individuals 50 years of age and older who received CAPVAXIVE were: injection-site pain (41.2%), fatigue (19.7%), and headache (11.0%).
Vaccination with CAPVAXIVE may not protect all vaccine recipients.
Clinical Data Supporting FDA Approval
CAPVAXIVE was approved based on data that included Phase 3 clinical studies designed to evaluate its safety and immunogenicity in a variety of adult populations. These included studies of:
- Vaccine-naïve adults : STRIDE-3 (NCT05425732) is a double-blind, Phase 3 study which evaluated CAPVAXIVE compared to PCV20 in individuals 18 years of age and older who had not previously received a pneumococcal conjugate vaccine. Participants 50 years of age and older were enrolled in cohort 1 (n=2,362), and participants 18 through 49 years of age were enrolled in cohort 2 (n=300). Participants were randomized to receive a single dose of either CAPVAXIVE or PCV20. Results from the study include:
- In adults 50 years of age and older (cohort 1), CAPVAXIVE was non-inferior to PCV20 for the 10 serotype polysaccharides shared with both vaccines (3, 6A, 7F, 8, 10A, 11A, 12F, 19A, 22F, 33F), as assessed by serotype-specific OPA geometric mean titers (GMTs) at 1 month postvaccination;
- CAPVAXIVE was superior to PCV20 for 10 of 11 serotype polysaccharides included in CAPVAXIVE but not in PCV20 (9N, 15A, 16F, 17F, 20A, 23A, 23B, 24F, 31, 35B), as assessed by serotype-specific OPA GMTs 1 month postvaccination and the proportions of patients with a greater than or equal to four-fold increase in OPA from prevaccination to 1 month postvaccination;
- Immune responses were observed for serotype 15C in participants receiving CAPVAXIVE but did not meet criteria for statistical significance.
- In individuals 18 through 49 years of age (cohort 2), CAPVAXIVE elicited non-inferior immune responses (immunobridged) compared to individuals 50 through 64 years of age, as assessed by serotype-specific OPA GMTs 1 month postvaccination;
- Across both cohorts, CAPVAXIVE had a safety profile comparable to PCV20.
- In adults 50 years of age and older (cohort 1), CAPVAXIVE was non-inferior to PCV20 for the 10 serotype polysaccharides shared with both vaccines (3, 6A, 7F, 8, 10A, 11A, 12F, 19A, 22F, 33F), as assessed by serotype-specific OPA geometric mean titers (GMTs) at 1 month postvaccination;
- Co-administration of CAPVAXIVE with quadrivalent influenza vaccine (QIV) : STRIDE-5 (NCT05526716) is a randomized, double-blind, Phase 3 study which evaluated CAPVAXIVE when administered concomitantly or sequentially (30 days later) with QIV in adults 50 years of age and older (n=1,080). Results from the study include:
- For the primary immunogenicity endpoints, CAPVAXIVE administered concomitantly with QIV was non-inferior to CAPVAXIVE administered sequentially with QIV for 20 of 21 serotypes in CAPVAXIVE (as assessed by OPA GMTs at 1 month postvaccination), as well as for three of four influenza strains in QIV (as assessed by hemagglutination inhibition (HAI) GMTs at 1 month postvaccination);
- The rates and severity of solicited systemic adverse reactions and solicited local adverse reactions at the CAPVAXIVE injection site were similar when CAPVAXIVE was administered with or without inactivated QIV.
- Vaccine-experienced adults : STRIDE-6 (NCT05420961) is a randomized descriptive Phase 3 study which evaluated CAPVAXIVE in individuals 50 years of age and older who had previously received a pneumococcal vaccine at least one year before enrollment. Participants were enrolled into one of three cohorts based on their previous pneumococcal vaccination history (cohort 1: PPSV23 [pneumococcal 23-valent polysaccharide vaccine], cohort 2: PCV13 [pneumococcal 13-valent conjugate vaccine], or cohort 3: PPSV23 followed by or preceded by PCV13, PPSV23 preceded by PCV15 [pneumococcal 15-valent conjugate vaccine], or PCV15 alone). Participants in cohort 1 were randomized to receive CAPVAXIVE (n=231) or PCV15 (n=119), participants in cohort 2 were randomized to receive CAPVAXIVE (n=176) or PPSV23 (n=85), and participants in cohort 3 were allocated to receive CAPVAXIVE (n=106). In each of the 3 cohorts, serotype-specific OPA GMTs and the proportion of individuals with ≥4-fold rise in OPA responses from baseline to 1-month postvaccination were assessed. Results from the study include:
- In cohort 1, CAPVAXIVE elicited OPA responses that were comparable to PCV15 for the 6 common serotypes, and higher for the 15 unique serotypes and serotype 15B;
- In cohort 2, CAPVAXIVE elicited OPA responses comparable to PPSV23 for the 12 common serotypes and serotype 15B, and higher for the 9 unique serotypes;
- OPA responses to CAPVAXIVE were similar across the 3 cohorts of participants who previously received one or more pneumococcal vaccines;
- CAPVAXIVE had a safety profile comparable to both PCV15 and PPSV23.
About Pneumococcal Disease
Pneumococcal disease is an infection caused by a bacteria called Streptococcus pneumoniae. There are about 100 different types (referred to as serotypes) of pneumococcal bacteria, which can affect adults differently than children. Pneumococcal disease can be invasive or non-invasive. Non-invasive pneumococcal illnesses include pneumonia (when pneumococcal disease is confined to the lungs), whereas invasive pneumococcal illnesses include pneumococcal bacteremia (infection in the bloodstream), bacteremic pneumococcal pneumonia (pneumonia with bacteremia) and pneumococcal meningitis (infection of the coverings of the brain and spinal cord). Pneumococcal pneumonia is a type of bacterial pneumonia, which is the most common clinical presentation of pneumococcal disease in adults. It’s estimated that over 150,000 adults are hospitalized from pneumococcal pneumonia each year in the U.S.
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.
Please see Prescribing Information for CAPVAXIVE (Pneumococcal 21-valent Conjugate Vaccine) at https://www.merck.com/product/usa/pi_circulars/c/capvaxive/capvaxive_pi.pdf and Patient Information/Medication Guide for CAPVAXIVE at https://www.merck.com/product/usa/pi_circulars/c/capvaxive/capvaxive_ppi.pdf.
Source: Merck & Co., Inc.
Merck gets FDA approval for Capvaxive pneumonia vaccine (update)
Jun. 17, 2024 5:51 PM ET
Merck & Co., Inc. (MRK) StockPFE
By: Val Brickates Kennedy, SA News Editor
Merck (NYSE:MRK) has received FDA approval for its Capvaxive 21-valent conjugate vaccine for the prevention of pneumonia in adults.
The drugmaker said the vaccine is designed to cover serotypes responsible for around 84% of invasive pneumococcal disease in people aged 50 years and older.
An advisory committee of the US Centers for Disease Control and Prevention is expected to meet later this month to discuss recommendations for use of the vaccine in adults.
ZW171
CAPVAXIVE™ (Pneumococcal 21-valent Conjugate Vaccine)
RYBREVANT® (amivantamab-vmjw)
Zymeworks Announces FDA Clearance Of Investigational New Drug Application For ZW171, A Novel 2+1 T-Cell Targeting Bispecific Antibody For Mesothelin-Expressing Cancers
06/17/2024 at 6:00 AM EDT
VANCOUVER, British Columbia, June 17, 2024 (GLOBE NEWSWIRE) -- Zymeworks Inc. (Nasdaq: ZYME), a clinical-stage biotechnology company developing a diverse pipeline of novel, multifunctional biotherapeutics to improve the standard of care for difficult-to-treat diseases, today announced that the United States Food and Drug Administration (FDA) has cleared the investigational new drug (IND) application for ZW171, a novel 2+1 T-cell targeting bispecific antibody for mesothelin (MSLN)-expressing cancers.
“We are excited to reach this R&D milestone with ZW171, reflecting our commitment to advancing innovative therapies for cancer treatment,” said Paul Moore, Chief Scientific Officer of Zymeworks. “ZW171’s unique design is intended to address the limitations of current bispecific T-cell engagers by enhancing tumor selectivity and improving safety. With promising preclinical results, ZW171 has the potential to provide a more effective and tolerable treatment option for patients with MSLN-expressing cancers, including ovarian cancer, non-small cell lung cancer, mesothelioma, and other cancers1. We look forward to initiating clinical development of ZW171 during 2024 and continuing to advance additional product candidates in our ‘5 by 5’ strategy over the next 24 months.”
The Company expects to file applications seeking regulatory permission to commence clinical studies for ZW171 in other non-US jurisdictions in the second half of 2024.
ZW171 is a bispecific antibody designed to enable T cell-mediated tumor cell killing through simultaneous binding to the extracellular domain of MSLN protein on tumor cells and the engagement of CD3 on T cells. Moderate to high membranous MSLN expression is frequent in ovarian cancer, non-small cell lung cancer, mesothelioma and other cancers1. Preliminary evidence of anti-tumor activity with engineered T-cell therapy supports utility of T-cell targeted therapies in treatment of MSLN-expressing solid tumors2. ZW171’s unique 2+1 format and incorporation of a novel low-affinity anti-CD3 binder aims to improve the therapeutic window in patients by limiting on-target, off-tumor effects and cytokine release syndrome (CRS) while maintaining potent anti-tumor activity against MSLN-expressing cancers3. By selectively binding to tumors and sparing normal tissues, ZW171 is designed to improve both tolerability and anti-tumor activity against MSLN-expressing cancers. Engineered and optimized using our Azymetric™ and EFECT™4 technologies, ZW171 demonstrates enhanced anti-tumor activity and safety in preclinical models, inducing potent, preferential killing of MSLN-overexpressing cells while mitigating the risk of on-target, off-tumor activity, peripheral T cell activation, and CRS.
1. Chang K, Pastan I, Proc Natl Acad Sci U S A. 1996;93(1):136-40
2. Hassan R, et al. Nat Med. 2023;29:2099-2109
3. 1. Wang L, et al., Cancer Immunol Res. 2019; 7(12): 2013–2024
4. Afacan N, et al. Presented at: AACR. 2023 (abstr #2942)
About Zymeworks Inc.
Zymeworks is a global clinical-stage biotechnology company committed to the discovery, development, and commercialization of novel, multifunctional biotherapeutics. Zymeworks’ mission is to make a meaningful difference in the lives of people impacted by difficult-to-treat cancers and other diseases. The Company’s complementary therapeutic platforms and fully integrated drug development engine provide the flexibility and compatibility to precisely engineer and develop highly differentiated antibody-based therapeutic candidates. Zymeworks engineered and developed zanidatamab, a HER2-targeted bispecific antibody using the Company’s proprietary Azymetric™ technology. Zymeworks has entered into separate agreements with BeiGene, Ltd. (BeiGene) and Jazz Pharmaceuticals Ireland Limited (Jazz), granting each exclusive rights to develop and commercialize zanidatamab in different territories. Zanidatamab is currently being evaluated in multiple global clinical trials as a potential best-in-class treatment for patients with HER2-expressing cancers. A Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) seeking accelerated approval for zanidatamab as a treatment for previously-treated, unresectable, locally advanced, or metastatic HER2-positive biliary tract cancer (BTC) has been accepted and granted Priority Review. A BLA has also been accepted for review by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) in China. If approved, zanidatamab would be the first HER2-targeted treatment specifically approved for BTC in the U.S. and China. Zymeworks is rapidly advancing a deep pipeline of product candidates based on its experience and capabilities in both antibody-drug conjugates and multispecific antibody therapeutics across multiple novel targets in indications that represent areas of significant unmet medical need. In addition to Zymeworks’ wholly owned pipeline, its therapeutic platforms have been further leveraged through strategic partnerships with global biopharmaceutical companies. For information about Zymeworks, visit www.zymeworks.com and follow @ZymeworksInc on X.
Source: Zymeworks Inc.
Zymeworks ZW171 IND for mesothelin-expressing cancers cleared by FDA
Jun. 17, 2024 2:49 PM ET
Zymeworks Inc. (ZYME) Stock, ZYME:CA Stock
By: Jonathan Block, SA News Editor
- The U.S. FDA has cleared Zymeworks' (NASDAQ:ZYME) Investigational New Drug application for ZW171, a 2+1 T-cell targeting bispecific antibody for mesothelin (MSLN)-expressing cancers.
- On its website, the company said that MSLN is expressed in many different types of cancer, including pancreatic, colorectal and ovarian.
- https://seekingalpha.com/news/4116745-zymeworks-zw171-ind-mesothelin-expressing-cancers-cleared-fda?source=content_type%3Areact%7Cfirst_level_url%3Amarket-news%7Csection_asset%3Amain%7Csection%3Ahealthcare
- Zymeworks Inc. (ZYME) Stock, ZYME:CA Stock
- https://www.zymeworks.com/
- https://www.zymeworks.com/pipeline/
RYBREVANT® (amivantamab-vmjw)
RYBREVANT® (amivantamab-vmjw)
RYBREVANT® (amivantamab-vmjw)
Subcutaneous amivantamab Biologics License Application submitted to U.S. FDA for patients with EGFR-mutated non-small cell lung cancer
Application based on Phase 3 PALOMA-3 results showing five-fold reduction in infusion-related reactions with five-minute administration of subcutaneous amivantamab
Longer overall survival, progression-free survival and duration of response also observed with subcutaneous amivantamab
June 17, 2024
RARATIN, N.J., June 17, 2024
/PR Newswire/ –
Johnson & Johnson (NYSE: JNJ) announced today the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for a fixed combination of amivantamab and recombinant human hyaluronidase for subcutaneous administration (SC amivantamab) for all currently approved or submitted indications of intravenous (IV) RYBREVANT® (amivantamab-vmjw) in certain patients with non-small cell lung cancer (NSCLC).
Data from the Phase 3 PALOMA-3 study (NCT05388669) presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and published in the Journal of Clinical Oncology showed SC amivantamab had comparable overall response rates to IV administration in patients with NSCLC with epidermal growth factor receptor (EGFR) exon 19 deletion or L858R mutations. SC amivantamab also demonstrated significantly shorter administration time and a five-fold reduction in infusion-related reactions, alongside longer overall survival, progression-free survival and duration of response.1 Efficacy results like these have not been seen before in a study assessing IV and SC comparability. The BLA submission includes data from the Phase 2 PALOMA-2 (NCT05498428) study evaluating SC amivantamab in settings where IV amivantamab has been previously submitted for approval and is intended to support dosing schedules of every two and every three weeks.2
“RYBREVANT administered intravenously is a foundational treatment for patients with EGFR-mutated NSCLC,” said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Johnson & Johnson Innovative Medicine. “This subcutaneous option, administered in approximately five minutes, is a clinically important advancement that could transform the treatment experience for patients, oncologists and nursing staff. We look forward to working with the FDA and global regulators in the review of these applications.”
Today’s submission follows two recent milestones for the RYBREVANT® IV formulation, including the approval of RYBREVANT® in combination with chemotherapy as the first FDA-approved therapy for first-line treatment of patients with NSCLC with EGFR exon 20 insertion mutations supported by the Phase 3 PAPILLON study and a CHMP positive opinion for RYBREVANT® in combination with chemotherapy for this indication in Europe.
About PALOMA-3
PALOMA-3 (NCT05388669), which enrolled 418 patients, is a randomized, open-label Phase 3 study evaluating the pharmacokinetics (PK), efficacy and safety of subcutaneous amivantamab (administered via manual injection) combined with lazertinib compared to IV amivantamab and lazertinib in patients with EGFR-mutated advanced or metastatic NSCLC after progression on osimertinib and chemotherapy. The co-primary PK endpoints of the study were trough concentration (Ctrough on Cycle [C] 2 Day [D] 1 or C4D1) and C2 area under the curve (AUCD1-D15). Key secondary endpoints were objective response rate and progression-free survival. Overall survival was a predefined exploratory endpoint. Prophylactic anticoagulation was recommended for the first four months of treatment.1
About the PALOMA-2 Study
PALOMA-2 (NCT05498428) is an open-label Phase 2 study evaluating the efficacy, safety, and PK of first-line SC amivantamab (administered via manual injection) combined with lazertinib and/or chemotherapy in patients with EGFR-mutated advanced or metastatic NSCLC. Sixty-eight and 58 patients were enrolled in Cohorts 1 and 6, respectively. Prophylactic anticoagulation for the first four months of treatment was recommended in Cohort 1 and mandatory in Cohort 6. The primary endpoint was objective response rate (ORR) as assessed by the investigator per RECIST v1.1.2
About RYBREVANT®
RYBREVANT® (amivantamab-vmjw), a fully-human bispecific antibody targeting EGFR and MET with immune cell-directing activity, is approved in the U.S., Europe, and in other markets around the world as monotherapy for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.3 In the subcutaneous formulation, amivantamab is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE® drug delivery technology.
RYBREVANT® is also approved in the U.S. in combination with chemotherapy (carboplatin and pemetrexed) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test. In October 2023, a type II extension of indication application was submitted to the European Medicines Agency (EMA) seeking approval of RYBREVANT® for this indication.
In December 2023, Johnson & Johnson submitted a supplemental Biologics License Application (sBLA) together with a New Drug Application (NDA) to the U.S. FDA for RYBREVANT® in combination with lazertinib for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or L858R substitution mutations, as detected by an FDA-approved test. This submission is based on the Phase 3 MARIPOSA study and was granted Priority Review in February 2024. A marketing authorization application (MAA) and type II extension of indication application were also submitted to the EMA seeking approval of lazertinib in combination with RYBREVANT® based on the MARIPOSA study.
In November 2023, Johnson & Johnson submitted an sBLA to the U.S. FDA for RYBREVANT® in combination with chemotherapy for the treatment of patients with EGFR-mutated NSCLC who progressed on or after osimertinib based on the MARIPOSA-2 study. A type II extension of indication application was also submitted to the EMA seeking approval of RYBREVANT® for this indication.
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for NSCLC§ prefer next-generation sequencing–based strategies over polymerase chain reaction–based approaches for the detection of EGFR exon 20 insertion variants. The NCCN Guidelines include:
- Amivantamab-vmjw (RYBREVANT®) plus carboplatin and pemetrexed as a preferred (Category 1 recommendation) first-line therapy in treatment-naive patients with newly diagnosed advanced or metastatic EGFR exon 20 insertion mutation-positive advanced NSCLC, or as a subsequent therapy option (Category 2A recommendation) for patients that have progressed on or after platinum-based chemotherapy with or without immunotherapy and have EGFR exon 20 insertion mutation-positive advanced NSCLC.4 †‡
- Amivantamab-vmjw (RYBREVANT®) plus chemotherapy as a preferred (Category 1 recommendation) subsequent therapy for patients with locally advanced or metastatic NCSLC with EGFR exon 19 deletions or exon 21 L858R mutations who experienced disease progression after treatment with osimertinib.4 †‡
- Amivantamab-vmjw (RYBREVANT®) as a subsequent therapy option (Category 2A recommendation) for patients that have progressed on or after platinum-based chemotherapy with or without an immunotherapy and have EGFR exon 20 insertion mutation-positive NSCLC.4 †‡
RYBREVANT® is being studied in multiple clinical trials in NSCLC, including:
- The Phase 1 PALOMA (NCT04606381) study assessing the feasibility of subcutaneous administration of amivantamab based on safety and pharmacokinetics and to determine a dose, dose regimen and formulation for amivantamab subcutaneous delivery.5
- The Phase 2 PALOMA-2 (NCT05498428) study assessing subcutaneous amivantamab in patients with advanced or metastatic solid tumors including EGFR-mutated NSCLC.2
- The Phase 3 PALOMA-3 (NCT05388669) study assessing lazertinib with subcutaneous amivantamab compared to intravenous amivantamab in patients with EGFR-mutated advanced or metastatic NSCLC.1
- The Phase 3 PAPILLON (NCT04538664) study assessing RYBREVANT® in combination with carboplatin-pemetrexed versus chemotherapy alone in the first-line treatment of patients with advanced or metastatic NSCLC with EGFR exon 20 insertion mutations.6
- The Phase 3 MARIPOSA-2 (NCT04988295) study assessing the efficacy of RYBREVANT® (with or without lazertinib) and carboplatin-pemetrexed versus carboplatin-pemetrexed alone in patients with locally advanced or metastatic EGFR ex19del or L858R substitution NSCLC after disease progression on or after osimertinib.7
- The Phase 3 MARIPOSA (NCT04487080) study assessing RYBREVANT® in combination with lazertinib versus osimertinib and versus lazertinib alone in the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR ex19del or L858R substitution mutations.8
- The Phase 1 CHRYSALIS (NCT02609776) study evaluating RYBREVANT® in patients with advanced NSCLC.9
- The Phase 1/1b CHRYSALIS-2 (NCT04077463) study evaluating RYBREVANT® in combination with lazertinib and lazertinib as a monotherapy in patients with advanced NSCLC with EGFR mutations.10
- The Phase 1/2 METalmark (NCT05488314) study assessing RYBREVANT® and capmatinib combination therapy in locally advanced or metastatic NSCLC.11
- The Phase 1/2 PolyDamas (NCT05908734) study assessing RYBREVANT® and cetrelimab combination therapy in locally advanced or metastatic NSCLC.12
- The Phase 2 SKIPPirr study (NCT05663866) exploring how to decrease the incidence and/or severity of first-dose infusion-related reactions with RYBREVANT® in combination with lazertinib in relapsed or refractory EGFR-mutated advanced or metastatic NSCLC.13
For more information, visit: https://www.RYBREVANT.com.
About Lazertinib
Lazertinib is an oral, third-generation, brain-penetrant EGFR tyrosine kinase inhibitor (TKI) that targets both the T790M mutation and activating EGFR mutations while sparing wild type-EGFR. An analysis of the efficacy and safety of lazertinib from the Phase 3 study was published in The Journal of Clinical Oncology in 2023. In 2018, Janssen Biotech, Inc., entered into a license and collaboration agreement with Yuhan Corporation for the development of lazertinib.14
About Non-Small Cell Lung Cancer
Worldwide, lung cancer is one of the most common cancers, with NSCLC making up 80 to 85 percent of all lung cancer cases.15,16 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.17 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division.18 EGFR mutations are present in 10 to 15 percent of Western patients with NSCLC with adenocarcinoma histology and occur in 40 to 50 percent of Asian patients.17, 17, 19, 20, 21, 22 EGFR ex19del or EGFR L858R mutations are the most common EGFR mutations.23 The five year survival rate for all people with advanced NSCLC and EGFR mutations treated with EGFR tyrosine kinase inhibitors (TKIs) is less than 20 percent.24, 25 EGFR exon 20 insertion mutations are the third most prevalent activating EGFR mutation.26 Patients with EGFR exon 20 insertion mutations have a real-world five-year overall survival (OS) of eight percent in the frontline setting, which is worse than patients with EGFR ex19del or L858R mutations, who have a real-world five-year OS of 19 percent.27
Please read full Prescribing Information for RYBREVANT®.
About Johnson & Johnson
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at https://www.jnj.com/ or at www.janssen.com/johnson-johnson-innovative-medicine. Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC, and Janssen Biotech, Inc., are Johnson & Johnson companies.
Source: Johnson & Johnson
Nipocalimab
RYBREVANT® (amivantamab-vmjw)
TALVEY® (talquetamab-tgvs)
Late-breaking results show nipocalimab significantly improves Sjögren’s disease activity in a Phase 2 study
Patients who received nipocalimab 15 mg/kg demonstrated a greater than 70 percent relative average improvement on the primary endpoint compared to patients who received placebo
Sjögren’s disease is a chronic, debilitating, and prevalent autoantibody disease with no approved advanced treatments
June 15, 2024
VIENNA (PRNewswire (June 15, 2024) – Johnson & Johnson (NYSE: JNJ) announces patients treated with nipocalimab demonstrated statistically significant (P=0.002) and clinically meaningful improvement in ClinESSDAIa score versus placebo at 24 weeks compared to baseline (primary endpoint) in the Phase 2 DAHLIAS dose-ranging study of nipocalimab in adult patients living with Sjögren’s disease (SjD). Response was demonstrated as early as Week 4 and continued to increase throughout the 24-week treatment period compared with patients receiving placebo. These data represent the first positive results in SjD for nipocalimab. The study results were featured in a late-breaking presentation (LBA0010) and are among 30 abstracts that the Company is presenting at the European Alliance of Associations for Rheumatology (EULAR) 2024 Congress.
“These data establish proof of concept for nipocalimab in Sjögren’s disease and support further clinical development, which is welcome news for the approximately four million people worldwide living with this chronic, debilitating disease,” said Prof. Jacques-Eric Gottenberg, M.D., Ph.D., Department of Rheumatology, Strasbourg University Hospital, National Centre for Rare Systemic Autoimmune Diseases and study investigator.b,1,2 “SjD patients need approved advanced therapies that can help address the serious health consequences of the disease, and I am encouraged by these results and the positive impact on disease measures that are clinically meaningful.”
In addition to achieving the primary endpoint, the nipocalimab 15 mg/kg treatment group demonstrated:
- Clinically meaningful improvements in secondary endpoints at Week 24 including multiple organ assessments (DALc), physician assessments (PhGAd), and composite tools for clinical trial endpoints (STARe, CRESSf)
- Improvement trends in important SjD symptoms including mouth dryness, eye dryness, and vaginal dryness
- Safety and tolerability consistent with other nipocalimab clinical studies
Furthermore, lowering levels of total IgG and autoantibodies associated with SjD (e.g. anti-Ro60 and -La/SSB) are highly consistent with the nipocalimab mechanism of action, exhibiting reductions similar to those observed in prior nipocalimab clinical studies.
“A clear need exists for patients living with Sjögren’s disease to have advanced therapies that target the underlying cause and systemic nature of this disease, as none have been approved to date,” said Terence Rooney, Vice President, Rheumatology, Immunology Disease Area Leader, Johnson & Johnson Innovative Medicine. “Johnson & Johnson is committed to delivering innovative and transformational approaches for autoantibody-mediated diseases like SjD, and the data presented at EULAR demonstrate the potential of nipocalimab in a disease where patients have very few options.”
Editor’s Note:
a. ClinESSDAI is an endpoint specific to SjD and is a composite scale that assesses organ disease activity across 11 organ system domains [cutaneous, pulmonary, renal, articular, muscular, peripheral nervous system (PNS), central nervous system (CNS), hematological, glandular, constitutional, lymphadenopathy and lymphoma]; a higher score indicates greater symptom severity.
b. Prof. Jacques-Eric Gottenberg, M.D., Ph.D. is a paid consultant for Johnson & Johnson. He has not been compensated for any media work.
c. Disease Activity Level (DAL) response is a reduction from baseline in disease activity level by at least 1 level in at least 1 clinESSDAI domain (eg, articular, hematological, cutaneous, constitutional, etc).
d. The Physician Global Assessment of Disease Severity (PhGA) is recorded by the investigator, independent of study participants’ assessment, on a visual analog scale (VAS) with responses ranging from 0 to 100 mm, with the anchors “No Sjögren’s Syndrome Activity” (0) at one end of the scale and “Extremely Active Sjögren’s Syndrome” (100 mm) at the opposite end of the scale. The baseline measurement for the PhGA is defined as the closest measurement taken prior to the initiation of the Week 0 administration.
e. Sjögren’s Tool for Assessing Response (STAR) is a composite responder index that includes all main SjD disease features, including systemic disease activity, patient-reported symptoms, tear gland item, salivary gland item and serology, in a single tool.
f. Composite of Relevant Endpoints for Sjögren’s Syndrome (CRESS) is a composite endpoint tool consisting of five complementary items, systemic disease activity, patient-reported symptoms, tear gland item, salivary gland item and serology, for use in trials of primary SjD
About Sjögren’s Disease (SjD)
Sjögren’s disease (SjD) is one of the most prevalent autoantibody driven diseases for which no therapies are currently approved that treat the underlying and systemic nature of the disease.3 It is a chronic autoimmune disease that is estimated to impact approximately four million people worldwide and is nine times more common in women than men.1,2 SjD is characterized by autoantibody production, chronic inflammation, and lymphocytic infiltration of exocrine glandular systems. Most patients are affected by mucosal dryness (eyes, mouth, vagina), joint pain and fatigue.3 Extraglandular manifestations are common and may impact multiple organ systems, including joints, lungs, kidneys, and nervous system.5 Patients with SjD have a high risk of developing numerous associated conditions, including up to 20 times higher risk of developing B-cell lymphomas when compared to the general population. SjD increases all-cause mortality risk by approximately 50% more than the general population, and high activity in more than one organ/disease domain increases mortality risk by up to five-fold.3,4 Disease burden can be as high as that of rheumatoid arthritis or systemic lupus erythematosus. It is usually associated with impaired quality of life and functional capacity.2,5
About DAHLIAS
DAHLIAS is a Phase 2 multicenter, randomized, placebo-controlled double-blind study to evaluate the effects of nipocalimab in participants with primary Sjögren’s disease. DAHLIAS includes a Phase 2 dose-ranging study for adults with moderately-to-severely active primary SjD who were seropositive for anti-Ro60 and/or anti-Ro52 IgG antibodies. One hundred sixty three adults aged 18-75 were randomized 1:1:1 to receive intravenous nipocalimab at 5 or 15 mg/kg or placebo every 2 weeks through Week 22 and received protocol-permitted background standard of care. Safety assessments were conducted through Week 30.
About Nipocalimab
Nipocalimab is an investigational monoclonal antibody, purposefully designed to bind with high affinity to block FcRn and reduce levels of circulating immunoglobulin G (IgG) antibodies, while preserving immune function without causing broad immunosuppression. This includes autoantibodies and alloantibodies that underlie multiple conditions across three key segments in the autoantibody space including Rare Autoantibody diseases, Maternal Fetal diseases mediated by maternal alloantibodies and Prevalent Rheumatology.6,7,8,9,10,11,12,13,14
Blockade of IgG binding to FcRn in the placenta is also believed to prevent transplacental transfer of maternal alloantibodies to the fetus.15,16
The U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) have granted several key designations to nipocalimab including:
- Fast Track designation in HDFN and warm autoimmune hemolytic anemia (wAIHA) in July 2019, gMG in December 2021 and fetal neonatal alloimmune thrombocytopenia (FNAIT) in March 2024
- Orphan drug status for wAIHA in December 2019, HDFN in June 2020, gMG in February 2021, chronic inflammatory demyelinating polyneuropathy (CIDP) in October 2021 and FNAIT in December 2023
- Breakthrough Therapy Designation for HDFN in February 2024
- Orphan medicinal product designation for HDFN by the European Medicines Agency in October 2019
About Johnson & Johnson
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at https://www.jnj.com/ or at www.janssen.com/johnson-johnson-innovative-medicine. Follow us at @JanssenUS and @JNJInnovMed.
Janssen Research & Development, LLC and Janssen Biotech, Inc. are Johnson & Johnson companies.
Source: Johnson & Johnson
TALVEY® (talquetamab-tgvs)
RYBREVANT® (amivantamab-vmjw)
TALVEY® (talquetamab-tgvs)
TALVEY® (talquetamab-tgvs) demonstrates highly durable, longer-term responses in patients with relapsed or refractory multiple myeloma
24-month overall survival rate of 67 percent achieved with TALVEY® 0.8 mg/kg biweekly dosing in the Phase 1/2 MonumenTAL-1 study
June 14, 2024
MADRID (PRNewswire (June 14, 2024) –
Johnson & Johnson (NYSE: JNJ) announced today that long-term data from the Phase 1/2 MonumenTAL-1 study showed that with 20 to 30 months of median follow-up, triple-class-exposed patients with relapsed or refractory multiple myeloma (RRMM) who were treated with TALVEY® (talquetamab-tgvs) maintained high overall response rates (ORR) and durable responses, irrespective of whether they had received prior T-cell redirection therapy.1 These data, featured in a poster presentation at the 2024 European Hematology Association (EHA) Congress (Abstract #P915) demonstrate the efficacy and durability of TALVEY® when used before or after chimeric antigen receptor T-cell (CAR-T) therapy or bispecific antibody therapies in triple-class-exposed patients with RRMM.1
“Results from the MonumenTAL-1 study continue to show deeper response levels and a longer duration of response in patients treated with either of the approved dose options of talquetamab, while the median overall survival has yet to be reached at two years,” said Dr. Leo Rasche, attending physician on the myeloma service, University Hospital of Würzburg.* “It is encouraging to see no notable increases in treatment-related discontinuations with this longer follow-up across cohorts.”
In MonumenTAL-1, 297 patients with no prior exposure to T-cell redirection therapy received TALVEY® at the recommended Phase 2 dose (RP2D) of 0.8 mg/kg biweekly (Q2W) [n=154] or 0.4 mg/kg weekly (QW) [n=143].1 At a median follow-up of 23.4 months, patients in the Q2W cohort demonstrated a median duration of response (DOR) of 17.5 months, with median DOR not reached in patients with complete response (CR) or better. For patients in the QW arm, a median follow-up of 29.8 months showed a median DOR of 9.5 months with a median DOR of 28.6 months in patients with a CR or better. At 24 months, 67.1 percent and 60.6 percent of patients were alive from the two dosing cohorts, respectively.1
At a median follow-up of 20.5 months, TALVEY® continued to show strong efficacy in patients with prior T-cell redirection therapy exposure (n=78), with 55.1 percent of patients achieving very good partial response (VGPR) or better and 57.3 percent alive at 24.2 months.1
Infection rates remained lower than in studies of B-cell maturation antigen–targeted bispecific antibodies (BsAbs), consistent with previous reports. No increase in grade 3/4 infections was observed, with longer follow-up GPRC5D-associated adverse events (AEs) led to few dose reductions and discontinuations. One additional patient discontinued treatment due to AEs since the previous report. Weight loss, as assessed by vital signs, was evident early but stabilized and improved over time, including in patients with oral toxicities. 1
Data from MonumenTAL-2 support continued durable responses at one year with investigational combination of TALVEY® and pomalidomide in patients with RRMM who had ≥ two prior lines of therapy
Longer follow-up from the Phase 1b MonumenTAL-2 study of the investigational use of TALVEY® and pomalidomide show deep responses and a manageable safety profile in patients with RRMM and support the potential to combine TALVEY® with an immunomodulatory agent (IMiD). These updated data, from the first-ever study of a regimen combining a GPRC5D-targeted therapy and an immunomodulatory agent, were featured as a poster presentation at the 2024 EHA Congress (Abstract #P911).2
Patients in the Phase 1b MonumenTAL-2 study (n=35) were treated with subcutaneous (SC) TALVEY® at the RP2D of 0.8 mg/kg (Q2W) (n=19) or 0.4 mg/kg (QW) (n=16) with step-up doses, plus 2.0 mg of oral pomalidomide daily. At a median follow-up of 16.8 months (range, 1.2-25.1), response-evaluable patients demonstrated an ORR of 88.6 percent (≥ VGPR, 80 percent).2
“With multiple dosing options and the ability to be used both before or after CAR-T therapy and BCMA bispecifics, TALVEY is an important and versatile treatment option for the treatment of relapsed or refractory multiple myeloma,” said Jordan Schecter, M.D., Vice President, Disease Area Leader, Multiple Myeloma, at Johnson & Johnson Innovative Medicine. “The low rate of grade 3/4 infections seen in MonumenTAL-2 suggests the flexibility of TALVEY as a combination partner with an immunomodulatory agent for patients who continue to face limited treatment options with this complex hematologic disease.”
At 12 months, 80.4 percent of patients who achieved a CR or better maintained their response.2 The progression-free survival (PFS) rate at 12 months was 72.6 percent.2
The most common grade 3/4 hematologic AEs were neutropenia (57.1 percent), anemia (25.7 percent), and thrombocytopenia (20 percent).2 Taste, nail, skin, and rash toxicities occurred in 85.7 percent, 68.6 percent, 74.3 percent, and 20 percent of patients, respectively; the majority were grade 1/2 with few discontinuations.2 Cytokine release syndrome (CRS) occurred in 74.3 percent and infections occurred in 80 percent (22.9 percent grade 3/4) of patients.2
*Dr. Leo Rasche has provided consulting, advisory, and speaking services to Johnson & Johnson; he has not been paid for any media work.
About TALVEY®
TALVEY® (talquetamab-tgvs) received approval from the U.S. FDA in August 2023 as a first-in-class GPRC5D-targeting bispecific antibody for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.3 Since FDA approval, 1,500 patients were treated with TALVEY®. The European Commission (EC) granted conditional marketing authorization (CMA) of TALVEY® ▼ (talquetamab-tgvs) in August 2023 as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma (RRMM) who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have demonstrated disease progression on the last therapy.4
TALVEY® is a bispecific T-cell engaging antibody that binds to the CD3 receptor expressed on the surface of T-cells and G protein-coupled receptor class C group 5 member D (GPRC5D), a novel multiple myeloma target which is highly expressed on the surface of multiple myeloma cells and non-malignant plasma cells, as well as some healthy tissues such as epithelial cells of the skin and tongue.
For more information, visit www.TALVEY.com.
About MonumenTAL-1
MonumenTAL-1 (Phase 1: NCT03399799, Phase 2: NCT04634552) is a Phase 1/2 single-arm, open-label, multicohort, multicenter dose-escalation study involving more than 300 patients.5,6 Phase 1 evaluated the safety and efficacy of TALVEY® in adults with relapsed or refractory multiple myeloma who received three or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. The study excluded patients who experienced T-cell redirection therapy within 3 months, prior Grade 3 or higher CRS related to any T-cell redirection therapy, an autologous stem cell transplant within 12 weeks, an allogenic stem cell transplant within 6 months, Eastern Cooperative Oncology Group (ECOG) performance score of 3 or higher, stroke or seizure within 6 months, CNS involvement or clinical signs of meningeal involvement of multiple myeloma, plasma cell leukemia, or active or documented history of autoimmune disease (exception of vitiligo, resolved childhood atopic dermatitis or resolved Graves’ Disease that is euthyroid based on clinical and laboratory testing).
Phase 2 of the study evaluated the efficacy of TALVEY® in participants with relapsed or refractory multiple myeloma at the recommended Phase 2 dose(s) (RP2D), established as SC 0.4 mg/kg weekly and 0.8 mg/kg every two weeks, respectively. Efficacy was based on overall response rate (ORR) and duration of response (DOR) as assessed by an Independent Review Committee using the International Myeloma Working Group (IMWG) criteria.1
About MonumenTAL-2
The MonumenTAL-2 (NCT05050097) study is an ongoing Phase 1 study of subcutaneous talquetamab in combination with carfilzomib, daratumumab SC, lenalidomide or pomalidomide for the treatment of patients with multiple myeloma. The primary objective of the MonumenTAL-2 study is to identify and characterize the safety of the treatment combinations. Secondary objectives of the MonumenTAL-2 study include overall response rates, duration of response and time to response.7
About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.8 In multiple myeloma, these plasma cells change, spread rapidly and replace normal cells in the bone marrow with tumors.9 Multiple myeloma is the third most common blood cancer and remains an incurable disease.10 In 2023, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 people will die from the disease.11 People living with multiple myeloma have a five-year relative survival rate of 59.8 percent.12 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels and kidney problems or infections.13,14
TALVEY® IMPORTANT SAFETY INFORMATION
INDICATION AND USAGE
TALVEY® (talquetamab-tgvs) is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Please read full Prescribing Information, including Boxed WARNING, for TALVEY®.
About Johnson & Johnson
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at https://www.jnj.com/ or at www.janssen.com/johnson-johnson-innovative-medicine. Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC and Janssen Biotech, Inc. are both Johnson & Johnson companies. Source: Johnson & Johnson
J&J's Talvey demonstrates robust long-term response in multiple myeloma
Jun. 14, 2024 11:23 AM ET
Johnson & Johnson (JNJ) StockCR
By: Jonathan Block, SA News Editor
- New data on Johnson & Johnson's Talvey (talquetamab) maintained durable responses and high overall response rates in patients with multiple myeloma over the long term.
- In a phase 1/2 study, the overall survival rate was 67% at 24 months.
- https://seekingalpha.com/news/4116283-johnson-johnson-talvey-demonstrates-robust-long-term-response-multiple-myeloma?source=content_type%3Areact%7Cfirst_level_url%3Amarket-news%7Csection_asset%3Amain%7Csection%3Ahealthcare
- Johnson & Johnson (JNJ) Stock
- https://www.jnj.com/
- https://www.talvey.com/#
biotecHOPE™ 2024
UGN-102 (mitomycin)
mRNA-1283, an investigational next-generation COVID-19 vaccine,
Augtyro™ (repotrectinib)
UroGen Announces Unprecedented 82.3% Duration of Response at 12 Months in the ENVISION Trial Investigating UGN-102 as Potentially the First FDA-Approved Non-Surgical Treatment for LG-IR-NMIBC
June 13, 2024
- Kaplan-Meier Estimate of Duration of Response at 12 Months in Patients Who Achieved a Complete Response at Three Months was 82.3% (95% CI, 75.9%, 87.1%)
- Side Effect Profile Consistent with Previous Clinical Trials of UGN-102
- UroGen will Host a Virtual Event Today at 11:00 AM Eastern Time
PRINCETON, N.J.--(BUSINESS WIRE)--Jun. 13, 2024-- UroGen Pharma Ltd. (Nasdaq: URGN), a biotech company dedicated to developing and commercializing novel solutions that treat urothelial and specialty cancers, today announced 82.3% (95% CI, 75.9%, 87.1%) 12-month duration of response (DOR) data by Kaplan-Meier estimate (n=108) from its Phase 3 ENVISION trial in patients who achieved complete response (CR) at three months after the first instillation of investigational drug UGN-102 (mitomycin) for intravesical solution. The ENVISION trial previously met its primary endpoint by demonstrating that patients treated with UGN-102 had a 79.6% (95% CI, 73.9%, 84.5%) CR rate at three months following the first instillation of UGN-102.
The ENVISION Phase 3 study is investigating UGN-102 in patients with low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC). In addition to the 12-month data, the DOR Kaplan Meier estimates at 15 (n=43) and 18 (n=9) months were both 80.9% (95%CI, 73.9%, 86.2%).
“UGN-102 has demonstrated a strong clinical profile across multiple trials, with these latest results of 79.6% three-month complete response rate and 82.3% DOR at 12 months reinforcing its potential to be the first FDA-approved non-surgical option for treatment of LG-IR-NMIBC,” said Liz Barrett, President and Chief Executive Officer of UroGen. “We estimate 82,000 patients suffer from this highly recurrent disease in the U.S. each year and may benefit from an innovative approach to treating their disease.”
The most common treatment-emergent adverse events (TEAEs) in the ENVISION trial were dysuria, hematuria, urinary tract infection, pollakiuria, fatigue, and urinary retention. TEAEs were typically mild-to-moderate in severity. The ENVISION trial demonstrated a similar safety profile to that observed in other studies of UGN-102.
“These DOR findings continue to support the development of UGN-102 as a non-surgical alternative to the current standard of care of repeated surgeries for LG-IR-NMIBC, which can impact patients’ physical health and quality of life,” said Sandip Prasad, MD, M.Phil., Director of Genitourinary Surgical Oncology, Morristown Medical Center/Atlantic Health System, NJ. “These results from the ENVISION study make me very optimistic about the opportunity for UGN-102, if approved, to provide another option for patients living with this highly recurrent disease.”
“While LG-IR-NMIBC’s highly recurrent nature often means patients must undergo numerous surgeries throughout their lifetime, I am excited about the potential for patients to better manage the ongoing burden of this disease,” said Mark Schoenberg, M.D., Chief Medical Officer, UroGen. “UGN-102, if approved, could provide a minimally invasive option for LG-IR-NMIBC patients whose existing treatment options currently center around repetitive surgeries.”
In January 2024, UroGen initiated the submission of a rolling New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for UGN-102 as a treatment for LG-IR-NMIBC. The latest DOR data are expected to support the UGN-102 NDA, which the Company plans to complete in the third quarter of 2024, with a potential FDA decision as early as the first quarter of 2025.
UGN-102 ENVISION DATA Virtual Event
The Company is hosting a data event featuring a panel discussion with leading bladder cancer experts today, Thursday, June 13, 2024, at 11:00 a.m. Eastern Time to discuss results from the Phase 3 ENVISION clinical trial.
Please register for the webinar under the Events & Presentations section of the Company’s Investor Relations site (https://investors.urogen.com/events-and-presentations).
Following the live webcast, a replay will be available on the Company's website (https://urogen.com).
About UGN-102
UGN-102 (mitomycin) for intravesical solution is an innovative drug formulation of mitomycin, currently in Phase 3 development for the treatment of LG-IR-NMIBC. Utilizing UroGen’s proprietary RTGel® technology, a sustained release, hydrogel-based formulation, UGN-102 is designed to enable longer exposure of bladder tissue to mitomycin, thereby enabling the treatment of tumors by non-surgical means. UGN-102 is delivered to patients using a standard urinary catheter in an outpatient setting by a trained healthcare professional. UroGen anticipates completing its NDA submission for UGN-102 in the third quarter of 2024 with a potential FDA decision as early as the first quarter of 2025.
About Non-Muscle Invasive Bladder Cancer (NMIBC)
In the U.S. bladder cancer is the second most common urologic cancer in men. LG-IR- NMIBC represents approximately 22,000 newly diagnosed bladder cancer patients each year and an estimated 60,000 recurrences annually among patients diagnosed from previous years. Bladder cancer primarily affects older populations with the median age of diagnosis 73 years and an increased risk of comorbidities. Guideline recommendations for the management of NMIBC include TURBT as the standard of care. Up to 70 percent of NMIBC patients experience at least one recurrence and LG-IR-NMIBC patients are even more likely to recur and face repeated TURBT procedures.
About ENVISION
The Phase 3 ENVISION trial is a single-arm, multinational, multicenter study evaluating the efficacy and safety of UGN-102 (mitomycin) for intravesical solution as primary chemoablative therapy in patients with LG-IR-NMIBC. The Phase 3 ENVISION trial completed target enrollment with approximately 240 patients across 56 sites. Study participants received six once-weekly intravesical instillations of UGN-102. The primary endpoint evaluated the CR rate at the three-month assessment after the first instillation, and the key secondary endpoint evaluated durability over time in patients who achieved a CR at the three-month assessment. Based on discussions with the FDA, UroGen anticipates completing its NDA submission for UGN-102 in the third quarter of 2024. Learn more about the Phase 3 ENVISION trial at www.clinicaltrials.gov (NCT05243550).
About UroGen Pharma Ltd.
UroGen is a biotech company dedicated to developing and commercializing innovative solutions that treat urothelial and specialty cancers because patients deserve better options. UroGen has developed RTGel reverse-thermal hydrogel, a proprietary sustained-release, hydrogel-based platform technology that has the potential to improve the therapeutic profiles of existing drugs. UroGen’s sustained release technology is designed to enable longer exposure of the urinary tract tissue to medications, making local therapy a potentially more effective treatment option. Our first product to treat low-grade upper tract urothelial cancer and investigational treatment UGN-102 (mitomycin) for intravesical solution for patients with LG-IR-NMIBC are designed to ablate tumors by non-surgical means. UroGen is headquartered in Princeton, NJ with operations in Israel. Visit www.UroGen.com to learn more or follow us on X (Twitter), @UroGenPharma.
Forward-Looking Statements
This press release contains forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, statements regarding: the potential for UGN-102 as the first FDA-approved non-surgical treatment for LG-IR-NMIBC; the estimated annual U.S. patient population and demographics for LG-IR-NMIBC; the potential opportunities for UGN-102, if approved, including to provide a minimally invasive option for patients with LG-IR-NMIBC and to help such patients better manage the ongoing burden of the disease; statements related to UroGen’s planned NDA submission for UGN-102 and the potential timing for a decision from the FDA thereon; the potential of UroGen’s proprietary RTGel technology to improve therapeutic profiles of existing drugs; and UroGen’s sustained release technology making local delivery potentially more effective as compared to other treatment options. These statements are subject to a number of risks, uncertainties and assumptions, including, but not limited to: the ENVISION DOR data may not be sufficient to support an NDA submission for UGN-102; even if an NDA for UGN-102 is accepted by the FDA, there is no guarantee that such NDA will be sufficient to support approval of UGN-102 on the timeframe expected, or at all; the ability to obtain regulatory approval within the timeframe expected, or at all; the ability to maintain regulatory approval; complications associated with commercialization activities; the labeling for any approved product; competition in UroGen’s industry; the scope, progress and expansion of developing and commercializing UroGen’s product candidates; the size and growth of the market(s) therefor and the rate and degree of market acceptance thereof vis-à-vis alternative therapies; UroGen’s ability to attract or retain key management, members of the board of directors and other personnel; UroGen’s RTGel technology may not perform as expected; UroGen may not successfully develop and receive regulatory approval of any other product that incorporates RTGel technology; UroGen’s financial condition and need for additional capital in the future. In light of these risks and uncertainties, and other risks and uncertainties that are described in the Risk Factors section of UroGen’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2024, filed with the SEC on May 13, 2024 (which is available at www.sec.gov), the events and circumstances discussed in such forward-looking statements may not occur, and UroGen’s actual results could differ materially and adversely from those anticipated or implied thereby. Any forward-looking statements speak only as of the date of this press release and are based on information available to UroGen as of the date of this release.
View source version on businesswire.com: https://www.businesswire.com/news/home/20240613476477/en/
Source: UroGen Pharma Ltd.
UroGen surges on updated late-stage data for bladder cancer therapy
Jun. 13, 2024 11:21 AM ET
UroGen Pharma Ltd. (URGN) Stock
By: Dulan Lokuwithana, SA News Editor1 Comment
UroGen Pharma (NASDAQ:URGN) announced Thursday that its Phase 3 ENVISION trial for bladder cancer therapy UGN-102 (mitomycin), which had previously reached the primary endpoint, indicated a nearly 82% duration of response at 12 months.
Augtyro™ (repotrectinib)
mRNA-1283, an investigational next-generation COVID-19 vaccine,
Augtyro™ (repotrectinib)
U.S. Food and Drug Administration Approves Augtyro™ (repotrectinib), a Next-Generation Tyrosine Kinase Inhibitor (TKI), for the Treatment of Patients with NTRK-Positive Locally Advanced or Metastatic Solid Tumors
06/13/2024
CATEGORY:
Augtyro is the only FDA-approved treatment option for NTRK-positive tumors studied in both TKI-na ï ve and TKI-pretreated patients across solid tumors , demonstrating clinically meaningful response rates in the TRIDENT-1 trial1
This accelerated approval marks the second indication for Augtyro in the U.S.1
PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval of Augtyro™ (repotrectinib) for the treatment of adult and pediatric patients 12 years of age and older with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, are locally advanced or metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory alternative therapy.1 The approval is based on results from the Phase 1/2 TRIDENT-1 study, which evaluated Augtyro in adult patients with NTRK-positive solid tumors.1 This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.1
“NTRK fusion-positive tumors can present challenges in the clinical setting, which is why it is important that we have additional treatment options for these patients,” said Alexander Drilon, MD, TRIDENT-1 global trial lead and Chief of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center.2,3 “The FDA approval of repotrectinib adds an important tool to our toolbox, offering oncologists a next-generation TKI that can be used across a broad range of NTRK fusion-positive solid tumors for both TKI-naïve and TKI-pretreated patients.”1
The TRIDENT-1 trial included both TKI-naïve (n=40) and TKI-pretreated (n=48) patients with NTRK-positive locally advanced/metastatic solid tumors collectively representing 15 different types of cancer.1 In TKI-naïve patients, with a median follow up of 17.8 months, 58% (95% CI: 41 to 73) had a confirmed objective response rate (cORR); of those, 43% experienced partial responses (PR) and 15% had complete responses (CR).1,4 Of the TKI-naïve responding patients, 83% were still in response at one year with Augtyro. The median duration of response (mDOR) was not yet reached. In TKI-pretreated patients, with a median follow up of 20.1 months, the cORR was 50% (95% CI: 35 to 65); of those, 50% experienced PR and no patients achieved CR.1,4 Additionally, 42% of TKI-pretreated responding patients were still in response at one year with Augtyro.1 The mDOR was 9.9 months (95% CI: 7.4 to 13.0).1 Among those who had measurable central nervous system (CNS) metastases at baseline, intracranial response was observed in 2 out of 2 TKI-naïve patients and in 3 out of 3 TKI-pretreated patients.1
Augtyro is associated with the following Warnings & Precautions: central nervous system (CNS) effects, interstitial lung disease (ILD)/pneumonitis, hepatotoxicity, myalgia with creatine phosphokinase elevation, hyperuricemia, skeletal fractures, and embryo-fetal toxicity.1 Please see Important Safety Information below.
“Today’s FDA approval of Augtyro for patients with NTRK-positive tumors adds to its indication in ROS1-positive NSCLC, showing its clinical value for more people across multiple genetic markers,” said Nick Botwood, senior vice president of Medical Oncology at Bristol Myers Squibb.1 “Previously, there was not an FDA approved treatment option for NTRK-positive cancers that was studied in both TKI-naïve and TKI-pretreated patients across solid tumors. This milestone helps address this area of unmet need and builds on Bristol Myers Squibb’s longstanding legacy of bringing innovations to individuals who are facing cancer and urgently seeking new treatment options.”
“Cancer can be frightening regardless of the type, but having a rare gene fusion driving it can be especially stressful and isolating,” said Susan Spinosa, president and patient co-founder of NTRKers, a patient advocacy group. “It’s exciting to know that there’s a new targeted therapy option for patients with NTRK-positive gene fusions, as this may offer hope to patients and their loved ones navigating this difficult journey.”
Based on clinical and pharmacokinetic data, the recommended dose for Augtyro for pediatric patients aged 12 years and older is the same as for adults, 160 mg orally once daily for 14 days followed by 160 mg twice daily until disease progression or unacceptable toxicity.1 The safety and effectiveness of Augtyro have not been established in pediatric patients younger than 12 years of age with solid tumors who have an NTRK gene fusion.1 This is the second indication for Augtyro in the U.S., following its full approval for the treatment of adult patients with locally advanced or metastatic ROS1-positive NSCLC in November 2023.1
Disclosure: Dr. Drilon has provided advisory and speaking services to Bristol Myers Squibb.
About TRIDENT-1
TRIDENT-1 is a global, multicenter, single-arm, open-label, multi-cohort Phase 1/2 clinical trial evaluating the safety, tolerability, pharmacokinetics and anti-tumor activity of Augtyro in patients with locally advanced or metastatic neurotrophic tyrosine receptor kinase (NTRK) gene fusion-positive (NTRK1/2/3) solid tumors.1,5 The trial excludes patients with symptomatic brain metastases, among other exclusion criteria.1 Phase 1 of the trial included the dose escalation that determined the recommended Phase 2 dose.5
Phase 2 of the trial in NTRK-positive locally advanced/metastatic solid tumor cohorts has a primary endpoint of objective response rate (ORR) as assessed by Blinded Independent Central Review (BICR).5 Among others, key secondary endpoints include duration of response (DOR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) as assessed by BICR, and intracranial response in patients with measurable brain metastases.5
Select Safety Profile from TRIDENT-1
The safety profile for Augtyro was evaluated in 426 patients who received Augtyro in the TRIDENT-1 pivotal trial.1 Permanent discontinuation of Augtyro due to an adverse reaction occurred in 7% of patients.1 There were no specific adverse reactions that accounted for ≥1% of permanent discontinuations. Augtyro dosage was interrupted due to an adverse reaction in 50% of patients, and dose reductions due to an adverse reaction occurred in 38% of patients.1 Serious adverse reactions occurred in 35% of patients who received Augtyro. 1 Serious adverse reactions in ≥2% of patients included pneumonia (6.3%), dyspnea (3.1%), pleural effusion (2.8%) and hypoxia (2.6%).1 Fatal adverse reactions occurred in 3.5% of patients who received Augtyro, including pneumonia, pneumonia aspiration, cardiac arrest, sudden cardiac death, cardiac failure, hypoxia, dyspnea, respiratory failure, tremor, and disseminated intravascular coagulation.1 The most common (≥20%) adverse reactions were dizziness (65%), dysgeusia (54%), peripheral neuropathy (49%), constipation (38%), dyspnea (30%), fatigue (30%), ataxia (28%), cognitive impairment (25%), muscular weakness (20%) and nausea (20%).1 Grade 3 dizziness occurred in 2.8% of patients.1
About NTRK-Positive Solid Tumors
Neurotrophic tropomyosin receptor kinase (NTRK) are a family of receptors involved in neural development.6 An NTRK gene fusion is an alteration that occurs when a piece of the chromosome containing the NTRK gene breaks off and joins with a gene on another chromosome.7 These fusions lead to abnormal proteins, which may cause cancer cells to grow.7 While NTRK gene fusions are rare in patients with solid tumors, testing for NTRK gene fusions allows for the identification of patients who may benefit from TRK inhibitor therapy.8,9,10,11
INDICATIONS
AUGTYRO™ is indicated for the treatment of:
- adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC)
- adult and pediatric patients 12 years of age and older with solid tumors that:
- have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion,
- are locally advanced or metastatic or where surgical resection is likely to result in severe morbidity, and
- have progressed following treatment or have no satisfactory alternative therapy.
This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial(s).
Please see U.S. Full Prescribing Information for AUGTYRO .
Bristol Myers Squibb: Creating a Better Future for People with Cancer
Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine and, through innovative digital platforms, are turning data into insights that sharpen their focus. Deep understanding of causal human biology, cutting-edge capabilities and differentiated research platforms uniquely position the company to approach cancer from every angle.
Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. As a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.
About Bristol Myers Squibb’s Patient Access Support
Bristol Myers Squibb remains committed to providing assistance so that cancer patients who need our medicines can access them and expedite time to therapy.
BMS Access Support®, the Bristol Myers Squibb patient access and reimbursement program, is designed to help appropriate patients initiate and maintain access to BMS medicines during their treatment journey. BMS Access Support offers benefit investigation, prior authorization assistance, as well as co-pay assistance for eligible, commercially insured patients. More information about our access and reimbursement support can be obtained by calling BMS Access Support at 1-800-861-0048 or by visiting www.bmsaccesssupport.com.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.
Source: Bristol Myers Squibb
Multimedia Files:
Download:Download original 99 KB 1497 x 206Download thumbnail 5 KB 200 x 28Download lowres 15 KB 480 x 66Download square 8 KB 250 x 250
Bristol Myers gets FDA approval for Autyro for NTRK-positive cancers
Jun. 13, 2024 5:28 PM ET
Bristol-Myers Squibb Company (BMY) Stock
By: Val Brickates Kennedy, SA News Editor
Bristol Myers (NYSE:BMY) said it has received accelerated FDA approval for its drug Augtyro, also known as repotrectinib, in the treatment of NTRK-positive locally advance or metastatic solid tumors.
Bristol-Myers Squibb Company (BMY) Stock
https://www.nasdaq.com/market-activity/stocks/bmy/dividend-history
mRNA-1283, an investigational next-generation COVID-19 vaccine,
mRNA-1283, an investigational next-generation COVID-19 vaccine,
mRNA-1283, an investigational next-generation COVID-19 vaccine,
Moderna Announces Positive Phase 3 Efficacy Data for mRNA-1283, the Company’s Next Generation COVID-19 Vaccine
June 13, 2024
mRNA-1283 met its primary vaccine efficacy endpoint in a Phase 3 trial, demonstrating non-inferior vaccine efficacy against COVID-19 compared to Spikevax® in participants 12 years of age and older
Higher efficacy was observed in mRNA-1283 compared to Spikevax in adults 18 years of age and older
CAMBRIDGE, MA / ACCESSWIRE / June 13, 2024 / Moderna, Inc. (NASDAQ:MRNA) today announced that its Phase 3 trial of mRNA-1283, an investigational next-generation COVID-19 vaccine, has met its primary efficacy endpoint, demonstrating non-inferior vaccine efficacy against COVID-19 compared to Spikevax. The Company also announced that higher efficacy was observed in adults 18 years of age and older compared to Spikevax (mRNA-1273), with a consistent trend observed in the subset of adults age 65 and older. Positive interim immunogenicity results for mRNA-1283 in this study were previously reported in March 2024.
"We are very pleased that mRNA-1283 has now met its primary vaccine efficacy endpoint in Phase 3, and showed higher efficacy in adults compared to Spikevax," said Stéphane Bancel, Chief Executive Officer of Moderna. "With five vaccine programs that have achieved positive Phase 3 results, Moderna's platform is consistently demonstrating its ability to address significant unmet needs in public health."
The ongoing Phase 3 clinical trial (ClinicalTrials.gov Identifier: NCT05815498) is a randomized, observer-blind, active-controlled study of approximately 11,400 individuals aged 12 years and older. Half of the participants received a 10 μg dose of mRNA-1283, while the other half received a 50 μg dose of mRNA-1273 (Spikevax). Today's vaccine efficacy data are consistent with the previously announced immunogenicity results from the study, which showed that mRNA-1283 had higher neutralizing antibody responses against both Omicron BA.4/5 and ancestral SARS-CoV-2 than mRNA-1273, with the highest geometric mean titer ratios observed in adults and in the subset of participants aged 65 years and older.
In the trial, mRNA-1283 was found to have a similar safety profile to Spikevax. The most commonly solicited side effects were injection site pain, fatigue, headache and myalgia.
Moderna's combination vaccine candidate against influenza and COVID-19, mRNA-1083, includes mRNA-1283. That vaccine candidate recently announced positive results in its separate Phase 3 trial.
Moderna plans to present the Phase 3 clinical data for mRNA-1283 at an upcoming conference as well as submit it for publication. The Company will also engage with regulators on the next steps for the program.
About Moderna
Moderna is a leader in the creation of the field of mRNA medicine. Through the advancement of mRNA technology, Moderna is reimagining how medicines are made and transforming how we treat and prevent disease for everyone. By working at the intersection of science, technology and health for more than a decade, the company has developed medicines at unprecedented speed and efficiency, including one of the earliest and most effective COVID-19 vaccines.
Moderna's mRNA platform has enabled the development of therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases and autoimmune diseases. With a unique culture and a global team driven by the Moderna values and mindsets to responsibly change the future of human health, Moderna strives to deliver the greatest possible impact to people through mRNA medicines. For more information about Moderna, please visit modernatx.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.
Spikevax® is a registered trademark of Moderna.
SOURCE: Moderna, Inc.
View the original press release on accesswire.com
Moderna reaffirms Phase 3 win for next-gen COVID shot
Jun. 13, 2024 7:26 AM ET
By: Dulan Lokuwithana, SA News Editor13 Comments
Moderna (NASDAQ:MRNA) announced Thursday that its next-generation COVID-19 vaccine candidate, mRNA-1283, achieved the primary efficacy endpoint in a Phase 3 trial consistent with previously disclosed interim data.
Citing data from more than 11,000 individuals aged 12 years and older, the Cambridge, Massachusetts-based biotech said mRNA-1283's performance against COVID was at least similar (non-inferior) to that of its FDA-approved vaccine, mRNA-1273 (Spikevax).
UX111 (ABO-102) Gene therapy
mRNA-1083, an investigational combination vaccine against influenza and COVID-19
mRNA-1283, an investigational next-generation COVID-19 vaccine,
Ultragenyx Announces Plans to File for Accelerated Approval of UX111 for the Treatment of Sanfilippo Syndrome Type A (MPS IIIA)
June 12, 2024
Agreement reached with FDA that cerebral spinal fluid (CSF) heparan sulfate (HS) can be used as a reasonable surrogate endpoint for accelerated approval
Data from existing clinical studies appear sufficient for a biologics license application (BLA) submission
NOVATO, Calif., June 12, 2024 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) today announced that the company held a successful meeting with the U.S. Food and Drug Administration (FDA or the Agency) during which the company reached agreement with the Agency that cerebral spinal fluid (CSF) heparan sulfate (HS) is a reasonable surrogate endpoint that could support submission of a biologics license application (BLA) seeking accelerated approval for UX111 (ABO-102) AAV gene therapy for the treatment of Sanfilippo syndrome (MPS IIIA). The company will need to finalize details of its BLA with the Agency in a pre-BLA meeting with the intent to file late this year or early next.
“Gaining alignment with the FDA that CSF HS is a relevant biomarker to enable accelerated approval in Sanfilippo syndrome is a pivotal moment for the community and paves the way for treatments for all fatal types of neuronopathic mucopolysaccharidoses,” said Emil D. Kakkis, M.D., Ph.D., chief executive officer and president of Ultragenyx. “We commend the FDA for appreciating the critical urgency to deliver potentially life-saving therapies to children with neurologically devastating diseases and we extend our gratitude to the patient and caregiver advocates, scientists and industry leaders that shared and collaborated to provide the comprehensive evidence needed to support this important decision.”
As discussed with the FDA, the BLA filing will be based on the available data including from the ongoing pivotal Transpher A study evaluating the safety and efficacy of UX111 in children with MPS IIIA. Results from the Transpher A and long-term follow-up studies were recently presented at the 20th Annual WORLDSymposium™.
About UX111
UX111 is a novel in vivo gene therapy in Phase 1/2/3 development for Sanfilippo syndrome type A (MPS IIIA), a rare fatal lysosomal storage disease with no approved treatment that primarily affects the central nervous system (CNS). UX111 is designed to be dosed in a one-time intravenous infusion using a self-complementary AAV9 vector to deliver a functional copy of the SGSH gene to cells. The therapy is designed to address the underlying SGSH enzyme deficiency responsible for abnormal accumulation of heparan sulfate, a glycosaminoglycan, in the brain that results in progressive cell damage and neurodegeneration. The UX111 program has received Regenerative Medicine Advanced Therapy, Fast Track, Rare Pediatric Disease, and Orphan Drug designations in the U.S., and PRIME and Orphan medicinal product designations in the EU.
About Sanfilippo Syndrome Type A (MPS IIIA)
Sanfilippo syndrome type A (MPS IIIA) is a rare, fatal lysosomal storage disease with no approved treatment that primarily affects the CNS and is characterized by rapid neurodegeneration, with onset in early childhood. Children with MPS IIIA present with global developmental delay which eventually leads to progressive language and cognitive decline, behavioral abnormalities and early death. MPS IIIA is estimated to affect approximately 3,000 to 5,000 patients in commercially accessible geographies with a median life expectancy of 15 years. MPS IIIA is caused by biallelic pathogenic variants in the SGSH gene that lead to a deficiency in the sulfamidase (SGSH) enzyme responsible for breaking down heparan sulfate, a glycosaminoglycans, which accumulate in cells throughout the body resulting in the observed rapid neurodegeneration that is associated with the disorder.
About Ultragenyx Pharmaceutical Inc.
Ultragenyx is a biopharmaceutical company committed to bringing novel products to patients for the treatment of serious rare and ultrarare genetic diseases. The company has built a diverse portfolio of approved therapies and product candidates aimed at addressing diseases with high unmet medical need and clear biology for treatment, for which there are typically no approved therapies treating the underlying disease.
The company is led by a management team experienced in the development and commercialization of rare disease therapeutics. Ultragenyx’s strategy is predicated upon time- and cost-efficient drug development, with the goal of delivering safe and effective therapies to patients with the utmost urgency.
For more information on Ultragenyx, please visit the company's website at: www.ultragenyx.com.
Ultragenyx to file for accelerated approval of rare metabolic disease candidate
Jun. 12, 2024 4:40 PM ET
Ultragenyx Pharmaceutical Inc. (RARE) Stock
By: Jonathan Block, SA News Editor
- Ultragenyx (NASDAQ:RARE) said it would submit a Biologics License Application to the U.S. FDA seeking accelerated approval of UX111, a gene therapy for Sanfilippo syndrome, a rare metabolic disease.
- The company noted that following a recent meeting with the agency, it was agreed that cerebral spinal fluid heparan sulfate could be used as a surrogate endpoint.
- https://seekingalpha.com/news/4115365-ultragenyx-file-accelerated-approval-rare-metabolic-disease-candidate?mailingid=35695974&messageid=2900&serial=35695974.779&source=email_2900&utm_campaign=rta-stock-news&utm_content=link-1&utm_medium=email&utm_source=seeking_alpha&utm_term=35695974.779
- Ultragenyx Pharmaceutical Inc. (RARE) Stock
- https://www.ultragenyx.com/
- https://www.ultragenyx.com/our-research/pipeline/ux111-for-mps-iiia/
RETEVMO® (selpercatinib) capsules/ tablets
mRNA-1083, an investigational combination vaccine against influenza and COVID-19
mRNA-1083, an investigational combination vaccine against influenza and COVID-19
FDA approves selpercatinib for RET fusion-positive thyroid cancer
On June 12, 2024, the Food and Drug Administration granted traditional approval to selpercatinib (Retevmo, Eli Lilly and Company) for adult and pediatric patients 2 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).
Selpercatinib received accelerated approval for this indication for patients 12 years of age and older in 2020.
Full prescribing information for Retevmo will be posted on Drugs@FDA.
Efficacy and Safety
Efficacy was evaluated in LIBRETTO-001 (NCT03157128), a multicenter, open-label, muti-cohort clinical trial in 65 patients with RET fusion-positive thyroid cancer who were radioactive iodine (RAI)-refractory (if RAI was an appropriate treatment option) and were systemic therapy naïve and patients who were previously treated, in separate cohorts.
The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR). The ORR was 85% (95% CI: 71%, 94%) in the 41 previously treated patients and 96% (95% CI: 79%, 100%) in the 24 systemic therapy naïve patients. Median DOR was 26.7 months (95% CI: 12.1, not evaluable [NE]) in the previously treated patients and NE (95% CI: 42.8, NE) in the systemic therapy naïve patients.
Supportive evidence included ORR and DOR data from 10 pediatric and young adult patients with RET fusion-positive thyroid cancer treated in Study LIBRETTO-121 (J2G-OX-JZJJ; NCT03899792), an international, single-arm, multi-cohort clinical trial of selpercatinib in pediatric and young adult patients with advanced RET-altered solid tumors. The ORR was 60% (95% CI: 26%, 88%), and 83% had an observed duration of response ≥ 12 months.
The most common adverse reactions (≥25%) were edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache. The most common Grade 3 or 4 laboratory abnormalities (≥5%) were decreased lymphocytes, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), decreased sodium, and decreased calcium.
The recommended selpercatinib dose for pediatric patients 2 to less than 12 years of age is based on body surface area. It is based on weight for patients 12 years of age and older. See the prescribing information for specific dosing information.
Expedited Programs
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted breakthrough designation and orphan drug designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.
Follow the Oncology Center of Excellence on X (formerly Twitter) @FDAOncology
Lilly's Retevmo gains traditional approval in thyroid cancer
Jun. 12, 2024 2:39 PM ET
Eli Lilly and Company (LLY) Stock
By: Jonathan Block, SA News Editor1 Comment
- Eli Lilly's (NYSE:LLY) Retevmo (selpercatinib) has been granted traditional U.S. FDA approval for thyroid cancer in adults and pediatric patients two years and older.
- The oncologic received accelerated approval for the indication, in RET fusion-positive thyroid cancer, in 2020 for patients 12 years and older.
- Efficacy was based on the LIBRETTO-001 trial which showed strong outcomes for overall response rate and duration of response.
- https://seekingalpha.com/news/4115326-lilly-retevmo-gains-traditional-approval-in-thyroid-cancer?mailingid=35694339&messageid=2900&serial=35694339.2330&source=email_2900&utm_campaign=rta-stock-news&utm_content=link-1&utm_medium=email&utm_source=seeking_alpha&utm_term=35694339.2330
- Eli Lilly and Company (LLY) Stock
- https://www.lilly.com/
- https://uspl.lilly.com/retevmo/retevmo.html#pi
- https://retevmo.lilly.com/
mRNA-1083, an investigational combination vaccine against influenza and COVID-19
mRNA-1083, an investigational combination vaccine against influenza and COVID-19
mRNA-1083, an investigational combination vaccine against influenza and COVID-19
Moderna Announces Positive Phase 3 Data for Combination Vaccine Against Influenza and COVID-19
June 10, 2024
mRNA-1083 met its primary endpoints, eliciting higher immune responses against influenza virus and SARS-CoV-2 than licensed flu and COVID vaccines in adults 50 years and older, including an enhanced influenza vaccine in adults 65 years and older
CAMBRIDGE, MA / ACCESSWIRE
/ June 10, 2024 /
Moderna, Inc. (NASDAQ:MRNA) today announced that its Phase 3 trial of mRNA-1083, an investigational combination vaccine against influenza and COVID-19, has met its primary endpoints, eliciting a higher immune response than the licensed comparator vaccines used in the trial.
"Combination vaccines have the potential to reduce the burden of respiratory viruses on health systems and pharmacies, as well as offer people more convenient vaccination options that could improve compliance and provide stronger protection from seasonal illnesses," said Stéphane Bancel, Chief Executive Officer of Moderna. "Moderna is the only company with a positive Phase 3 flu and COVID combination vaccine. Building on the momentum of positive Phase 3 data across our respiratory portfolio, we continue to address significant unmet medical needs and advance public health."
mRNA-1083 comprises components of mRNA-1010, Moderna's vaccine candidate for seasonal influenza, and mRNA-1283, Moderna's next-generation COVID-19 vaccine candidate. Each investigational vaccine has independently demonstrated positive Phase 3 clinical trial results.
The ongoing Phase 3 clinical trial (ClinicalTrials.gov Identifier:NCT06097273) is a randomized, observer-blind, active control study evaluating the safety, reactogenicity and immunogenicity of mRNA-1083 in two independent age group cohorts of approximately 4,000 adults each. One cohort, consisting of adults 65 years and older, compared mRNA-1083 to co-administered Fluzone HD®, an enhanced influenza vaccine, and Spikevax®, Moderna's currently licensed COVID-19 vaccine. The other cohort of adults 50 to 64 years of age compared mRNA-1083 to co-administered, Fluarix®, a standard dose influenza vaccine, and Spikevax.
The immune responses from a single dose of mRNA-1083 were found to be non-inferior versus the co-administered, routinely recommended, licensed comparators. In both age cohorts, mRNA-1083 also elicited statistically significantly higher immune responses against three influenza virus strains (H1N1, H3N2, and B/Victoria) and against SARS-CoV-2. In the 65 years and older cohort, overall Geometric Mean Ratios (GMRs) of the mRNA-1083 group compared to the Fluzone HD group for the influenza strains were 1.155 (95% CI: 1.094, 1.220) for A/H1N1, 1.063 (95% CI: 1.007, 1.122) for A/H3N2 and 1.118 (95% CI: 1.070, 1.167) for B/Victoria. The GMR of mRNA-1083 compared to Spikevax for the SARS-CoV-2 variant Omicron XBB.1.5 was 1.641 (95% CI: 1.526, 1.765).
In the 50 to 64 years of age cohort the GMRs of the mRNA-1083 group compared to the Fluarix group for the influenza virus strains were 1.414 (95% CI: 1.333, 1.500) for A/H1N1, 1.380 (95% CI: 1.310, 1.454) for A/H3N2, and 1.216 (95% CI: 1.163, 1.270) for B/Victoria. The GMR of mRNA-1083 compared to Spikevax for the SARS-CoV-2 variant Omicron XBB.1.5 was 1.308 (95% CI: 1.219, 1.404).
Immunogenicity was also tested against the B/Yamagata strain of influenza and mRNA-1083 met non-inferiority criteria in both age cohorts. Due to the disappearance of the B/Yamagata lineage from circulation, WHO has recommended a trivalent influenza vaccine composition without B/Yamagata for 2024/2025 vaccines.
mRNA-1083 showed an acceptable tolerability and safety profile. The majority of solicited adverse reactions were grade 1 or 2 in severity and consistent with the licensed vaccines used in the trial. The most commonly solicited adverse reactions were injection site pain, fatigue, myalgia and headache.
Moderna plans to present the Phase 3 clinical data for mRNA-1083 at an upcoming medical conference as well as submit it for publication. The Company will engage with regulators on next steps.
About Moderna
Moderna is a leader in the creation of the field of mRNA medicine. Through the advancement of mRNA technology, Moderna is reimagining how medicines are made and transforming how we treat and prevent disease for everyone. By working at the intersection of science, technology and health for more than a decade, the company has developed medicines at unprecedented speed and efficiency, including one of the earliest and most effective COVID-19 vaccines.
Moderna's mRNA platform has enabled the development of therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases and autoimmune diseases. With a unique culture and a global team driven by the Moderna values and mindsets to responsibly change the future of human health, Moderna strives to deliver the greatest possible impact to people through mRNA medicines. For more information about Moderna, please visit modernatx.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.
Spikevax® is a registered trademark of Moderna.
Fluzone HD® is a registered trademark of Sanofi Pasteur.
Fluarix® is a registered trademark of the GlaxoSmithKline group of companies.
SOURCE: Moderna, Inc.
Moderna’s COVID/flu combo vaccine succeeds in late-stage trial
Jun. 10, 2024 8:10 AM ET
Moderna, Inc. (MRNA) StockGSK, SNY
By: Preeti Singh, SA News Editor16 Comments
Moderna (NASDAQ:MRNA) said Monday that its investigational combination vaccine to protect against both COVID-19 and influenza elicited higher immune responses in adults 50 years and older compared to licensed comparator vaccines used in a late-stage trial.
mRNA-1083 comprises components of mRNA-1010, Moderna's vaccine candidate for seasonal influenza, and mRNA-1283, the drugmaker’s next-generation COVID-19 vaccine candidate.
Mounjaro® (Tirzepatide)
Mounjaro® (Tirzepatide)
Mounjaro® (Tirzepatide)
Lilly's tirzepatide was superior to placebo for MASH resolution, and more than half of patients achieved improvement in fibrosis at 52 weeks
June 8, 2024
SYNERGY-NASH results were presented at the European Association for the Study of the Liver Congress 2024 and simultaneously published in The New England Journal of Medicine
INDIANAPOLIS, June 8, 2024 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) announced detailed results from SYNERGY-NASH, a phase 2 study of 190 patients, with or without type 2 diabetes, to evaluate the investigational use of tirzepatide in adults with biopsy-proven metabolic dysfunction-associated steatohepatitis (MASH) with stage 2 or 3 fibrosis. The efficacy estimandi showed 51.8%, 62.8% and 73.3% of participants taking 5 mg, 10 mg and 15 mg, respectively, achieved an absence of MASH with no worsening of fibrosis on liver histology compared to 13.2% of participants on placebo at 52 weeks of treatment, meeting the study's primary endpoint. The data were presented at the European Association for the Study of the Liver (EASL) Congress 2024 and simultaneously published in The New England Journal of Medicine (NEJM).
In a secondary endpoint, the efficacy estimand showed 59.1%, 53.3% and 54.2% of participants taking 5 mg, 10 mg and 15 mg, respectively, achieved a 1-stage or greater fibrosis improvement without worsening of MASH compared to 32.8% of participants on placebo. Evaluation of additional secondary endpoints showed tirzepatide was associated with improvements in body weight, blood markers of liver injury, and biomarkers of liver fat, inflammation and fibrosis. While the phase 2 study was not designed to prove that tirzepatide improves fibrosis, the study results showed the potential for a clinically meaningful treatment effect across all doses.
"MASH is the second most common contributor to liver transplantation in the U.S., highlighting the need for novel therapies1," said Rohit Loomba, MD, MHSc, chief of the division of gastroenterology and hepatology at University of California San Diego School of Medicine. "The study is significant, given the urgent need for treatment options that are capable of slowing the progression of the disease and potentially reducing serious health complications."
Lilly is engaged with regulatory authorities on the next steps for tirzepatide for the treatment of MASH.
About SYNERGY-NASH
SYNERGY-NASH was a multicenter, double-blind, randomized, placebo-controlled phase 2 study evaluating the efficacy and safety of tirzepatide at various doses in adults with biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH), previously referred to as nonalcoholic steatohepatitis (NASH), with stage 2 or 3 fibrosis. The trial randomized 190 participants to receive tirzepatide 5 mg, 10 mg, 15 mg or placebo, administered subcutaneously once weekly for 52 weeks. The primary endpoint was MASH resolution without worsening of fibrosis at 52 weeks. Secondary endpoints included fibrosis improvement without worsening of MASH.
About tirzepatide
Tirzepatide is a once-weekly GIP (glucose-dependent insulinotropic polypeptide) receptor and GLP-1 (glucagon-like peptide-1) receptor agonist. Tirzepatide is a single molecule that activates the body's receptors for GIP and GLP-1, which are natural incretin hormones. Both GIP and GLP-1 receptors are found in areas of the human brain important for appetite regulation. Tirzepatide has been shown to decrease food intake and modulate fat utilization. Tirzepatide is being studied as a potential treatment for people with obesity and/or overweight with heart failure with preserved ejection fraction (HFpEF), obstructive sleep apnea (OSA) and metabolic dysfunction-associated steatohepatitis (MASH). Studies of tirzepatide in chronic kidney disease (CKD) and in morbidity/mortality in obesity (MMO) are also ongoing.
Tirzepatide was approved by the FDA as Mounjaro® for adults with type 2 diabetes to improve glycemic control on May 13, 2022, and as Zepbound® for adults with obesity (a BMI of 30 kg/m2 or greater) or those who are overweight (a BMI of 27 kg/m2 or greater) who also have a weight-related comorbid condition on November 8, 2023. Both Mounjaro and Zepbound should be used as an adjunct to diet and exercise.
INDICATION AND SAFETY SUMMARY WITH WARNINGS
Zepbound™ (ZEHP-bownd) is an injectable prescription medicine that may help adults with obesity, or with excess weight (overweight) who also have weight-related medical problems, lose weight and keep it off. It should be used with a reduced-calorie diet and increased physical activity.
- Zepbound contains tirzepatide and should not be used with other tirzepatide-containing products or any GLP-1 receptor agonist medicines. It is not known if Zepbound is safe and effective when taken with other prescription, over-the-counter, or herbal weight loss products. It is not known if Zepbound can be used in people who have had pancreatitis. It is not known if Zepbound is safe and effective for use in children under 18 years of age.
- https://mounjaro.lilly.com/
Learn more:
Zepbound is a prescription medicine. For more information, call 1-800-LillyRx (1-800-545-5979) or go to www.zepbound.lilly.com.
This summary provides basic information about Zepbound but does not include all information known about this medicine. Read the information that comes with your prescription each time your prescription is filled. This information does not take the place of talking with your healthcare provider. Be sure to talk to your healthcare provider about Zepbound and how to take it. Your healthcare provider is the best person to help you decide if Zepbound is right for you.
ZP CON CBS 08NOV2023
Zepbound™ and its delivery device base are trademarks owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates.
INDICATION AND SAFETY SUMMARY WITH WARNINGS
Mounjaro® (mown-JAHR-OH) is an injectable medicine for adults with type 2 diabetes used along with diet and exercise to improve blood sugar (glucose).
- It is not known if Mounjaro can be used in people who have had inflammation of the pancreas (pancreatitis). Mounjaro is not for use in people with type 1 diabetes. It is not known if Mounjaro is safe and effective for use in children under 18 years of age.
Learn more
Mounjaro is a prescription medicine. For more information, call 1-833-807-MJRO (833-807-6576) or go to www.mounjaro.com.
This summary provides basic information about Mounjaro but does not include all information known about this medicine. Read the information that comes with your prescription each time your prescription is filled. This information does not take the place of talking with your healthcare provider. Be sure to talk to your healthcare provider about Mounjaro and how to take it. Your healthcare provider is the best person to help you decide if Mounjaro is right for you.
TR CON CBS 14SEP2022
Mounjaro® and its delivery device base are registered trademarks owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates.
About Lilly
Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help more than 51 million people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news, or follow us on Facebook, Instagram and LinkedIn. P-LLY
i The efficacy estimand represents efficacy prior to study treatment discontinuation.
ii The treatment-regimen estimand represents the efficacy for randomized participants regardless of treatment discontinuation.
iii The NAFLD Activity Score (NAS) is a histological score that assesses the severity of disease activity for metabolic dysfunction-associated steatotic liver disease (MASLD), formerly called non-alcoholic fatty liver disease (NAFLD).
View original content to download multimedia:https://www.prnewswire.com/news-releases/lillys-tirzepatide-was-superior-to-placebo-for-mash-resolution-and-more-than-half-of-patients-achieved-improvement-in-fibrosis-at-52-weeks-302167649.html
SOURCE Eli Lilly and Company
Barzolvolimab
Mounjaro® (Tirzepatide)
Mounjaro® (Tirzepatide)
Celldex Therapeutics Presents Data Demonstrating Profound Improvements in Angioedema in Barzolvolimab Phase 2 Study in Chronic Spontaneous Urticaria at EAACI 2024
Jun 2, 2024
PDF Version(opens in a new tab)
- Clinically meaningful and statistically significant improvements across multiple angioedema measurements and barzolvolimab dose groups -
- Sustained activity with rapid onset within 2 weeks -
- Data further support barzolvolimab clinical benefit to patients with CSU -
HAMPTON, N.J., June 02, 2024 (GLOBE NEWSWIRE) -- Celldex Therapeutics, Inc. (NASDAQ:CLDX) today announced data demonstrating that barzolvolimab profoundly improves angioedema at 12 weeks in the Company’s Phase 2 clinical trial in chronic spontaneous urticaria (CSU). Angioedema, characterized by swelling of the deeper dermal layers of the skin and mucous membranes, is a painful, debilitating symptom of CSU that has significant impact on quality of life. It commonly affects the face (lips and eyelids), hands, feet, and genitalia but can also involve the tongue, uvula, soft palate, and pharynx1.
The data were presented today by Dr. Marcus Maurer, Professor of Dermatology and Allergy at Charité – Universitätsmedizin in Berlin, in an oral presentation at the European Academy of Allergy and Clinical Immunology (EAACI) Congress 2024. Celldex previously announced that the Phase 2 study in CSU met its primary and secondary endpoints at 12 weeks with clinically meaningful and statistically significant decreases in UAS7 (weekly urticaria activity score) compared to placebo across multiple dose groups and demonstrated a favorable safety profile. The data presented today further support these results by demonstrating improvements in AAS7 (weekly angioedema activity score) and additional measures of angioedema control.
“The majority of patients with severe CSU suffer with angioedema, which is often extremely painful and causes disfigurement, dramatically impacting quality of life,” said Diane C. Young, MD, Senior Vice President and Chief Medical Officer of Celldex Therapeutics. "Consistent with previously reported clinical outcomes, we observed rapid, durable and significant angioedema relief, including in omalizumab refractory disease. These data continue to support barzolvolimab’s potential to become a transformative treatment option for CSU and we look forward to moving closer to this goal with the initiation of our Phase 3 studies this summer.”
- Barzolvolimab demonstrated significant improvements in AAS7 in patients with angioedema across all doses at Week 12. This improvement was rapid (within 2 weeks) and durable (continued through 12 weeks).
- Barzolvolimab demonstrated strong improvement in AAS7 independent of omalizumab status at Week 12. Approximately 20% (n=41) of enrolled patients received prior treatment with omalizumab and more than half of these patients had omalizumab-refractory disease. These patients experienced a similar clinical benefit as the overall treated population within their individual dosing groups consistent with the barzolvolimab mechanism of action.
- Patients on barzolvolimab experienced a > 8 point improvement in AAS7 (considered a clinically meaningful result) across all doses compared to placebo (p<0.05).
- Barzolvolimab increased angioedema free days compared to placebo through 12 weeks. Patients in the 300 mg cohort were angioedema free 77% of the time over the 12 week period.
Phase 2 Study Design
The randomized, double-blind, placebo-controlled, parallel group Phase 2 study is evaluating the efficacy and safety profile of multiple dose regimens of barzolvolimab in patients with CSU who remain symptomatic despite antihistamine therapy, to determine the optimal dosing strategy. 208 patients were randomly assigned on a 1:1:1:1 ratio to receive subcutaneous injections of barzolvolimab at 75 mg every 4 weeks, 150 mg every 4 weeks, 300 mg every 8 weeks or placebo during a 16-week placebo-controlled treatment period. After 16 weeks, patients then enter a 36-week active treatment period, in which patients receiving placebo or the 75 mg dose are randomized to receive barzolvolimab 150 mg every 4 weeks or 300 mg every 8 weeks; patients already randomized to the 150 mg and 300 mg treatment arms remain on the same regimen as during the placebo-controlled treatment period. After 52 weeks, patients then enter a follow-up period for an additional 24 weeks. The primary endpoint of the study is mean change in baseline to Week 12 in UAS7 (weekly activity score). Secondary endpoints include other assessments of safety and clinical activity including ISS7 (weekly itch severity score), HSS7 (weekly hives severity score) and AAS7 (weekly angioedema activity score).
For additional information on this trial (NCT05368285), please visit www.clinicaltrials.gov(opens in a new tab)
About Chronic Spontaneous Urticaria (CSU)
CSU is characterized by the occurrence of hives or wheals for 6 weeks or longer without identifiable specific triggers or causes. The activation of the mast cells in the skin (release of histamines, leukotrienes, chemokines) results in episodes of itchy hives, swelling and inflammation of the skin that can go on for years or even decades. Current therapies provide symptomatic relief only in some patients.
About Barzolvolimab
Barzolvolimab is a humanized monoclonal antibody that binds the receptor tyrosine kinase KIT with high specificity and potently inhibits its activity. KIT is expressed in a variety of cells, including mast cells, which mediate inflammatory responses such as hypersensitivity and allergic reactions. KIT signaling controls the differentiation, tissue recruitment, survival and activity of mast cells. In certain inflammatory diseases, such as chronic urticaria, mast cell activation plays a central role in the onset and progression of the disease. Barzolvolimab is currently being studied in chronic spontaneous urticaria (CSU), chronic inducible urticaria (CIndU), prurigo nodularis (PN) and eosinophilic esophagitis (EOE) with additional indications planned for the future, including atopic dermatitis (AD).
About Celldex Therapeutics, Inc.
Celldex is a clinical stage biotechnology company leading the science at the intersection of mast cell biology and the development of transformative therapeutics for patients. Our pipeline includes antibody-based therapeutics which have the ability to engage the human immune system and/or directly affect critical pathways to improve the lives of patients with severe inflammatory, allergic, autoimmune and other devastating diseases. Visit www.celldex.com(opens in a new tab).
Source: Celldex Therapeutics, Inc.
Celldex initiated to outperform at Wolfe on barzolvolimab for skin disease
Jun. 11, 2024 12:56 PM ET
Celldex Therapeutics, Inc. (CLDX) Stock
By: Jonathan Block, SA News Editor
- Wolfe Research has started Celldex Therapeutics off to outperform, citing the promise of barzolvolimab for chronic spontaneous urticaria.
- The firm has a $51 price target (~47% upside based on Jan. 10 close).
- https://seekingalpha.com/news/4114909-celldex-initiated-outperform-wolfe-barzolvolimab-skin-disease?mailingid=35680456&messageid=2900&serial=35680456.1112&source=email_2900&utm_campaign=rta-stock-news&utm_content=link-1&utm_medium=email&utm_source=seeking_alpha&utm_term=35680456.1112
- Celldex Therapeutics, Inc. (CLDX) Stock
- https://celldex.com/
- https://celldex.com/pipeline/overview/
KEVZARA® (SARILUMAB)
Mounjaro® (Tirzepatide)
LEQEMBI® (LECANEMAB-IRMB)
KEVZARA® (SARILUMAB) APPROVED BY FDA FOR THE TREATMENT OF ACTIVE POLYARTICULAR JUVENILE IDIOPATHIC ARTHRITIS (PJIA)
Approval in patients with pJIA weighing 63kg or greater adds to Kevzara’s position in treating adult chronic inflammatory conditions of moderately to severely active rheumatoid arthritis and polymyalgia rheumatica
TARRYTOWN, N.Y. and CAMBRIDGE, MA, June 11, 2024 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi today announced that the U.S. Food and Drug Administration has approved Kevzara® (sarilumab) for the treatment of patients weighing 63 kg or greater with active polyarticular juvenile idiopathic arthritis (pJIA), a form of arthritis that impacts multiple joints at a time.
“Polyarticular juvenile idiopathic arthritis can be a painful disease for children where multiple joints are impacted by this chronic infammation,” said George D. Yancopoulos, M.D., Ph.D., Board co-Chair, President and Chief Scientific Officer at Regeneron. "Not only are their daily lives impacted, but their futures can be disrupted without adequate treatment. The approval of Kevzara in polyarticular juvenile idiopathic arthritis provides these vulnerable patients and their families a new FDA-approved treatment option to help navigate this disease.”
The FDA approval in this patient population is supported by evidence from adequate and well-controlled studies and pharmacokinetic data from adults with rheumatoid arthritis as well as a pharmacokinetic, pharmacodynamic, dose finding and safety study in pediatric patients with pJIA.
People living with pJIA may experience joint symptoms such as pain, stiffness and swelling, which may restrict their activities and make certain aspects of their day-to-day life incredibly challenging. The disease can lead to an increased risk of permanent joint damage as well as delayed growth and development, due to chronic joint inflammation.
No new adverse reactions (ARs) and safety concerns were identified in the pJIA population compared to the rheumatoid arthritis population. The most common adverse drug reactions for patients with pJIA were nasopharyngitis, neutropenia, upper respiratory tract infection, and injection site erythema. The most common AR that resulted in permanent discontinuation of therapy with Kevzara was neutropenia. Overall, patients treated with Kevzara are at increased risk for developing serious infections that may lead to hospitalization or death.
“This latest approval for Kevzara brings a new treatment option with an established efficacy and safety profile to pediatric patients living with polyarticular juvenile idiopathic arthritis,” said Brian Foard, Executive Vice President, Head, Specialty Care at Sanofi. “This milestone highlights our ongoing commitment to bringing medicines to our younger patients living with this chronic condition that can cause debilitating joint pain and inflammation.”
Sanofi and Regeneron are committed to helping patients in the U.S. who are prescribed Kevzara gain access to the medicine and receive the support they may need. KevzaraConnect®, a comprehensive and specialized program that provides support services to patients throughout every step of the treatment process, can help eligible patients who are uninsured, lack coverage, or need copay assistance. For more information, please call: 1-844-Kevzara (1-844-538-9272) or visit www.Kevzara.com.
About Kevzara
In addition to pJIA, Kevzara is currently approved in 25 countries to treat adults with moderately to severely active rheumatoid arthritis after at least one other medicine, called a disease modifying antirheumatic drug (DMARD), has been used and did not work well or could not be tolerated. Kevzara is also approved in the U.S. for the treatment of polymyalgia rheumatica – an inflammatory rheumatic disease – in adult patients who have had an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper.
Kevzara binds specifically to the IL-6 receptor and has been shown to inhibit IL-6-mediated signaling. IL-6 is an immune system protein produced in increased quantities in patients with rheumatoid arthritis and has been associated with disease activity, joint destruction and other systemic problems.
Sarilumab is being jointly developed by Sanofi and Regeneron under a global collaboration agreement.
About Regeneron's VelocImmune® Technology
Regeneron's VelocImmune technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies. When Regeneron's co-Founder, President and Chief Scientific Officer George D. Yancopoulos was a graduate student with his mentor Frederick W. Alt in 1985, they were the first to envision making such a genetically humanized mouse, and Regeneron has spent decades inventing and developing VelocImmune and related VelociSuite® technologies. Dr. Yancopoulos and his team have used VelocImmune technology to create a substantial proportion of all original, FDA-approved or authorized fully human monoclonal antibodies. This includes REGEN-COV® (casirivimab and imdevimab), Dupixent® (dupilumab), Libtayo® (cemiplimab-rwlc), Praluent® (alirocumab), Kevzara, Evkeeza® (evinacumab-dgnb), Inmazeb® (atoltivimab, maftivimab and odesivimab-ebgn) and Veopoz® (pozelimab-bbfg).
U.S. Indications and Important Safety Information
KEVZARA® (sarilumab) is an injectable prescription medicine called an interleukin-6 (IL-6) receptor blocker. KEVZARA is used to treat:
- adult patients with moderately to severely active rheumatoid arthritis (RA) after at least one other medicine called a disease-modifying antirheumatic drug (DMARD) has been used and did not work well or could not be tolerated.
- adult patients with polymyalgia rheumatica (PMR) after corticosteroids have been used and did not work well or when a slow decrease in the dose of corticosteroids (taper) cannot be tolerated.
- people with active polyarticular juvenile idiopathic arthritis (pJIA) who weigh 63kg (139 lbs) or more.
It is not known if KEVZARA is safe and effective in children with pJIA under 2 years of age.
To learn more, talk about KEVZARA with your healthcare provider or pharmacist. The FDA-approved Medication Guide and Prescribing Information can be found at www.KEVZARA.com or by calling 1-844- KEVZARA.
Please click here to see full Prescribing Information including risk of SERIOUS SIDE EFFECTS and Medication Guide.
About Regeneron
Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led for over 35 years by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous FDA-approved treatments and product candidates in development, almost all of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, hematologic conditions, infectious diseases and rare diseases.
Regeneron is accelerating and improving the traditional drug development process through our proprietary VelociSuite® technologies, such as VelocImmune, which uses unique genetically humanized mice to produce optimized fully human antibodies and bispecific antibodies, and through ambitious research initiatives such as the Regeneron Genetics Center®, which is conducting one of the largest genetics sequencing efforts in the world.
For more information, please visit www.Regeneron.com or follow Regeneron on LinkedIn.
About Sanofi
We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people’s lives. Our team, across the world, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of our ambitions.
Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY
Source: Regeneron Pharmaceuticals, Inc.
Regeneron, Sanofi win FDA label expansion for arthritis therapy Kevzara
Jun. 11, 2024 7:49 AM ET
Regeneron Pharmaceuticals, Inc. (REGN) Stock, SNY Stock, GCVRZ Stock, SNYNF Stock
By: Dulan Lokuwithana, SA News Editor
Regeneron (NASDAQ:REGN) announced Tuesday that the U.S. FDA has expanded the approval for its arthritis therapy Kevzara (sarilumab), developed with Sanofi (NASDAQ:SNY), allowing its use in children with the joint disorder active polyarticular juvenile idiopathic arthritis (pJIA).
pJIA is a painful arthritic condition that leads to inflammation in multiple joints. Kevzara's latest approval brings a new FDA-licensed therapy to help address the disorder, Regeneron (REGN) CEO George Yancopoulos said.
Regeneron Pharmaceuticals, Inc. (REGN) Stock, SNY Stock, GCVRZ Stock, SNYNF Stock
LEQEMBI® (LECANEMAB-IRMB)
LEQEMBI® (LECANEMAB-IRMB)
LEQEMBI® (LECANEMAB-IRMB)
FDA ACCEPTS EISAI'S FILING OF LEQEMBI® (LECANEMAB-IRMB) SUPPLEMENTAL BIOLOGICS LICENSE APPLICATION FOR IV MAINTENANCE DOSING FOR THE TREATMENT OF EARLY ALZHEIMER'S DISEASE
TOKYO and CAMBRIDGE, Mass., June 9, 2024 /PRNewswire/ -- Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") and Biogen Inc. (Nasdaq: BIIB, Corporate headquarters: Cambridge, Massachusetts, CEO: Christopher A. Viehbacher, "Biogen") announced today that the U.S. Food and Drug Administration (FDA) has accepted Eisai's Supplemental Biologics License Application (sBLA) for monthly lecanemab-irmb (U.S. brand name: LEQEMBI®) intravenous (IV) maintenance dosing. A Prescription Drug User Fee Act (PDUFA) action date is set for January 25, 2025. LEQEMBI is indicated for the treatment of Alzheimer's disease (AD) in patients with mild cognitive impairment or mild dementia stage of disease (collectively referred to as early AD).
As part of the proposed monthly IV maintenance regimen, the patients who have completed the biweekly IV initiation phase, exact period under discussion with the FDA, would receive a monthly IV dose that maintains effective drug concentration to sustain the clearance of highly toxic protofibrils* which can continue to cause neuronal injury. The sBLA is based on modeling of observed data from the Phase 2 study (Study 201) and its open-label extension (OLE) as well as the Clarity AD study (Study 301) and its OLE study.
AD is a progressive disease caused by toxic amyloid proteins. Once established, this pathophysiological process continues throughout the patient's life and therefore sustained treatment may be necessary. In those who are eligible, treatment should be initiated after diagnosis as early as possible to maximize patient outcomes. Data from studies 201, 301 and their OLEs show that continued treatment with LEQEMBI beyond the 18-month core phase prolongs the benefit as highly toxic protofibrils are continuously removed. If the sBLA is approved, the clinical and biomarker benefits may be maintained through the once-monthly dosing regimen that is less burdensome and easier for patients and care partners to continue long-term.
Additionally, Eisai initiated the rolling submission of a BLA to the FDA for the LEQEMBI subcutaneous autoinjector for weekly maintenance dosing after it was granted Fast Track designation by the FDA in May 2024.
LEQEMBI is now approved in the U.S., Japan, China and South Korea, and applications have been submitted for review in the European Union, Australia, Brazil, Canada, Hong Kong, Great Britain, India, Israel, Russia, Saudi Arabia, Taiwan, Singapore, and Switzerland.
Eisai serves as the lead for lecanemab's development and regulatory submissions globally with both Eisai and Biogen co-commercializing and co-promoting the product and Eisai having final decision-making authority.
* Protofibrils are believed to contribute to the brain injury that occurs with AD and are considered to be the most toxic form of Aβ, having a primary role in the cognitive decline associated with this progressive, debilitating condition.1 Protofibrils cause injury to neurons in the brain, which in turn, can negatively impact cognitive function via multiple mechanisms, not only increasing the development of insoluble Aβ plaques but also increasing direct damage to brain cell membranes and the connections that transmit signals between nerve cells or nerve cells and other cells. It is believed the reduction of protofibrils may prevent the progression of AD by reducing damage to neurons in the brain and cognitive dysfunction.2
INDICATION
LEQEMBI® [(lecanemab-irmb) 100 mg/mL injection for intravenous use] is indicated for the treatment of Alzheimer's disease (AD). Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment (MCI) or mild dementia stage of disease, the population in which treatment was initiated in clinical trials.
Please see full Prescribing Information for LEQEMBI, including Boxed WARNING.
Notes to Editors
1. About lecanemab (LEQEMBI®)
Lecanemab is the result of a strategic research alliance between Eisai and BioArctic. It is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibril) and insoluble forms of amyloid-beta (Aβ).3 Lecanemab is approved in the U.S.,4 Japan,5 China6 and South Korea7. In the U.S., Japan and China, the indications are as follows.
- U.S.: For the treatment of Alzheimer's disease (AD). It should be initiated in patients with MCI or mild dementia stage of disease.4
- Japan: For slowing progression of MCI and mild dementia due to AD.5
- China: For the treatment of MCI due to AD and mild AD dementia.6
- South Korea: For the treatment in adult patients with MCI due to AD or Mild AD.7
LEQEMBI's FDA approval was based on Phase 3 data from Eisai's, global Clarity AD clinical trial, in which it met its primary endpoint and all key secondary endpoints with statistically significant results.3 The primary endpoint was the global cognitive and functional scale, Clinical Dementia Rating Sum of Boxes (CDR-SB). In the Clarity AD clinical trial, treatment with lecanemab reduced clinical decline on CDR-SB by 27% at 18 months compared to placebo.8 The mean CDR-SB score at baseline was approximately 3.2 in both groups. The adjusted least-squares mean change from baseline at 18 months was 1.21 with lecanemab and 1.66 with placebo (difference, −0.45; 95% confidence interval [CI], −0.67 to −0.23; P<0.001).8 In addition, the secondary endpoint from the AD Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL), which measures information provided by people caring for patients with AD, noted a statistically significant benefit of 37% compared to placebo.8 The adjusted mean change from baseline at 18 months in the ADCS-MCI-ADL score was −3.5 in the lecanemab group and −5.5 in the placebo group (difference, 2.0; 95% CI, 1.2 to 2.8; P<0.001).8 The ADCS MCI-ADL assesses the ability of patients to function independently, including being able to dress, feed themselves and participate in community activities. The most common adverse events (>10%) in the lecanemab group were infusion reactions, ARIA-H (combined cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis), ARIA-E (edema/effusion), headache, and fall.8
Eisai has also submitted applications for approval of lecanemab in 13 countries and regions, including the European Union (EU).
Since July 2020 the Phase 3 clinical study (AHEAD 3-45) for individuals with preclinical AD, meaning they are clinically normal and have intermediate or elevated levels of amyloid in their brains, is ongoing. AHEAD 3-45 is conducted as a public-private partnership between the Alzheimer's Clinical Trial Consortium that provides the infrastructure for academic clinical trials in AD and related dementias in the U.S, funded by the National Institute on Aging, part of the National Institutes of Health, Eisai and Biogen. Since January 2022, the Tau NexGen clinical study for Dominantly Inherited AD (DIAD), that is conducted by Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU), led by Washington University School of Medicine in St. Louis, is ongoing and includes lecanemab as the backbone anti-amyloid therapy.
2. About the Collaboration between Eisai and Biogen for AD
Eisai and Biogen have been collaborating on the joint development and commercialization of AD treatments since 2014. Eisai serves as the lead of lecanemab development and regulatory submissions globally with both companies co-commercializing and co-promoting the product and Eisai having final decision-making authority.
3. About the Collaboration between Eisai and BioArctic for AD
Since 2005, Eisai and BioArctic have had a long-term collaboration regarding the development and commercialization of AD treatments. Eisai obtained the global rights to study, develop, manufacture and market lecanemab for the treatment of AD pursuant to an agreement with BioArctic in December 2007. The development and commercialization agreement on the antibody lecanemab back-up was signed in May 2015.
4. About Eisai Co., Ltd.
Eisai's Corporate Concept is "to give first thought to patients and people in the daily living domain, and to increase the benefits that health care provides." Under this Concept (also known as human health care (hhc) Concept), we aim to effectively achieve social good in the form of relieving anxiety over health and reducing health disparities. With a global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to create and deliver innovative products to target diseases with high unmet medical needs, with a particular focus in our strategic areas of Neurology and Oncology.
In addition, we demonstrate our commitment to the elimination of neglected tropical diseases (NTDs), which is a target (3.3) of the United Nations Sustainable Development Goals (SDGs), by working on various activities together with global partners.
For more information about Eisai, please visit www.eisai.com (for global headquarters: Eisai Co., Ltd.), and connect with us on X, LinkedIn and Facebook. The website and social media channels are intended for audiences outside of the UK and Europe. For audiences based in the UK and Europe, please visit www.eisai.eu and Eisai EMEA LinkedIn.
5. About Biogen
Founded in 1978, Biogen is a leading biotechnology company that pioneers innovative science to deliver new medicines to transform patients' lives and to create value for shareholders and our communities. We apply deep understanding of human biology and leverage different modalities to advance first-in-class treatments or therapies that deliver superior outcomes. Our approach is to take bold risks, balanced with return on investment to deliver long-term growth.
The company routinely posts information that may be important to investors on its website at www.biogen.com. Follow Biogen on social media – Facebook, LinkedIn, X, YouTube.
SOURCE Eisai Inc.
Biogen, Eisai get January 2025 FDA action date for monthly Leqembi
Jun. 10, 2024 12:09 PM ET
Biogen Inc. (BIIB) Stock, ESAIY Stock, ESALF StockLLY
By: Jonathan Block, SA News Editor
- The U.S. FDA has set Jan. 25, 2025 as the PDUFA date to act on Eisai's (OTCPK:ESAIY) supplemental New Drug Application for a monthly, intravenous version of its Alzheimer's drug Leqembi (lecanemab).
- The med is currently dosed every two weeks.
- The companies said that patients would still need to go through a biweekly initiation phase of Leqembi -- that period of time is to be determined with the FDA -- before switching to monthly dosing.
- https://seekingalpha.com/news/4114537-biogen-eisai-get-january-2025-fda-action-date-monthly-leqembi?source=content_type%3Areact%7Cfirst_level_url%3Amarket-news%7Csection_asset%3Amain%7Csection%3Ahealthcare
- Biogen Inc. (BIIB) Stock, ESAIY Stock, ESALF Stock
- https://us.eisai.com/
- https://investors.biogen.com/news-releases/news-release-details/fda-accepts-eisais-filing-leqembir-lecanemab-irmb-supplemental
- https://www.biogen.com/
- https://www.leqembi.com/
Iqirvo® (elafibranor)
LEQEMBI® (LECANEMAB-IRMB)
Iqirvo® (elafibranor)
Ipsen’s Iqirvo® receives U.S. FDA accelerated approval as a first-in-class PPAR treatment for primary biliary cholangitis
Rare Diseases - 10 June 2024 - 12 mins read
- Iqirvo® (elafibranor) 80 mg tablets is the first new medicine approved in nearly a decade for the treatment of the rare liver disease called primary biliary cholangitis
- Approval based on positive Phase III ELATIVE trial data
- Primary biliary cholangitis impacts approximately 100,000 people in the US and is growing in global prevalence. If inadequately treated, it can cause liver failure
- U.S. approval of Iqirvo establishes Ipsen as a leader in the treatment of rare cholestatic liver diseases
PARIS, FRANCE, 10 June 2024 Ipsen (Euronext: IPN; ADR: IPSEY) today announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval for Iqirvo® (elafibranor) 80 mg tablets for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA. Iqirvo may be prescribed immediately in the U.S. for eligible patients.
This indication is approved under accelerated approval based on reduction of alkaline phosphatase (ALP). Improvement in survival or prevention of liver decompensation events have not been demonstrated. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). Iqirvo is not recommended for people who have or develop decompensated cirrhosis (e.g., ascites, variceal bleeding, hepatic encephalopathy).
“For a significant number of people living with PBC, available treatments do not control the condition and may exacerbate symptoms of PBC. Left unmanaged, PBC can progress, leading to liver failure and in some cases, the need for a liver transplant,” said Christelle Huguet, Executive Vice President, Head of Research and Development at Ipsen. “Iqirvo demonstrated statistically significant improvements in biochemical response compared to UDCA alone. Iqirvo is therefore a much-needed treatment option and the first new medicine for PBC in nearly a decade.”
Iqirvo is a first-in-class oral, once-daily peroxisome proliferator-activated receptor (PPAR) agonist. Iqirvo was in-licensed from GENFIT in 2021. The accelerated approval of Iqirvo is based on data from the Phase III ELATIVE trial published in the New England Journal of Medicine1. The ELATIVE trial demonstrated that 13 times more patients achieved the composite primary endpoint of biochemical response when treated with Iqirvo plus UDCA (n=108) versus placebo plus UDCA (=53) (respectively 51% versus 4% for a 47% treatment difference). ALP is a biochemical marker and is used as a surrogate endpoint in PBC trials. Secondary endpoints showed normalization in ALP levels in only Iqirvo-treated patients (15% for Iqirvo plus UDCA (n=108) versus 0% for placebo plus UDCA (n=53)). Most patients (95%) received study treatment (Iqirvo or placebo) in combination with UDCA.
The most common adverse reactions with Iqirvo reported in ≥10% of study participants were weight gain, abdominal pain, diarrhea, nausea and vomiting. Some study participants treated with Iqirvo experienced myalgia, myopathy and rhabdomyolysis; fractures; adverse effects on fetal and newborn development; drug-induced liver injury; hypersensitivity reactions; or biliary obstruction. See full Important Safety Information below.
“Data from the pivotal Phase III ELATIVE clinical trial demonstrated that Iqirvo is an effective second-line treatment for patients with PBC with favorable benefit and risk data,” said Dr. Kris Kowdley, Director at Liver Institute Northwest, Washington and a primary investigator on the ELATIVE study. “The approval of Iqirvo will allow healthcare providers in the U.S. to address an unmet need with the potential to significantly reduce ALP levels for our patients with PBC.”
PBC is a rare, autoimmune, cholestatic liver disease where a build-up of bile and toxins (cholestasis) and chronic inflammation causes irreversible fibrosis (scarring) of the liver and destruction of the bile ducts. Impacting approximately 100,000 people in the U.S.2, the majority being women, PBC is a lifelong condition that can worsen over time if not effectively treated, leading to liver transplant and in some cases, premature death. PBC also affects day-to-day life, with people most commonly experiencing severe fatigue symptoms and debilitating itch (pruritus).
“People living with PBC can feel like the symptoms they experience are dismissed by family members, friends or even their doctors, because they have not experienced something similarly disruptive in their lives. People with PBC may also feel uncertainty around the disease progression and if, or when, their liver health may deteriorate,” said Carol Roberts, Executive President of PBCers, a patient advocacy organization in the U.S. providing support to people living with PBC. “Earlier diagnosis and education about PBC, along with new treatment options are important to meet the current needs of people living with PBC.”
Iqirvo has been submitted to the European Medicines Agency (EMA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA), seeking authorization for PBC, with final EMA and MHRA regulatory decisions anticipated in the second half of 2024. The FDA approval of Iqirvo further strengthens Ipsen’s portfolio of treatments for rare cholestatic liver diseases available to patients in the U.S. This includes our FDA approved medicine for the treatment of pruritus in patients three months and older with progressive familial intrahepatic cholestasis (PFIC) and for the treatment of cholestatic pruritus in patients from 12 months of age with Alagille syndrome (ALGS).
Please see full Prescribing Information for IQIRVO.
About Iqirvo
Iqirvo (pronounced EYE-KER-VO) is an oral, once-daily, peroxisome proliferator-activated receptor (PPAR) agonist indicated for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have an inadequate response to UDCA, or as monotherapy in patients unable to tolerate UDCA. While the mechanism is not well understood, pharmacological activity that is potentially relevant to Iqirvo therapeutic effects includes inhibition of bile acid synthesis through activation of PPAR-alpha and PPAR-delta. In 2019, Iqirvo was granted Breakthrough Therapy Designation by the U.S Food and Drug Administration (FDA) in adults with PBC who have an inadequate response to ursodeoxycholic acid (UDCA) the existing first-line therapy for PBC. Iqirvo has not received approval by regulatory authorities outside of the U.S. Iqirvo is currently under regulatory review with the European Medicines Agency (EMA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Iqirvo was discovered and developed by GENFIT and Ipsen licensed the exclusive worldwide rights (except China, Hong Kong, Taiwan and Macau) to elafibranor from GENFIT in 2021.
Iqirvo has been granted approval under the FDA accelerated approval program, which allows for approval of medicines that treat serious conditions and fill an unmet medical need based on a surrogate endpoint. Under the program, Ipsen is required to conduct a trial to confirm anticipated clinical benefit. The confirmatory trial for Iqirvo, ELFIDENCE, is ongoing.
Iqirvo is an 80 mg tablet administered orally once daily. To ensure access to Iqirvo for eligible individuals in the U.S., the IPSEN CARES® patient support program is available as a resource to people living with PBC and their caregivers to provide educational support and address coverage, access and reimbursement questions (1-866-435-5677).
About the Phase III ELATIVE trial
ELATIVE is a multi-center, randomized double-blind, placebo-controlled Phase III clinical trial (n=161) that evaluated the efficacy and safety of Iqirvo 80mg once daily plus UDCA (n=108) versus placebo plus UDCA (n=53). Iqirvo or placebo was administered in combination with UDCA in 95% of patients and as monotherapy in 5% of patients who were unable to tolerate UDCA. The 52-week study was completed by 92% of participants with 97% of those who completed the study continuing in an extension study. The results were published in the New England Journal of Medicine1.
- The ELATIVE trial demonstrated that Iqirvo had a statistically significant treatment benefit with 51% of patients on Iqirvo achieving a biochemical response compared with 4% on the placebo arm, a treatment benefit of 47% (95% CI 32, 57; p<0.0001). Biochemical response was defined as ALP less than 1.67 Upper Limit of Normal (ULN), an ALP decrease of greater than or equal to 15% from baseline and total bilirubin (TB) ≤ ULN at week 52.
- ALP normalization at week 52 was a key secondary endpoint with 15% of Iqirvo-treated patients demonstrating normalization versus 0% placebo (p=0.002).
- The significant biochemical response to Iqirvo was further supported by data demonstrating reductions from baseline in ALP levels were sustained through week 52 and response was rapid, seen as early as Week 4 in the Iqirvo group.
- The most common adverse reactions with Iqirvo reported in ≥10% of study participants were weight gain, abdominal pain, diarrhea, nausea and vomiting.
ENDS
About Ipsen
We are a global biopharmaceutical company with a focus on bringing transformative medicines to patients in three therapeutic areas: Oncology, Rare Disease and Neuroscience.
Our pipeline is fueled by external innovation and supported by nearly 100 years of development experience and global hubs in the U.S., France and the U.K. Our teams in more than 40 countries and our partnerships around the world enable us to bring medicines to patients in more than 80 countries.
Ipsen is listed in Paris (Euronext: IPN) and in the U.S. through a Sponsored Level I American Depositary Receipt program (ADR: IPSEY). For more information, visit ipsen.com.
Ipsen gains accelerated approval for elafibranor for rare liver disease
Jun. 10, 2024 5:33 PM ET
By: Jonathan Block, SA News Editor
- The U.S. FDA has approved Ipsen's (OTCPK:IPSEY) Iqirvo (elafibranor) for primary biliary cholangitis, a type of rare liver disease, in combination with ursodeoxycholic acid (UDCA) or as monotherapy.
- The drug, a first-in-class oral, once-daily peroxisome proliferator-activated receptor (PPAR) agonist, was approved based on the results from the phase 3 ELATIVE trial. The study found that 51% of patients on elafibranor + UDCA achieved the primary endpoint of biochemical response versus 4% for placebo + UDCA.
- https://seekingalpha.com/news/4114642-ipsen-gains-accelerated-approval-elafibranor-rare-liver-disease?source=content_type%3Areact%7Cfirst_level_url%3Amarket-news%7Csection_asset%3Amain%7Csection%3Ahealthcare
- Ipsen S.A. (IPSEY) Stock
- https://www.ipsen.com/
- https://www.ipsen.com/pipeline/
Foralumab
LEQEMBI® (LECANEMAB-IRMB)
Iqirvo® (elafibranor)
FDA Accepts Tiziana Life Sciences Fast Track Designation Submission for Treatment of Multiple Sclerosis
11th June 2024
NEW YORK, June 11, 2024 – Tiziana Life Sciences, Ltd. (Nasdaq: TLSA) (“Tiziana” or the “Company”), a biotechnology company developing breakthrough immunomodulation therapies via novel routes of drug delivery, today announced it has received acceptance of its submission for intranasal foralumab to receive Fast Track Designation approval for the treatment of non-active, secondary-progressive multiple sclerosis (na-SPMS) to the U.S. Food and Drug Administration (FDA). .
Foralumab, a fully human anti-CD3 monoclonal antibody, is a biological drug candidate shown to cause T regulatory (Treg) cell induction when dosed intranasally. At present, ten (10) na-SPMS patients have been dosed in an Intermediate-Sized Patient Population Expanded Access (ISPPEA) Program with clinically meaningful reduction in fatigue scores (MFIS) in 70% of patients, and stability of disease noted within six months in all ten patients. In addition, intranasal foralumab is currently being studied in a Phase 2a, double-blind randomized, placebo-controlled, multicenter trial in patients with na-SPMS (NCT06292923). The Fast Track Designation request provided data from both animal models and clinical experience from the ISPPEA program. Foralumab would be the only intranasal monoclonal antibody designated as other Multiple Sclerosis monoclonal antibody therapies require intravenous or subcutaneous dosing. Fast Track Designation, if granted will affirm the serious disease condition and progressive disability seen in na-SPMS, and also the unmet medical need, as no therapies are currently approved for na-SPMS.
“Fast track is designed to expedite the review of drugs in development to treat serious conditions for which there are limited or no therapies,” commented Gabriele Cerrone, Chairman, acting CEO and founder of Tiziana Life Sciences. “The progressive nature of na-SPMS and lack of FDA-approved therapies for this disease aligns with the Food and Drug Administration’s criteria for Fast Track Designation. The increased interaction and partnership with the FDA afforded by this designation would be a tremendous asset to our foralumab development program, if granted,” he added.
About FDA Fast Track Designation
At this stage of development, a drug that receives Fast Track designation is eligible for some or all of the following[1]:
- More frequent meetings with FDA to discuss the drug’s development plan and ensure collection of appropriate data needed to support drug approval
- More frequent written communication from FDA about such things as the design of the proposed clinical trials and use of biomarkers
- Eligibility for Accelerated Approval and Priority Review, if relevant criteria are met
About Foralumab
Activated T cells play an important role in the inflammatory process. Foralumab, the only fully human anti-CD3 monoclonal antibody (mAb), binds to the T cell receptor and dampens inflammation by modulating T cell function, thereby suppressing effector features in multiple immune cell subsets. This effect has been demonstrated in patients with COVID and with multiple sclerosis, as well as in healthy normal subjects. The non-active SPMS intranasal foralumab Phase 2 trial (NCT06292923) began screening patients in November of 2023. Immunomodulation by nasal anti-CD3 mAb represents a novel avenue for treatment of neuroinflammatory and neurodegenerative human diseases.[2],[3]
About Tiziana Life Sciences
Tiziana Life Sciences is a clinical-stage biopharmaceutical company developing breakthrough therapies using transformational drug delivery technologies to enable alternative routes of immunotherapy. Tiziana’s innovative nasal approach has the potential to provide an improvement in efficacy as well as safety and tolerability compared to intravenous (IV) delivery. Tiziana’s lead candidate, intranasal foralumab, which is the only fully human anti-CD3 mAb, has demonstrated a favorable safety profile and clinical response in patients in studies to date. Tiziana’s technology for alternative routes of immunotherapy has been patented with several applications pending and is expected to allow for broad pipeline applications.
For more information please visit our website: www.tizianalifesciences.com
For further inquiries:
Tiziana Life Sciences Ltd
[2] https://www.pnas.org/doi/10.1073/pnas.2220272120
[3] https://www.pnas.org/doi/10.1073/pnas.2309221120
Tiziana multiple sclerosis asset foralumab Fast Track application accepted
Jun. 11, 2024 8:39 AM ET
Tiziana Life Sciences Ltd (TLSA) Stock
By: Jonathan Block, SA News Editor
- The U.S. FDA has accepted a Fast Track Designation application from Tiziana Life Sciences (NASDAQ:TLSA) for its multiple sclerosis candidate foralumab.
- https://seekingalpha.com/news/4114811-tiziana-multiple-sclerosis-asset-foralumab-fast-track-application-accepted?source=content_type%3Areact%7Cfirst_level_url%3Amarket-news%7Csection_asset%3Amain%7Csection%3Ahealthcare
- Tiziana Life Sciences Ltd (TLSA) Stock
- https://www.tizianalifesciences.com/
- https://www.tizianalifesciences.com/drug-pipeline/intranasal-foralumab/
biotecHOPE™ 2024
(mRNA-3705)
Mirvetuximab Soravtansine (ELAHERE®)
Mirvetuximab Soravtansine (ELAHERE®)
Moderna's Investigational Therapeutic for Methylmalonic Acidemia (mRNA-3705) Selected by U.S. Food & Drug Administration for START Pilot Program
June 6, 2024
Center for Biologics Evaluation and Research has chosen mRNA-3705 as one of four investigational medicines for accelerated development to address unmet medical needs for rare diseases
CAMBRIDGE, MA / ACCESSWIRE / June 6, 2024 / Moderna, Inc. (NASDAQ:MRNA) today announced that the U.S. Food and Drug Administration (FDA) has selected mRNA-3705 for the Support for Clinical Trials Advancing Rare Disease Therapeutics (START) pilot program. mRNA-3705 is an investigational therapeutic for methylmalonic acidemia (MMA) due to methylmalonic-CoA mutase (MUT) deficiency.
"We are excited about this opportunity and proud that our investigational mRNA therapeutic for MMA was selected by the U.S. FDA for the START pilot program. This selection highlights the promise of Moderna's innovative mRNA platform beyond vaccines and the potential this novel medicine may have in addressing the serious and unmet medical needs of MMA," said Kyle Holen, M.D., Moderna's Senior Vice President and Head of Development, Therapeutics and Oncology. "Selection for this program will enable enhanced communication with the U.S. FDA, resulting in acceleration of our development program as we prepare for pivotal study initiation for mRNA-3705 in 2024."
The START pilot program was initiated by the U.S. FDA in September 2023 to accelerate the development of novel treatments addressing unmet medical needs in rare diseases, with an initial selection of up to seven novel treatments, three by the Center for Drug Evaluation and Research (CDER) and four by the Center for Biologics Evaluation and Research (CBER). The milestone-driven initiative is intended to help the progression to pivotal clinical studies or pre-BLA/NDA meeting stages by enhancing communications between manufacturers and the U.S. FDA. Selected manufacturers will benefit from rapid, ad-hoc U.S. FDA interactions to support clinical development, such as study design, patient population, and statistical methods, beyond standard formal meetings. The program is designed to generate high-quality, reliable data to support marketing approvals, ensuring promising treatments advance efficiently through regulatory milestones.
MMA is a rare, life-threatening, inherited metabolic disorder that is most commonly (approximately 60% of cases) caused by a deficiency in the mitochondrial enzyme MUT. This deficiency can lead to metabolic crises due to a toxic buildup of acids in the body, progressing into multi-organ disease. As a result, MMA is associated with significant mortality and morbidity, and there are no approved therapies. Standard of care includes dietary and palliative measures. Currently, liver or combined liver and kidney transplants are the only effective treatments.
mRNA-3705 is being investigated in a Phase 1/2 study, called the "Landmark study," an adaptive, open-label study designed to evaluate the safety and tolerability of the investigational therapeutic administered via intravenous infusion in patients one year and older with isolated MMA due to methylmalonyl-CoA mutase (hMUT) deficiency.
About mRNA-3705
mRNA-3705 is designed to instruct the body to restore the missing or dysfunctional proteins that cause MMA and consists of mRNA encoding human MUT, the mitochondrial enzyme commonly deficient in MMA, encapsulated within Moderna's proprietary lipid nanoparticle (LNP). mRNA-3705 uses the same proprietary LNP formulation as the Company's propionic acidemia (mRNA-3927) program. mRNA-3705 has been granted Orphan Drug, Fast Track, and Rare Pediatric Disease designation by the U.S. FDA.
About Moderna
Moderna is a leader in the creation of the field of mRNA medicine. Through the advancement of mRNA technology, Moderna is reimagining how medicines are made and transforming how we treat and prevent disease for everyone. By working at the intersection of science, technology and health for more than a decade, the company has developed medicines at unprecedented speed and efficiency, including one of the earliest and most effective COVID-19 vaccines.
Moderna's mRNA platform has enabled the development of therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases and autoimmune diseases. With a unique culture and a global team driven by the Moderna values and mindsets to responsibly change the future of human health, Moderna strives to deliver the greatest possible impact to people through mRNA medicines. For more information about Moderna, please visit modernatx.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.
SOURCE: Moderna, Inc.
Moderna mRNA candidate chosen for FDA rare disease therapy acceleration program
Jun. 06, 2024 10:13 AM ET
Moderna, Inc. (MRNA) StockLRMR
By: Jonathan Block, SA News Editor7 Comments
- The U.S. FDA has selected Moderna's (NASDAQ:MRNA) mRNA therapeutic mRNA-3705 for methylmalonic acidemia ("MMA") due to methylmalonic-CoA mutase ("MUT") deficiency for a pilot program designed to accelerate development of rare disease drugs.
- mRNA-3705, which is currently in a phase 1/2 study, is designed to treat MMA, an inherited metabolic disorder that is most commonly caused by a deficiency in the mitochondrial enzyme MUT that can lead to a toxic buildup of acids in the body and eventually into multi-organ disease.
- https://seekingalpha.com/news/4113677-moderna-mrna-candidate-chosen-fda-rare-disease-therapy-acceleration-program
- Moderna, Inc. (MRNA) Stock
- https://www.modernatx.com/en-US
- https://www.modernatx.com/en-US/research/product-pipeline
Mirvetuximab Soravtansine (ELAHERE®)
Mirvetuximab Soravtansine (ELAHERE®)
Mirvetuximab Soravtansine (ELAHERE®)
June 06, 2024
AbbVie Announces Positive Topline Results from Phase 2 PICCOLO Trial Evaluating Mirvetuximab Soravtansine (ELAHERE®) for High Folate Receptor-Alpha (FRα) Expressing Platinum-Sensitive Ovarian Cancer
- Open a printable version of this page
- Email the URL of this page to a friend
- PICCOLO trial met its primary endpoint of objective response rate (ORR)
- Data from the study will be presented at a future medical meeting
NORTH CHICAGO, Ill., June 6, 2024 /PRNewswire/ -- AbbVie (NYSE: ABBV) announced today positive topline results from the Phase 2 PICCOLO trial evaluating investigational mirvetuximab soravtansine (ELAHERE®) monotherapy in heavily pre-treated patients with folate receptor-alpha (FRα) positive, platinum-sensitive ovarian cancer (PSOC). The study met its primary endpoint with an objective response rate (ORR) of 51.9% (95%CI 40.4 – 63.3%).
In addition, the median duration of response (DOR), a key secondary endpoint, was 8.25 months.
The safety profile of mirvetuximab soravtansine was consistent with findings from previous studies, and no new safety concerns were identified. Full data from the PICCOLO study will be presented at a future medical meeting.
"Significant unmet needs remain for patients with platinum sensitive disease, as each subsequent line of therapy in this setting is associated with decreased efficacy and tolerability, which reinforces the need for treatment alternatives for these patients," said Angeles Alvarez Secord, M.D., M.H.Sc., from the Duke Cancer Institute. "The PICCOLO data further support the potential of mirvetuximab soravtansine for platinum-sensitive ovarian cancer patients."
About PICCOLO
PICCOLO is a single arm Phase 2 trial evaluating the efficacy and safety of mirvetuximab soravtansine monotherapy in patients with FR-alpha high platinum-sensitive ovarian cancer who have received at least two prior lines of platinum containing therapy or have a documented platinum allergy. The primary end point is objective response rate (ORR), and the key secondary endpoint is duration of response (DOR).
The PICCOLO study was designed to statistically rule out an objective response rate of 28% or lower, as excluded by the lower bound of the confidence interval, a response rate which has been observed with non-platinum, single-agent chemotherapy in platinum-sensitive disease. Patients with PSOC with multiple prior lines of platinum-based therapy or who are ineligible for platinum-based therapy, as in the population in PICCOLO, have no established benchmark standard of care, particularly after disease progression on a PARP inhibitor.
Mirvetuximab soravtansine is also being studied in PSOC in the Phase 3 GLORIOSA trial, in combination with bevacizumab versus bevacizumab alone in maintenance after second-line platinum-doublet therapy.
About Ovarian Cancer
Ovarian cancer is the leading cause of death from gynecological cancers in the United States. Each year, approximately 20,000 patients are diagnosed. Most patients present with late-stage disease and will typically undergo surgery followed by platinum-based chemotherapy. Unfortunately, the majority of patients will experience recurrence of their disease and require multiple subsequent lines of therapy, with decreasing efficacy and tolerability. Patients who initially respond to platinum-based chemotherapy and relapse 6 months or longer after the initial treatment were classified as platinum sensitive, while patients who relapse within under 6 months after platinum-based chemotherapy were considered platinum resistant.
Platinum-based chemotherapy remains the most active treatment for earlier lines of ovarian cancer. The benefit of retreatment with platinum is generally less with each subsequent line of therapy. While platinum-based doublets predominate treatment for front- and second-line patients based on results from randomized trials, there is no generally accepted standard of care with a clear efficacy benchmark based on prospective trials in third-line or later patients, particularly those whose cancers have progressed on PARP inhibitors.
About Mirvetuximab Soravtansine
Mirvetuximab soravtansine is a first-in-class ADC comprising a folate receptor alpha-binding antibody, cleavable linker, and the maytansinoid payload DM4, a potent tubulin inhibitor designed to kill the targeted cancer cells.
Mirvetuximab soravtansine approved under the brand name ELAHERE® in the United States has received regulatory approval in adults with folate receptor-alpha (FRα) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. Select patients for therapy based on an FDA-approved test. The Marketing Authorization Application (MAA) for ELAHERE in Europe has been accepted by the European Medicines Agency (EMA). Regulatory submissions for ELAHERE are also under review in multiple other countries. The safety and efficacy of mirvetuximab soravtansine has not been established for platinum-sensitive ovarian cancer.
ELAHERE® (mirvetuximab soravtansine-gynx) U.S. USE and IMPORTANT SAFETY INFORMATION
What is ELAHERE?
ELAHERE is a prescription medicine used to treat adults with folate receptor-alpha positive ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who:
• have not responded to or are no longer responding to treatment with platinum-based chemotherapy
and
• have received 1 to 3 prior types of chemotherapy.
Your healthcare provider will perform a test to make sure that ELAHERE is right for you.
It is not known if ELAHERE is safe and effective in children.
Please see Full Prescribing Information, including Boxed WARNING and Medication Guide
About AbbVie in Oncology
At AbbVie, we are committed to transforming standards of care for patients living with difficult-to-treat cancers. We are advancing a dynamic pipeline of investigational therapies across a range of cancer types in both blood cancers and solid tumors. We are focusing on creating targeted medicines that either impede the reproduction of cancer cells or enable their elimination. We achieve this through various, targeted treatment modalities including Antibody Drug Conjugates (ADCs), Immuno-Oncology, bi-specific antibody and CAR-T platforms. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potential breakthrough medicines.
Today, our expansive oncology portfolio comprises of approved and investigational treatments for a wide range of blood and solid tumors. We are evaluating more than 20 investigational medicines in multiple clinical trials across some of the world's most widespread and debilitating cancers. As we work to have a remarkable impact on people's lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit http://www.abbvie.com/oncology.
About AbbVie
AbbVie's mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas – immunology, oncology, neuroscience, and eye care – and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on LinkedIn, Facebook, Instagram, X (formerly Twitter), and YouTube.
SOURCE AbbVie
AbbVie succeeds in mid-stage trial for overran cancer drug, Elahere
Jun. 06, 2024 9:08 AM ET
By: Dulan Lokuwithana, SA News Editor
AbbVie (NYSE:ABBV) announced Thursday that its antibody-drug conjugate Elahere reached the main goal in its Phase 2 PICCOLO trial for patients with platinum-sensitive ovarian cancer.
Citing topline data, AbbVie (ABBV) said Elahere led to a 52% of objective response rate, reaching PICCOLO’s primary goal.
https://seekingalpha.com/news/4113625-abbvie-posts-mid-stage-trial-win-elahere
ABBV-383
Mirvetuximab Soravtansine (ELAHERE®)
PREZCOBIX® (darunavir and cobicistat) tablets,
June 05, 2024
AbbVie Advances Oncology Pipeline With Start of Multiple Myeloma Phase 3 Clinical Trial for Investigational Asset ABBV-383
- Open a printable version of this page
- ABBV-383 is a B-cell maturation antigen (BCMA) bispecific antibody T-cell engager being evaluated in relapsed/refractory multiple myeloma (r/r MM)
- The CERVINO Phase 3 trial will evaluate the efficacy, safety, and tolerability of ABBV-383 monotherapy compared with standard available therapies (SATs) in patients with r/r MM who have received at least two lines of prior therapy
NORTH CHICAGO, Ill., June 5, 2024 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced that the first patient has been treated with investigational ABBV-383 in the CERVINO Phase 3 study. ABBV-383 is a distinctive B-cell maturation antigen (BCMA) and CD3 bispecific antibody T-cell engager composed of bivalent BCMA-binding domains allowing for high BCMA-avidity and a low-affinity CD3 binding domain.1 ABBV-383 is being evaluated in a Phase 3, multicenter, randomized, open-label study compared with standard available therapies in patients with r/r MM who received at least two lines of prior therapy.
"Despite notable advances in treatment, most patients with multiple myeloma will eventually relapse. Patients with advanced disease, especially in the community setting, often have limited access to novel treatment options and existing options have a high treatment burden, including frequent dosing," said Dr. Peter Voorhees, clinical professor of medicine, director of plasma cell disorders, Atrium Health Levine Cancer Institute. "The CERVINO Phase 3 trial is designed to evaluate the efficacy of ABBV-383 with monthly dosing and we look forward to seeing the data as it emerges."
Multiple myeloma is a blood cancer characterized by abnormal proliferation of plasma cells, which can cause end-organ damage and is the second most commonly occurring blood cancer in the world.2 An estimated 176,000 people globally were diagnosed with multiple myeloma in 2020, and 117,000 people died from the disease.3
"The start of the CERVINO Phase 3 trial marks an important step forward in AbbVie's continued commitment to advance new oncology treatments and elevate the standard of care for blood cancer patients," said Mariana Cota Stirner, M.D., vice president, therapeutic area head oncology, hematology, AbbVie. "ABBV-383 is being evaluated with monthly dosing from the beginning of treatment, with the goal of maximizing treatment simplicity for physicians and patients, if proven in the clinical trials."
About the CERVINO Study
CERVINO (NCT06158841) is a global, Phase 3, multicenter, randomized, open-label, parallel-group study evaluating ABBV-383 in adult patients (≥18 years) with r/r MM and an Eastern Cooperative Oncology Group performance status ≤2 who received at least two prior lines of therapy, including exposure to a PI, an IMiD, and an anti-CD38 mAb. Patients who received prior BCMA-targeted therapy will be excluded. Patients will be randomized 1:1 to receive intravenous ABBV-383 60mg Q4W or the investigator's choice of SAT (carfilzomib + dexamethasone, elotuzumab + pomalidomide + dexamethasone, or selinexor + bortezomib + dexamethasone), and will continue treatment until confirmed progressive disease or other discontinuation criteria are met.
The dual primary end points are progression-free survival and overall response rate. Secondary end points include overall survival, complete response (CR) or better, very good partial response or better, rate of minimum residual disease negativity, and change in disease symptoms and physical functioning.
Approximately 140 sites globally will enroll approximately 380 total patients.
Additional information about the study can be found at https://clinicaltrials.gov/ under the identifier NCT06158841.
About ABBV-383
ABBV-383 is an investigational distinctive BCMA x CD3 bispecific antibody T-cell engager composed of bivalent high-avidity BCMA-binding domains, a low-affinity CD3-binding domain designed to reduce cytokine release, and a silenced Fc tail designed for an extended half-life that may support once every 4-week (Q4W) dosing. Clinical relevance of these structure activity relationships has not been established.
BCMA is highly expressed on the surface of malignant plasma cells in multiple myeloma, making it an ideal target for therapy. BCMA plays a crucial role in the survival of myeloma cells by promoting their growth and inhibiting their apoptosis (programmed cell death).4
About AbbVie in Oncology
At AbbVie, we are committed to transforming standards of care for patients living with difficult-to-treat cancers. We are advancing a dynamic pipeline of investigational therapies across a range of cancer types in both blood cancers and solid tumors. We are focusing on creating targeted medicines that either impede the reproduction of cancer cells or enable their elimination. We achieve this through various, targeted treatment modalities including Antibody Drug Conjugates (ADCs), Immuno-Oncology, and bi-specific and CAR-T platforms. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potential breakthrough medicines.
Today, our expansive oncology portfolio is comprised of approved and investigational treatments for a wide range of blood and solid tumors. We are evaluating more than 20 investigational medicines across some of the world's most widespread and debilitating cancers. As we work to have a remarkable impact on people's lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit us at http://www.abbvie.com/oncology.
About AbbVie
AbbVie's mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas – immunology, oncology, neuroscience, and eye care – and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on LinkedIn, Facebook, Instagram, X (formerly Twitter), and YouTube.
SOURCE AbbVie
AbbVie doses first patient in phase 3 trial of multiple myeloma asset
Jun. 05, 2024 10:10 AM ET
By: Jonathan Block, SA News Editor
- AbbVie (NYSE:ABBV) has started the phase CERVINO trial of ABBV-383 for multiple myeloma by dosing the first patient.
- The candidate is a B-cell maturation antigen (BCMA) and CD3 bispecific antibody T-cell engager.
- https://seekingalpha.com/news/4113186-abbvie-doses-first-patient-phase-3-trial-multiple-myeloma-asset
- AbbVie Inc. (ABBV) Stock
- https://www.abbvie.com/
PREZCOBIX® (darunavir and cobicistat) tablets,
PREZCOBIX® (darunavir and cobicistat) tablets,
PREZCOBIX® (darunavir and cobicistat) tablets,
Johnson & Johnson Submits Supplemental New Drug Application to U.S. FDA Seeking Expanded Pediatric Indication for HIV-1 Therapy PREZCOBIX®
If approved, PREZCOBIX® would offer a new HIV-1 treatment option for pediatric patients aged 6 and older weighing at least 25 kg
June 04, 2024
Titusville, N.J. (June 4, 2024) – Johnson & Johnson today announced the submission of a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) seeking to expand the indication of PREZCOBIX® (darunavir/cobicistat) to include the treatment of HIV-1 infection in younger children at least 6 years of age weighing at least 25 kg. A parallel line extension application and type 2 variation application have also been submitted to the European Medicines Agency (EMA) for expanded pediatric use in Europe, where the product is marketed as REZOLSTA®.
If the applications are approved, PREZCOBIX®/REZOLSTA® could be administered to adults and pediatric patients at least 6 years of age, weighing at least 25kg. A new co-formulated tablet containing a weight-adjusted pediatric dose (darunavir 675 mg/cobicistat 150 mg) has been developed to aid administration for younger children. The new pediatric tablets are scored to facilitate breaking for ease of swallowing.
“We are proud of this latest step in our years of work to ensure that some of the youngest people living with HIV have access to different treatment regimens that can work for them,” said Penny Heaton, M.D., Global Therapeutic Area Head, Infectious Diseases and Vaccines and Global Public Health R&D at Johnson & Johnson. “If approved, this medicine could offer healthcare providers a new treatment option that ensures weight-appropriate dosing to better meet the needs of young people living with HIV.”
The applications to the FDA and EMA are supported by data from a clinical study sponsored by Janssen Research & Development, LLC, that evaluated the pharmacokinetics of the new combination tablet and established that it is bioequivalent to darunavir and cobicistat when dosed as single agents (NCT04718805). The efficacy, safety and tolerability of cobicistat-boosted darunavir for the treatment of younger children with HIV-1 was established in a Phase 2/3 clinical trial conducted by Gilead Sciences (NCT02016924).
Based on these data, Janssen Products, LP, a division of Johnson & Johnson, is seeking an expanded indication to allow the use of PREZCOBIX®/REZOLSTA® in treatment-naïve and treatment-experienced pediatric patients aged 6 years and older, weighing at least 25 kg, and who have no viral resistance mutations associated with darunavir. These filings reflect Johnson & Johnson’s work toward expanding access to its treatment portfolio to support people of many ages living with HIV.
About PREZCOBIX®/REZOLSTA®
PREZCOBIX®/REZOLSTA® is a two-drug fixed-dose combination tablet containing darunavir, an HIV-1 protease inhibitor, and cobicistat, a CYP3A inhibitor that serves as a PK enhancer or “booster.” The booster enables once-daily dosing and optimal therapeutic levels of darunavir.
This product is currently indicated for the treatment of HIV-1 infection in treatment-naïve and treatment-experienced adults and adolescent patients weighing at least 40 kg with no darunavir resistance-associated mutations.
Darunavir as a single agent is marketed by Janssen Products, LP as PREZISTA® in the United States, and cobicistat, developed by Gilead Sciences, Inc., is marketed as TYBOST®. The fixed-dose combination PREZCOBIX®/REZOLSTA® is a collaboration between Janssen R&D Ireland and Gilead Sciences, Inc.
Please see full Prescribing Information for important safety information.
IMPORTANT SAFETY INFORMATION
What is the most important information I should know about PREZCOBIX?
- PREZCOBIX® may cause liver problems. Some people taking PREZCOBIX® may develop liver problems which may be life-threatening. Your healthcare provider should do blood tests before and during your treatment with PREZCOBIX®. If you have chronic hepatitis B or C infection, your healthcare provider should check your blood tests more often because you have an increased chance of developing liver problems. Tell your healthcare provider if you have any of the below signs and symptoms of liver problems.
- dark (tea colored) urine
- yellowing of your skin or whites of your eyes
- pale colored stools (bowel movements)
- nausea
- vomiting
- pain or tenderness on your right side below your ribs
- loss of appetite
- PREZCOBIX® may cause severe or life-threatening skin reactions or rash. Sometimes these skin reactions and skin rashes can become severe and require treatment in a hospital. Call your healthcare provider right away if you develop a rash. Stop taking PREZCOBIX® and call your healthcare provider right away if you develop any skin changes with symptoms below:
- fever
- tiredness
- muscle or joint pain
- blisters or skin lesions
- mouth sores or ulcers
- red or inflamed eyes, like “pink eye” (conjunctivitis)
- PREZCOBIX®, when taken with certain other medicines can cause new or worse kidney problems, including kidney failure. Your healthcare provider should check your kidneys before you start and while you are taking PREZCOBIX®.
See “What are the possible side effects of PREZCOBIX®?” for more information about side effects.
What is PREZCOBIX®?
PREZCOBIX® is a prescription medicine that is used with other HIV-1 medicines to treat HIV-1 infection in adults and in children who weigh at least 88 pounds (40 kg).
HIV-1 is the virus that causes Acquired Immune Deficiency Syndrome (AIDS). PREZCOBIX® contains the prescription medicines darunavir and cobicistat.
It is not known if PREZCOBIX® is safe and effective in children weighing less than 88 pounds (40 kg).
Please see full Product Information for more details.
About Johnson & Johnson
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at https://www.jnj.com.
Learn more at https://www.janssen.com/johnson-johnson-innovative-medicine and follow us at https://twitter.com/JNJInnovMed and https://twitter.com/JNJNews. Janssen R&D Ireland, Janssen Research & Development, LLC, and Janssen Products, LP are Johnson & Johnson companies.
© Janssen Products, LP [2024]. All rights reserved.
J&J seeks to expand HIV med Prezcobix indication to children as young as six
Jun. 04, 2024 4:56 PM ET
By: Jonathan Block, SA News Editor3 Comments
- Johnson & Johnson (NYSE:JNJ) has submitted a supplemental New Drug Application to the U.S. FDA to expand the indication for the HIV medicine Prezcobix (darunavir/cobicistat) to children as young as six weighing at least 25 kilograms.
- If approved, the drug would be produced with a weight-adjusted pediatric dose.
- https://seekingalpha.com/news/4112875-johnson-johnson-seeks-expand-hiv-med-prezcobix-indication-children-young-six
- Johnson & Johnson (JNJ) Stock
- https://www.jnj.com/
- https://www.prezcobix.com/
VK2809 (TRβ Agonist)
PREZCOBIX® (darunavir and cobicistat) tablets,
VK2809 (TRβ Agonist)
Viking Therapeutics Announces Positive 52-Week Histologic Data from Phase 2b VOYAGE Study of VK2809 in Patients with Biopsy-Confirmed Non-Alcoholic Steatohepatitis (NASH)
Jun. 04, 2024 7:05 AM ET
Viking Therapeutics, Inc. (VKTX)
Up to 75% of Patients Treated with VK2809 Achieved NASH Resolution with No Worsening of Fibrosis as Compared to 29% for Placebo (p=0.0001)
Up to 57% of VK2809-Treated Patients Achieved ≥1-Stage Improvement in Fibrosis with No Worsening of NASH as Compared to 34% for Placebo (p<0.05)
Up to 48% of VK2809-Treated Patients Achieved Both Resolution of NASH and a ≥1-Stage Improvement in Fibrosis as Compared to 20% for Placebo (p=0.01)
Adverse Events, Including GI-Related AEs, Similar Among VK2809-Treated Patients vs. Placebo at Week 52; Consistent with Prior Data Reported at Week 12
Conference Call Scheduled for 8:00 a.m. ET Today
SAN DIEGO, June 3, 2024 /PRNewswire/ -- Viking Therapeutics, Inc. (VKTX) ("Viking") (NASDAQ: VKTX), a clinical-stage biopharmaceutical company focused on the development of novel therapies for metabolic and endocrine disorders, today announced positive 52-week histologic data from its Phase 2b VOYAGE study of VK2809, the company's novel liver-selective thyroid hormone receptor beta agonist, in patients with biopsy-confirmed non-alcoholic steatohepatitis (NASH). As previously reported, the study successfully achieved its primary endpoint, with patients receiving VK2809 experiencing statistically significant reductions in liver fat content from baseline to Week 12 as compared with placebo. The results announced today highlight achievement of secondary endpoints evaluating histologic changes assessed by hepatic biopsy after 52 weeks of treatment with VK2809.
Histologic Results at 52 Weeks
On the secondary endpoint of NASH resolution with no worsening of fibrosis, VK2809-treated patients demonstrated NASH resolution ranging from 63% to 75%, compared with 29% for placebo (p<0.05 for each VK2809 treatment group). Across the combined VK2809 treatment groups, 69% achieved NASH resolution (p<0.0001 vs. placebo). Resolution of NASH was defined as a non-alcoholic fatty liver disease activity score (NAS) of 0 or 1 for inflammation and 0 for ballooning.
On the secondary endpoint evaluating improvement in fibrosis with no worsening of NASH, VK2809-treated patients demonstrated improvement in fibrosis ranging from 44% to 57%, compared with 34% for placebo (p<0.05 for the 5 mg and 10 mg QOD cohorts). Across the combined VK2809 treatment groups, 51% achieved improvement in fibrosis with no worsening of NASH (p=0.03 vs. placebo). Improvement in fibrosis without worsening of NASH was defined as a ≥1-stage improvement in fibrosis and no increase in NAS for ballooning, inflammation, or steatosis.
On the secondary endpoint evaluating the proportion of patients experiencing both resolution of NASH and improvement in fibrosis, VK2809-treated patients demonstrated improvement ranging from 40% to 50%, compared with 20% for placebo (p<0.05 for the 5 mg and 10 mg QOD cohorts). Across the combined VK2809 treatment groups, 44% achieved this endpoint (p=0.003 vs. placebo). Resolution of NASH and improvement in fibrosis were defined as described above.
Study Design
The VOYAGE study was a randomized, double-blind, placebo-controlled, multicenter, international trial designed to assess the efficacy, safety and tolerability of VK2809 in patients with biopsy-confirmed NASH and fibrosis. Enrollment included patients with at least 8% liver fat content as measured by MRI-PDFF, as well as F2 and F3 fibrosis. The study allowed for up to 25% of enrolled patients to have F1 fibrosis provided they also possessed at least one additional risk factor, such as diabetes, obesity or hypertension, among others. The primary endpoint of the study evaluated the change in liver fat content from baseline to Week 12 in patients treated with VK2809 as compared to patients receiving placebo. Secondary objectives include the evaluation of histologic changes assessed by hepatic biopsy after 52 weeks of treatment.
Conference Call Today at 8:00 a.m. ET
Viking will hold a conference call today at 8:00 a.m. ET to discuss the top-line results from the Phase 2b VOYAGE study of VK2809. To participate on the conference call, please dial 844-850-0543 from the U.S. or 412-317-5199 from outside the U.S. In addition, following the completion of the call, a telephone replay will be accessible until June 11, 2024, by dialing 877-344-7529 from the U.S. or 412-317-0088 from outside the U.S. and entering conference ID 5121997. Those interested in listening to the conference call live via the internet may do so by visiting the Investor Relations section of Viking's website at https://ir.vikingtherapeutics.com/webcasts. An archive of the webcast will be available for 7 days on the company's website at https://ir.vikingtherapeutics.com/webcasts.
About VK2809
VK2809 is an orally available, tissue and receptor-subtype selective agonist of the thyroid hormone beta receptor (TRβ) that possesses selectivity for liver tissue, as well as the beta receptor subtype, suggesting promising therapeutic potential in a range of lipid disorders. The compound recently completed the Phase 2b VOYAGE study in patients with biopsy-confirmed non-alcoholic steatohepatitis (NASH) and fibrosis, successfully achieving both the trial's primary and secondary endpoints. VK2809 also successfully achieved primary and secondary endpoints in a Phase 2a study for the treatment of patients with elevated LDL-C and non-alcoholic fatty liver disease (NAFLD). Selective activation of the thyroid hormone beta receptor in liver tissue is believed to favorably affect cholesterol and lipoprotein levels via multiple mechanisms, including increasing the expression of genes associated with lipid metabolism and clearance.
About Viking Therapeutics, Inc.
Viking Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on the development of novel first-in-class or best-in-class therapies for the treatment of metabolic and endocrine disorders, with three compounds currently in clinical trials. Viking's research and development activities leverage its expertise in metabolism to develop innovative therapeutics designed to improve patients' lives. Viking's clinical programs include VK2809, a novel, orally available, small molecule selective thyroid hormone receptor beta agonist for the treatment of lipid and metabolic disorders. The compound successfully achieved both the primary and secondary endpoints in a recently completed Phase 2b study for the treatment of biopsy-confirmed non-alcoholic steatohepatitis (NASH) and fibrosis. In a Phase 2a trial for the treatment of non-alcoholic fatty liver disease (NAFLD) and elevated LDL-C, patients who received VK2809 demonstrated statistically significant reductions in LDL-C and liver fat content compared with patients who received placebo. Viking is also developing VK2735, a novel dual agonist of the glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors for the potential treatment of various metabolic disorders. Data from a Phase 1 and a Phase 2 trial evaluating VK2735 (dosed subcutaneously) for metabolic disorders demonstrated an encouraging safety and tolerability profile as well as positive signs of clinical benefit. The company is also evaluating an oral formulation of VK2735 in a Phase 1 trial. In the rare disease space, Viking is developing VK0214, a novel, orally available, small molecule selective thyroid hormone receptor beta agonist for the potential treatment of X-linked adrenoleukodystrophy (X-ALD). VK0214 is currently being evaluated in a Phase 1b clinical trial in patients with the adrenomyeloneuropathy (AMN) form of X-ALD. Viking holds exclusive worldwide rights to a portfolio of five therapeutic programs, including VK2809 and VK0214, which are based on small molecules licensed from Ligand Pharmaceuticals Incorporated.
For more information about Viking Therapeutics, please visit www.vikingtherapeutics.com.
View original content to download multimedia:https://www.prnewswire.com/news-releases/viking-therapeutics-announces-positive-52-week-histologic-data-from-phase-2b-voyage-study-of-vk2809-in-patients-with-biopsy-confirmed-non-alcoholic-steatohepatitis-nash-302162714.html
SOURCE Viking Therapeutics, Inc.
Viking falls despite positive mid-stage data for liver drug
Jun. 04, 2024 3:40 PM ET
Viking Therapeutics, Inc. (VKTX) StockLLY, MDGL
By: Dulan Lokuwithana, SA News Editor3 Comments
Despite early gains in the premarket, Viking Therapeutics (NASDAQ:VKTX) shares trended lower in regular trading Tuesday after the company held a conference call to discuss the latest data from a successful mid-stage trial for its liver disease therapy VK2809.
Before the opening bell, the San Diego, California-based biotech announced promising 52-week data from its Phase 2b VOYAGE trial for VK2809 in non-alcoholic steatohepatitis (NASH), which had previously reached the primary goal.
Viking Therapeutics, Inc. (VKTX) Stock
Achondroplasia
PREZCOBIX® (darunavir and cobicistat) tablets,
VK2809 (TRβ Agonist)
bridgebio announces durable month 12 and 18 phase 2 cohort 5 results of oral infigratinib in achondroplasia, and first participant consented in accel for hypochondroplasia
06.04.2024 at 7:30 AM EDT
- In Cohort 5 of PROPEL 2 (0.25 mg/kg/day), oral treatment with infigratinib resulted in a statistically significant and sustained increase in annualized height velocity (AHV), with a mean change from baseline of +2.51cm/yr at Month 12, and +2.50 cm/yr at Month 18 (p=0.0015)
- At Month 18, there was a statistically significant improvement in body proportionality (p-value of 0.001). The mean upper to lower body segment ratio was 1.88 at Month 18, as compared to 2.02 at baseline
- Infigratinib continues to be well-tolerated as a single daily oral therapy with no adverse events (AEs) assessed as treatment-related in any participant in Cohort 5
- PROPEL 3, the global Phase 3 registrational study of infigratinib in achondroplasia, continues to enroll on schedule, with completion estimated by end of 2024
- BridgeBio announces first child consented in ACCEL, the observational run-in study for infigratinib in children living with hypochondroplasia, a skeletal dysplasia closely related to achondroplasia and similarly driven by FGFR3 gain-of-function variants
PALO ALTO, Calif., June 04, 2024 (GLOBE NEWSWIRE) -- BridgeBio Pharma, Inc. (Nasdaq: BBIO) (BridgeBio), a commercial-stage biopharmaceutical company focused on genetic diseases, today announced sustained positive results from PROPEL 2, a Phase 2 trial of the investigational therapy infigratinib in children with achondroplasia, demonstrating continued potential best-in-class efficacy and an encouraging safety profile. Infigratinib is an oral small molecule designed to inhibit FGFR3 signaling and target achondroplasia and hypochondroplasia at their source. BridgeBio will also host an investor call on June 4, 2024, at 8:00 am ET with Ravi Savarirayan, M.D., Ph.D., of Murdoch Children’s Research Institute in Melbourne, Australia, and the global lead investigator for PROPEL 2, to discuss the results from the Phase 2 study.
To date, key results from the Cohort 5 dose escalation cohort in PROPEL 2 trial include:
- Sustained and statistically significant mean increase in AHV of +2.51cm/year from baseline at 12 months, and +2.50 cm/yr at 18 months (p=0.0015)
- Statistically significant improvement in body proportionality (mean upper to lower body segment ratio), from 2.02 at baseline to 1.88 at Month 18 (mean change from baseline, p=0.001)
- A continued well-tolerated safety profile, with no treatment-related adverse events assessed as related to infigratinib
“These data indicate that treatment with infigratinib is continuing to show increased growth velocity and improvements in body proportionality in children with achondroplasia. This is encouraging and suggests that infigratinib has the potential to enhance functionality for people living with achondroplasia in addition to increasing growth. We hope to see these improvements reflected in the ongoing PROPEL 3 pivotal study that will build toward providing a safe and effective oral therapy to those in the achondroplasia community who are seeking treatment,” said Dr. Savarirayan.
PROPEL 3, the global Phase 3 registrational study of infigratinib in achondroplasia, continues to enroll on schedule, with completion of enrollment anticipated by the end of the year.
Given the promising results from PROPEL 2, BridgeBio is committed to expanding the FGFR3-related skeletal dysplasias franchise for infigratinib by accelerating development in hypochondroplasia. Positive interactions with both the U.S. FDA and EMA support development in children with hypochondroplasia, with a small open-label Phase 2 portion testing a single dose of 0.25 mg/kg/day, leading into a double-blinded, placebo-controlled Phase 3 study. ACCEL, the observational lead-in program for hypochondroplasia, was initiated with the first participant consented in May 2024. The interventional program, ACCEL 2/3, will be a global Phase 2/3 multicenter, single-dose study, to evaluate the efficacy and safety of 0.25mg/kg/day of infigratinib in children living with hypochondroplasia. The open-label Phase 2 portion in children aged 5 to 11 years old will be followed by a pivotal Phase 3, one-year, 2:1 randomized, double-blinded, placebo-controlled study in children aged 3 to < 18 years old with growth potential. In addition to changes from baseline in AHV measurements, the study will evaluate changes in other indicators of growth, body proportions, medical complications associated with hypochondroplasia, and changes in quality-of-life measures. BridgeBio has previously presented promising preclinical data for hypochondroplasia at ENDO 2023 and ASHG 2022.
“We are very excited to see a persistence of response to infigratinib in linear growth. We are especially encouraged by the promising effect on body proportions, which supports infigratinib’s potential to provide benefits that could impact the lives of children with achondroplasia. These results motivate us to continue evaluating infigratinib in other FGFR-related skeletal dysplasias and genetic conditions. The initiation of our observational study in hypochondroplasia and the obtainment of FDA and EMA alignment on the interventional study underlie our excitement for the potential of infigratinib as a treatment option for children with hypochondroplasia,” said Daniela Rogoff, M.D., Ph.D., Chief Medical Officer, Skeletal Dysplasias at BridgeBio.
“The journey of living with skeletal dysplasia varies from person to person, but many are impacted by functional limitations, social stigma and medical complications due to their condition and the way their bones develop. We are encouraged to see infigratinib’s potential to improve body proportionality, which could help address functional complications meaningful to people living with skeletal dysplasia. The Chandler Project values the collaborative partnership we’ve developed with BridgeBio and QED, to ensure that the community’s true needs are prioritized throughout the discovery and development process. We are also thrilled for the launch of an observational study in hypochondroplasia, a community that has been eager for further research and development of treatment options,” said Chandler Crews, founder of The Chandler Project, a patient advocacy organization based in Baltimore, MD.
Information about PROPEL 3 (NCT06164951) can be found here on clinicaltrials.gov. Information about PROPEL (NCT04035811), BridgeBio’s observational lead-in study in achondroplasia for PROPEL 3 and other studies, can be found here on clinicaltrials.gov. Information about ACCEL (NCT06410976), BridgeBio’s observational lead-in study in hypochondroplasia can be found here on clinicaltrials.gov. BridgeBio is committed to exploring the potential of infigratinib on wider medical and functional impacts of achondroplasia, hypochondroplasia and other skeletal dysplasias, which hold significant unmet needs for families.
Webcast Information
BridgeBio will host an investor call and simultaneous webcast to discuss the Phase 2 data at Months 12 and 18 of infigratinib in children with achondroplasia on June 4, 2024 at 8:00 am ET. A link to the webcast may be accessed from the event calendar page of BridgeBio’s website at https://investor.bridgebio.com/. A replay of the conference call and webcast will be archived on the Company’s website and will be available for at least 30 days following the event.
About Achondroplasia
Achondroplasia is the most common cause of disproportionate short stature, affecting approximately 55,000 people in the United States (US) and European Union (EU), including up to 10,000 children and adolescents with open growth plates. Achondroplasia impacts overall health and quality of life, leading to medical complications such as obstructive sleep apnea, middle ear dysfunction, kyphosis, and spinal stenosis. The condition is uniformly caused by an activating variant in FGFR3.
About Hypochondroplasia
Hypochondroplasia is also an FGFR3-associated skeletal dysplasia and is a rare condition with similar prevalence in achondroplasia. Hypochondroplasia presents with a wide spectrum of phenotypes including disproportionate short stature, mild joint laxity and macrocephaly. Currently, no treatments for hypochondroplasia are approved in the United States.
About BridgeBio Pharma, Inc.
BridgeBio Pharma (BridgeBio) is a commercial-stage biopharmaceutical company founded to discover, create, test and deliver transformative medicines to treat patients who suffer from genetic diseases. BridgeBio’s pipeline of development programs ranges from early science to advanced clinical trials. BridgeBio was founded in 2015 and its team of experienced drug discoverers, developers and innovators are committed to applying advances in genetic medicine to help patients as quickly as possible. For more information visit bridgebio.com and follow us on LinkedIn and Twitter.
BridgeBio releases new phase 2 results for infigratinib for achondroplasia
Jun. 04, 2024 11:42 AM ET
BridgeBio Pharma, Inc. (BBIO) Stock
By: Jonathan Block, SA News Editor
- Additional phase 2 data from a dose escalation cohort of BridgeBio Pharma's (NASDAQ:BBIO) achondroplasia candidate infigratinib showed the drug continued to improve height at months 12 and 18.
- The mean increase in annualized height velocity was +2.51cm/year at 12 months and +2.50 cm/yr at 18 months compared to baseline.
- There was also a statistically significant improvement in body proportionality from 2.02 at baseline to 1.88 at month 18.
- https://seekingalpha.com/news/4112758-bridgebio-releases-new-phase-2-results-infigratinib-achondroplasia
- BridgeBio Pharma, Inc. (BBIO) Stock
- https://bridgebio.com/
DARZALEX® (daratumumab)
RYBREVANT® (amivantamab) combined with lazertinib
TECVAYLI® (teclistamab-cqyv)
DARZALEX® (daratumumab)-based regimens significantly improve clinical outcomes in both transplant-eligible and -ineligible patients who are newly diagnosed with multiple myeloma
88 percent of transplant-eligible patients achieved a complete response or better, and 47 percent of patients sustained MRD-negativity for longer than one year with DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj)-based induction, consolidation and maintenance regimens in the Phase 3 PERSEUS study
7.5 years median overall survival achieved with DARZALEX®-based regimen in Phase 3 MAIA final analysis is the longest reported in patients ineligible for transplant
June 03, 2024
CHICAGO (June 3, 2024) –
Johnson & Johnson today announced data from the Phase 3 PERSEUS study showing deepening of responses and sustained minimal residual disease (MRD) negativity at both 10-5 and 10-6 levels with an induction regimen of DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) in combination with bortezomib, lenalidomide and dexamethasone (D-VRd) followed by a maintenance regimen of DARZALEX FASPRO® plus lenalidomide (D-R) for the treatment of patients with transplant-eligible (TE) newly diagnosed multiple myeloma (NDMM). The rates of deep and sustained MRD negativity were associated with improved progression-free survival (PFS) with DARZALEX FASPRO®-based quadruplet induction, consolidation and doublet maintenance regimen in these patients versus VRd. The data are featured as oral presentations at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #7502) and the 2024 European Hematology Association (EHA) Congress (Abstract #S201).
“MRD-negativity is an important measure in predicting long-term progression-free survival for patients with multiple myeloma,” said Dr. Paula Rodriguez-Otero, Department of Hematology, Cancer Center Clínica Universidad de Navarra, Pamplona, Navarra, Spain.* “The higher rates of deep and sustained MRD negativity with this DARZALEX FASPRO-based regimen underscore the potential of D-VRd and D-R maintenance to shift the treatment paradigm for transplant-eligible patients with newly diagnosed multiple myeloma and bring us closer to the potential for a functional cure.”
In the PERSEUS study, the D-VRd arm showed deeper responses and higher rates of MRD negativity over time at both 10-5 and 10-6 levels compared to the VRd arm (n=354), with higher rates of complete response at the end of consolidation (44.5 percent vs. 34.7 percent) and maintenance (87.9 percent vs. 70.1 percent). Rates of MRD negativity at 10-6 increased over time and were consistently higher in the D-VRd vs. VRd arm: 43.9 percent vs. 20.9 percent (P=0.0001) at 12 months; 57.7 percent vs. 27.4 percent (P=0.0001) at 24 months and 63.9 percent vs. 30.8 percent (P=0.0001) at 36 months.1
The D-VRd arm also demonstrated higher rates of sustained MRD negativity at 10-6 for at least 12 months compared to the VRd arm: 47.3 percent vs. 18.6 percent (P <0.0001). The PFS rate at 48 months was 84.3 percent for the D-VRd arm compared to 67.7 percent for the VRd arm (hazard ratio [HR], 0.42; 95 percent confidence interval [CI], 0.30-0.59; P<0.0001).1
Final survival analysis from Phase 3 MAIA study of DARZALEX®-based regimen as a frontline combination therapy to be presented at EHA
Follow-up data from MAIA showed a median overall survival of 7.5 years for DARZALEX® plus lenalidomide and dexamethasone (D-Rd), with a 33 percent reduction in the risk of death versus lenalidomide plus dexamethasone (Rd) in transplant-ineligible patients with NDMM (HR, 0.67;95 percent CI,0.55-0.82; nominal P<0.0001).2 Median overall survival was 90.3 months with D-Rd versus 64.1 months with Rd. The overall survival benefit with D-Rd versus Rd was consistent across pre-specified subgroups.2 The median age of patients enrolled in MAIA was 73 (range: 45 to 90) years, with 43.6 percent of participants over the age of 75 years.2 Data will be presented in a poster at EHA (Abstract #P968).
“The median overall survival of 7.5 years seen in the MAIA study reinforces the efficacy of DARZALEX as a foundational treatment in the frontline setting for patients with multiple myeloma who are not eligible for transplant,” said Jordan Schecter, M.D., Vice President, Disease Area Leader, Multiple Myeloma, at Johnson & Johnson Innovative Medicine. “DARZALEX has shown an overall survival benefit across three studies in newly diagnosed multiple myeloma, supporting it as a standard-of-care. DARZALEX-based quadruplet and triplet regimens have advanced outcomes for newly diagnosed patients in the transplant-eligible and ineligible settings.”
Long-term data from Phase 3 CASSIOPEIA study evaluating DARZALEX®-based therapy and maintenance in TE patients with NDMM to be presented at EHA
More than six years of follow-up data from CASSIOPEIA show that post-transplant maintenance with DARZALEX® reduced the risk of disease progression or death by 51 percent versus observation, with the median PFS not reached at six years with DARZALEX® vs median PFS of less than four years (45.8 months) with observation (HR, 0.49; 95 percent CI, 0.40 - 0.59; P< 0.0001).3 The results will be presented in an oral presentation at EHA (Abstract #S204).
In the PERSEUS, MAIA and CASSIOPEIA studies, the safety profiles were consistent with the known safety profiles for DARZALEX® and DARZALEX FASPRO®.1,2,3
* Dr. Paula Rodriguez-Otero, Department of Hematology, Cancer Center Clínica Universidad de Navarra, has provided consulting, advisory, and speaking services to Johnson & Johnson; she has not been paid for any media work.
About the PERSEUS study
The PERSEUS study (NCT03710603) is being conducted in collaboration with the European Myeloma Network as the sponsor. PERSEUS is an ongoing, randomized, open-label, Phase 3 study comparing the efficacy and safety of D-VRd and ASCT followed by D-R maintenance vs VRd and ASCT followed by R maintenance in patients with transplant-eligible NDMM. The primary endpoint is PFS, and secondary endpoints include overall CR or better rate, overall MRD-negativity (in patients with CR or better), and overall survival. DARZALEX FASPRO® was discontinued after at least 24 months of D-R maintenance therapy in patients who had a CR or better and had sustained MRD–negative status for at least 12 months.4 The median age is 61.0 (range, 32-70) years for patients in the D-VRd arm and 59.0 (range, 31-70) years for patients in the VRd arm. The study is being conducted in 14 countries in Europe and Australia.
Data from the PERSEUS study were featured as a late-breaking oral presentation (LBA-1) at the 2023 American Society of Hematology (ASH) Annual Meeting and simultaneously published in The New England Journal of Medicine in 2023.
About the MAIA Trial
The randomized, open-label, multicenter Phase 3 (NCT02076009) study included 737 newly diagnosed patients with multiple myeloma ineligible for high-dose chemotherapy and autologous stem cell transplant (ASCT), aged 45-90 years (median age of 73).5 Patients were randomized to receive either D-Rd or Rd alone in 28-day cycles. In the D-Rd arm, patients received DARZALEX® 16 milligrams per kilogram (mg/kg) IV weekly for cycles 1 – 2, every two weeks for cycles 3 – 6 and every four weeks for cycle 7 and thereafter.5 Patients in the D-Rd and Rd treatment arms received 25 mg of lenalidomide on days 1 – 21 of each 28-day cycle, and dexamethasone at 40 mg once a week for each cycle. Patients in both treatment arms continued until disease progression or unacceptable toxicity.6
Earlier results from the MAIA study supported the U.S. Food and Drug Administration (FDA) approval of DARZALEX® in combination with Rd. These data were also published in The New England Journal of Medicine in 2019. An updated OS analysis was published in The Lancet Oncology in 2021.
About the CASSIOPEIA Trial
The randomized, open-label, multicenter, Phase 3 (NCT02541383) study is sponsored by the French Intergroupe Francophone du Myelome in collaboration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology and Janssen Research & Development, LLC. This Phase 3 study included 1,085 newly diagnosed patients with previously untreated, symptomatic multiple myeloma who were eligible for high-dose chemotherapy and stem cell transplant. Part one of the study compared DARZALEX® (D) in combination with bortezomib, thalidomide and dexamethasone (VTd) versus VTd induction and consolidation therapy in patients with NDMM who were eligible for autologous stem cell transplantation (ASCT) and demonstrated that D-VTd yielded deeper responses and improved PFS. Part two of the study compared D-maintenance therapy given every 8 weeks (at a reduced frequency treatment schedule compared to the standard long-term dosing frequency of every 4 weeks) versus observation. The primary endpoint in this part of the study is the proportion of patients who achieve a sCR 100 days after transplant. In the second part of the study, which is ongoing, patients who achieved a partial response or better in part one will undergo a second randomization to receive maintenance treatment with DARZALEX® 16 mg/kg every eight weeks for up to two years or will be observed with no further treatment. The primary endpoint in this part of the study is PFS.7
About Multiple Myeloma
Multiple myeloma is a blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.8 In multiple myeloma, these malignant plasma cells proliferate and replace normal cells in the bone marrow.9 Multiple myeloma is the second most common blood cancer worldwide and remains an incurable disease.10 In 2024, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 will die from the disease.11 People with multiple myeloma have a 5-year survival rate of 59.8 percent.8 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.12,13
About DARZALEX FASPRO® and DARZALEX®
DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) received U.S. FDA approval in May 2020 and is approved for eight indications in multiple myeloma, three of which are for frontline treatment in newly diagnosed patients who are transplant eligible or ineligible.14 It is the only subcutaneous CD38-directed antibody approved to treat patients with MM. DARZALEX FASPRO® is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE® drug delivery technology.
DARZALEX® (daratumumab) received U.S. FDA approval in November 2015 and is approved in eight indications, three of which are in the frontline setting, including newly diagnosed patients who are transplant eligible and ineligible.6
DARZALEX® is the first CD38-directed antibody approved to treat multiple myeloma.6 DARZALEX®-based regimens have been used in the treatment of more than 518,000 patients worldwide and more than 68,000 patients in the U.S. alone.
In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize daratumumab.
Since 2020, the National Comprehensive Cancer Network® (NCCN®) has recommended daratumumab-based combination regimens for the treatment of newly diagnosed multiple myeloma and relapsed and refractory multiple myeloma.† For newly diagnosed multiple myeloma in non-transplant candidates, the NCCN® guidelines recommend daratumumab in combination with lenalidomide and dexamethasone as a Category 1 preferred regimen; daratumumab in combination with bortezomib, melphalan, and prednisone as another recommended Category 1 regimen; and daratumumab in combination with bortezomib, cyclophosphamide, and prednisone as another recommended Category 2A regimen. For newly diagnosed multiple myeloma in transplant candidates, the NCCN® guidelines recommend daratumumab in combination with bortezomib, lenalidomide and dexamethasone as another recommended Category 2A regimen; daratumumab in combination with bortezomib, thalidomide and dexamethasone as a Category 2A regimen useful in certain circumstances; daratumumab in combination with carfilzomib, lenalidomide and dexamethasone as a Category 2A regimen useful in certain circumstances; and daratumumab in combination with cyclophosphamide, bortezomib and dexamethasone as a Category 2A regimen useful in certain circumstances. For maintenance in transplant candidates, the NCCN guidelines recommend daratumumab in combination with lenalidomide as useful in certain circumstances. In relapsed/refractory myeloma, four daratumumab regimens are listed as Category 1 preferred regimens for early relapses (1-3 prior therapies): daratumumab in combination with lenalidomide and dexamethasone; daratumumab in combination with bortezomib and dexamethasone; daratumumab in combination with carfilzomib and dexamethasone; and daratumumab in combination with pomalidomide and dexamethasone [after one prior therapy including lenalidomide and a proteasome inhibitor (PI)]. The NCCN® also recommends daratumumab in combination with cyclophosphamide, bortezomib and dexamethasone as another Category 2A regimen for early relapses (1-3 prior therapies) and as monotherapy as a Category 2A regimen useful in certain circumstances for early relapse patients after at least three prior therapies, including a PI and an immunomodulatory agent, or for patients who are double refractory to a PI and an immunomodulatory agent.
For more information, visit www.DARZALEX.com.
DARZALEX® INDICATIONS AND IMPORTANT SAFETY INFORMATION
INDICATIONS
DARZALEX® (daratumumab) is indicated for the treatment of adult patients with multiple myeloma:
- In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
- In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy
- In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant
- In combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor
- In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
- In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
- As monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent
Please click here to see the full Prescribing Information.
DARZALEX FASPRO® INDICATIONS AND IMPORTANT SAFETY INFORMATION
INDICATIONS
DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) is indicated for the treatment of adult patients with multiple myeloma:
- In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
- In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy
- In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant
- In combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor
- In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
- In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
- As monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent
Please click here to see the full Prescribing Information.
About Johnson & Johnson
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at https://www.jnj.com/ or at www.janssen.com/johnson-johnson-innovative-medicine. Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC, and Janssen Biotech, Inc., are Johnson & Johnson companies.
https://www.nasdaq.com/market-activity/stocks/jnj/dividend-history
TECVAYLI® (teclistamab-cqyv)
RYBREVANT® (amivantamab) combined with lazertinib
TECVAYLI® (teclistamab-cqyv)
TECVAYLI® (teclistamab-cqyv) shows sustained deep and durable responses in patients with relapsed or refractory multiple myeloma
New MajesTEC-1 data show a median duration of response of 24 months, with responses deepening, including in patients who switched to biweekly dosing1
Separate analyses from the MajesTEC-1 and OPTec studies are the first to underscore the opportunity for outpatient administration of TECVAYLI®
June 03, 2024
CHICAGO (June 3, 2024) –
Johnson & Johnson today announced longer-term data from the pivotal Phase 1/2 MajesTEC-1 study of TECVAYLI® (teclistamab-cqyv) showing deep and durable responses in patients with relapsed or refractory multiple myeloma (RRMM) who are triple-class exposed (TCE)a and who previously received three or more prior lines of therapy, including in patients who switched to less frequent dosing (Abstract #7540).1 These data were featured at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in a poster presentation.1
Additional presentations highlight the potential for outpatient step-up administration with prophylactic tocilizumab from the MajesTEC-1 study (Abstract #7517) and the first-in-class Phase 2 OPTec study (Abstract #7528), as well as first results from the subgroup analysis of patients with high-risk (HR) features that will be presented at the 2024 European Hematology Association (EHA) Congress (Abstract #923).2,3,4 The safety run-in MajesTEC-7 study in frontline TECVAYLI® administration (Abstract #7506) will also be presented at ASCO.4
“With the longest follow-up of any bispecific antibody, teclistamab demonstrates continued deep and durable responses observed in patients with relapsed or refractory multiple myeloma who have limited treatment options,” said Niels van de Donk, M.D., Professor of Hematology at Amsterdam University Medical Centers, and principal study investigator.* “The results of the MajesTEC-1 study indicate the potential of teclistamab to transform the treatment paradigm, and clinical studies are investigating whether teclistamab may be a pivotal advancement for improved care and management in the broader patient population.”
Results from the MajesTEC-1 study show that, at a median follow-up of 30.4 months, patients treated with TECVAYLI® at the recommended Phase 2 dose (RP2D)b (n=165) demonstrated an overall response rate (ORR) of 63 percent, with responses continuing to deepen and 46 percent of patients achieving a complete response (CR) or better.1 For patients with a CR or better, mDOR, mPFS, and mOS were not yet reached, and estimated 30-month DOR, PFS, and OS rates were 61, 61 and 74 percent, respectively.1 Patients who achieved a partial response or better after a minimum of four cycles of therapy (Phase 1), or maintained a CR or better for a minimum of six months (Phase 2) per protocol, had the option to switch to biweekly dosing (every two weeks) (Q2W).1 Additionally, 37 out of 38 patients who switched to Q2W dosing maintained responses.1
The safety profile remained consistent, with a notable decrease in new onset of severe infections over time.1 Adverse events (AEs) included neutropenia (any grade, 72 percent; grade 3/4, 66 percent), anemia (any grade, 55 percent; grade 3/4, 38 percent), thrombocytopenia (any grade, 42 percent; grade 3/4, 23 percent), lymphopenia (any grade, 36 percent; grade 3/4, 35 percent), and infections (any grade, 79 percent; grade 3/4, 55 percent).1 Of 22 grade 5 infections, 18 were due to COVID-19.1 The decrease in new-onset grade 3 or greater infections may be due to switching to Q2W dosing or other factors such as implementing the use of intravenous immunoglobulin.1
“Over the past two years, TECVAYLI has helped over 10,000 patients with relapsed or refractory multiple myeloma,” said Rachel Kobos, M.D., Vice President, Oncology Research & Development, Johnson & Johnson Innovative Medicine. “Through robust clinical data and real-world evidence, and by leveraging our team’s expertise, we’re working relentlessly to address unmet needs for patients with myeloma and drive the development of new treatment options for use across the treatment paradigm, including in the frontline setting.”
TECVAYLI® studies investigate outpatient administration in patients with RRMM, examining a more convenient approach to treatment, including in a community setting
Extended follow-up of patients from a MajesTEC-1 cohort, investigating the prophylactic use of tocilizumab for the reduction of cytokine release syndrome (CRS) in patients treated with TECVAYLI®, were also presented at ASCO in an oral presentation (Abstract #7517).2 Results show a single dose of tocilizumab before TECVAYLI® in patients with RRMM (n=24) reduced the incidence of CRS with a 65 percent relative reduction versus the overall MajesTEC-1 population.2 This approach is continuing to be evaluated in the first-in-class Phase 2, multicenter, prospective OPTec study of TECVAYLI® in the community setting, presented as a poster presentation (Abstract #7528) at ASCO.3 Data showed preliminary evidence that prophylactic tocilizumab potentially reduces the incidence of CRS, with no new safety concerns to date and underscores the opportunity for outpatient administration.3
Evaluation of patients with high-risk multiple myeloma from MajesTEC-1 study shows clinical benefit from treatment with TECVAYLI®
Subgroup analysis from the MajesTEC-1 study of TECVAYLI® investigating patients with HR RRMM will be presented at EHA (Abstract #923).4 Results show at a median follow-up of 30 months, patients who were aged 75 years or older, patients who had HR cytogenetics and patients who were penta-drug refractory demonstrated similar efficacy as the overall RP2D population with an ORR of 54 percent, 61 percent and 60 percent and a CR or better rate of 42 percent, 42 percent and 48 percent, respectively.4 The data demonstrate the clinical benefit of TECVAYLI® as an additional treatment option for some patients with HR features who typically face poor outcomes.4 The safety profile across subgroups was consistent with the RP2D population, including overall incidence and severity of TEAEs.4
Data from a single-arm run-in cohort of the Phase 3 MajesTEC-7 study shows early clinical profile of TECVAYLI®-based regimen in patients with transplant ineligible/not intended newly diagnosed multiple myeloma
The results, presented in an oral presentation (Abstract #7506) at ASCO, of the first safety run-in (SRI) from a single-arm cohort of the Phase 3 MajesTEC-7 study provide preliminary data for a TECVAYLI®-based regimen in transplant- ineligible/not intended newly diagnosed multiple myeloma.5 Patients (n=26) received TECVAYLI® in combination with daratumumab and lenalidomide (DR).5 At a median follow-up of 13.8 months, the ORR was 92 percent, with 23 patients remaining on treatment.5 Treatment-emergent adverse events (TEAEs) occurred in 100 percent of patients, where 61.5 percent of patients experienced grade 1/2 CRS in cycle one - all of which resolved.5
About the MajesTEC-1 Study
MajesTEC-1 (NCT03145181, NCT04557098) is a Phase 1/2 single-arm, open-label, multicohort, multicenter dose-escalation study evaluating the safety and efficacy of teclistamab in adults with RRMM who received three or more prior lines of therapy.6,7
Phase 1 of the study (NCT03145181) was conducted in two parts: dose escalation (Part 1) and dose expansion (Part 2).6 It evaluated safety, tolerability, pharmacokinetics, and preliminary efficacy of teclistamab in adult participants with RRMM.6 Phase 2 of the study (NCT04557098) evaluated the efficacy of teclistamab at the RP2D, established at subcutaneous 1.5 mg/kg weekly, as measured by ORR.
About the OPTec Study
OPTec (NCT05972135) is a Phase 2, single-arm, non-randomized, multicenter, prospective study evaluating the use of prophylactic tocilizumab in patients with RRMM to reduce the incidence and severity of CRS associated with administration of the step-up dosing regimen of teclistamab in the outpatient setting.
About the MajesTEC-7 Study
MajesTEC-7 (NCT05552222), is a Phase 3 randomized study, comparing teclistamab in combination with daratumumab SC and lenalidomide (Tec-DR) and talquetamab in combination with daratumumab SC and lenalidomide (Tal-DR) versus daratumumab SC, lenalidomide, and dexamethasone (DRd) in participants with newly diagnosed multiple myeloma who are either ineligible or not intended for autologous stem cell transplant as initial therapy.8
About TECVAYLI®
TECVAYLI® (teclistamab-cqyv) received approval from the U.S. FDA in October 2022 as an off-the-shelf (or ready-to-use) antibody that is administered as a subcutaneous treatment for adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody.2 The European Commission (EC) granted TECVAYLI® conditional marketing authorization (CMA) in August 2022 as monotherapy for the treatment of adult patients with RRMM who have received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody, and have demonstrated disease progression since the last therapy. In August 2023, the EC granted the approval of a Type II variation application for TECVAYLI®, providing the option for a reduced dosing frequency of 1.5 mg/kg every two weeks in patients who have achieved a complete response (CR) or better for a minimum of six months. TECVAYLI® is a first-in-class, bispecific T-cell engager antibody therapy that uses innovative science to activate the immune system by binding to the CD3 receptor expressed on the surface of T-cells and to the B-cell maturation antigen (BCMA) expressed on the surface of multiple myeloma cells and some healthy B-lineage cells. In February 2024, the U.S. FDA approved the supplemental Biologics License Application (sBLA) for TECVAYLI® for a reduced dosing frequency of 1.5 mg/kg every two weeks (Q2W) in patients with relapsed or refractory multiple myeloma who have achieved and maintained a CR or better for a minimum of six months.
For more information, visit www.TECVAYLI.com.
About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.9 In multiple myeloma, these plasma cells proliferate and spread rapidly and replace normal cells in the bone marrow with tumors.10 Multiple myeloma is the third most common blood cancer worldwide and remains an incurable disease.11 In 2024, it was estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 people would die from the disease.12 People living with multiple myeloma have a 5-year survival rate of 59.8 percent.13 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels and kidney problems or infections.14,15
TECVAYLI® IMPORTANT SAFETY INFORMATION
WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME
Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving TECVAYLI®. Initiate treatment with TECVAYLI® step-up dosing schedule to reduce risk of CRS. Withhold TECVAYLI® until CRS resolves or permanently discontinue based on severity.
Neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) and serious and life-threatening reactions, can occur in patients receiving TECVAYLI®. Monitor patients for signs or symptoms of neurologic toxicity, including ICANS, during treatment. Withhold TECVAYLI® until neurologic toxicity resolves or permanently discontinue based on severity.
TECVAYLI® is available only through a restricted program called the TECVAYLI® and TALVEY™ Risk Evaluation and Mitigation Strategy (REMS).
INDICATION AND USAGE
TECVAYLI® (teclistamab-cqyv) is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody.
This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
Please read full Prescribing Information, including Boxed WARNING, for TECVAYLI®.
About Johnson & Johnson
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at https://www.jnj.com/ or at www.janssen.com/johnson-johnson-innovative-medicine. Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC and Janssen Biotech, Inc. are both Johnson & Johnson companies.
https://www.nasdaq.com/market-activity/stocks/jnj/dividend-history
RYBREVANT® (amivantamab) combined with lazertinib
RYBREVANT® (amivantamab) combined with lazertinib
mRNA-4157 (V940) in Combination With KEYTRUDA® (pembrolizumab)
Late-breaking results from PALOMA-2 study of subcutaneous amivantamab in combination with lazertinib show clinically meaningful antitumor response and improved safety profile in patients with EGFR-mutated non-small cell lung cancer
Significantly lower infusion-related reactions seen with subcutaneous amivantamab compared with intravenous administration in new Phase 2 data
June 03, 2024
CHICAGO (June 3, 2024) –
Johnson & Johnson announced today new data from the Phase 2 PALOMA-2 study evaluating subcutaneous (SC) amivantamab combined with lazertinib as a first-line treatment in patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletion (ex19del) or L858R mutations. These data, which were featured in a late-breaking poster presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #LBA8612), showed a comparable response rate in patients treated with SC amivantamab and lazertinib compared to those treated with the intravenous (IV) formulation in the MARIPOSA study, which established the combination of amivantamab and lazertinib as superior to osimertinib. SC amivantamab was associated with significantly lower rates of infusion-related reactions (IRRs) and shorter treatment time compared with the IV formulation.1
“These encouraging data show similar response rates in patients treated with the subcutaneous administration of amivantamab compared with the IV formulation,” said Professor Nicolas Girard, Head of Medical Oncology, Institut Curie, and Professor of Thoracic Oncology and Respiratory Medicine at the Paris Saclay University, France, and study author.* “With favorable tolerability based on fewer infusion-related reactions, this formulation has the potential to address a current unmet need in the treatment of EGFR-mutant lung cancer.”
In the PALOMA-2 study, Cohorts 1 and 6 enrolled patients with treatment-naïve, EGFR ex19del or L858R-mutated advanced NSCLC, a patient population similar to the MARIPOSA study population. In Cohort 1 prophylactic anticoagulation use was recommended, and in Cohort 6 it was required. As of January 6, 2024, 68 and 58 patients were enrolled in Cohorts 1 and 6, respectively. At a median follow-up of 8.6 months, across all patients, SC amivantamab combined with lazertinib demonstrated an overall response rate (ORR) of 77 percent (95 percent Confidence Interval [CI], 68-84) as assessed by the investigator per RECIST v1.1.** (primary endpoint) and 79 percent (95 percent CI, 70-86) as assessed by blinded independent central review. A similar ORR of 86 percent (95 percent CI, 83-89) was observed with IV amivantamab in combination with lazertinib, as determined by a blinded independent central review in the Phase 3 MARIPOSA study. Average administration time was approximately five minutes versus the IV administration of 2-4 hours. Median duration of response was not estimable in both cohorts.1
The pooled analysis from Cohort 1 and Cohort 6 showed the safety profile for SC amivantamab was consistent with previous reports, with no new safety signals identified. The most common treatment-emergent adverse events (AEs) (≥ 20 percent) across all patients were paronychia (71 percent), rash (61 percent) and hypoalbuminemia (48 percent). IRRs were reported in 15 percent of patients across the two cohorts. Discontinuation of all medicines due to treatment-related AEs occurred in approximately nine percent of all patients. Prophylactic anticoagulation was administered to 71 percent of patients in Cohort 1 and 100 percent of those in Cohort 6. Venous thromboembolic events (VTEs) were reported in 18 and seven percent of patients in Cohorts 1 and 6, respectively, with no dose reductions or discontinuations reported due to VTEs. These findings suggest prophylactic anticoagulation can be safely implemented and reduce the incidence of VTEs with the combination of amivantamab plus lazertinib.1
“The safety and tolerability data from the PALOMA-2 study highlight the potential of subcutaneous amivantamab as an important therapy in the first-line treatment of patients with EGFR-mutant lung cancer,” said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Johnson & Johnson Innovative Medicine. “As we advance our robust pipeline and portfolio for patients with lung cancer, we remain dedicated to developing safe and effective therapies that offer distinct benefits in the treatment of this disease.”
About the PALOMA-2 Study
PALOMA-2 (NCT05498428) is an open-label Phase 2 study evaluating the efficacy, safety, and pharmacokinetics (PK) of first-line SC amivantamab (administered via manual injection) combined with lazertinib and/or chemotherapy in patients with EGFR-mutated advanced or metastatic NSCLC. Sixty-eight and 58 patients were enrolled in Cohorts 1 and 6, respectively. Prophylactic anticoagulation for the first four months of treatment was recommended in Cohort 1 and mandatory in Cohort 6. The primary endpoint was objective response rate (ORR) as assessed by the investigator per RECIST v1.1.2
About RYBREVANT®
RYBREVANT® (amivantamab-vmjw), a fully-human bispecific antibody targeting EGFR and MET with immune cell-directing activity, is approved in the U.S., Europe, and in other markets around the world as monotherapy for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.3 In the subcutaneous formulation, amivantamab is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE® drug delivery technology.
RYBREVANT® is also approved in the U.S. in combination with chemotherapy (carboplatin and pemetrexed) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test. In October 2023, a type II extension of indication application was submitted to the European Medicines Agency (EMA) seeking approval of RYBREVANT® for this indication.
In December 2023, Johnson & Johnson submitted a supplmental Biologics License Application (sBLA) together with a New Drug Application (NDA) to the U.S. FDA for RYBREVANT® in combination with lazertinib for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or L858R substitution mutations, as detected by an FDA-approved test. This submission is based on the Phase 3 MARIPOSA study and was granted Priority Review in February 2024. A marketing authorization application (MAA) and type II extension of indication application were also submitted to the EMA seeking approval of lazertinib in combination with RYBREVANT® based on the MARIPOSA study.
In November 2023, Johnson & Johnson submitted an sBLA to the U.S. FDA for RYBREVANT® in combination with chemotherapy for the treatment of patients with EGFR-mutated NSCLC who progressed on or after osimertinib based on the MARIPOSA-2 study. A type II extension of indication application was also submitted to the EMA seeking approval of RYBREVANT® for this indication.
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for NSCLC§ prefer next-generation sequencing–based strategies over polymerase chain reaction–based approaches for the detection of EGFR exon 20 insertion variants. The NCCN Guidelines include:
- Amivantamab-vmjw (RYBREVANT®) plus carboplatin and pemetrexed as a preferred (Category 1 recommendation) first-line therapy in treatment-naive patients with newly diagnosed advanced or metastatic EGFR exon 20 insertion mutation-positive advanced NSCLC, or as a subsequent therapy option (Category 2A recommendation) for patients that have progressed on or after platinum-based chemotherapy with or without immunotherapy and have EGFR exon 20 insertion mutation-positive advanced NSCLC.4 †‡
- Amivantamab-vmjw (RYBREVANT®) plus chemotherapy as a preferred (Category 1 recommendation) subsequent therapy for patients with locally advanced or metastatic NCSLC with EGFR exon 19 deletions or exon 21 L858R mutations who experienced disease progression after treatment with osimertinib.4 †‡
- Amivantamab-vmjw (RYBREVANT®) as a subsequent therapy option (Category 2A recommendation) for patients that have progressed on or after platinum-based chemotherapy with or without an immunotherapy and have EGFR exon 20 insertion mutation-positive NSCLC.4 †‡
RYBREVANT® is being studied in multiple clinical trials in NSCLC, including:
- The Phase 1 PALOMA (NCT04606381) study assessing the feasibility of subcutaneous administration of amivantamab based on safety and pharmacokinetics and to determine a dose, dose regimen and formulation for amivantamab subcutaneous delivery.5
- The Phase 2 PALOMA-2 (NCT05498428) study assessing subcutaneous amivantamab in patients with advanced or metastatic solid tumors including EGFR-mutated NSCLC.2
- The Phase 3 PALOMA-3 (NCT05388669) study assessing lazertinib with subcutaneous amivantamab compared to intravenous amivantamab in patients with EGFR-mutated advanced or metastatic NSCLC.6
- The Phase 3 PAPILLON (NCT04538664) study assessing RYBREVANT® in combination with carboplatin-pemetrexed versus chemotherapy alone in the first-line treatment of patients with advanced or metastatic NSCLC with EGFR exon 20 insertion mutations.7
- The Phase 3 MARIPOSA-2 (NCT04988295) study assessing the efficacy of RYBREVANT® (with or without lazertinib) and carboplatin-pemetrexed versus carboplatin-pemetrexed alone in patients with locally advanced or metastatic EGFR ex19del or L858R substitution NSCLC after disease progression on or after osimertinib.8
- The Phase 3 MARIPOSA (NCT04487080) study assessing RYBREVANT® in combination with lazertinib versus osimertinib and versus lazertinib alone in the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR ex19del or L858R substitution mutations.9
- The Phase 1 CHRYSALIS (NCT02609776) study evaluating RYBREVANT® in patients with advanced NSCLC.10
- The Phase 1/1b CHRYSALIS-2 (NCT04077463) study evaluating RYBREVANT® in combination with lazertinib and lazertinib as a monotherapy in patients with advanced NSCLC with EGFR mutations.11
- The Phase 1/2 METalmark (NCT05488314) study assessing RYBREVANT® and capmatinib combination therapy in locally advanced or metastatic NSCLC.12
- The Phase 1/2 PolyDamas (NCT05908734) study assessing RYBREVANT® and cetrelimab combination therapy in locally advanced or metastatic NSCLC.13
- The Phase 2 SKIPPirr (NCT05663866) study exploring how to decrease the incidence and/or severity of first-dose infusion-related reactions with RYBREVANT® in combination with lazertinib in relapsed or refractory EGFR-mutated advanced or metastatic NSCLC.14
For more information, visit: https://www.RYBREVANT.com.
About Non-Small Cell Lung Cancer
Worldwide, lung cancer is one of the most common cancers, with NSCLC making up 80 to 85 percent of all lung cancer cases.15,16 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.17 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division.18 EGFR mutations are present in 10 to 15 percent of Western patients with NSCLC with adenocarcinoma histology and occur in 40 to 50 percent of Asian patients.17,18,19,20,21,22 EGFR ex19del or EGFR L858R mutations are the most common EGFR mutations.23 The five year survival rate for all people with advanced NSCLC and EGFR mutations treated with EGFR tyrosine kinase inhibitors (TKIs) is less than 20 percent.24,25 EGFR exon 20 insertion mutations are the third most prevalent activating EGFR mutation.26 Patients with EGFR exon 20 insertion mutations have a real-world five-year overall survival (OS) of eight percent in the frontline setting, which is worse than patients with EGFR ex19del or L858R mutations, who have a real-world five-year OS of 19 percent.27
Please read the full Prescribing Information for RYBREVANT®.
About Johnson & Johnson
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at https://www.jnj.com/ or at www.janssen.com/johnson-johnson-innovative-medicine. Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC, and Janssen Biotech, Inc., are Johnson & Johnson companies.
https://www.nasdaq.com/market-activity/stocks/jnj/dividend-history
mRNA-4157 (V940) in Combination With KEYTRUDA® (pembrolizumab)
mRNA-4157 (V940) in Combination With KEYTRUDA® (pembrolizumab)
mRNA-4157 (V940) in Combination With KEYTRUDA® (pembrolizumab)
Moderna & Merck Announce 3-Year Data For mRNA-4157 (V940) in Combination With KEYTRUDA(R) (pembrolizumab) Demonstrated Sustained Improvement in Recurrence-Free Survival & Distant Metastasis-Free Survival Versus KEYTRUDA in Patients With High-Risk Stage III/IV Melanoma Following Complete Resection
June 3, 2024
At a median planned follow-up of the Phase 2b study at 34.9 months, mRNA-4157 (V940) in combination with KEYTRUDA reduced the risk of recurrence or death by 49% and the risk of distant metastasis or death by 62% compared to KEYTRUDA alone in these patients
The 2.5-year recurrence-free survival rate of mRNA-4157 (V940) in combination with KEYTRUDA was 74.8% as compared to 55.6% for KEYTRUDA alone, with the benefit observed across exploratory subgroups
The companies have initiated Phase 3 studies in patients with high-risk melanoma and non-small cell lung cancer, in addition to Phase 2 studies in patients with renal cell carcinoma and urothelial carcinoma and a Phase 2/3 study for cutaneous squamous cell carcinoma
CAMBRIDGE, MA and RAHWAY, NJ / ACCESSWIRE / June 3, 2024 / Moderna, Inc. (NASDAQ:MRNA) and Merck (NYSE:MRK), known as MSD outside of the United States and Canada, today announced the first presentation of results from a planned analysis from the Phase 2b randomized KEYNOTE-942/mRNA-4157-P201 study, a clinical trial evaluating mRNA-4157 (V940), an investigational individualized neoantigen therapy (INT), in combination with KEYTRUDA, Merck's anti-PD-1 therapy, in patients with resected high-risk melanoma (stage III/IV) following complete resection (n=157). With a median follow-up of approximately three years (34.9 months), adjuvant treatment with mRNA-4157 (V940) in combination with KEYTRUDA continued to demonstrate a clinically meaningful and durable improvement in recurrence-free survival (RFS), the primary endpoint of the study, reducing the risk of recurrence or death by 49% (HR [95% CI], 0.510 [0.288-0.906]; two-sided nominal p-value 0.019) compared with KEYTRUDA alone. mRNA-4157 (V940) in combination with KEYTRUDA also continued to demonstrate a meaningful improvement in distant metastasis-free survival (DMFS), a key secondary endpoint of the study, compared with KEYTRUDA alone, reducing the risk of developing distant metastasis or death by 62% (HR [95% CI], 0.384 [0.172-0.858], two-sided nominal p-value 0.015).
These data are being presented today during a rapid oral abstract session at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (abstract #LBA9512). With an additional year of planned follow-up, these data build on the earlier analysis of the primary and key secondary endpoints of the study, presented in 2023. The 2.5-year recurrence-free survival rate of mRNA-4157 (V940) in combination with KEYTRUDA was 74.8%, as compared to 55.6% for KEYTRUDA alone, with the benefit observed across exploratory subgroups.
"We are encouraged by the latest results from the KEYNOTE-942/mRNA-4157-P201 study. These data highlight the sustained benefit in RFS and DMFS of mRNA-4157 (V940) as adjuvant treatment in combination with KEYTRUDA in people with resected high-risk melanoma. Importantly, this benefit was observed across various patient exploratory subgroups, reflecting the potential of mRNA-4157 (V940) for a broad range of these patients," said Kyle Holen, M.D., Moderna's Senior Vice President and Head of Development, Therapeutics and Oncology. "These findings reinforce our commitment to advancing this innovative treatment in collaboration with Merck, and we are dedicated to harnessing mRNA technology to potentially transform cancer therapy and improve patient outcomes."
"The sustained improvements in recurrence-free survival and distant metastasis-free survival observed at approximately three years in the KEYNOTE-942/mRNA-4157-P201 study provide further support of the potential of mRNA-4157 (V940) in combination with KEYTRUDA to help patients with resected high-risk melanoma," said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. "We look forward to building on our legacy of turning breakthrough science into medicines that may have a meaningful impact on patients' lives as we continue advancing our broad clinical development program evaluating this novel approach with Moderna."
Additional efficacy and subgroup data
Data from an exploratory subgroup analysis of the Phase 2b KEYNOTE-942/mRNA-4157-P201 study in patients with resected high-risk melanoma (stage III/IV) following complete resection showed that improvement in RFS was observed with mRNA-4157 (V940) in combination with KEYTRUDA compared to KEYTRUDA alone regardless of tumor mutational burden (TMB) or programmed death-ligand 1 (PD-L1) status.
The RFS benefit of mRNA-4157 (V940) in combination with KEYTRUDA compared to KEYTRUDA alone was maintained across both TMB high (HR [95% CI], 0.564 [0.253-1.258]), TMB non-high (0.571 [0.245-1.331]), PD-L1 positive (0.471 [0.226-0.979]), PD-L1 negative (0.147 [0.034-0.630]), and circulating tumor DNA (ctDNA) negative (0.207 [0.091-0.470]) subpopulations. ctDNA positive HR was not estimable due to the small sample size. There were no significant associations between individual human leukocyte antigen (HLA) alleles and RFS observed for mRNA-4157 (V940) in combination with KEYTRUDA.
The exploratory endpoint of overall survival (OS) favored mRNA-4157 (V940) in combination with KEYTRUDA compared to KEYTRUDA alone, with a 2.5-year OS rate of 96.0% vs. 90.2%, respectively (HR [95% CI], 0.425 [0.114-1.584]).
The safety profile with mRNA-4157 (V940) in combination with KEYTRUDA in KEYNOTE-942/mRNA-4157-P201 remains consistent with the primary analysis. The most common adverse events attributed to mRNA-4157 (V940) in combination with KEYTRUDA were fatigue (60.6%), injection site pain (56.7%), and chills (49.0%). The majority of the adverse events attributed to mRNA-4157 (V940) were Grade 1-2, with fatigue being the most common Grade 3 event and no Grade 4-5 events. Immune-related adverse events occurred in 37.5% of patients receiving the combination and 36% receiving KEYTRUDA alone.
Ongoing clinical development programs
Merck and Moderna have initiated Phase 3 randomized clinical trials evaluating mRNA-4157 (V940) in combination with KEYTRUDA as an adjuvant treatment in patients with resected high-risk (Stage IIB-IV) melanoma (INTerpath-001, NCT05933577) and non-small cell lung cancer (INTerpath-002, NCT06077760). Both trials are actively enrolling.
In 2024, Merck and Moderna also initiated a two-part Phase 2/3 randomized clinical trial evaluating mRNA-4157 (V940)in combination with KEYTRUDA as neoadjuvant and adjuvant treatment in patients with resectable locally advanced Stage II-IV (M0) cutaneous squamous cell carcinoma (INTerpath-007, NCT06295809), a Phase 2 randomized clinical trial evaluating mRNA-4157 (V940) in combination with KEYTRUDA as adjuvant treatment in patients with intermediate-high-risk, high-risk, or M1 no evidence of disease renal cell carcinoma (INTerpath-004, NCT06307431), and a Phase 2 randomized clinical trial evaluating mRNA-4157 (V940) in combination with KEYTRUDA as adjuvant treatment in patients with high-risk muscle-invasive urothelial carcinoma post-radical resection (INTerpath-005, NCT06305767).
About mRNA-4157 (V940)
mRNA-4157 (V940) is a novel investigational messenger RNA (mRNA)-based individualized neoantigen therapy (INT) consisting of a synthetic mRNA coding for up to 34 neoantigens that is designed and produced based on the unique mutational signature of the DNA sequence of the patient's tumor. Upon administration into the body, the algorithmically derived and RNA-encoded neoantigen sequences are endogenously translated and undergo natural cellular antigen processing and presentation, a key step in adaptive immunity.
Individualized neoantigen therapies are designed to train and activate an antitumor immune response by generating specific T-cell responses based on the unique mutational signature of a patient's tumor. KEYTRUDA is an immunotherapy that works by increasing the ability of the body's immune system to help detect and fight tumor cells. As previously announced from the Phase 2b KEYNOTE-942/mRNA-4157-P201 trial evaluating patients with high-risk stage III/IV melanoma, combining mRNA-4157 (V940) with KEYTRUDA may provide a meaningful benefit over KEYTRUDA alone.
About KEYNOTE-942/mRNA-4157-P201 (NCT03897881)
KEYNOTE-942 is an ongoing randomized, open-label Phase 2b trial that enrolled 157 patients with high-risk stage III/IV melanoma. Following complete surgical resection, patients were assigned 2:1 (stratified by stage) to receive mRNA-4157 (V940) (1 mg every three weeks for nine doses) and KEYTRUDA (200 mg every three weeks up to 18 cycles [for approximately one year]) versus KEYTRUDA alone for approximately one year until disease recurrence or unacceptable toxicity. The primary endpoint is RFS, defined as the time from first dose of KEYTRUDA until the date of first recurrence (local, regional, or distant metastasis), a new primary melanoma, or death from any cause in the intention-to-treat population. Secondary endpoints include distant metastasis-free survival and safety, and exploratory endpoints include distribution of TMB expression in baseline tumor samples across study arms and their association with the primary RFS endpoint. The KEYNOTE-942 trial is ongoing to collect additional translational data, and an additional 100 patients are currently being enrolled.
Key eligibility criteria for the trial included: patients with resectable cutaneous melanoma metastatic to a lymph node and at high risk of recurrence, patients with complete resection within 13 weeks prior to the first dose of KEYTRUDA, patients were disease free at study entry (after surgery) with no loco-regional relapse or distant metastasis and no clinical evidence of brain metastases, patients had a formalin fixed paraffin embedded (FFPE) tumor sample available suitable for sequencing, Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 and patients with normal organ and marrow function reported at screening.
About Melanoma
Melanoma, the most serious form of skin cancer, is characterized by the uncontrolled growth of pigment-producing cells. The rates of melanoma have been rising over the past few decades, with more than 330,000 new cases diagnosed worldwide in 2022. In the U.S., skin cancer is one of the most common types of cancer diagnosed, and melanoma accounts for a large majority of skin cancer deaths. It is estimated there will be more than 100,000 new cases of melanoma diagnosed and more than 8,000 deaths resulting from the disease in the U.S. in 2024.
About KEYTRUDA® (pembrolizumab) injection, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body's immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes, which may affect both tumor cells and healthy cells.
Merck has the industry's largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.
KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.
See additional selected KEYTRUDA indications in the U.S. after the Selected Important Safety Information.
Additional Selected KEYTRUDA Indications in the U.S.
Non-Small Cell Lung Cancer
KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:
- stage III where patients are not candidates for surgical resection or definitive chemoradiation, or
- metastatic.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.
KEYTRUDA is indicated for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with stage IB (T2a ≥4 cm), II, or IIIA NSCLC.
Head and Neck Squamous Cell Cancer
KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.
Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).
KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.
Primary Mediastinal Large B-Cell Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.
Urothelial Cancer
KEYTRUDA, in combination with enfortumab vedotin, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma:
who are not eligible for any platinum-containing chemotherapy, or
who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.
Microsatellite Instability-High or Mismatch Repair Deficient Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.
Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC) as determined by an FDA-approved test.
Gastric Cancer
KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval of this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
KEYTRUDA, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Esophageal Cancer
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:
- in combination with platinum- and fluoropyrimidine-based chemotherapy, or
- as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
Cervical Cancer
KEYTRUDA, in combination with chemoradiotherapy (CRT), is indicated for the treatment of patients with FIGO 2014 Stage III-IVA cervical cancer.
KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
Hepatocellular Carcinoma
KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) secondary to hepatitis B who have received prior systemic therapy other than a PD-1/PD-L1-containing regimen.
Biliary Tract Cancer
KEYTRUDA, in combination with gemcitabine and cisplatin, is indicated for the treatment of patients with locally advanced unresectable or metastatic biliary tract cancer (BTC).
Merkel Cell Carcinoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC).
Renal Cell Carcinoma
KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.
Endometrial Carcinoma
KEYTRUDA, as a single agent, is indicated for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Tumor Mutational Burden-High Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.
Cutaneous Squamous Cell Carcinoma
KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.
Triple-Negative Breast Cancer
KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
Merck's focus on cancer
Every day, we follow the science as we work to discover innovations that can help patients, no matter what stage of cancer they have. As a leading oncology company, we are pursuing research where scientific opportunity and medical need converge, underpinned by our diverse pipeline of more than 25 novel mechanisms. With one of the largest clinical development programs across more than 30 tumor types, we strive to advance breakthrough science that will shape the future of oncology. By addressing barriers to clinical trial participation, screening and treatment, we work with urgency to reduce disparities and help ensure patients have access to high-quality cancer care. Our unwavering commitment is what will bring us closer to our goal of bringing life to more patients with cancer. For more information, visit https://www.merck.com/research/oncology/.
About Merck's research in melanoma
Merck is committed to delivering meaningful advances for patients with melanoma and to continuing research in skin cancers through a broad clinical development program across investigational and approved medicines. KEYTRUDA has been established as an important treatment option for the adjuvant treatment of patients with resected Stage IIB, IIC, or III melanoma based on results of KEYNOTE-054 and KEYNOTE-716. KEYTRUDA is also approved worldwide for the treatment of patients with unresectable or metastatic melanoma.
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world - and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com/ and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.
About Moderna
Moderna is a leader in the creation of the field of mRNA medicine. Through the advancement of mRNA technology, Moderna is reimagining how medicines are made and transforming how we treat and prevent disease for everyone. By working at the intersection of science, technology and health for more than a decade, the company has developed medicines at unprecedented speed and efficiency, including one of the earliest and most effective COVID-19 vaccines.
Moderna's mRNA platform has enabled the development of therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases and autoimmune diseases. With a unique culture and a global team driven by the Moderna values and mindsets to responsibly change the future of human health, Moderna strives to deliver the greatest possible impact to people through mRNA medicines. For more information about Moderna, please visit modernatx.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.
Moderna's focus on cancer
At Moderna, we are delivering on the promise of mRNA science to create a new generation of transformative medicines for patients. We are relentlessly working to grow our cancer therapeutic modality by discovering mRNA medicines that harness the body's immune system to identify and kill cancer cells in the same way the immune system identifies and targets infections. One example of a promising oncology candidate is the creation of individualized, mRNA-based cancer therapies. We also continue to strengthen our portfolio through strategic collaborations that increase our potential to improve treatment options for patients with cancer.
SOURCE: Moderna, Inc.
https://www.modernatx.com/en-US
CARVYKTI® (ciltacabtagene autoleucel)
mRNA-4157 (V940) in Combination With KEYTRUDA® (pembrolizumab)
CARVYKTI® (ciltacabtagene autoleucel)
CARVYKTI® (ciltacabtagene autoleucel) significantly improved progression-free survival and deepened responses versus two standard therapies for patients with functional high-risk multiple myeloma
73 percent reduction in risk of disease progression or death seen with CARVYKTI® in the CARTITUDE-4 study in a subset of patients who had early relapse after initial multiple myeloma therapy1
June 03, 2024
CHICAGO (June 3, 2024) –
Johnson & Johnson announced today results from a subgroup analysis of the Phase 3 CARTITUDE-4 study. The data show CARVYKTI® (ciltacabtagene autoleucel; cilta-cel) significantly improved progression-free survival (PFS) compared to standard therapies of pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) for patients with lenalidomide-refractory multiple myeloma after one prior line of therapy (LOT), including patients with functional high-risk (FHR) multiple myeloma.1 FHR was defined as progressive disease within 18 months after receiving autologous stem cell transplant (ASCT) or the start of initial frontline therapy in patients with no ASCT.1 These data were featured as an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #7504) and will also be shared at the 2024 European Hematology Association (EHA) Congress (Abstract #P959).1,2
Data from the CARTITUDE-4 study supported the recent U.S. FDA approval of CARVYKTI®, the first and only B-cell maturation antigen (BCMA)-targeted therapy approved for the treatment of patients with relapsed/refractory multiple myeloma as early as after first relapse.
A Phase 3 CARTITUDE-4 subgroup analysis included 136 patients (CARVYKTI®, n=68; standard therapies, n=68) who received one prior LOT, including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD), and were lenalidomide-refractory.1 After a median follow-up of 16 months (range, 0.1-27), median PFS was not reached (NR) (95 percent Confidence Interval [CI]; not estimable [NE]-NE) among patients who received CARVYKTI® compared to 17 months (95 percent CI, 11-NE) for the control arm as a second-line treatment (hazard ratio [HR]=0.35 [95 percent CI, 0.2-0.7; P=.0007]).1
In an additional subgroup analysis of 79 patients with FHR multiple myeloma (CARVYKTI®, n=40; standard therapies, n=39) median PFS was NR [18-NE] with CARVYKTI® versus 12 months (8-NE) with standard therapies (HR=0.27 [95 percent CI, 0.1-0.6; P=.0006]).1 Patients treated with CARVYKTI® had deeper overall response rates (88 percent; 80 percent), complete response (CR) or better (68 percent; 39 percent), minimal residual disease (MRD) negativity (65 percent; ten percent), and longer median duration of response (mDOR) (NR [16-NE]; 16 [8-NE]) compared to those treated with standard therapies.1
“Patients with functional high-risk myeloma whose disease progressed during the first 18 months of initial myeloma therapy are known to have poor prognosis, yet they have not been well represented in any clinical trial,” said Luciano J. Costa, M.D., Ph.D., Professor of Medicine and Director of the Multiple Myeloma Program, University of Alabama at Birmingham, and principal study investigator.* “This subset analysis of CARTITUDE-4 provides strong evidence that these patients greatly benefit from cilta-cel and will help healthcare professionals better understand the potential of this therapy.”
The proportion of patients with grade 3 or higher treatment-emergent adverse events (TEAEs) was comparable among patients who received CARVYKTI® versus standard therapies as second-line treatment (96 percent, 96 percent) and those with one prior LOT and FHR multiple myeloma (100 percent, 97 percent), respectively.1 Overall, 11 patients in the CARVYKTI® one prior LOT subgroup and 11 patients in the standard therapies one prior LOT subgroup died.1 Of patients with FHR multiple myeloma, seven patients from the CARVYKTI® arm and nine who received standard therapies died.1 Of the seven deaths in patients with one prior LOT and FHR multiple myeloma, two did not receive CARVYKTI® as study treatment and three received CARVYKTI® as subsequent therapy.1
“Many patients with FHR multiple myeloma from the CARTITUDE-4 subgroup analysis experienced deep and durable responses following the single-infusion of CARVYKTI, further supporting the potential to treat a broader patient population,” said Jordan Schecter, M.D., Vice President, Disease Area Leader, Multiple Myeloma, at Johnson & Johnson Innovative Medicine. “At Johnson & Johnson, we aspire to eliminate cancer and remain steadfast in our commitment to realizing the full potential of CARVYKTI to improve outcomes for patients.”
CARTITUDE-2: Cilta-cel results in patients with suboptimal response to frontline autologous stem cell transplant ± lenalidomide maintenance (Abstract #7505)
Results from Cohort D of the CARTITUDE-2 study demonstrated deep and durable responses following a single infusion of cilta-cel with or without lenalidomide maintenance.3 This cohort evaluated patients who had a suboptimal response after ASCT frontline therapy.3 These data were presented as an oral presentation at the 2024 ASCO Annual Meeting (Abstract #7505).3
At a median follow-up of 22 months, patients treated with cilta-cel (n=17) demonstrated a 94 percent overall response rate, with 94 percent also achieving a CR or better.3 Of the 15 MRD-evaluable patients, 80 percent achieved MRD negativity at 10–5.3 The mDOR was NR.3 Eighteen-month PFS and OS rates were 94 percent each.3 Patients in Cohort D had robust CAR-T expansion, but numerically shorter persistence compared to patients with lenalidomide-refractory multiple myeloma and one to three prior LOT (CARTITUDE-4) and heavily pretreated patients (CARTITUDE-1).3
All patients had grade 3 or 4 TEAEs including any grade neutropenia (94 percent), lymphopenia (65 percent), thrombocytopenia (47 percent), leukopenia (41 percent), infections (71 percent), or cytokine release syndrome (CRS) (82 percent; median onset of eight days).3 One patient had a secondary malignancy of grade 3 myelodysplastic syndromes (MDS). No cases of movement and neurocognitive treatment-emergent (MNT) AEs/parkinsonism were observed.3
About CARTITUDE-4
CARTITUDE-4 (NCT04181827) is the first international, randomized, open-label Phase 3 study evaluating the efficacy and safety of cilta-cel versus pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) in adult patients with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior lines of therapy.4 Results were presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting and published in The New England Journal of Medicine.
About CARTITUDE-2
CARTITUDE-2 (NCT04133636) is an ongoing, multi-cohort Phase 2 study evaluating the safety and efficacy of cilta-cel in patients with multiple myeloma.5 Cohort D evaluates cilta-cel with lenalidomide maintenance in patients who achieved less than complete response (CR) after autologous stem cell transplant (ASCT) frontline therapy.
About CARVYKTI® (ciltacabtagene autoleucel; cilta-cel)
CARVYKTI® (cilta-cel) received U.S. Food and Drug Administration approval in February 2022 for the treatment of adults with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. In April 2024, CARVYKTI® was approved in the U.S. for the second-line treatment of adult patients with relapsed or refractory myeloma who have received at least one prior line of therapy including a proteasome inhibitor, an immunomodulatory agent, and who are refractory to lenalidomide, following a unanimous (11 to 0) FDA Oncologic Drugs Advisory Committee (ODAC) recommendation in support of this new indication. In April 2024, the European Medicines Agency (EMA) approved a Type II variation for CARVYKTI® for the treatment of adults with relapsed and refractory multiple myeloma who have received at least one prior therapy, including an immunomodulatory agent and a proteasome inhibitor, have demonstrated disease progression on the last therapy, and are refractory to lenalidomide. In September 2022, Japan’s Ministry of Health, Labour and Welfare (MHLW) approved CARVYKTI® for the treatment of adults with relapsed or refractory multiple myeloma in patients that have no history of CAR-positive T cell infusion therapy targeting BCMA and who have received three or more lines of therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 monoclonal antibody, and in whom multiple myeloma has not responded to or has relapsed following the most recent therapy.
CARVYKTI® is a BCMA-directed, genetically modified autologous T-cell immunotherapy, which involves reprogramming a patient’s own T-cells with a transgene encoding chimeric antigen receptor (CAR) that directs the CAR-positive T cells to eliminate cells that express BCMA. BCMA is primarily expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B cells and plasma cells. The CARVYKTI® CAR protein features two BCMA-targeting single domains designed to confer high avidity against human BCMA. Upon binding to BCMA-expressing cells, the CAR promotes T-cell activation, expansion, and elimination of target cells.
In December 2017, Janssen Biotech, Inc., a Johnson & Johnson company, entered into an exclusive worldwide license and collaboration agreement with Legend Biotech USA, Inc. to develop and commercialize CARVYKTI®.
For more information, visit www.CARVYKTI.com.
About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.6 In multiple myeloma, these plasma cells proliferate and spread rapidly and replace normal cells in the bone marrow with tumors.7 Multiple myeloma is the third most common blood cancer worldwide and remains an incurable disease.8 In 2024, it was estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 people would die from the disease.9 People living with multiple myeloma have a 5-year survival rate of 59.8 percent.10 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels and kidney problems or infections.11,12
CARVYKTI® IMPORTANT SAFETY INFORMATION
INDICATIONS AND USAGE
CARVYKTI® (ciltacabtagene autoleucel) is a B-cell maturation antigen (BCMA)-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory multiple myeloma, who have received at least 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide.
Please read full Prescribing Information, including Boxed Warning, for CARVYKTI®.
About Johnson & Johnson
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at https://www.jnj.com/ or at www.janssen.com/johnson-johnson-innovative-medicine. Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC, and Janssen Biotech, Inc., are Johnson & Johnson companies.
J&J, Legend release promising results on Carvykti in earlier treatment line
Jun. 03, 2024 6:09 PM ET
Johnson & Johnson (JNJ) Stock, LEGN Stock
By: Jonathan Block, SA News Editor
- Johnson & Johnson (NYSE:JNJ) and Legend Biotech (NASDAQ:LEGN) said that after a single infusion, the CART-T therapy Carvykti (ciltacabtagene autoleucel) led to durable responses in multiple myeloma patients who didn't achieve complete response after frontline autologous stem cell transplant.
- https://seekingalpha.com/news/4112513-johnson-johnson-legend-release-promising-results-carvykti-earlier-treatment-line
- Johnson & Johnson (JNJ) Stock, LEGN Stock
- https://www.jnj.com/
- https://www.carvykti.com/#
Zimberelimab
mRNA-4157 (V940) in Combination With KEYTRUDA® (pembrolizumab)
CARVYKTI® (ciltacabtagene autoleucel)
June 02, 2024
Gilead and Arcus Announce Etrumadenant Plus Zimberelimab Regimen Significantly Reduced the Risk of Death in Third-line Metastatic Colorectal Cancer
– In Cohort B of the ARC-9 mCRC Study, Etrumadenant Plus Zimberelimab, FOLFOX Chemotherapy and Bevacizumab Significantly Reduced the Risk of Death by 63% and Risk of Disease Progression by 73% Compared to Regorafenib in a Phase 1b/2 Trial –
– Results will be Presented Today During an Oral Session at the ASCO Annual Meeting –
FOSTER CITY, Calif. & HAYWARD, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) and Arcus Biosciences, Inc. (NYSE: RCUS) today announced new data from Cohort B of ARC-9, a Phase 1b/2 study evaluating the safety and efficacy of etrumadenant, a dual A2a/b adenosine receptor antagonist, plus anti-PD-1 monoclonal antibody zimberelimab, FOLFOX chemotherapy and bevacizumab (EZFB) in third-line metastatic colorectal cancer (mCRC). These results will be presented today during an oral session at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting by Zev A. Wainberg, M.D., MSc, Co-Director of the GI Oncology Program at University of California Los Angeles and a principal investigator of the ARC-9 trial (Abstract 3508).
“ARC-9 is the first randomized Phase 2 study to show that combining an adenosine receptor blocker with anti-PD-1, anti-VEGF and chemotherapy can meaningfully improve clinical outcomes for people with metastatic colorectal cancer who have progressed on at least two prior therapies,” said Dr. Wainberg. “19.7 months is the longest median overall survival reported in third-line mCRC and warrants further investigation of an etrumadenant-based regimen as a potential treatment option in CRC1.”
Cohort B of ARC-9 randomized 112 patients with comparable baseline characteristics between two arms: EZFB or regorafenib. At the time of data cut-off (November 13, 2023) median follow-up was 20.4 months. Patient baseline characteristics were similar to those of third-line patients who have progressed on oxaliplatin- and irinotecan-based regimens in mCRC1. OS and PFS were consistently longer in the EZFB arm versus regorafenib, in all sub-groups analyzed, including in patients with liver metastases.
The EZFB regimen had a safety profile consistent with the known safety profiles of each individual molecule to date, without unexpected toxicities. A higher percentage of patients treated with regorafenib (17%) had a treatment emergent adverse event (TEAE) leading to discontinuation of all study drugs than those treated with EZFB (5%). A lower percentage of patients experienced Grade ≥3 TEAEs attributed to etrumadenant or zimberelimab versus regorafenib (23.0% vs 25.7%).
Etrumadenant and zimberelimab are investigational molecules. Neither Gilead nor Arcus has received approval from any regulatory authority for any use of these molecules, and their safety and efficacy for the treatment of colorectal cancer have not been established.
About the ARC-9 Study
ARC-9 (NCT04660812) is a Phase 1b/2 trial evaluating the safety and efficacy of etrumadenant (E), a dual A2a/A2b adenosine receptor antagonist, plus anti-PD-1 antibody zimberelimab (Z), FOLFOX and bevacizumab (if not contraindicated) in three cohorts of patients with mCRC. The primary endpoint is PFS per RECIST 1.1, and OS is a key secondary endpoint. Cohort B enrolled patients who previously progressed on both oxaliplatin- and irinotecan-containing chemotherapy in combination with anti-VEGF (R) therapy or anti-EGFR. Patients were randomized 2:1 to the etrumadenant plus zimberelimab regimen: E (150 mg orally [PO] once daily [QD]) + Z (240 mg intravenous [IV] once every 2 weeks [Q2W]) + mFOLFOX-6 + bevacizumab (5 mg/kg IV Q2W), or regorafenib (administered at a starting dose of 80 mg/day for the first week, followed by a dose escalation of 40 mg every week to 120 mg/day for the second week and 160 mg/day for the third week during Cycle 1 followed by 160 mg/day on Days 1-21 of each subsequent 28-day cycle). Patients who progressed on regorafenib were allowed to crossover to the etrumadenant plus zimberelimab regimen.
ARC-9 is a multi-cohort study in mCRC including Cohort A, which enrolled patients who previously progressed on FOLFOX/FOLFIRI in combination with anti-VEGF(R) or anti-EGFR. Patients were randomized 2:1 to the etrumadenant plus zimberelimab regimen, or FOLFOX-6 + bevacizumab. Data from Cohort A will be presented when they are mature.
About Etrumadenant
Etrumadenant is an investigational small molecule, selective dual antagonist of the A2a and A2b receptors designed to prevent adenosine-mediated immunosuppression. Adenosine elicits its immunosuppressive effects within the tumor microenvironment by binding and activating adenosine-specific receptors expressed on the surface of tumor-infiltrating immune cells, which can help cancer cells evade host antitumor immunity. Once etrumadenant binds to the A2a and A2b receptors and blocks the immunosuppressive effects of adenosine, activation of antitumor immune cells may be restored, which could result in tumor cell death.
Etrumadenant is being evaluated in combination with other cancer immunotherapies, including the investigational Fc-silent anti-TIGIT monoclonal antibody domvanalimab and anti-PD-1 monoclonal antibody zimberelimab, in certain types of non-small cell lung and colorectal cancers.
About Zimberelimab
Zimberelimab is an anti-programmed cell death protein-1 (PD-1) monoclonal antibody that binds PD-1, with the goal of restoring the antitumor activity of T cells. Zimberelimab has demonstrated high affinity, selectivity and potency in various tumor types.
Zimberelimab is being evaluated in the U.S. and globally as a foundational anti-PD-1 treatment option in multiple ongoing and planned early and late-stage clinical studies in combination with other immunotherapies, including investigational Fc-silent anti-TIGIT monoclonal antibody domvanalimab and A2a/A2b adenosine receptor antagonist etrumadenant.
Guangzhou Gloria Biosciences Co. Ltd., which holds commercialization rights for zimberelimab in greater China, has obtained approval for zimberelimab for the treatment of recurrent or metastatic cervical cancer and for relapsed or refractory classical Hodgkin's lymphoma. Zimberelimab is not approved for any use in the U.S. or other regions outside of China. Gloria conducts its development and commercialization activities independent of Arcus and Gilead.
About Arcus Biosciences
Arcus Biosciences is a clinical-stage, global biopharmaceutical company developing differentiated molecules and combination medicines for people with cancer. In partnership with industry collaborators, patients and physicians around the world, Arcus is expediting the development of first- or best-in-class medicines against well-characterized biological targets and pathways and studying novel, biology-driven combinations that have the potential to help people with cancer live longer. Founded in 2015, the company has expedited the development of multiple investigational medicines into clinical studies, including new combination approaches that target TIGIT, PD-1, the adenosine axis (CD73 and dual A2a/A2b receptor), HIF-2a, CD39 and AXL. For more information about Arcus Biosciences’ clinical and preclinical programs, please visit www.arcusbio.com.
About Gilead Sciences
Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California.
Gilead and the Gilead logo are trademarks of Gilead Sciences, Inc., or its related companies.
Arcus name and logo are trademarks of Arcus Biosciences, Inc.
For more information about Gilead, please visit the company’s website at www.gilead.com, follow Gilead on X/Twitter (@Gilead Sciences) and LinkedIn (@Gilead-Sciences).
Source: Gilead Sciences, Inc.
Gilead, Arcus combo significantly reduces death risk in colorectal cancer
Jun. 03, 2024 2:01 PM ET
Gilead Sciences, Inc. (GILD) Stock, RCUS StockRHHBY, BAYRY, BAYZF
By: Jonathan Block, SA News Editor8 Comments
- Phase 1b/2 data from a cohort of a trial examining a combination of Gilead Sciences (NASDAQ:GILD) and Arcus Biosciences' (NYSE:RCUS) experimental etrumadenant and zimberelimab along with chemotherapy and Roche's (OTCQX:RHHBY) Avastin led to a significantly reduced death risk compared to Bayer's (OTCPK:BAYZF)(OTCPK:BAYRY) Stivarga (regorafenib) in colorectal cancer.
- https://seekingalpha.com/news/4112420-gilead-arcus-combo-significantly-reduces-death-risk-colorectal-cancer
- Gilead Sciences, Inc. (GILD) Stock, RCUS Stock
- https://www.gilead.com/
- https://arcusbio.com/
biotecHOPE™ 2024
Blenrep (belantamab mafodotin), in combination with pomalidomide plus dexamethasone (PomDex)
Blenrep (belantamab mafodotin), in combination with pomalidomide plus dexamethasone (PomDex)
Blenrep (belantamab mafodotin), in combination with pomalidomide plus dexamethasone (PomDex)
02 June 2024
Issued: London, UK
For media and investors only
Blenrep combination reduced the risk of disease progression or death by nearly 50% versus standard of care combination in relapsed/refractory multiple myeloma
- DREAMM-8 phase III trial showed statistically significant and clinically meaningful improvement in primary endpoint of progression-free survival (PFS)
- Median PFS not yet reached at 21.8 months median follow-up versus 12.7 months in bortezomib combination
- Second trial to show robust efficacy for a Blenrep combination versus a standard of care in second line and later relapsed/refractory multiple myeloma
- Results simultaneously published in the New England Journal of Medicine
GSK plc (LSE/NYSE: GSK) today announced positive results from an interim analysis of the DREAMM-8 phase III head-to-head trial evaluating Blenrep (belantamab mafodotin), in combination with pomalidomide plus dexamethasone (PomDex), versus a standard of care, bortezomib plus PomDex, as a second line and later treatment for relapsed or refractory multiple myeloma. These late-breaking data, being presented today at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (31 May – 4 June) in Chicago, IL, were featured in the official ASCO press programme and simultaneously published in the New England Journal of Medicine.
On the primary endpoint of progression-free survival (PFS), a statistically significant and clinically meaningful improvement (hazard ratio [HR]: 0.52 [95% confidence interval (CI): 0.37-0.73], p-value<0.001) was observed with the belantamab mafodotin combination (n=155) compared to the bortezomib combination (n=147). At a median follow-up of 21.8 months, the median PFS was not yet reached (95% CI: 20.6-not yet reached [NR]) with the belantamab mafodotin combination compared to 12.7 months (95% CI: 9.1-18.5) in the bortezomib combination. At the end of one year, 71% (95% CI: 63-78) of patients in the belantamab mafodotin combination group compared to 51% (95% CI: 42-60) in the bortezomib combination group were alive and had not progressed. A benefit for belantamab mafodotin plus PomDex was observed across all pre-specified subgroups including those with poor prognostic features, such as patients who were refractory to lenalidomide and patients with high-risk cytogenetics.
Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said: “With the robust results from the DREAMM-8 phase III head-to-head trial, we now have consistent data from two phase III trials supporting the potential for Blenrep combinations to redefine the treatment of multiple myeloma at or after first relapse. This is exciting news given the high unmet need for new and efficacious combinations once patients relapse or stop responding to initial treatments. We continue to share data and discuss our path forward with regulators.”
A positive overall survival (OS) trend was observed but not statistically significant (HR: 0.77 [95% CI: 0.53-1.14]) at the interim analysis. OS follow-up continues and further analyses are planned. At the end of one year, 83% (95% CI: 76-88) of patients were alive in the belantamab mafodotin combination group versus 76% (95% CI: 68-82) in the bortezomib combination group. The safety and tolerability profile of the belantamab mafodotin combination was broadly consistent with the known profile of the individual agents.
Suzanne Trudel, MD, Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada, said: “The profound progression-free survival benefit seen in DREAMM-8 highlights the potential for belantamab mafodotin, when used with pomalidomide and dexamethasone, to improve outcomes for patients with relapsed/refractory multiple myeloma. This combination may have potential to redefine treatment of multiple myeloma at or after first relapse, a setting where patients may benefit from novel therapies.
Similar to the results seen in the DREAMM-7 phase III head-to-head trial, in DREAMM-8 the belantamab mafodotin combination also resulted in clinically meaningful improvements consistently across secondary efficacy endpoints, showing that the belantamab mafodotin combination resulted in deeper and more durable responses compared to the bortezomib combination. Key improvements included rate of complete response (CR) or better (more than twofold improvement); minimal residual disease (MRD) negativity rate (nearly fivefold improvement); and duration of response (median not yet reached with the belantamab mafodotin combination versus 17.5 months with the bortezomib combination).
About DREAMM-8
The DREAMM-8 phase III clinical trial is a multicentre, open-label, randomised trial evaluating the efficacy and safety of belantamab mafodotin in combination with PomDex compared to a combination of bortezomib and PomDex in patients with relapsed/refractory multiple myeloma previously treated with at least one prior line of multiple myeloma therapy, including a lenalidomide-containing regimen, and who have documented disease progression during or after their most recent therapy. Compared to the patient population studied in the DREAMM-7 trial, patients in DREAMM-8 were more heavily pre-treated in that all had prior exposure to lenalidomide, 75% were refractory to lenalidomide, 25% had prior daratumumab exposure and of those most were daratumumab refractory.
A total of 302 participants were randomised at a 1:1 ratio to receive either belantamab mafodotin plus PomDex, or bortezomib plus PomDex.
The primary endpoint is PFS as per an independent review committee. Key secondary endpoints include OS, minimal residual disease negativity as assessed by next-generation sequencing, and duration of response. Other secondary endpoints include ORR, patient-reported quality of life outcomes, adverse events, eye exam findings, and laboratory investigations.
About multiple myeloma
Multiple myeloma is the third most common blood cancer globally and is generally considered treatable but not curable.2,3 There are approximately 176,000 new cases of multiple myeloma diagnosed globally each year.4 Research into new therapies is needed as multiple myeloma commonly becomes refractory to available treatments.5
About Blenrep
Blenrep is an antibody-drug conjugate comprising a humanised B-cell maturation antigen monoclonal antibody conjugated to the cytotoxic agent auristatin F via a non-cleavable linker. The drug linker technology is licensed from Seagen Inc.; the monoclonal antibody is produced using POTELLIGENT Technology licensed from BioWa Inc., a member of the Kyowa Kirin Group.
Refer to the Blenrep UK Summary of Product Characteristics6 for a full list of adverse events and the complete important safety information in the United Kingdom.
GSK in oncology
Oncology is an emerging therapeutic area for GSK where we are committed to maximising patient survival with a current focus on haematologic malignancies, gynaecologic cancers, and other solid tumours through breakthroughs in immuno-oncology and tumour-cell targeting therapies.
About GSK
GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com.
GSK says Blenrep combo cuts disease progression, death in multiple myeloma
Jun. 03, 2024 12:03 PM ET
By: Jonathan Block, SA News Editor
- GSK (NYSE:GSK) said that new data found that a combination of Blenrep (belantamab mafodotin) and Bristol-Myers Squibb's (BMY) Pomalyst (pomalidomide) plus dexamethasone reduced the risk of disease progression or death by nearly 50% compared to a combo of Johnson & Johnson's (JNJ) 's Velcade (bortezomib), Pomalyst, and dexamethasone.
- The results are significant given that GSK announced in late 2022 it was pulling Blenrep from the U.S. market after a phase 3 trial failed to confirm the drug's efficacy. The new data could help the drugmaker's case for Blenrep's return.
- https://seekingalpha.com/news/4112369-gsk-says-belnrep-combo-cuts-disease-progression-death-multiple-myeloma?mailingid=35587370&messageid=2900&serial=35587370.53&utm_campaign=rta-stock-news&utm_content=link-1&utm_medium=email&utm_source=seeking_alpha&utm_term=35587370.53
- GSK plc (GSK) StockJNJ, BMY
- https://www.gsk.com/en-gb/
- https://www.gsk.com/en-gb/innovation/pipeline/
Remibrutinib
Blenrep (belantamab mafodotin), in combination with pomalidomide plus dexamethasone (PomDex)
Blenrep (belantamab mafodotin), in combination with pomalidomide plus dexamethasone (PomDex)
Novartis Phase III data confirm sustained efficacy and long-term safety of oral remibrutinib in chronic spontaneous urticaria
May 31, 2024
- Patients treated with remibrutinib experienced improvements in weekly urticaria activity scores (UAS7) observed as early as Week 1 and sustained to 1 year (Week 52)1
- Remibrutinib, an oral Bruton’s tyrosine kinase inhibitor, demonstrated a favorable and consistent safety profile up to 1 year, including balanced liver function tests versus placebo1
- Novartis intends to submit remibrutinib for approval in chronic spontaneous urticaria (CSU) to global health authorities starting in H2 2024, and continues to investigate remibrutinib in multiple immune-mediated conditions
- Data reaffirm the first-in-class potential of remibrutinib for the more than 50% of patients with CSU uncontrolled by H1-antihistamines who continue to live with painful and debilitating symptoms1,2
Basel, May 31, 2024 – Novartis today announced new data that confirm the long-term efficacy and safety of remibrutinib, a highly selective Bruton’s tyrosine kinase (BTK) inhibitor, in chronic spontaneous urticaria (CSU)1. In the pivotal Phase III studies, REMIX-1 and REMIX-2, remibrutinib treatment showed significant symptom improvement early, which was sustained up to Week 52, in patients with CSU who remained symptomatic despite second-generation H1-antihistamine use1. These data are being presented at the 2024 European Academy of Allergy and Clinical Immunology (EAACI) Congress in Valencia, Spain, May 31–June 3.
“A large majority of people with CSU are living with uncontrolled and debilitating symptoms, often trying to manage the condition by cycling through antihistamines at higher doses with no lasting respite, impacting heavily on their day-to-day lives,” said Martin Metz, Professor of Dermatology, Charité – Universitätsmedizin Berlin, Germany. “Remibrutinib has become an important investigational treatment for CSU as it blocks the BTK cascade and inhibits the release of histamine. These data show that remibrutinib has the potential to offer patients and physicians a well-tolerated oral treatment that provides early and lasting efficacy.”
New long-term Phase III REMIX-1 and REMIX-2 data assessed at Week 52 show that1:
- Significant improvements with remibrutinib versus placebo, as previously shown at Week 12, were confirmed at Week 24, including in weekly urticaria activity score (UAS7), weekly itch severity score (ISS7), and weekly hive severity score (HSS7)
- At Week 24, patients receiving placebo were transitioned to remibrutinib; responses with remibrutinib were observed as early as the first week after switching and were sustained until the end of the study (28 weeks of treatment)
- Almost half of patients were completely free of itch and hives (UAS7=0) as assessed at Week 52
“Living with CSU can be very distressing due to its unpredictable nature and never knowing when a flare-up may happen. Symptoms can occur on the face, throat, hands, and feet, and people may experience burning and pain on their skin,” said Tonya Winders, President and CEO, Global Allergy and Airways Patient Platform. “Unfortunately, many people continue to cope with uncontrolled symptoms. We welcome further research advancing our knowledge about chronic spontaneous urticaria.”
Remibrutinib was well-tolerated and demonstrated a favorable and consistent safety profile up to 52 weeks, including balanced liver function tests versus placebo1. Adverse events (AEs), including serious AEs and treatment discontinuations due to AEs, were comparable between remibrutinib and placebo during the 24-week placebo-controlled period1. In addition, exposure-adjusted rates did not increase with long-term treatment1. Liver transaminase elevations were balanced across the remibrutinib and placebo treatment groups; all were asymptomatic, transient, and reversible1. None of the serious AEs were considered related to study medication by investigators.
“Urticaria is a disease that significantly impacts patients' quality of life and there is an urgent need for new treatment options,” said Angelika Jahreis, Global Head, Development, Immunology, Novartis. “The 52-week REMIX-1 and REMIX-2 Phase III data are significant as many patients who had moderate to severe urticaria at study start were completely free of itch and hives after 52 weeks of treatment and remibrutinib, a highly selective oral BTK inhibitor, continued to be well tolerated. These exciting long-term data will be submitted to global health authorities later this year.”
In addition to CSU, remibrutinib is being investigated in several other immune-mediated conditions, such as hidradenitis suppurativa, where it met its primary endpoint in a Phase II study3. It is also being investigated in food allergy, chronic inducible urticaria, and multiple sclerosis4-8. Novartis will submit remibrutinib for approval in CSU to global health authorities starting in H2 2024.
About remibrutinib
Remibrutinib is an investigational, highly selective, covalent, oral BTK inhibitor that blocks the BTK cascade and prevents the release of histamine that causes itchy hives (wheals) and swelling9-11. When remibrutinib is used alongside standard-dose antihistamines, it results in a “two-pronged approach” where two parts of the inflammatory pathway are targeted, with remibrutinib inhibiting histamine release and antihistamines inhibiting histamine receptors, reducing CSU symptoms12,13. In the pivotal Phase III studies, REMIX-1 and REMIX-2, remibrutinib met all primary endpoints in patients with CSU who remained symptomatic despite second-generation H1-antihistamine use1. Treatment with remibrutinib showed significant symptom improvement early, which was sustained up to Week 521. Remibrutinib has been shown to be well-tolerated, with a favorable safety profile up to 52 weeks, including balanced liver function tests versus placebo1. Most commonly (≥5%) observed AEs in the Phase III REMIX studies were respiratory tract infections (including COVID-19 and nasopharyngitis) and headache, all comparable with placebo1,14. If approved in CSU, remibrutinib would offer an effective oral option within the Novartis immunology portfolio, which currently includes Xolair® (omalizumab), the first and only injectable biologic indicated for CSU15. In the US, Novartis Pharmaceuticals Corporation and Genentech, a member of the Roche Group, work together to develop and co-promote Xolair. In addition to CSU, remibrutinib is being investigated in several other immune-mediated conditions and has the potential to be a pipeline in a product4-8.
About REMIX-1 and REMIX-2
REMIX-1 (NCT05030311) and REMIX-2 (NCT05032157) are two identically designed, global, multicenter, randomized, double-blind, parallel-group, placebo-controlled Phase III studies, with REMIX-1 consisting of 470 participants and REMIX-2 consisting of 455 participants16,17. Both studies are designed to establish the efficacy, safety, and tolerability of twice-daily remibrutinib 25 mg treatment in adult participants with CSU that is inadequately controlled by second-generation H1-antihistamines compared with placebo1,16,17. The primary outcome measures were absolute change from baseline in weekly urticaria activity score (UAS7) as well as weekly itch severity score (ISS7) and weekly hive severity score (HSS7) at Week 1216,17. All participants were on a stable, local label-approved dose of a second-generation H1-antihistamine throughout the entire study16,17.
About CSU
CSU is the medical term for chronic hives that last for 6 weeks or longer, where the underlying cause is internal rather than exposure to any allergen or external trigger2,11,18. CSU affects approximately 40 million people worldwide2,19. It is characterized by the sudden appearance of itchy hives (wheals) and/or deep tissue swelling (angioedema, which can occur on the face, throat, hands, and feet)11,20. CSU affects all ages but occurs most frequently between the ages of 20–40 years, with women affected nearly twice as often as men2. CSU causes significant emotional distress, with the majority of patients suffering from sleep deprivation, and high rates of mental disorders, such as anxiety or depression, as well as impacting on their work productivity2. Antihistamines are often prescribed for CSU as they block histamine receptors and prevent the pro-inflammatory action of histamine, which causes itching and swelling13,18. However, more than 50% of people with CSU are uncontrolled by H1-antihistamines alone2.
Novartis reports positive Phase 3 data for remibrutinib for chronic hives
May 31, 2024 11:11 AM ET
By: Val Brickates Kennedy, SA News Editor
Novartis (NYSE:NVS) reported positive Phase 3 data for its autoimmune drug remibrutinib in the treatment of chronic spontaneous urticaria, also known as chronic spontaneous hives.
The Swiss drugmaker said remibrutinib demonstrated sustained symptom improvement up to week 52 in patients with the condition who remained symptomatic despite taking second-generation H1 antihistamines. The drug also exhibited a favorable and consistent safety profile, according to a statement.
Researchers plan to present the data at the 2024 European Academy of Allergy and Clinical Immunology Congress, which is being held in Spain from May 31 through June 3.
Acasunlimab (DuoBody® -PD-L1x4-1BB) in Combination with Pembrolizumab
Blenrep (belantamab mafodotin), in combination with pomalidomide plus dexamethasone (PomDex)
Acasunlimab (DuoBody® -PD-L1x4-1BB) in Combination with Pembrolizumab
Investigational Acasunlimab (DuoBody® -PD-L1x4-1BB) in Combination with Pembrolizumab Demonstrates Meaningful Clinical Activity in Phase 2 Trial in Patients with Previously Treated Metastatic Non-small Cell Lung Cancer (mNSCLC)
1 June 2024
- Initial data from the ongoing Phase 2 trial showed a 12-month overall survival rate of 69% and a median overall survival of 17.5 months in patients with previously treated PD-L1-positive metastatic non-small cell lung cancer treated with a combination of acasunlimab and pembrolizumab every six weeks
- Data from this ongoing Phase 2 study to inform the planned pivotal Phase 3 trial, which is expected to start before the end of 2024
COPENHAGEN, Denmark, and MAINZ, Germany, June 1, 2024 — Genmab A/S (Nasdaq: GMAB, “Genmab”) and BioNTech SE (Nasdaq: BNTX, “BioNTech”) today announced initial data from the ongoing Phase 2 trial (NCT05117242) evaluating acasunlimab (DuoBody-PD-L1x4-1BB), an investigational bispecific antibody also known as GEN1046/BNT311, as monotherapy and in combination with pembrolizumab in patients with PD-L(1)-positive metastatic non-small cell lung cancer (“mNSCLC”) who had disease progression following one or more prior lines of anti-PD(L)1-containing treatment. The results showed a 12-month overall survival (“OS”) rate of 69%, a median overall survival (“mOS”) of 17.5 months, and a 30% overall response rate (“ORR”) (confirmed ORR 17%) at the time of data cut-off in patients treated with the combination of acasunlimab and pembrolizumab every six weeks. The findings were presented at the 2024 American Society of Clinical Oncology (“ASCO”) Annual Meeting held in Chicago, IL from May 31-June 4, 2024.
The Phase 2 study randomized a total of 113 patients in three arms, evaluating acasunlimab alone (Arm A) and in combination with pembrolizumab (Arms B and C). The objective response analysis was conducted for 62 centrally confirmed PD-L1-positive efficacy-evaluable patients. The OS was evaluated in all centrally confirmed PD-L1-positive patients (n=80). Arm A showed a mOS rate of 5.5 months, a 50% disease control rate (DCR) and a 31% ORR (confirmed ORR 13%) in patients treated with acasunlimab alone. An 8.6 months mOS, a 59% DCR and a 21% ORR (confirmed ORR 18%) for treatment of acasunlimab in combination with pembrolizumab every three weeks (Arm B) and a 17.5 months mOS, a 75% DCR and a 30% ORR (confirmed ORR 17%) when the combination was administered every six weeks (Arm C). Anti-tumor activity was observed in patients with a tumor proportion score (“TPS”) of 1–49% and ≥50%, in patients with <6 months and ≥6 months of previous immune checkpoint inhibitor (“CPI”) treatment, and in patients with squamous and non-squamous histology.
Adverse events were consistent with the safety profiles of the individual drugs and treatment related adverse events (“TRAEs”) were primarily grade 1 and 2. The most common TRAEs (all grades) in Arm A were asthenia (22.7%), diarrhea (18.2%), nausea (18.2%), anemia (13.6%), and liver-related events (13.6%). In the combination arms (Arms B and C), the most common TRAEs were liver-related events (28.6%, 18.4%), fatigue (21.4%, 8.2%), asthenia (12%, 12.2%), and diarrhea (12%, 10.2%). Overall, a lower incidence of grade ≥3 TRAEs, treatment-related liver-related events and lower discontinuation rates were observed with the combination regimen therapy administered every six weeks. Transaminase elevations were generally asymptomatic and manageable with the administration of steroids and/or treatment delay and resolved more rapidly in patients treated with the combination therapy administered every six weeks.
“We are encouraged by the findings of this ongoing Phase 2 study. The initial results of acasunlimab in combination with pembrolizumab administered every 6 weeks suggest a potential meaningful impact on patients with metastatic non-small cell lung cancer,” said Judith Klimovsky, Executive Vice President & Chief Development Officer at Genmab. “We will continue to evaluate these data to inform further development of acasunlimab including a planned Phase 3 trial as we remain committed to investigate acasunlimab as a potential treatment option.”
“Most patients with mNSCLC have limited treatment options following progression on first-line checkpoint inhibitor therapy. For these patients, chemotherapy remains the main treatment despite limited efficacy and considerable toxicity,” said Prof. Özlem Türeci, M.D., Chief Medical Officer and Co-Founder at BioNTech. “The data of our Phase 2 trial show that the combination of acasunlimab with PDL1-blockade may be a suitable approach in this heavily pretreated patient population.”
About the GCT1046-04 Clinical Trial
The GCT1046-04 trial (NCT05117242) is a randomized, open-label trial evaluating the safety and efficacy of acasunlimab in patients with relapsed/refractory metastatic non-small cell lung cancer (“mNSCLC”) after treatment with standard of care therapy containing immune checkpoint inhibitor therapy. Patients with stage IV NSCLC with at least one prior line of systemic therapy containing an anti-PD-1/PD-L1 and a tumor PD-L1 expression in ≥1% of the tumor cells are included in the study. The primary endpoint of the trial is the overall response rate (“ORR”). Key secondary endpoints include overall survival (“OS”), progression free survival (“PFS”), time to response (“TTR”), duration of response (“DOR”), and safety. More information on this trial can be found at clinicaltrials.gov.
About Non-small Cell Lung Cancer (NSCLC)
Non-small cell lung cancer (“NSCLC”) is the most common type of lung cancer, accounting for about 85% of all reported cases. NSCLC starts in cells that line the airways and can grow into nearby tissues or spread to other parts of the body. NSCLC is often diagnosed at an advanced stage, when it is hard to treat and has a poor prognosis. The survival rate of patients with NSCLC varies depending on the stage at diagnosis.i,ii,iii,The treatment of NSCLC depends on the stage, subtype, and biomarker status of the disease, and may include surgery, radiation therapy, chemotherapy, targeted therapy, immunotherapy, or a combination of these modalities.
About Acasunlimab (GEN1046/BNT311)
Acasunlimab (GEN1046/BNT311) is an investigational PD-L1x4-1BB bispecific antibody fusing Genmab's proprietary DuoBody® technology platform and BioNTech’s proprietary immunomodulatory antibodies. Acasunlimab is designed to elicit an antitumor response via conditional activation of 4-1BB on T cells and natural killer cells, which is strictly dependent on simultaneous binding of the PD-L1 arm. Acasunlimab is being developed in collaboration by BioNTech and Genmab under a license and collaboration agreement. The candidate is currently being investigated in three clinical trials: (1) a Phase 1/2 safety trial in patients with multiple solid tumors, (2) a Phase 1 dose escalation trial in patients with advanced solid tumors in Japan, and (3) a randomized Phase 2 safety and efficacy trial with acasunlimab as a monotherapy and in combination with pembrolizumab in patients with NSCLC who have failed previous standard of care treatments with immune checkpoint inhibitors. Please visit www.clinicaltrials.gov for more information.
About Genmab
Genmab is an international biotechnology company with a core purpose of guiding its unstoppable team to strive toward improving the lives of patients with innovative and differentiated antibody therapeutics. For 25 years, its passionate, innovative and collaborative team has invented next-generation antibody technology platforms and leveraged translational, quantitative and data sciences, resulting in a proprietary pipeline including bispecific T-cell engagers, antibody-drug conjugates, next-generation immune checkpoint modulators and effector function-enhanced antibodies. By 2030, Genmab’s vision is to transform the lives of people with cancer and other serious diseases with knock-your-socks-off (KYSO®) antibody medicines.
Established in 1999, Genmab is headquartered in Copenhagen, Denmark, with international presence across North America, Europe and Asia Pacific. For more information, please visit Genmab.com and follow us on LinkedIn and X.
About BioNTech
Biopharmaceutical New Technologies (BioNTech) is a global next generation immunotherapy company pioneering novel therapies for cancer and other serious diseases. BioNTech exploits a wide array of computational discovery and therapeutic drug platforms for the rapid development of novel biopharmaceuticals. Its broad portfolio of oncology product candidates includes individualized and off-the-shelf mRNA-based therapies, innovative chimeric antigen receptor (CAR) T cells, several protein-based therapeutics, including bispecific immune checkpoint modulators, targeted cancer antibodies and antibody-drug conjugate (ADC) therapeutics, as well as small molecules. Based on its deep expertise in mRNA vaccine development and in-house manufacturing capabilities, BioNTech and its collaborators are developing multiple mRNA vaccine candidates for a range of infectious diseases alongside its diverse oncology pipeline. BioNTech has established a broad set of relationships with multiple global and specialized pharmaceutical collaborators, including Biotheus, DualityBio, Fosun Pharma, Genentech, a member of the Roche Group, Genevant, Genmab, MediLink, OncoC4, Pfizer and Regeneron.
For more information, please visit www.BioNTech.com.
BioNTech/Genmab lung cancer therapy improves survival with Keytruda
Jun. 01, 2024 1:30 PM ET
BioNTech SE (BNTX) Stock, GMAB StockMRK
By: Dulan Lokuwithana, SA News Editor5 Comments
BioNTech (NASDAQ:BNTX) and Genmab (GMAB) announced Saturday that their investigational bispecific antibody acasunlimab improved survival rates among lung cancer patients in combination with Merck’s (MRK) immunotherapy Keytruda.
Citing early results from a mid-stage trial for the candidate, the companies said acasunlimab with Keytruda, also known as pembrolizumab, when administered every six weeks led to 17.5 months of median overall survival (mOS).
https://seekingalpha.com/news/4112133-biontech-genmab-post-early-data-lung-cancer-therapy
BioNTech SE (BNTX) Stock, GMAB StockMRK
https://www.biontech.com/int/en/home.html
https://www.genmabmedicalaffairs.com/resource/DuoBody_Infographic
Zanidatamab
Zanidatamab
Acasunlimab (DuoBody® -PD-L1x4-1BB) in Combination with Pembrolizumab
Jazz Pharmaceuticals Presents Overall Survival and Longer Follow-Up Data from HERIZON-BTC-01 Trial Evaluating Zanidatamab in Previously Treated HER2-Positive Biliary Tract Cancer at ASCO 2024
June 01, 2024
Zanidatamab demonstrated a median overall survival (OS) of 15.5 months in patients with centrally confirmed immunohistochemistry (IHC) 2+ or 3+ and a median OS of 18.1 months in patients with IHC 3+ tumors
With approximately two years of median follow-up, as of July 28, 2023, median duration of response (DOR) increased by two months from initial analysis to 14.9 months
DUBLIN, June 1, 2024 /PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced long-term follow-up results, including the first-ever overall survival (OS) findings, from the Phase 2b HERIZON-BTC-01 clinical trial of zanidatamab in previously treated, unresectable, locally advanced, or metastatic HER2-positive biliary tract cancer (BTC). These data will be featured at the American Society of Clinical Oncology (ASCO) Annual Meeting in a poster presentation during the Gastrointestinal Cancer – Gastroesophageal, Pancreatic, and Hepatobiliary session on June 1, 2024, at 1:30-4:30 p.m. CDT. Zanidatamab is a human epidermal growth factor receptor 2 (HER2)-targeted bispecific antibody being studied in multiple solid tumors.
For the trial's primary endpoint, results demonstrated that a confirmed objective response rate (cORR) by independent central review (ICR) was maintained at 41.3% (95% confidence interval (CI): 30.4, 52.8) and one additional patient achieved a complete response (n=2; 2.5%) since initial findings were presented at the ASCO Annual Meeting in 2023. The median duration of response (DoR), one of the trial's key secondary endpoints, increased by approximately 2 months to 14.9 months (95% CI: 7.4, not reached), compared to the previously reported findings. In this data cut, zanidatamab demonstrated a median estimated OS, another secondary endpoint, of 15.5 months (95% CI: 10.4, 18.5) in all patients with HER2+ BTC, 18.1 months (95% CI:12.2, 23.2) in patients with IHC 3+ tumors, and 5.2 months (95% CI: 3.1, 10.2) in patients with IHC 2+ tumors. Results highlight the clinically meaningful benefits of sustained and durable responses with continued treatment with zanidatamab.
"Patients with BTC are typically diagnosed when their disease is at an advanced stage, which is associated with a poor prognosis," said Shubham Pant, M.D., M.B.B.S. professor in the Department of Gastrointestinal Medical Oncology and Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center. "Historically, overall survival with standard-of-care chemotherapy in second-line patients with advanced BTC is reported to be between 6-9 months1 so there is a significant unmet need for targeted therapies that can potentially improve survival. The deep and durable responses seen in this study signal the potential to fill a critical unmet patient need with zanidatamab, a chemotherapy-free option, among patients with HER2-expressing cancers."
"We are encouraged by the updated results from the pivotal HERIZON-BTC-01 trial demonstrating sustained clinical activity in previously treated patients with advanced HER2-positive BTC. Results from HERIZON-BTC-01 were included in the Biologics License Application (BLA) for zanidatamab, which was granted Priority Review by the FDA earlier this week, as well as in the Marketing Authorization Application for zanidatamab which was recently submitted to the European Medicines Agency," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development of Jazz Pharmaceuticals. "Clinical development of zanidatamab for the treatment of advanced HER2-positive BTC continues with HERIZON-BTC-302 (NCT06282575), the ongoing, global, randomized Phase 3 trial of zanidatamab in combination with standard-of-care therapy in the first-line setting for patients with HER2-positive BTC. We also look forward to investigating zanidatamab's potential in other HER2-expressing solid tumors, including in cases resistant to prior HER2-targeted therapies."
Trial Results
Results from this long-term analysis of the Phase 2b HERIZON-BTC-01 trial (NCT04466891) indicate that zanidatamab monotherapy demonstrated sustained and durable antitumor responses in previously treated patients with HER2-positive unresectable, locally advanced, or metastatic BTC and support the clinically meaningful benefit of continued treatment with zanidatamab. The safety profile in all enrolled patients remained manageable with favorable tolerability compared with the initial analysis. Two (2.3%) patients discontinued treatment due to treatment-related adverse events (TRAEs).
The trial evaluated zanidatamab (20 mg/kg IV once every 2 weeks) in patients with HER2-positive, locally advanced unresectable, or metastatic BTC who had received prior gemcitabine-containing therapy. Patients with prior HER2-targeted therapy use were excluded from the trial. All patients were required to have centrally confirmed HER2-amplified tumors (assessed by in situ hybridization). Patients (n=87) were assigned into two cohorts based on tumor IHC status: Cohort 1 (n=80) included patients who were IHC 2+/3+ (HER2-positive) and Cohort 2 (n=7) included patients who were IHC 0/1+. The median duration of follow-up was 21.9 (16-34) months. Tumors were assessed every 8 weeks per RECIST v1.1. Updated efficacy analyses include only Cohort 1, while safety analyses include Cohorts 1 and 2.
As of July 28, 2023, data from HER2-positive BTC patients enrolled in Cohort 1 (n=80) demonstrated:
- With longer follow-up, the cORR was maintained from the initial analysis (n=33; 41.3%) (95% CI: 30.4, 52.8), with one additional complete response (n=2; 2.5%).
- Although the trial was not designed to detect treatment effects by HER2 status, as previously reported, in a pre-planned subgroup analysis of cORR by HER2 expression, responses were observed in patients with IHC 3+ tumors (cORR: 51.6% [95% CI: 38.6%-64.5%]) and IHC 2+ tumors (cORR: 5.6% [95% CI: 0.1-27.3%])2.
- A two-month increase in the median DoR to 14.9 months (95% CI: 7.4, not reached).
- In patients with IHC3+ tumors, the median DoR was 14.9 months (95% CI: 7.4, not reached).
- The DOR in the 1 responder with IHC 2+ tumors was 7.5 months.
- A median OS (95% CI) of 15.5 months (95% CI: 10.4, 18.5).
- The median OS in patients with IHC 3+ was 18.1 months (95% CI: 12.2, 23.2).
- The median OS in patients with IHC 2+ was 5.2 months (95% CI: 3.1, 10.2).
- Median progression-free survival (PFS) was maintained (5.5 months [95% CI: 3.6, 7.3]) compared with the initial analysis, which had a data cutoff of October 10, 2022.
- In patients with IHC 3+ tumors, the median PFS was 7.2 months (95% CI: 5.4, 9.4) months.
- In patients with IHC 2+ tumors, the median PFS was 1.7 months (95% CI: 1.0, 3.3) months.
As previously reported for Cohorts 1 and 2, zanidatamab demonstrated a manageable and tolerable safety profile, with no new safety signals identified and no deaths that were treatment related. TRAEs leading to dose reductions remained infrequent. Serious TRAEs occurred in eight (9.2%) patients. One patient experienced serious TRAEs since the initial analysis (alanine aminotransferase increased and aspartate aminotransferase increased).Treatment discontinuation rate was 2.3% and no additional patients discontinued treatment due to TRAEs since the initial analysis.
About BTC
BTC, including gallbladder cancer and intrahepatic and extrahepatic cholangiocarcinoma, account for <1% of all adult cancers globally and are often associated with a poor prognosis.3,4 The human epidermal growth factor receptor 2 (HER2) is a well-validated target for antitumor therapy in other cancers. Across the U.S., Europe, and Japan, approximately 12,000 people are diagnosed with HER2+ BTC annually.5,6,7,8
About Zanidatamab
Zanidatamab is an investigational HER2-targeted bispecific antibody that can simultaneously bind two non-overlapping epitopes of the HER2 receptor, known as biparatopic binding. This unique design and increased binding results in multiple mechanisms of action, including dual HER2 signal blockade, removal of HER2 protein from the cell surface, and immune-mediated cytotoxicity leading to encouraging antitumor activity in patients. Zanidatamab is being developed in multiple clinical trials as a targeted treatment option for patients with solid tumors that express HER2. Zanidatamab is being developed by Jazz and BeiGene, Ltd. (BeiGene) under license agreements from Zymeworks, which first developed the molecule.
The U.S. Food and Drug Administration (FDA) has accepted and granted Priority Review of the Biologics License Application (BLA) for zanidatamab with a Prescription Drug User Fee Act (PDUFA) action date of November 29, 2024. Zanidatamab was also granted Breakthrough Therapy designation in patients with previously treated HER2 gene-amplified biliary tract cancers (BTC) and given two Fast Track designations: one as a single agent for refractory BTC and one in combination with standard of care chemotherapy for 1L gastroesophageal adenocarcinoma (GEA). Additionally, zanidatamab has received Orphan Drug designations from FDA for the treatment of BTC and GEA, as well as Orphan Drug designation from the European Medicines Agency for the treatment of BTC and gastric cancer. Zanidatamab was also granted Breakthrough Therapy designation from the Center for Drug Evaluation (CDE) in China.
About Jazz Pharmaceuticals
Jazz Pharmaceuticals plc (Nasdaq: JAZZ) is a global biopharma company whose purpose is to innovate to transform the lives of patients and their families. We are dedicated to developing life-changing medicines for people with serious diseases—often with limited or no therapeutic options. We have a diverse portfolio of marketed medicines, including leading therapies for sleep disorders and epilepsy, and a growing portfolio of cancer treatments. Our patient-focused and science-driven approach powers pioneering research and development advancements across our robust pipeline of innovative therapeutics in oncology and neuroscience. Jazz is headquartered in Dublin, Ireland with research and development laboratories, manufacturing facilities and employees in multiple countries committed to serving patients worldwide. Please visit www.jazzpharmaceuticals.com for more information.
8 Major markets: U.K, France, Germany, Spain, Italy. Note: HER2+ BTC patients in Jazz-controlled commercial territories, which includes Japan, and excludes other certain Asia Pacific countries licensed to BeiGene, Ltd
Jazz presents additional phase 2 data on zanidatamab for biliary tract cancer
Jun. 01, 2024 5:13 PM ET
Jazz Pharmaceuticals plc (JAZZ) Stock
By: Jonathan Block, SA News Editor
- Phase 2 follow-up data on Jazz Pharmaceuticals' (NASDAQ:JAZZ) zanidatamab found that the bispecific antibody led to median overall survival of 15.5 months in previously treated patients with HER2-positive biliary tract cancer.
- Data showed that the objective response rate was 41.3%, the study's primary endpoint.
- https://seekingalpha.com/news/4112139-jazz-presents-additional-phase-2-data-zanidatamab-biliary-tract-cancer
- Jazz Pharmaceuticals plc (JAZZ) Stock
- https://www.zymeworks.com/pipeline/
DTX401
Zanidatamab
Donidalorsen
Ultragenyx Announces Positive Top-Line Results from Phase 3 Study of DTX401 Gene Therapy for Glycogen Storage Disease Type Ia (GSDIa)
May 30, 2024
Treatment with DTX401 resulted in a statistically significant reduction in daily cornstarch intake at Week 48 (p<0.0001) with maintenance of glucose control
Company will host investor call today at 5:00 p.m. ET
NOVATO, Calif., May 30, 2024 (GLOBE NEWSWIRE) -- Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE) today announced positive topline results from the Phase 3 GlucoGene study (NCT05139316) evaluating DTX401, an investigational gene therapy for the treatment of patients aged eight years and older with glycogen storage disease type Ia (GSDIa).
The study achieved its primary endpoint, demonstrating that treatment with DTX401 resulted in a statistically significant and clinically meaningful reduction in daily cornstarch intake compared with placebo at Week 48. The mean percent reduction was 41.3% in the DTX401 group (n=20) compared with 10.3% in the placebo group (n=24) at Week 48 (p<0.0001). Across patients treated with DTX401, the mean reduction in cornstarch continued to decline over the 48-week period. In the treatment group, all patients achieved a reduction in cornstarch, with 68% achieving ≥30% reduction and 37% achieving ≥50% reduction compared to the placebo group, which achieved the same reductions in 13% and 4% of patients, respectively, at Week 48.
“This is an incredible milestone for the DTX401 program. These clinically important and statistically significant results are consistent with our Phase 1/2 findings, and the continued improvement in these treated patients reflects the acquired ability to break down glycogen as a source of endogenous glucose from their treated livers,” said Eric Crombez, M.D., chief medical officer at Ultragenyx. “We want to thank the patients, families and treating community for their ongoing participation in this study and their support of progress for the broader GSDIa community.”
The study also successfully met key secondary endpoints of reduction in the number of cornstarch doses per day and maintenance of glucose control at Week 48. Treatment with DTX401 resulted in a mean reduction of 1.1 cornstarch doses per day in the DTX401 treatment group compared with a mean reduction of 0.2 in the placebo group (p=0.0011). Patients in the DTX401 group also showed significant improvement in both frequency and quantity of nighttime cornstarch dosing compared with the placebo group. This blinded study established non-inferiority (p<0.0001) of glucose control between the study groups while the treatment group significantly reduced daily cornstarch intake.
The Patient Global Impression of Change (PGIC) at Week 48 showed a median score of 2.0 (moderately improved) for the DTX401 treatment group and 1.0 (minimally improved) for the placebo group (p=0.132). Moderately or higher improved PGIC scores correlated with a ≥30% reduction in total daily cornstarch intake indicating that this is a clinically meaningful threshold for patients.
“With these Phase 3 results, the significant reduction in cornstarch intake with continued management of glucose control has the potential to offer meaningful benefit to patients while improving their quality of life on a daily basis,” stated Rebecca Riba-Wolman, M.D., director of the Glycogen Storage Disease Program & Disorders of Hypoglycemia at Connecticut Children’s Medical Center/University of Connecticut Medical School and study investigator. “GSDIa is a disease that never takes a break, where you must constantly think about your own, or your child's, safety and risk of severe low blood sugar and acidosis throughout the day and especially at night. A treatment that can improve these daily concerns for people with GSDIa without significant risks is essential.”
The study demonstrated an acceptable and expected safety profile for DTX401 consistent with Phase 1/2 study results. Anticipated vector-induced hepatic effects were all non-serious and manageable with a prophylactic corticosteroid regimen. No AAV8 class effects of dorsal root ganglion toxicity or thrombotic microangiopathy were observed in the study through Week 48.
Full 48 Week data from the Phase 3 study will be presented at a scientific conference later this year. These results will be discussed with regulatory authorities to support a marketing application in 2025.
Phase 1/2 Data Presented at American Society of Gene and Cell Therapy 2024
Ultragenyx recently presented long-term DTX401 Phase 1/2 data demonstrating durable response, with sustained, clinically meaningful reductions in cornstarch lasting up to 5 years in patients treated with open-label DTX401 as of the data cut-off. All 12 patients in the study have been followed for an average of 4 years and continue to demonstrate improved glucose control, with a mean total daily reduction of cornstarch intake of 72% (p<0.0001) from baseline to their last available timepoint.
Conference Call and Webcast Information
Ultragenyx will host a conference call at 5:00 p.m. ET today to discuss the topline data from the DTX401 Phase 3 GlucoGene study. The live and replayed webcast of the call will be available through the company’s website at https://ir.ultragenyx.com/events-presentations.
About the Phase 3 GlucoGene study
The 48-week randomized, double-blind, placebo-controlled study treated 46 patients aged eight years and older with DTX401 (1.0 x 10^13 GC/kg dose measured by ddPCR) or placebo. There were 44 patients in the modified intention-to-treat (mITT) population with efficacy data within the Week 48 analysis period following treatment with DTX401 (n=20) or placebo (n=24). At Week 48, eligible patients crossed over and received the alternate treatment. After crossover, patients will be followed for an additional 96 weeks. After study completion, patients will be offered enrollment into a Disease Monitoring Program (DMP) where they will be followed for at least 10 years post-DTX401 infusion.
About Glycogen Storage Disease Type Ia (GSDIa)
GSDIa is a serious inherited glycogen storage disease. It is caused by a defective gene coding for the enzyme G6Pase-α, resulting in the inability to regulate blood sugar (glucose). Hypoglycemia in patients with GSDIa can be life-threatening, while the accumulation of the complex sugar glycogen in certain organs and tissues can impair the ability of these tissues to function normally. If chronically untreated, patients can develop severe lactic acidosis, progress to renal failure, and potentially die in infancy or childhood. There are no approved pharmacologic therapies. An estimated 6,000 patients worldwide are affected by GSDIa.
About DTX401
DTX401 is an investigational AAV8 gene therapy designed to deliver stable expression and activity of G6Pase-α under control of the native promoter to allow the treated liver cells to respond to normal hormonal signals intended to manage glucose, including insulin, glucagon and cortisol. DTX401 is administered as a single intravenous infusion and has been shown in preclinical studies to improve G6Pase-α activity and reduce hepatic glycogen levels, a well-described biomarker of disease progression. DTX401 has been granted orphan drug designation, regenerative medicine advanced therapy (RMAT) designation and Fast Track designation from the U.S. FDA, as well as PRIority MEdicines (PRIME) and orphan drug designation from the European Medicines Agency.
About Ultragenyx Pharmaceutical Inc.
Ultragenyx is a biopharmaceutical company committed to bringing novel products to patients for the treatment of serious rare and ultrarare genetic diseases. The company has built a diverse portfolio of approved therapies and product candidates aimed at addressing diseases with high unmet medical need and clear biology for treatment, for which there are typically no approved therapies treating the underlying disease.
The company is led by a management team experienced in the development and commercialization of rare disease therapeutics. Ultragenyx’s strategy is predicated upon time- and cost-efficient drug development, with the goal of delivering safe and effective therapies to patients with the utmost urgency.
For more information on Ultragenyx, please visit the company's website at: www.ultragenyx.com.
Ultragenyx Phase 3 study for DTX401 meets primary endpoint
May 30, 2024 4:32 PM ET
Ultragenyx Pharmaceutical Inc. (RARE) Stock
By: Val Brickates Kennedy, SA News Editor
Ultragenyx Pharmaceutical (NASDAQ:RARE) said a Phase 3 study of its gene therapy candidate DTX401 met its primary endpoint in the treatment of patients with glycogen storage disease type Ia, or GSDIa.
The biotech company said the endpoint was to show the treatment resulted in a clinically meaningful and statistically significant reduction in daily cornstarch intake compared with placebo at week 48.
The study also met its secondary endpoints of reduction of the number of cornstarch doses per day and maintenance of glucose control at week 48, Ultragenyx said.
https://seekingalpha.com/news/4111748-ultragenyx-phase-3-study-for-dtx401-meets-primary-endpoint
Ultragenyx Pharmaceutical Inc. (RARE) Stock
https://www.ultragenyx.com/our-research/pipeline/dtx401-for-gsdia/
Donidalorsen
Zanidatamab
Donidalorsen
Ionis presents positive results from OASIS-HAE and OASISplus studies of investigational medicine donidalorsen in patients with hereditary angioedema
May 31, 2024 at 7:00 AM EDT
- Donidalorsen delivered significant and sustained reductions in HAE attacks, with high levels of disease control and improvement in quality of life measures with monthly or every two-month dosing; continued attack rate reduction over time
- In first-of-its-kind prospective analysis, patients switching from prior prophylactic treatment to donidalorsen experienced further reductions in mean monthly HAE attack rates from baseline
- Donidalorsen demonstrated a favorable safety and tolerability profile across all cohorts
- Data to be presented today at EAACI Congress 2024
- Ionis to host webcast on Friday, May 31 at 8:00am ET
CARLSBAD, Calif., May 31, 2024 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) today announced positive results from the Phase 3 OASIS-HAE and OASISplus studies of donidalorsen in patients with hereditary angioedema (HAE) demonstrating significant and sustained reduction in mean monthly HAE attack rates and continued attack rate improvement of >90% with one year of treatment for both monthly or every two-month dosing. Patients who switched to donidalorsen from prior prophylactic treatment also showed 62% further reduction in mean monthly HAE attack rates from baseline, and 84% of patients who switched reported a preference for donidalorsen. Donidalorsen had a favorable safety and tolerability profile across both studies, including when self-administered via an auto-injector. Results will be presented in three late-breaking oral presentations at the 2024 European Academy of Allergy and Clinical Immunology (EAACI) Annual Congress in Valencia, Spain. Based on these data, Ionis is pursuing regulatory approval of donidalorsen as a potential treatment for HAE.
HAE is a rare and potentially life-threatening genetic condition that involves recurrent attacks of severe swelling (angioedema) in various parts of the body, including the hands, feet, genitals, stomach, face and/or throat. Donidalorsen is an investigational RNA-targeted prophylactic medicine designed to reduce the production of prekallikrein (PKK), interrupting the pathway that leads to HAE attacks.
"We're delighted by the results from the OASIS clinical program, which we believe position donidalorsen to advance the prophylactic treatment paradigm for people living with HAE. Despite currently available therapies, people living with HAE still face significant disease burden and new prophylactic treatments are needed," said Brett Monia, Ph.D., chief executive officer of Ionis. "These data underscore the potential of donidalorsen to continually improve HAE attack rates and quality of life over time, positioning donidalorsen as an attractive potential treatment option. In our prospective switch cohort, patients switched to donidalorsen from another prophylactic without increased breakthrough attacks and achieved greater disease control. In fact, a majority of patients who switched reported a preference for donidalorsen. We thank the patients, families and clinicians who participated in these important studies. Based on these results, Ionis will pursue regulatory approval for donidalorsen, and we look forward to launching it as part of our growing independent commercial pipeline, if approved."
OASIS-HAE Study Results
In the Phase 3 OASIS-HAE study, patients with HAE were treated with donidalorsen (80 mg) via subcutaneous injection every four weeks (Q4W) (n=45) or every eight weeks (Q8W) (n=23), or placebo (n=22), over 24 weeks.
- The study met its primary endpoint, demonstrating 81% lower monthly HAE attack rate with donidalorsen Q4W compared to placebo over weeks one to 25 (p<0.001), and 55% reduction with Q8W (p=0.004).
- In weeks five to 25, donidalorsen Q4W significantly reduced mean monthly HAE attack rates by 87% (p<0.001) compared to placebo, a key secondary endpoint.
- In the same time frame, treatment with donidalorsen Q4W reduced severe to moderate attacks per month by 89% (p<0.001).
- Donidalorsen Q4W also reduced HAE attacks that require acute therapy by 92% (p<0.001).
- At week 25, 91% of donidalorsen Q4W patients were well-controlled as measured by the Angioedema Control Test (AECT).
- Donidalorsen resulted in clinically significant improvement in quality of life as measured by the Angioedema Quality of Life Questionnaire (AE-QoL).
- Donidalorsen Q8W had a similar benefit as Q4W dosing over time on attack rate reduction and quality of life measures.
- Donidalorsen was well-tolerated, with no serious treatment emergent adverse events (TEAEs) related to donidalorsen. Most adverse events (AEs) were mild or moderate in severity, and injection site reactions were the most common AE. One patient in the donidalorsen Q8W group discontinued based on investigator recommendation due to patient noncompliance and a TEAE.
OASISplus Study Results – Open-Label Extension and Switch
The OASISplus study included an open-label extension (OLE) cohort and a first-of-its-kind prospective cohort to assess patients switching from both newer oral and injectable long-term prophylactic treatments to donidalorsen.
Open-Label Extension Cohort
Following completion of the placebo-controlled treatment period in OASIS-HAE, 94% of eligible patients enrolled in the OLE cohort. Participants continued to receive treatment with donidalorsen via subcutaneous injection dosed every four weeks (n=69) or every eight weeks (n=14). As of the February 28, 2024 data cut:
- Attack rates continued to improve over time, resulting in 93% and 92% improvement from baseline measured at the start of OASIS-HAE across Q4W and Q8W, respectively.
- Extended treatment resulted in further improved quality of life measures and high levels of disease control.
- At week 25, 91% (Q4W) and 100% (Q8W) of patients reported well-controlled disease as measured by the AECT.
- AE-QoL scores improved by 28 points (Q4W) and 24 points (Q8W) at week 25 compared to baseline in OASIS-HAE. An improvement of 6 points is considered clinically meaningful.
- Safety results were consistent with findings from OASIS-HAE, with no serious safety concerns and no patient discontinuations.
Switch Cohort
The OASISplus switch cohort evaluated the safety and efficacy of long-term dosing of donidalorsen every four weeks in patients (n=64) who were previously treated with another prophylactic HAE medication (lanadelumab, berotralstat or C1-esterase inhibitor) for at least 12 weeks prior to entering the study. Patients followed a pre-defined specific protocol to transition from their prior therapy to donidalorsen. Results from a pre-defined endpoint of 17 weeks indicate:
- Patients switched to donidalorsen from prior prophylactic treatment without an increase in breakthrough attacks.
- Patients experienced a 62% further improvement in mean monthly HAE attack rate compared to baseline for previous prophylactic treatment.
- 84% of patients who switched reported a preference for donidalorsen over their previous treatment, citing better disease control, less time to administer, and less injection site pain or reactions.1
- Quality of life measures also showed continued improvement, with 93% of patients reporting well-controlled disease compared to 67% at baseline with prior prophylactic treatment. Results also demonstrated ≥8-point improvement in AE-QoL scores.
- Safety results were consistent with findings from OASIS-HAE, with no serious safety concerns. One patient discontinued due to TEAE not related to donidalorsen.
"People living with HAE are facing a lifelong battle, and I see that impact firsthand in my practice. It's critical for treatment options to have lasting, durable efficacy," said Marc Riedl, M.D., M.S. clinical director, U.S. HAEA Angioedema Center; clinical service chief, Division of Allergy & Immunology, University of California, San Diego. "The OASISplus study demonstrated patients are able to change therapy to donidalorsen without the risk of increased breakthrough HAE attacks while continuing to improve in measures of quality of life and disease control."
"The comprehensive OASIS clinical program demonstrates how donidalorsen can potentially address key concerns patients may experience with currently available treatment options," said Kenneth Newman, M.D., senior vice president of clinical development at Ionis. "Donidalorsen significantly reduced HAE attack rates, and with the simplicity of monthly or every two-month self-administration via autoinjector, we believe that donidalorsen has a unique profile that may address the needs of people with HAE."
Ionis plans to file a New Drug Application this year with the U.S. Food and Drug Administration (FDA), marking progress toward the goal of launching our second wholly owned medicine. Otsuka Pharmaceutical Co., Ltd., which has exclusive rights to commercialize donidalorsen in Europe, is also preparing to submit a Marketing Authorization Application to the European Medicines Agency this year.
All presentations can be found on Ionis' website after today's presentations at 10:45am ET.
Webcast
Ionis will hold a webcast today at 8:00am ET to discuss this update. Interested parties may access the webcast here. A webcast replay will be available for a limited time.
About the OASIS-HAE Study
The global, multicenter, randomized, double-blind, placebo-controlled Phase 3 OASIS-HAE study (NCT05139810) enrolled 91 participants, age 12 and above, with HAE-1 and HAE-2 hereditary angioedema. Participants were randomized in a 2:1 ratio to receive donidalorsen (80mg) or placebo via subcutaneous injection once every four weeks for 24 weeks or donidalorsen (80mg) or placebo via subcutaneous injection once every eight weeks for 24 weeks. Within each cohort, participants were randomized in a 3:1 ratio to receive donidalorsen or matching-placebo. The primary endpoint was the time-normalized number of investigator-confirmed HAE attacks from week one to week 25 compared to placebo. Following completion of the treatment period, 94% of eligible patients entered the Phase 3 OASISplus open-label extension study.
About the OASISplus Study
The Phase 3 OASISplus open-label extension (OLE) study is a 53-week global, multicenter study of subcutaneous injections of donidalorsen administered every four weeks (80mg) and every eight weeks (80mg) in patients completing the OASIS-HAE study. These are patients aged 12 and above, with HAE-1 and HAE-2 hereditary angioedema. The study is designed to evaluate the safety and efficacy of extended dosing of donidalorsen following completion of the Phase 3 OASIS-HAE study. The OASISplus switch cohort is evaluating the safety and efficacy of long-term dosing of donidalorsen every four weeks in patients who were previously treated with another prophylactic HAE medication. Additional information about OASISplus (NCT04307381) may be found at ClinicalTrials.gov.
About Hereditary Angioedema (HAE)
HAE is a rare and potentially life-threatening genetic condition that involves recurrent attacks of severe swelling (angioedema) in various parts of the body, including the hands, feet, genitals, stomach, face and/or throat.2,3,4,5,6 HAE is estimated to affect more than 20,000 patients in the U.S. and Europe.7 In the U.S., doctors frequently use prophylactic treatment approaches to prevent and reduce the severity of HAE attacks in patients.
About Donidalorsen
Donidalorsen is an investigational LIgand-Conjugated Antisense (LICA) medicine designed to target prekallikrein (PKK), which plays an important role in activating inflammatory mediators associated with acute attacks of hereditary angioedema (HAE). By reducing the production of PKK, donidalorsen could be an effective prophylactic approach to preventing HAE attacks.
About Ionis Pharmaceuticals, Inc.
For three decades, Ionis has invented medicines that bring better futures to people with serious diseases. Ionis currently has five marketed medicines and a leading pipeline in neurology, cardiology, and other areas of high patient need. As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in RNA therapies in addition to advancing new approaches in gene editing. A deep understanding of disease biology and industry-leading technology propels our work, coupled with a passion and urgency to deliver life-changing advances for patients.
To learn more about Ionis, visit Ionispharma.com and follow us on X (Twitter) and LinkedIn.
Cision View original content to download multimedia:https://www.prnewswire.com/news-releases/ionis-presents-positive-results-from-oasis-hae-and-oasisplus-studies-of-investigational-medicine-donidalorsen-in-patients-with-hereditary-angioedema-302160162.html
SOURCE Ionis Pharmaceuticals, Inc.
Ionis hereditary angioedema therapy succeeds in late-stage trials
May 31, 2024 7:46 AM ET
Ionis Pharmaceuticals, Inc. (IONS) Stock
By: Dulan Lokuwithana, SA News Editor
Ionis Pharmaceuticals (NASDAQ:IONS) announced Friday that its investigational therapy donidalorsen generated positive results in two late-stage trials for hereditary angioedema (HAE), a rare genetic disorder characterized by body swelling.
Citing data from its Phase 3 OASIS-HAE and OASISplus studies, the company said that donidalorsen, an RNA-targeted therapy, cut HAE attack rates after one year of treatment with monthly or every two-month-dosing.
https://seekingalpha.com/news/4111890-ionis-stock-gains-data-hae-therapy
Ionis Pharmaceuticals, Inc. (IONS) Stock
https://www.ionispharma.com/ionis-technology/antisense-pipeline/
XeriSol™-Formulated Once-Weekly Subcutaneous (SC) Levothyroxine (XP-8121)
XeriSol™-Formulated Once-Weekly Subcutaneous (SC) Levothyroxine (XP-8121)
XeriSol™-Formulated Once-Weekly Subcutaneous (SC) Levothyroxine (XP-8121)
Xeris Biopharma Announces Positive Topline Phase 2 Clinical Data of Its Investigational XeriSol™-Formulated Once-Weekly Subcutaneous (SC) Levothyroxine (XP-8121)
XeriSol™ formulation enabled predictable bioavailability and sustained levels of levothyroxine in a once-weekly subcutaneous presentation
Once-weekly SC levothyroxine (XP-8121) participants normalized TSH/T4 levels using 45% less drug than would be needed for their daily oral dose on a weekly basis
Data established an average once-weekly SC dose of XP-8121 and confirmed previous Phase 1 study of a 4X target dose conversion factor when switching from once-daily oral administration of levothyroxine
Participants who completed the study rated higher treatment satisfaction with XP-8121 compared to oral and a majority (72%) indicated a strong preference for the SC route of administration
Study exposed the challenges of achieving and maintaining normal TSH with daily oral levothyroxine therapy
FDA End-of-Phase 2 interaction to facilitate a Phase 3 pivotal study program is expected by year-end
CHICAGO--(BUSINESS WIRE)--May 30, 2024-- Xeris Biopharma Holdings, Inc. (Nasdaq: XERS), a growth-oriented biopharmaceutical company committed to improving patients’ lives by developing and commercializing innovative products across a range of therapies, today announced topline results from its recently completed Phase 2 multi-center, open label, study of XP-8121 for the treatment of adults with hypothyroidism. XP-8121 employs the Company’s XeriSol™ formulation technology to enable a novel once-weekly SC injection of levothyroxine. This novel formulation significantly increases the bioavailability of levothyroxine reducing overall drug exposure and enabling a dosing regimen with the potential to mitigate the many challenges associated with achieving and maintaining a normal level of thyroid stimulating hormone (TSH) with daily oral formulations of levothyroxine.
The Phase 2 study (NCT05823012) was a non-randomized, open-label, single arm, self-controlled study of XP-8121 (levothyroxine sodium) to determine a target dose conversion factor from stably dosed oral levothyroxine to XP-8121 (levothyroxine sodium) in 46 patients with hypothyroidism and to assess the safety and tolerability of XP-8121 (levothyroxine sodium) after once-weekly SC injections. The Phase 2 study leveraged the bioavailability observations of a previous Phase 1 study in which PK analysis showed that participants could achieve comparable systemic exposure with XP-8121 at only 57% of a weekly oral dose. The Phase 2 study included the following periods: Screening, Titration Period (2 to 8 weeks), and Maintenance Period (4 weeks). Participants entered the study on a stable oral dose (≥ 3 months) with normal TSH and free T4 laboratory values.
Participants were receiving a daily oral levothyroxine dose of 83.7 ± 31.14 mcg (mean ± SD) at study entry. To ensure the safety of study participants, once-weekly SC injection of XP-8121 was initiated at 2X their daily dose and titrated every 2 weeks to a target of 4X their daily dose. Participants completing the Maintenance Period were receiving a weekly XP-8121 dose of 324.4 ± 125.59 mcg. The geometric mean ratio of the once-weekly dose of XP-8121 to the daily dose levothyroxine (aka dose conversion factor) was 4.02 [90% CI 3.79, 4.27]. A total of 30 participants (65.2%) experienced at least 1 TEAE (Treatment Emergent Adverse Event) with most rated mild (87%) and moderate (13%) in severity. The most frequent (> 2 participants) TEAE included fatigue (21.7%), injection site pain (10.9%), headache (8.7%) and urinary tract infection (6.5%). No deaths or other serious adverse events (SAEs) were reported. Injection site tolerability was assessed with every SC administration of XP-8121 (> 450 injections). There were very few reports of discomfort (18%; mostly mild intensity), erythema (7%; Draize scale) or edema (1%; Draize scale). No participant discontinued from the study due to an injection site reaction. The Treatment Satisfaction Questionnaire for Medication (TSQM-9) was administered to assess patient satisfaction. XP-8121 scored consistently higher in all three domains (effectiveness, convenience, and global satisfaction) compared to oral levothyroxine. At the conclusion of the study, participants were asked to rate preference for once-weekly XP-8121. A majority (72%) indicated a strong preference for the SC route of administration based on categorical attributes of convenience (60.6%), ease of administration (45.5%), frequency of administration (54.5%), level of compliance (27.3%) and confidence in therapy (36.4%).
“A 2022 study published in the Journal of the Endocrine Society estimated the prevalence of hypothyroidism in the U.S. grew to 11.7% or approximately 30 million adults in 2019*. Innumerable reports have been published documenting the various compliance and absorption challenges that can interfere with the bioavailability of oral levothyroxine. Interestingly, in our own Phase 2 study, 40% of patients considered stable at the time of screening were found to have their TSH or T4 outside of normal range. We believe our once-weekly SC injection can enable control in patients who struggle with oral preparations for a variety of reasons,” said Paul R. Edick, Xeris’ Chairman and CEO.
“We are excited by the initial top line results of our Phase 2 dose-finding study of XP-8121. These results are further evidence of our target dose conversion and consistent with the estimates generated from the prior Phase 1 study in healthy volunteers,” said Kenneth E. Johnson, PharmD, Xeris’ Senior Vice President, Global Development and Medical Affairs. “Given the known challenges of oral bioavailability of levothyroxine and further by the high rate of screen failures observed in our phase 2 study, we believe that XP-8121 could fill a substantial unmet medical need. We look forward to meeting with the FDA later this year and expect to present complete study results at upcoming medical meetings as well as submission to peer-reviewed medical journals.”
About Hypothyroidism
Hypothyroidism, or underactive thyroid, happens when your thyroid gland doesn't make enough thyroid hormones to meet your body's needs. Your thyroid is a small, butterfly-shaped gland in the front of your neck. It makes hormones that control the way the body uses energy. These hormones affect nearly every organ in your body and control many of your body's most important functions. For example, they affect your breathing, heart rate, weight, digestion, and moods. Without enough thyroid hormones, many of your body's functions slow down.
About Levothyroxine
Therapeutically, levothyroxine is administered when the body is deficient in the endogenous hormone. Administration of levothyroxine is thus indicated for acquired thyroid disease (primary hypothyroidism), in cases of decreased secretion of TSH from the anterior pituitary gland (secondary hypothyroidism), and in cases of decreased secretion of TRH from the hypothalamus (tertiary hypothyroidism) and for congenital hypothyroidism. In most patients, hypothyroidism is a permanent condition requiring lifelong treatment. The goal of therapy is restoration of the euthyroid state, which can reverse the clinical manifestations of hypothyroidism and significantly improve quality of life.
About XeriSol™
The proprietary XeriSol™ non-aqueous formulation technology platform is designed to address the limitations of aqueous formulations for peptide and small molecule drugs. The solutions are formulated using biocompatible, non-aqueous solutions that impart high stability and solubility to drugs allowing for development of room temperature stable, ready-to-use formulations. XeriSol™ formulations have been used extensively in global commercial products (Gvoke®/Ogluo®) and clinical trials. The technology is protected by an extensive patent estate, trade secrets and know-how, and it is available for licensing.
About Xeris
Xeris (Nasdaq: XERS) is a growth-oriented biopharmaceutical company committed to improving patient lives by developing and commercializing innovative products across a range of therapies. Xeris has three commercially available products; Gvoke®, a ready-to-use liquid glucagon for the treatment of severe hypoglycemia, Keveyis®, a proven therapy for primary periodic paralysis, and Recorlev® for the treatment of endogenous Cushing’s syndrome. Xeris also has a robust pipeline of development programs to extend the current marketed products into important new indications and uses and bring new products forward using its proprietary formulation technology platforms, XeriSol™ and XeriJect®, supporting long-term product development and commercial success.
Xeris Biopharma Holdings is headquartered in Chicago, IL. For more information, visit www.xerispharma.com, or follow us on X, LinkedIn, or Instagram.
View source version on businesswire.com: https://www.businesswire.com/news/home/20240530612890/en/
Source: Xeris Biopharma Holdings, Inc.
Xeris stock jumps 14% on Phase 2 data for injected levothyroxine
May 30, 2024 10:29 AM ET
Xeris Biopharma Holdings, Inc. (XERS) Stock
By: Val Brickates Kennedy, SA News Editor4 Comments
Shares of Xeris Biopharma (NASDAQ:XERS) jumped 14% Thursday morning after the company reported positive topline data from a Phase 2 study of its drug XP-8121, a once-weekly, subcutaneous formulation of the drug levothyroxine for the treatment of hypothyroidism.
The product is formulated using Xeris’s XeriSol technology. Xeris said patients in the study showed normalized TSH/T4 levels using 45% less medication than would have been needed had they taken an oral formulation of the drug.
https://seekingalpha.com/news/4111602-xeris-stock-jumps-on-phase-2-data-for-injected-levothyroxine
Xeris Biopharma Holdings, Inc. (XERS) Stock
Datopotamab deruxtecan (Dato-DXd)
XeriSol™-Formulated Once-Weekly Subcutaneous (SC) Levothyroxine (XP-8121)
XeriSol™-Formulated Once-Weekly Subcutaneous (SC) Levothyroxine (XP-8121)
Datopotamab deruxtecan showed clinically meaningful overall survival improvement vs. chemotherapy in patients with advanced nonsquamous non-small cell lung cancer in TROPION-Lung01 Phase III trial
PUBLISHED27 May 2024
This announcement contains inside information
In the overall trial population, survival results numerically favoured AstraZeneca and Daiichi Sankyo’s datopotamab deruxtecan but did not reach statistical significance
TROPION-Lung01 previously met the dual primary endpoint
of progression-free survival in the overall trial population
Results support applications currently under review by
regulatory authorities globally including in the US and EU
High-level overall survival (OS) results from the TROPION-Lung01 Phase III trial, which previously met the dual primary endpoint of progression-free survival (PFS), numerically favoured datopotamab deruxtecan (Dato-DXd) compared to docetaxel in the overall trial population of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) treated with at least one prior line of therapy. Survival results did not reach statistical significance in the overall trial population. In the prespecified subgroup of patients with nonsquamous NSCLC, datopotamab deruxtecan showed a clinically meaningful improvement in OS compared to docetaxel, the current standard-of-care chemotherapy.
The final analysis of OS builds on the positive progression-free survival (PFS) results presented at the 2023 European Society for Medical Oncology Congress which showed datopotamab deruxtecan demonstrated a statistically significant improvement in PFS in the overall trial population and a clinically meaningful PFS benefit in patients with nonsquamous NSCLC. In TROPION-Lung01, patient enrolment by tumour histology was balanced across treatment arms and consistent with real-world incidence with approximately 75% of patients having nonsquamous NSCLC.1,2
The safety profile of datopotamab deruxtecan in TROPION-Lung01 was consistent with the previous analysis including fewer dose reductions or discontinuations due to adverse events compared to docetaxel, and no new safety concerns identified. No new interstitial lung disease events of any grade were adjudicated as drug-related.
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “Datopotamab deruxtecan is the only investigational therapy to show a clinically meaningful survival improvement in patients with previously treated nonsquamous non-small cell lung cancer versus docetaxel, which has long been unsurpassed in this post-targeted treatment and post-immunotherapy setting. These results reinforce the potential for datopotamab deruxtecan to replace conventional chemotherapy in this late-line setting and underscore our confidence in ongoing trials evaluating this therapy in first-line lung cancer.”
Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: “The improvement in overall survival seen with datopotamab deruxtecan coupled with the previously reported clinically meaningful progression-free survival, more than doubling of overall response and prolonged duration of response compared to docetaxel suggest that this TROP2-directed antibody drug conjugate could potentially become an important new treatment for patients with nonsquamous non-small cell lung cancer in this advanced setting. These data will support our ongoing discussions with regulatory authorities globally to potentially bring datopotamab deruxtecan to patients as quickly as possible and mark another step forward in creating new standards of care for patients with cancer.”
Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate discovered by Daiichi Sankyo and being jointly developed by AstraZeneca and Daiichi Sankyo.
The data will be presented at a forthcoming medical meeting and will support regulatory applications currently under review globally, including in the US and EU for the treatment of adult patients with locally advanced or metastatic nonsquamous NSCLC who have received prior systemic therapy.
Notes
Advanced non-small cell lung cancer
Nearly 2.5 million lung cancer cases were diagnosed globally in 2022.3 NSCLC is the most common type of lung cancer, accounting for about 80% of cases.4 Approximately 75% and 25% of NSCLC tumours are of nonsquamous or squamous histology, respectively.1 While immunotherapy and targeted therapies have improved outcomes in the 1st-line setting, most patients eventually experience disease progression and receive chemotherapy.5-7 For decades, chemotherapy has been the last treatment available for patients with advanced NSCLC, despite limited effectiveness and known side effects.5-7
TROP2 is a protein broadly expressed in the majority of NSCLC tumours.8 There is currently no TROP2-directed ADC approved for the treatment of lung cancer.9,10
TROPION-Lung01
TROPION-Lung01 is a global, randomised, multicentre, open-label Phase III trial evaluating the efficacy and safety of datopotamab deruxtecan (6.0mg/kg) versus docetaxel (75mg/m2) in adult patients with locally advanced or metastatic NSCLC with and without actionable genomic alterations who require systemic therapy following prior treatment. Patients with actionable genomic alterations were previously treated with platinum-based chemotherapy and an approved targeted therapy. Patients without known actionable genomic alterations were previously treated, concurrently or sequentially, with platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor.
The dual primary endpoints of TROPION-Lung01 are PFS as assessed by blinded independent central review (BICR) and OS. Key secondary endpoints include investigator-assessed PFS, objective response rate, duration of response, time to response, disease control rate as assessed by both BICR and investigator, and safety.
TROPION-Lung01 enrolled approximately 600 patients in Asia, Europe, North America and South America. For more information visit ClinicalTrials.gov.
Datopotamab deruxtecan (Dato-DXd)
Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, datopotamab deruxtecan is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programmes in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanised anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.
A comprehensive global clinical development programme is underway with more than 20 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, triple-negative breast cancer and HR-positive, HER2-negative breast cancer.
Daiichi Sankyo collaboration
AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise Enhertu in March 2019 and datopotamab deruxtecan in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and datopotamab deruxtecan.
AstraZeneca in lung cancer
AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and investigating innovative approaches, the Company aims to match medicines to the patients who can benefit most.
The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including Tagrisso (osimertinib) and Iressa (gefitinib); Imfinzi (durvalumab) and Imjudo (tremelimumab); Enhertu (trastuzumab deruxtecan) and datopotamab deruxtecan in collaboration with Daiichi Sankyo; Orpathys (savolitinib) in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action.
AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment.
AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.
The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.
AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca.
https://seekingalpha.com/symbol/AZN
Acoramidis
XeriSol™-Formulated Once-Weekly Subcutaneous (SC) Levothyroxine (XP-8121)
AFM24 WITH ATEZOLIZUMAB
additional data showing acoramidis increases serum transthyretin which is associated with improved cardiovascular outcomes presented at isa from bridgebio pharma’s phase 3 attribute-cm study in transthyretin amyloid cardiomyopathy (attr-cm)
05.29.2024 at 4:01 PM EDT
- Acoramidis treatment resulted in increased serum transthyretin (TTR) levels by Day 28 that were sustained and were correlated with a reduced risk of all-cause mortality (ACM), cardiovascular mortality (CVM), and cardiovascular-related hospitalization (CVH) in ATTR-CM participants through month 30
- Acoramidis treatment resulted in a significant improvement in the composite endpoint of CVM and CVH in ATTR-CM participants, with benefit evident as early as Month 3
- In ATTRibute-CM, participants with at least one CVH had a significantly higher risk of mortality, highlighting the need for ATTR-CM treatments that reduce risk of CVH
- BridgeBio also shared the rationale and design of ACT-EARLY, the acoramidis ATTR amyloidosis prevention trial, which it expects to initiate later this year
- BridgeBio will host an investor call on Wednesday, May 29, 2024 at 5:30 pm ET, with presentations from Mathew Maurer, M.D., of Columbia University Irving Medical Center, U.S., and Ahmad Masri, M.D., M.S., of Oregon Health & Science University, U.S.
PALO ALTO, Calif., May 29, 2024 (GLOBE NEWSWIRE) -- BridgeBio Pharma, Inc. (Nasdaq: BBIO) (“BridgeBio” or the “Company”), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, announced positive results of five new analyses of clinical endpoint events from its Phase 3 ATTRibute-CM study of acoramidis in ATTR-CM. These new analyses were shared in oral presentations and posters at the 2024 International Symposium of Amyloidosis (ISA). ATTRibute-CM was designed to study the efficacy and safety of acoramidis, an investigational, next-generation, orally administered, highly potent, small molecule stabilizer of TTR.
BridgeBio will host an investor call on Wednesday, May 29th at 5:30 pm ET to discuss these results.
“The data presented at ISA confirm that improved stabilization as reflected in higher serum TTR levels is directly correlated with improved clinical outcomes. Prior analyses from ATTRibute-CM demonstrated that the near-complete stabilization by acoramidis rapidly and durably increased serum TTR levels. Clinically, we now have evidence that acoramidis-mediated increase in serum TTR independently predicted statistically significant improvement in survival, and risk reduction of CVM and CVH,” said Mathew Maurer M.D. of Columbia University Irving Medical Center, U.S.
Three analyses presented from ATTRibute-CM emphasized the correlation between increased serum TTR and improved clinical outcomes, including the reduced risk of both all-cause mortality and cardiovascular death as well as cardiovascular-related hospitalization:
- Early increase in serum transthyretin level is an independent predictor of improved survival in ATTR cardiomyopathy: Insights from acoramidis Phase 3 study ATTRibute-CM, presented by Mathew Maurer, M.D., Columbia University Irving Medical Center, U.S.
- Statistically significant correlation between increasing serum TTR and decreasing risk of death: for every 5mg/dL increase in serum TTR level at day 28 after treatment initiation, the risk of death through Month 30 was reduced by 30.9% (by the logistic model) and 26.1% (by the Cox proportional hazards model)
- Statistical modeling suggests that the acoramidis-mediated increase in serum TTR at Day 28 is an independent predictor of survival
- Treatment-related early increase in serum TTR is associated with lower cardiovascular mortality in ATTR-CM: Insights from ATTRibute-CM, presented by Nitasha Sarswat, M.D., University of Chicago Medicine, U.S.
- For each 1 mg/dL increase in serum TTR on day 28 after treatment initiation, there was a 5.5% risk reduction in cardiovascular death observed through Month 30
- To the company’s knowledge, this is the first prospective demonstration of the relationship between change from baseline in serum TTR and subsequent risk of cardiovascular death in ATTR-CM
- Acoramidis treatment-related increase in serum TTR is associated with a lower risk of cardiovascular-related hospitalization in ATTR-CM Patients: Insights from the ATTRibute-CM trial, presented by Margot Davis, M.D., Vancouver General Hospital, CA
- Each 1 mg/dL serum TTR increase at Day 28 after treatment initiation was associated with a 4.7% lower risk of a first cardiovascular hospitalization over 30 months
- The analysis, the first from a prospective study of the relationship between change from baseline in TTR and subsequent risk of first CVH in ATTR, demonstrated that a greater increase in TTR is significantly associated with a lower risk of CVH
- The Kaplan-Meier curves for time to first CVH were also presented; the curves separated early, showing treatment benefit at Month 3 and continuing to separate through Month 30
The results from the analysis highlighting the early reduction in cardiovascular mortality (CVM) or CVH in ATTR in the ATTRibute-CM trial were shared by Kevin M. Alexander, M.D., Stanford University School of Medicine, U.S., in an oral presentation. Key findings included:
- Acoramidis time-to-first event Kaplan-Meier (K-M) curves for a composite of CVM and CVH in ATTR-CM patients separated beginning at Month 3, representing an early and profound reduction on the composite endpoint of CVM and CVH in ATTR-CM patients, with a 15.2% absolute risk reduction and a 38.2% hazard reduction by Month 30 (p=0.0003).
On behalf of the authors, John Whang, M.D., Chief Medical Affairs Officer of BridgeBio Cardiorenal, presented data showing a higher risk of mortality in previously hospitalized participants. Insights included:
- Participants with no CVH during the study had a 30-month survival rate of 86.7%, vs 60.1% in participants who had at least one CVH during the study
- To the company’s knowledge, this is the first time a prospective trial demonstrates that CVH portends a higher subsequent mortality in ATTR-CM patients
- This suggests that effective treatments to reduce CVH risk are critically important, and a targeted therapy for ATTR-CM that reduces CVH can improve the prognosis of patients with ATTR-CM
The rationale and design of ACT-EARLY, the acoramidis TTR amyloidosis prevention trial, was also presented by Pablo Garcia-Pavia, M.D., Ph.D., Iron Gate Majadahonda University Hospital, ES. ACT-EARLY will be the first Phase 3 trial to evaluate prophylactic therapy for the prevention or delay of ATTR amyloidosis in asymptomatic pathogenic TTR variant carriers with study initiation planned in 2024.
Jonathan Fox, M.D., Ph.D., President and Chief Medical Officer of BridgeBio Cardiorenal, shared the following: “The totality of acoramidis data across clinical outcomes, biomarkers, quality of life, and cardiac imaging continues to expand with the analyses shared at ISA and the data recently presented at ACC and ESC-HF. We remain encouraged by the potential benefits of targeting near-complete TTR stabilization, the resulting increases in serum TTR, and the corresponding statistically significant benefits on clinical event outcomes. We are committed to bringing acoramidis to the ATTR-CM community as quickly as possible, working toward our November 29th PDUFA date.”
Additionally, BridgeBio presented six encore poster presentations on its ATTRibute-CM data, which were previously shared at the European Society of Cardiology Heart Failure (ESC-HF) Congress 2024, the American College of Cardiology (ACC) Annual Scientific Sessions & Expo 2024 and the American Heart Association (AHA) Scientific Sessions 2023.
Based on the positive results from ATTRibute-CM, BridgeBio submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration, which has been accepted with a Prescription Drug User Fee Act (PDUFA) action date of November 29, 2024, and a Marketing Authorization Application (MAA) to the European Medicines Agency, with a decision expected in 2025.
Webcast Information
BridgeBio will host an investor call and simultaneous webcast to discuss the recent analyses and positive data from the ATTRibute-CM Phase 3 trial and emerging real-world evidence in ATTR-CM presented at the 2024 ISA, ESC Heart Failure 2024 and the 2024 ACC Annual Scientific Sessions & Expo on Wednesday, May 29 at 5:30 pm ET. A link to the webcast may be accessed from the event calendar page of BridgeBio’s website at https://investor.bridgebio.com/. A replay of the conference call and webcast will be archived on the Company’s website and will be available for at least 30 days following the event.
About BridgeBio Pharma, Inc.
BridgeBio Pharma Inc. (BridgeBio) is a commercial-stage biopharmaceutical company founded to discover, create, test, and deliver transformative medicines to treat patients who suffer from genetic diseases and cancers with clear genetic drivers. BridgeBio’s pipeline of development programs ranges from early science to advanced clinical trials. BridgeBio was founded in 2015 and its team of experienced drug discoverers, developers, and innovators are committed to applying advances in genetic medicine to help patients as quickly as possible. For more information visit bridgebio.com and follow us on LinkedIn and Twitter.
BridgeBio reports additional positive data for acoramidis in ATTR-CM
May 29, 2024 5:11 PM ET
BridgeBio Pharma, Inc. (BBIO) StockPFE
By: Val Brickates Kennedy, SA News Editor
BridgeBio (NASDAQ:BBIO) released additional positive data for its drug acoramidis in the treatment of ATTR-CM, a type of heart failure.
The biotech company said the data included the results of five new analyses of clinical data endpoint events from its Phase 3 study of the drug called ATTRibute-CM.
BridgeBio Pharma, Inc. (BBIO) Stock
AFM24 WITH ATEZOLIZUMAB
RETEVMO® (selpercatinib)
AFM24 WITH ATEZOLIZUMAB
AFFIMED RECEIVES FAST TRACK DESIGNATION FOR COMBINATION THERAPY OF AFM24 WITH ATEZOLIZUMAB FOR EGFR WILD-TYPE NON-SMALL CELL LUNG CANCER
Press Release - May 29, 2024
- Efficacy and safety of AFM24 in combination with atezolizumab, a checkpoint inhibitor, is being evaluated in non-small cell lung cancer patients with EGFR wild-type and EGFR mutant advanced/metastatic cancers in the ongoing AFM24-102 phase 1/2a study
- The FDA’s Fast Track designation was granted after its review of the initial efficacy data of the EGFR wild-type cohort from the AFM24-102 study
- Fast Track is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need
- Company to host a conference call / webcast on June 1, 2024 at 7:00 p.m. EDT to discuss the updated data from the AFM24-102 trial
MANNHEIM, Germany, May 29, 2024 (GLOBE NEWSWIRE) — Affimed N.V. (Nasdaq: AFMD), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, today announced that the FDA has granted Fast Track designation to the combination of its innate cell engager (ICE®) AFM24 with atezolizumab for the treatment of patients with advanced and/or metastatic non-small cell lung cancer (NSCLC) not harboring any activating EGFR mutations (EGFR wild-type) after progression on PD-(L)1 targeted therapy and platinum-based chemotherapy. Data from the AFM24-102 study in this patient population will be presented at the upcoming annual meeting of the American Society of Clinical Oncology on June 1, 2024.
“The clinical data of AFM24 in combination with the checkpoint inhibitor atezolizumab is compelling. We’re observing meaningful responses in patients resistant to prior checkpoint inhibitor treatment,” said Dr. Wolfgang Fischer, Chief Operating Officer at Affimed. “The Fast Track designation emphasizes the belief in the potential of this combination therapy to address currently unmet needs of patients with this devastating, life threatening disease who have exhausted all standard of care options, including chemotherapy and checkpoint inhibitors.”
Fast Track is a process designed to facilitate the development and expedite the review of new drugs that are intended to treat or prevent serious conditions and have the potential to address an unmet medical need. The FDA’s decision is based on initial activity observed in the first evaluable patients of the phase 2 part of the AFM24-102 study of AFM24 in combination with atezolizumab in heavily pretreated patients with NSCLC EGFRwt. With the Fast Track designation, the therapeutic development of the combination can benefit from more frequent engagement with the FDA, which will support the collection of appropriate data needed to accelerate its development.
About FDA Fast Track Designation
Fast Track is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. Its purpose is to get important new drugs to patients earlier. Fast Track addresses a broad range of serious conditions. With Fast Track designation, a new therapy is eligible for some or all of the following:
- More frequent meetings with FDA to discuss the drug’s development plan and ensure collection of appropriate data needed to support drug approval
- More frequent written communication from FDA about such things as the design of the proposed clinical trials and use of biomarkers
- Eligibility for Accelerated Approval and Priority Review, if relevant criteria are met
- Rolling Review, which means that a drug company can submit completed sections of its Biologic License Application (BLA) or New Drug Application (NDA) for review by FDA, rather than waiting until every section of the NDA is completed before the entire application can be reviewed. BLA or NDA review usually does not begin until the drug company has submitted the entire application to the FDA.
Please refer to Fast Track | FDA for further information.
Conference Call and Webcast Information
Affimed will host a conference call and webcast for the financial community on June 1, 2024, at 6:00 p.m. CDT / 7:00 p.m. EDT. The conference call will be available via phone and webcast. The live audio webcast of the call will be available in the “Webcasts” section on the “Investors” page of the Affimed website at https://www.affimed.com/investors/webcasts-and-corporate-presentation/. To access the call by phone, please use link:
https://register.vevent.com/register/BIff607338e5d247f99b548240be2ad413, and you will be provided with dial-in details and a pin number.
About AFM24
AFM24 is a tetravalent, bispecific ICE® that activates the innate immune system by binding to CD16A on innate immune cells and epidermal growth factor receptors (EGFR), a protein widely expressed on solid tumors, to kill cancer cells. Generated by Affimed’s fit-for-purpose ROCK® platform, AFM24 represents a distinctive mechanism of action that uses EGFR as a docking site to engage innate immune cells for tumor cell killing through antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis.
About Affimed N.V.
Affimed (Nasdaq: AFMD) is a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer by actualizing the untapped potential of the innate immune system. The Company’s innate cell engagers (ICE®) enable a tumor-targeted approach to recognize and kill a range of hematologic and solid tumors. ICE® are generated on the Company’s proprietary ROCK® platform which predictably generates customized molecules that leverage the power of innate immune cells to destroy tumor cells. A number of ICE® molecules are in clinical development, being studied as mono- or combination therapy. Headquartered in Mannheim, Germany, Affimed is led by an experienced team of biotechnology and pharmaceutical leaders united by the bold vision to stop cancer from ever derailing patients’ lives. For more about the Company’s people, pipeline and partners, please visit: www.affimed.com.
Affimed gets FDA fast track status for AFM24 for EGFR lung cancer
May 29, 2024 10:25 AM ET
By: Val Brickates Kennedy, SA News Editor1 Comment
Affimed (NASDAQ:AFMD) said it has received fast track designation from the FDA for its drug candidate AFM24 in combination with atezolizumab in the treatment of EGFR wild-type non-small cell lung cancer.
AFM24 in combination with atezolizumab is currently being evaluated in a Phase 1/2 study for the treatment of EGFR wild-type and EGFR mutant advanced/metastatic non-small cell lung cancers, according to Affimed.
RETEVMO® (selpercatinib)
RETEVMO® (selpercatinib)
RETEVMO® (selpercatinib)
FDA grants accelerated approval to selpercatinib for pediatric patients two years and older with RET-altered metastatic thyroid cancer or solid tumors
On May 29, 2024, the Food and Drug Administration granted accelerated approval to selpercatinib (Retevmo, Eli Lilly and Company) for pediatric patients two years of age and older with the following:
- advanced or metastatic medullary thyroid cancer (MTC) with a RET mutation, as detected by an FDA-approved test, who require systemic therapy;
- advanced or metastatic thyroid cancer with a RET gene fusion, as detected by an FDA-approved test, who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate); and
- locally advanced or metastatic solid tumors with a RET gene fusion, as detected by an FDA-approved test, that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options.
- https://retevmo.lilly.com/
This is the first FDA approval of a targeted therapy for pediatric patients < 12 years of age with RET alterations. Selpercatinib was previously granted accelerated approval for the thyroid cancer indications in adults and pediatric patients 12 years of age and older. It also was previously granted accelerated approval for the solid tumor indication in adults.
Full prescribing information for Retevmo will be posted here.
Efficacy in pediatric and young adult patients was evaluated in LIBRETTO-121 (NCT03899792), an international, single-arm, multi-cohort trial. Patients received selpercatinib, 92 mg/m2 orally twice daily, until disease progression, unacceptable toxicity, or other reason for treatment discontinuation. The primary efficacy population included 25 patients ages 2 to 20 with locally advanced or metastatic RET-activated solid tumors non-responsive to available therapies or with no standard systemic curative therapy available.
The major efficacy outcome measures were confirmed overall response rate (ORR) and duration of response (DOR). The confirmed ORR (RECIST 1.1), as determined by blinded independent review committee was 48% (95% CI: 28, 69). The median DOR was not reached (95% CI: not evaluable [NE], NE), with 92% of responders remaining in response at 12 months. Durable responses were observed in pediatric and young adult patients with RET-mutant MTC (n=14; ORR 43% [95% CI: 18%, 71%]) and RET fusion-positive thyroid cancer (n=10; ORR 60% [95% CI: 26%, 88%]).
The most common adverse reactions (≥25%) were musculoskeletal pain, diarrhea, headache, nausea, vomiting, coronavirus infection, abdominal pain, fatigue, pyrexia, and hemorrhage. The most common Grade 3 or 4 laboratory abnormalities (≥5%) were decreased calcium, decreased hemoglobin, and decreased neutrophils.
The recommended selpercatinib dose for pediatric patients 2 to less than 12 years of age is based on body surface area. It is based on weight for patients 12 years of age and older. See the prescribing information for specific dosing information.
LIBRETTO-121 was conducted as part of a pediatric Written Request (WR) under the Best Pharmaceuticals for Children Act (BPCA).
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted priority review and orphan drug designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.
Follow the Oncology Center of Excellence on X (formerly Twitter) @FDAOncologyExternal Link Disclaimer.
Lilly's Retevmo gains approval for children as young as two with thyroid cancer
May 29, 2024 12:32 PM ET
Eli Lilly and Company (LLY) Stock
By: Jonathan Block, SA News Editor
- The U.S. FDA has granted accelerated approval to Eli Lilly's (NYSE:LLY) Retevmo (Selpercatinib) for pediatric patients two and older for thyroid cancer.
- The drug was already approved for patients 12 years and older for thyroid cancer with a type of genetic mutation or gene fusion.
- https://seekingalpha.com/news/4111200-lilly-retevmo-gains-approval-children-as-young-as-two-thyroid-cancer?mailingid=35535011&messageid=2900&serial=35535011.343&utm_campaign=rta-stock-news&utm_content=link-1&utm_medium=email&utm_source=seeking_alpha&utm_term=35535011.343
- Eli Lilly and Company (LLY) Stock
- https://www.lilly.com/
- https://retevmo.lilly.com/
SELTOREXANT
RETEVMO® (selpercatinib)
RETEVMO® (selpercatinib)
Johnson & Johnson pivotal study of seltorexant shows statistically significant and clinically meaningful improvement in depressive symptoms and sleep disturbance outcomes
Seltorexant, an investigational first-in-class therapy, met all primary and secondary endpoints in pivotal Phase 3 study in patients with major depressive disorder (MDD) with insomnia symptoms, as presented at ASCP 2024
Approximately 60 percent of MDD patients on standard-of-care oral antidepressants experience residual insomnia symptoms1, underscoring the high level of unmet need
Positive topline results for SPRAVATO® (esketamine) CIII nasal spray as a monotherapy were also presented, demonstrating rapid and sustained efficacy in treatment-resistant depression (TRD)
May 29, 2024Share
Titusville, New Jersey (May 29, 2024) – Johnson & Johnson announced today positive topline results from the pivotal Phase 3 MDD3001 clinical trial evaluating the efficacy and safety of seltorexant as an adjunctive treatment to baseline antidepressants in adult and elderly patients with major depressive disorder (MDD) with insomnia symptoms. Seltorexant is an investigational first-in-class selective antagonist of the human orexin-2 receptor being studied for the adjunctive treatment of MDD with insomnia symptoms. The findings will be presented at this year’s American Society of Clinical Psychopharmacology (ASCP) Annual Meeting, which is being held from May 28-31 in Miami, Florida.
The Phase 3 randomized, double-blind, multicenter, placebo-controlled study achieved all primary and secondary endpoints, with seltorexant demonstrating both a statistically significant and clinically meaningful improvement in depressive symptoms based on the Montgomery-Asberg Depression Rating Scale (MADRS) total score at day 43, and improved sleep disturbance outcomes, in patients who had a prior inadequate response to SSRI/SNRI antidepressants alone. These results were observed in a patient population that was assessed to be moderately-to-severely depressed despite ongoing treatment with SSRI/SNRIs and suffered from significant sleep disturbance. Seltorexant was also safe and well-tolerated in the study, with similar rates of common adverse events seen in both trial arms, consistent with previous seltorexant clinical trials.
“Depression is a leading cause of disability worldwide and shares a strong link with sleep disturbances. In MDD, insomnia symptoms exacerbate the risk of depressive relapse, increase healthcare costs and impact quality of life, and it often goes under treated despite being one of the most common residual symptoms2,3,4,” said Andrew Krystal, MD, Professor, Psychiatry, University of California, San Francisco Weill Institute for Neurosciences. “Seltorexant has the potential to fill a significant unmet need for new therapies to treat patients experiencing depression and insomnia, and most importantly, to improve outcomes and quality of life for these patients.”
MDD is often accompanied by sleep disturbances such as insomnia or hypersomnia. With insomnia, patients may have trouble falling asleep, staying asleep, or getting good quality sleep. Approximately 60 percent of MDD patients on standard-of-care oral antidepressants experience residual insomnia symptoms.1 Currently, no therapies are approved to treat MDD with insomnia symptoms.
“For nearly seven decades, Johnson & Johnson has delivered transformational treatments and solutions for people living with serious mental illness, and we are proud to present these data from our marketed and late-stage neuropsychiatry portfolios at ASCP,” said Bill Martin, Ph.D., Global Therapeutic Area Head, Neuroscience. “As global leaders, we must continue to drive innovation in the treatment of depression, bringing new mechanisms of action and potentially first-in-class therapies to the millions of people living with mental health disorders.”
DELIVERING RAPID AND SUSTAINED EFFICACY FOR TREATMENT-RESISTANT DEPRESSION (TRD)
Additional data presented at ASCP includes positive topline results from the placebo-controlled Phase 4 TRD4005 study of SPRAVATO® (esketamine) CIII nasal spray as a monotherapy in patients with TRD, which met both its primary and secondary endpoints. The randomized, double-blind, multicenter study showed SPRAVATO® provided rapid, statistically significant, and clinically meaningful improvement in depressive symptoms ~24 hours after the first dose and sustained through 4 weeks of treatment, as assessed by changes in MADRS total score.
The safety profile of SPRAVATO® monotherapy was consistent with the registration Phase 3 studies of TRD in combination with an oral antidepressant, and no new safety concerns were identified.
SPRAVATO® is approved by the U.S. Food and Drug Administration (FDA), in combination with an oral antidepressant, for adults with TRD and depressive symptoms in adults with MDD with suicidal thoughts or behaviors. With its approval in 2019, SPRAVATO® offered the first novel mechanism of action in decades for the treatment of MDD. To date, SPRAVATO® has been administered to more than 100,000 people living with challenging-to-treat forms of depression around the world.
Other accepted data at ASCP showcase our innovative data science usage in MDD research, including leveraging machine learning and similar measures that support our precision approach to neuropsychiatry. A complete listing of Company-sponsored abstracts can be viewed here.
ABOUT SELTOREXANT
Seltorexant, an investigational first-in-class therapy, is a selective antagonist of the human orexin-2 receptor currently being developed as an adjunctive treatment for adults with MDD with insomnia symptoms. Seltorexant selectively antagonizes the orexin-2 receptors, potentially improving mood and sleep symptoms associated with depression. When orexin-2 receptors are stimulated for too long or at inappropriate times, their activation can cause hyperarousal manifestations, including insomnia and excessive cortisol release, which may contribute to depression and insomnia.
ABOUT MDD3001
The Phase 3 MDD3001 study was a randomized, double-blind, multicenter, placebo-controlled study designed to compare the efficacy and safety of oral, once daily seltorexant 20 milligrams to that of placebo, adjunctive to background SSRI/SNRI, for improving depressive symptoms in adult and elderly patients with MDD with insomnia symptoms.
ABOUT MAJOR DEPRESSIVE DISORDER WITH INSOMNIA SYMPTOMS
MDD is one of the most common psychiatric disorders and leading causes of disability worldwide,5 with an estimated 280 million people living with the disorder around the world.6 MDD is often accompanied by sleep disturbances such as insomnia or hypersomnia, with approximately 60 percent of MDD patients experiencing insomnia symptoms despite being on an SSRI/SNRI.1 Disturbed sleep and insomnia symptoms have a significant impact on a patient’s quality of life and exacerbate the risk of depressive relapse and suicide.2,4
ABOUT SPRAVATO®
SPRAVATO® (esketamine) CIII nasal spray is approved by the U.S. Food and Drug Administration in combination with an oral antidepressant for adults with TRD and depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior. It is the first novel mechanism of action in decades for the treatment of MDD. SPRAVATO® is a non-selective, non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor and is believed to work differently by acting on a pathway in the brain that affects glutamate. To date, SPRAVATO® has been approved in 77 countries and administered to more than 100,000 patients worldwide.
ABOUT TRD4005
The Phase 4 TRD4005 clinical trial was a randomized, double-blind, multicenter, placebo-controlled study designed to evaluate the efficacy, safety, and tolerability of esketamine monotherapy at either 56 milligrams or 84 milligrams, administered bi-weekly, compared with placebo nasal spray in improving depressive symptoms in adult patients with TRD.
ABOUT TREATMENT-RESISTANT DEPRESSION
It is estimated that at least 30 percent of people living with MDD have treatment-resistant depression, which is defined as not responding to at least two or more different antidepressants of adequate dose and duration.7 TRD has a significant negative impact, emotionally and functionally, on the individual and their loved ones, and has one of the highest economic burdens of all psychiatric disorders.7
IMPORTANT SAFETY INFORMATION
What is SPRAVATO® (esketamine) CIII nasal spray?
SPRAVATO® is a prescription medicine, used along with an antidepressant taken by mouth to treat:
- Adults with treatment-resistant depression (TRD)
- Depressive symptoms in adults with major depressive disorder (MDD) with suicidal thoughts or actions
SPRAVATO® is not for use as a medicine to prevent or relieve pain (anesthetic). It is not known if SPRAVATO® is safe or effective as an anesthetic medicine.
It is not known if SPRAVATO® is safe and effective for use in preventing suicide or in reducing suicidal thoughts or actions. SPRAVATO® is not for use in place of hospitalization if your healthcare provider determines that hospitalization is needed, even if improvement is experienced after the first dose of SPRAVATO®.
It is not known if SPRAVATO® is safe and effective in children.
Please see full Prescribing Information, including Boxed WARNINGS, and Medication Guide for SPRAVATO® and discuss any questions you may have with your healthcare provider.
cp-170363v3
ABOUT JOHNSON & JOHNSON
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and where solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity.
Learn more at http://www.jnj.com or at https://www.janssen.com/johnson-johnson-innovative-medicine. Follow us at @JNJInnovMed.
Janssen Research & Development, LLC and Janssen Biotech, Inc. are both Johnson & Johnson companies.
© Johnson & Johnson 2024. All rights reserved.
Johnson & Johnson depression candidate seltorexant meets phase 3 goals
May 29, 2024 8:48 AM ET
By: Jonathan Block, SA News Editor2 Comments
- Johnson & Johnson's (NYSE:JNJ) seltorexant, a potentially first-in-class adjunctive treatment for depression, met primary and secondary endpoints in a phase 3 study in patients with co-occurring insomnia symptoms.
- https://seekingalpha.com/news/4111111-johnson-johnson-depression-candidate-seltorexant-meets-phase-3-goals?mailingid=35530920&messageid=2900&serial=35530920.21535&utm_campaign=rta-stock-news&utm_content=link-1&utm_medium=email&utm_source=seeking_alpha&utm_term=35530920.21535
- Johnson & Johnson (JNJ) Stock
- https://www.jnj.com/
- https://www.spravato.com/
biotecHOPE™ 2024
Atrasentan
Sarclisa (isatuximab-irfc) in combination with bortezomib
Avutometinib and Defactinib Combination
Novartis atrasentan Phase III data show clinically meaningful proteinuria reduction further advancing company's IgA nephropathy (IgAN) portfolio
May 25, 2024
- In the ALIGN study, atrasentan, in addition to supportive care with a renin-angiotensin system (RAS) inhibitor, demonstrated a statistically significant 36.1% proteinuria (protein in urine) reduction vs. placebo + supportive care at 36 weeks1
- Endothelin A (ETA) receptor activation contributes to elevated proteinuria in IgAN2-5; atrasentan is a potent, selective ETA receptor antagonist with potential to reduce persistent proteinuria and preserve kidney function for a broad patient population1
- IgAN is a heterogeneous, progressive, rare kidney disease with a need for effective, targeted therapies6,7; up to 30% of patients with persistent proteinuria (≥1 g/day) progress to kidney failure within 10 years8
- Through its rare kidney disease portfolio, Novartis is committed to exploring a range of treatment options with different modes of action to slow IgAN progression
Basel, May 25, 2024 –
Novartis today presented results from a pre-specified interim analysis of the Phase III ALIGN study of atrasentan, an investigational oral selective endothelin A (ETA) receptor antagonist, in patients with IgA nephropathy (IgAN)1. Patients treated with atrasentan, in addition to supportive care (maximally tolerated and stable dose of a renin-angiotensin system [RAS] inhibitor), achieved a 36.1% (p<0.0001) reduction in proteinuria (as measured by 24-hour urine protein to creatinine ratio [UPCR]) at 36 weeks when compared to placebo on top of supportive care1. The results were presented during a late-breaking clinical trials session at the European Renal Association (ERA) Congress1. The study also showed atrasentan has a favorable safety profile consistent with previously reported data1,9.
Proteinuria reduction is a recognized surrogate marker correlating with delaying progression to kidney failure and has been used as an endpoint in IgAN clinical trials to support accelerated regulatory approvals10. US FDA submission for atrasentan in IgAN is on track for the first half of 2024.
“For those living with IgAN and their families, the disease can have a significant impact not only physically, but also mentally. When my son Eddie was diagnosed with IgAN 20 years ago, there were no FDA-approved medicines developed to treat IgAN. That was as devastating as the diagnosis itself because we felt completely in the dark about how to manage the condition,” said Bonnie Schneider, Director and Co-Founder, IgAN Foundation. “It’s a disease that affects people differently, and what works for one person may not work for another. We’re pleased to see ongoing research into different treatments and are excited for a future where the community will have options to meet their individual needs."
The ALIGN study continues in a blinded manner, and therefore only limited interim analysis results can be presented11,12. The final analysis, including the key secondary endpoint of change from baseline in estimated glomerular filtration rate (eGFR) at 136 weeks, and the results in participants receiving a sodium-glucose co-transporter-2 (SGLT2) inhibitor as background care in an exploratory cohort, is expected in 202611,12.
“ETA receptor activation causes proteinuria, which is usually one of the first clinical signs of IgAN. Patients with persistent proteinuria have a poorer prognosis and are more likely to progress to kidney failure,” said Professor Hiddo Heerspink, Professor of Clinical Trials and Personalized Medicine at the Department of Clinical Pharmacy and Pharmacology at the University Medical Center Groningen and ALIGN blinded Steering Committee Chair. “We need targeted treatment options that can support patients with IgAN across the care pathway. These data from the ALIGN study further demonstrate the ability of atrasentan to significantly reduce proteinuria and, if approved, its potential to become a new foundational treatment for people living with IgAN that can be seamlessly added to current supportive therapy.”
“Atrasentan has the potential to help transform how IgAN is managed for many people living with this complex illness,” said David Soergel, M.D., Global Head, Cardiovascular, Renal and Metabolism Development Unit, Novartis. “Our multi-product IgAN portfolio aims to address the needs of a broad, heterogenous patient population with different modes of action to target distinct drivers of the disease, with the ultimate goal of improving patient care in this therapeutic area.”
At ERA, Novartis is also presenting new data across its rare disease portfolio, including 6-month data for Fabhalta® (iptacopan) in C3 glomerulopathy (C3G) from the Phase III APPEAR-C3G study, long-term 33-month efficacy and safety data for Fabhalta in C3G from the Phase II extension study, additional data for Fabhalta in IgAN from the 9-month interim analysis of the Phase III APPLAUSE-IgAN study, 1-year Phase I/II data for investigational zigakibart in IgAN, and data from real-world studies in C3G and atypical hemolytic uremic syndrome (aHUS)13-16.
About ALIGN
The ALIGN study (NCT04573478) is a global, randomized, multicenter, double-blind, placebo-controlled Phase III clinical trial comparing the efficacy and safety of atrasentan versus placebo in patients with IgAN at risk of progressive loss of kidney function11,12. In total, 340 patients with biopsy-proven IgAN with baseline total proteinuria ≥1 g/day despite optimized RAS inhibitor treatment were randomized to receive once-daily oral doses of atrasentan (0.75 mg) or placebo for approximately 2.5 years (132 weeks)11,12. Patients continue receiving a maximally tolerated and stable dose of a RAS inhibitor as supportive care (unless they are unable to tolerate RAS inhibitor therapy)11,12. An additional group of 64 patients receiving a stable dose of SGLT2 inhibitor for at least 12 weeks have also been enrolled11,12.
The primary efficacy endpoint of the study is change in proteinuria as measured by 24-hour UPCR from baseline to 36 weeks11,12. Secondary and exploratory objectives include evaluating the change in kidney function from baseline to 136 weeks as measured by eGFR, as well as safety and tolerability11,12.
About atrasentan
Atrasentan is an investigational potent and selective oral ETA receptor antagonist, currently in Phase III development for IgAN and early-stage development for other rare kidney diseases1,11,12,17. Activation of the ETA receptor contributes to elevated proteinuria, which is associated with kidney damage, fibrosis and loss of kidney function in IgAN2-5. Atrasentan has potential to be added to current supportive therapy to reduce persistent proteinuria and preserve kidney function for a broad patient population1. Preclinical models have also suggested that atrasentan may reduce inflammation and fibrosis in IgAN18-21.
About IgA nephropathy (IgAN)
IgAN is a heterogeneous, progressive, rare kidney disease6. Each year, approximately 25 people per million worldwide are newly diagnosed with IgAN22.
Up to 30% of people who have IgAN with persistent higher levels of proteinuria (≥1 g/day) may progress to kidney failure within 10 years8. There is a need for effective, targeted therapies for IgAN that can help slow or prevent progression to kidney failure6,7,23.
Novartis commitment in rare kidney diseases
At Novartis, our journey in nephrology began more than 40 years ago when the development and introduction of cyclosporine helped reimagine the field of transplantation and immunosuppression. We continue today with the same bold ambition to transform the lives of people living with kidney diseases.
Through our portfolio, we are exploring potential therapeutic options to address the current unmet needs of people living with rare diseases, including IgAN, C3G, aHUS, immune complex membranoproliferative glomerulonephritis (IC-MPGN) and lupus nephritis (LN). Innovative treatment options that target the underlying causes of these diseases may preserve kidney function and help people live longer without the need for dialysis or transplantation.
IgAN is a heterogeneous disease presenting with a variety of clinical manifestations, phenotypes, and variable speeds of progression6. In addition to atrasentan, Novartis is advancing the development of two other therapies in IgAN with highly differentiated mechanisms of action: Fabhalta, an investigational oral Factor B inhibitor of the alternative complement pathway, and zigakibart, an investigational subcutaneously administered anti-APRIL monoclonal antibody, which are both in Phase III development24-26. Through our IgAN pipeline, we are committed to creating a portfolio of innovative medicines that improve and extend the lives of people living with kidney disease.
About Novartis
Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach more than 250 million people worldwide.
Reimagine medicine with us: Visit us at https://www.novartis.com and connect with us on LinkedIn, Facebook, X/Twitter and Instagram.
Novartis reports Phase 3 results for IgA nephropathy treatment
May 28, 2024 9:44 AM ET
By: Val Brickates Kennedy, SA News Editor
Novartis (NYSE:NVS) reported interim results from a Phase 3 study of its drug candidate astrasentan in the treatment of IgA nephropathy, a rare type of kidney disease.
The Swiss drugmaker said the study showed a statistically significant 36.1% reduction in proteinuria, or protein in the urine, at 36 weeks in patients who received the treatment on top of supportive care versus those who received a placebo along with supportive care.
Novartis said reduction in proteinuria is recognized as a surrogate marker correlating with delaying the progression of kidney failure. The company has used reduction in proteinuria as an endpoint in the IgA nephropathy clinical trials to support accelerated regulatory approval.
https://seekingalpha.com/news/4110745-novartis-reports-phase-3-results-for-iga-nephropathy-treatment
https://www.novartis.com/research-development/novartis-pipeline
Avutometinib and Defactinib Combination
Sarclisa (isatuximab-irfc) in combination with bortezomib
Avutometinib and Defactinib Combination
MAY 24, 2024 AT 7:00 AM EDT
Verastem Oncology Announces the Initiation of a Rolling Submission of NDA to FDA Seeking Accelerated Approval of Avutometinib and Defactinib Combination for the Treatment of Adult Patients with Recurrent KRAS Mutant Low-Grade Serous Ovarian Cancer
Plan to complete NDA submission with the mature RAMP 201 dataset, anticipated to include 12 months of follow-up, in the second half of 2024
Plan to present the mature dataset from RAMP 201 at a medical conference in the second half of 2024
Avutometinib and defactinib combination have continued to show robust and durable response rates in ongoing RAMP 201 trial in patients with recurrent low-grade serous ovarian cancer
Company to host investor conference call and webcast on Friday, May 24, 2024 at 8:00 am EDT to provide update on RAMP 201 and rolling NDA submission
BOSTON--(BUSINESS WIRE)--May 24, 2024-- Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with cancer, today announced that it has initiated the rolling submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking accelerated approval of the combination of avutometinib, a RAF/MEK clamp, and defactinib, a selective FAK inhibitor, for adult patients with recurrent KRAS mutant (KRAS mt) low-grade serous ovarian cancer (LGSOC), who received at least one prior systemic therapy. The rolling review process allows the Company to submit completed sections of an application for review by the FDA before all sections become available. The initial sections of the application will include the nonclinical and quality sections. In discussions with the FDA, Verastem reached agreement to submit a primary efficacy analysis based on the RAMP 201 study with 12 months of follow up. Based on discussions with the FDA, we understand that the proposed indication for final submission of the clinical module can be expanded in the event Verastem provides data that demonstrates a substantial improvement over available therapy in the KRAS wild-type (KRAS wt) population. FDA has accepted Verastem’s plan to submit the clinical module in the second half of 2024 to complete the NDA application. Previously, the FDA granted Breakthrough Therapy Designation (BTD) for the combination for treatment of patients with recurrent LGSOC, regardless of KRAS status, following one or more previous lines of therapy and Orphan Drug Designation (ODD) for the combination in certain LGSOC indications. The Company plans to request a priority review of the NDA. Currently, there are no FDA-approved treatments specifically for recurrent LGSOC.
"The initiation of our rolling NDA submission of the avutometinib and defactinib combination for accelerated approval, is an important step towards addressing the significant unmet needs that patients face living with KRAS mutant low-grade serous ovarian cancer," said Dan Paterson, president and chief executive officer of Verastem Oncology. "The data from our ongoing RAMP 201 trial continues to support our belief that the avutometinib and defactinib combination has the potential to be a new standard of care in patients with recurrent low-grade serous ovarian cancer, if approved. In the second half of this year, we anticipate completing our NDA submission with the mature data from the RAMP 201 trial and discussing with the FDA a path forward for patients with KRAS wild-type disease. We also expect to present the mature dataset at a medical meeting in the second half of 2024."
RAMP 201 is a Phase 2 registration-directed study evaluating avutometinib and defactinib combination in patients with recurrent LGSOC. The enrollment in RAMP 201 is completed, with 115 patients being treated at the recommended Phase 2 dose (RP2D) of avutometinib 3.2 mg twice weekly and defactinib 200 mg twice daily for 3 out of every 4 weeks, and follow-up continues. Verastem expects to complete the NDA submission after obtaining mature safety and efficacy data from the RAMP 201 trial, including 12 months of follow-up, anticipated in the second half of 2024. Verastem also plans to further discuss the KRAS wt data with FDA to inform the potential path forward for approval for this patient population. The Company plans to present the mature dataset from RAMP 201 at a medical meeting in the second half of 2024. As of February 2024, the interim data continued to show robust overall response rates (ORR) and durable responses with low discontinuation rates due to adverse events (AEs) in patients from RAMP 201 Parts A, B, C, who had a minimum follow-up of five (5) months.
The FDA granted Breakthrough Therapy Designation of the investigational combination of avutometinib and defactinib for the treatment of all patients with recurrent LGSOC regardless of KRAS status after one or more prior lines of therapy, including platinum-based chemotherapy in May 2021. Avutometinib alone or in combination with defactinib was also granted Orphan Drug Designation by the FDA for the treatment of LGSOC in March 2024. The Company believes that this Orphan Drug Designation signifies that LGSOC is a rare ovarian cancer that is a distinct and different disease from other forms of ovarian cancer such as high-grade serous ovarian cancer (HGSOC). LGSOC is highly recurrent and fatal, with no FDA-approved treatment options, and the current standard of care treatments include hormonal therapy or chemotherapy, which have demonstrated an ORR between 6-13% with discontinuation due to AEs of 17-30%.
The Company is currently enrolling patients and activating sites for RAMP 301, an international confirmatory Phase 3 trial, evaluating the avutometinib and defactinib combination versus standard of care chemotherapy or hormonal therapy for the treatment of patients with KRAS mt and KRAS wt recurrent LGSOC.
Conference Call and Webcast Information
Verastem will hold an investor conference call and webcast on Friday, May 24 at 8:00 am EDT, to review the initiation of the NDA submission and limited, topline data from the RAMP 201 trial, with a minimum follow-up of five (5) months and the RAMP 205 data. The call will feature members of Verastem’s management team. To access the conference call, please dial (844) 763-8274 (local) or (412) 717-9224 (international) at least 10 minutes prior to the start time and ask to be joined into the Verastem Oncology conference call. A live audio webcast of the call, along with accompany slides, will be accessible here. The Company expects to file an 8-K pertaining to this update.
About RAMP 201
RAMP 201 (ENGOTov60/GOG3052) is an adaptive, two-part multicenter, parallel cohort, randomized, open-label trial to evaluate the efficacy and safety of avutometinib alone and in combination with defactinib in patients with recurrent low-grade serous ovarian cancer. The first part of the study (Part A) determined the selection of the go forward regimen, which was the combination of avutometinib and defactinib versus avutometinib alone, based on overall response rates. The expansion phases of the trial (Parts B and C) are evaluating the safety and efficacy of the go forward regimen of avutometinib 3.2 mg twice weekly and defactinib 200 mg twice daily. The Part D portion of the trial is evaluating a low dose of avutometinib in combination with defactinib to inform individualized dose reduction.
About RAMP 301
RAMP 301 (GOG-3097; ENGOT-ov81/NCRI) is an international collaboration between The GOG Foundation, Inc. (GOG) and the European Network of Gynaecological Oncological Trial groups (ENGOT) sponsored by Verastem Oncology. The trial is expected to enroll a total of 270 patients in the U.S., Canada, the United Kingdom, Europe, Australia and South Korea, who will be randomized to either the combination of avutometinib and defactinib or investigator’s choice chemotherapy (pegylated liposomal doxorubicin, paclitaxel, topotecan) or hormone therapy (letrozole, anastrozole). The primary endpoint is progression free survival (PFS) by Blinded Independent Central Review. Secondary endpoints include ORR, duration of response, disease control rate, safety and tolerability, patient reported outcomes, and overall survival.
About Low-Grade Serous Ovarian Cancer (LGSOC)
LGSOC is a rare ovarian cancer that is insidious, persistent and ultimately fatal. LGSOC is distinct and different from high-grade serous ovarian cancer (HGSOC) and requires different treatment. LGSOC is highly recurrent and less sensitive to chemotherapy compared to HGSOC. Approximately 6,000-8,000 women in the U.S. and 80,000 worldwide are living with this disease. LGSOC affects younger women with bimodal peaks of diagnosis at ages between 20-30 and 50-60 and has a median survival of approximately ten years. The majority of patients report negative impact of LGSOC on their mental and physical health, fertility, and long-term quality of life. The current standard of care for this disease includes hormone therapy and chemotherapy, but there are no treatments specifically approved by the U.S. Food and Drug Administration to treat LGSOC.
About the Avutometinib and Defactinib Combination
Avutometinib is a n investigational RAF/MEK clamp that is designed to induce inactive complexes of MEK with ARAF, BRAF and CRAF potentially creating a more complete and durable anti-tumor response through maximal RAS/MAPK pathway inhibition. Avutometinib is designed to block both MEK kinase activity and the ability of RAF to phosphorylate MEK. This differentiated proposed mechanism potentially allows avutometinib to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other MEK-only inhibitors. The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation of the investigational combination of avutometinib and defactinib, a selective FAK inhibitor, for the treatment of all patients with recurrent low-grade serous ovarian cancer (LGSOC) regardless of KRAS status after one or more prior lines of therapy, including platinum-based chemotherapy. Avutometinib alone or in combination with defactinib was also granted Orphan Drug Designation by the FDA for the treatment of LGSOC.
Verastem Oncology is currently conducting clinical trials with avutometinib in RAS/MAPK driven tumors as part of its Raf And Mek Program or RAMP. RAMP 301 (NCT06072781) is an international Phase 3 confirmatory trial evaluating the combination of avutometinib and defactinib versus standard chemotherapy or hormonal therapy for the treatment of recurrent LGSOC. RAMP 201 (NCT04625270) is a Phase 2 registration-directed trial of avutometinib in combination with defactinib in patients with recurrent LGSOC and enrollment has been completed in each of the dose optimization and expansion phases and the low-dose evaluation.
Verastem Oncology has established clinical collaborations with Amgen and Mirati to evaluate LUMAKRAS™ (sotorasib) in combination with avutometinib and defactinib and KRAZATI™ (adagrasib) in combination with avutometinib in KRAS G12C mutant NSCLC as part of the RAMP 203 (NCT05074810) and RAMP 204 (NCT05375994) trials, respectively. The RAMP 205 (NCT05669482), a Phase 1b/2 clinical trial evaluating avutometinib and defactinib with gemcitabine/Nab-paclitaxel in patients with front-line metastatic pancreatic cancer, is supported by a PanCAN Therapeutic Accelerator Award.
About Verastem Oncology
Verastem Oncology (Nasdaq: VSTM) is a late-stage development biopharmaceutical company committed to the development and commercialization of new medicines to improve the lives of patients diagnosed with cancer. Our pipeline is focused on RAS/MAPK-driven cancers, specifically novel small molecule drugs that inhibit critical signaling pathways in cancer that promote cancer cell survival and tumor growth, including RAF/MEK inhibition and FAK inhibition. For more information, please visit www.verastem.com and follow us on LinkedIn.
View source version on businesswire.com: https://www.businesswire.com/news/home/20240524990712/en/
Source: Verastem Oncology
Verastem stock rallies on positive data for pancreatic cancer drug combo
May 23, 2024 6:14 PM ET
By: Val Brickates Kennedy, SA News Editor7 Comments
Shares of Verastem (NASDAQ:VSTM) jumped 20% in post-market trading Thursday after the biotech company released positive interim data from a Phase 1/2 study of its drugs avutometinib and defactinib in the treatment of metastatic pancreatic cancer.
Verastem is testing avutometinib and defactinib in combination with gemcitabine and nab-paclitaxel as a first-line treatment for metastatic pancreatic cancer.
The study showed that 83% of patients achieved a confirmed partial response in cohort 1, the most mature dose level. It added that one incident of dose-limiting toxicity was observed, but the dose level was subsequently cleared after the enrollment of more patients, according to the company.
https://www.verastem.com/research/ras-pathway/#raf-mek-inhibition
Sarclisa (isatuximab-irfc) in combination with bortezomib
Sarclisa (isatuximab-irfc) in combination with bortezomib
Sarclisa (isatuximab-irfc) in combination with bortezomib
Sarclisa accepted for FDA priority review for the treatment of transplant-ineligible newly diagnosed multiple myeloma
- FDA Priority Review granted based on positive results from IMROZ phase 3 study
- If approved, Sarclisa would be the first anti-CD38 therapy in combination with standard-of-care treatment for patients with newly diagnosed transplant-ineligible multiple myeloma
- Pivotal IMROZ phase 3 study results to be featured during oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting
Paris, May 27, 2024. The U.S. Food and Drug Administration (FDA) has accepted for Priority Review the supplemental Biologics License Application (sBLA) for the investigational use of Sarclisa (isatuximab-irfc) in combination with bortezomib, lenalidomide and dexamethasone (VRd) for the treatment of patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM). If approved, Sarclisa would be the first anti-CD38 therapy in combination with standard-of-care VRd in newly diagnosed patients not eligible for transplant, which would be the third indication for Sarclisa in multiple myeloma. The target action date for the FDA decision is September 27, 2024. A regulatory submission is also under review in the European Union (EU).
Dietmar Berger, M.D., Ph.D.
Chief Medical Officer, Global Head of Development at Sanofi
“Despite recent advancements in multiple myeloma treatment, there remains a significant unmet need for new frontline therapies, particularly for transplant-ineligible patients who can face poor outcomes from the disease. The filing acceptances, as well as the FDA’s Priority Review designation, reinforce our confidence in Sarclisa as a potential best-in-class treatment and represent a critical step toward advancing this combination in a difficult-to-treat cancer.”
The sBLA, as well as the submission in the EU, is based on positive results from the IMROZ phase 3 clinical study evaluating the investigational use of Sarclisa in combination with standard-of-care VRd. In December 2023, the study met its primary endpoint at a planned interim analysis for efficacy, demonstrating statistically significant improvement in progression-free survival (PFS) with Sarclisa in combination with VRd compared with VRd alone in transplant-ineligible patients with NDMM. The safety and tolerability of Sarclisa observed in this study was consistent with the established safety profile of Sarclisa and VRd.
The IMROZ study is the fourth phase 3 study investigating Sarclisa combinations in NDMM patients to show superiority versus standard-of-care VRd and KRd, reinforcing its best-in-class potential. Results from the IMROZ study will also be featured during an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and during the plenary scientific session at the 2024 European Hematology Association (EHA) Annual Congress.
Priority Review is granted to regulatory applications seeking approval for therapies that have the potential to provide significant improvements in the treatment, diagnosis or prevention of serious conditions.
The investigational use of Sarclisa in combination with VRd in patients with transplant-ineligible NDMM is currently under clinical development, and its safety and efficacy for this indication have not been fully evaluated by any regulatory authority.
About the study
The global, randomized, multi-center, open-label IMROZ phase 3 clinical study enrolled 446 patients with newly diagnosed, transplant-ineligible MM across 21 countries and 104 centers. During the study, Sarclisa was administered through an intravenous infusion at a dose of 10 mg/kg once weekly for five weeks during first 42-day cycle and once every two weeks in cycles 2 to 4 in combination with subcutaneous bortezomib, oral lenalidomide and intravenous or oral dexamethasone. Then Sarclisa was administered every 2 weeks from cycle 5 to 17 and every 4 weeks in cycles 18+ during 28-day cycles in combination with lenalidomide and dexamethasone at the standard dose, until disease progression, unacceptable safety profile or patient’s decision to stop the study treatment.
The primary endpoint was progression-free survival. Key secondary endpoints include complete response rate, minimal residual disease (MRD) negativity rate for patients with a complete response, very good partial response or better rate, and overall survival. Other secondary endpoints were overall response rate, time to progression, duration of response, time to first response, time to best response, progression-free survival on next line of therapy, progression-free survival by MRD status, sustained MRD negativity greater than or equal to 12 months rate, safety, pharmacokinetic profile, immunogenicity, disease-specific and generic health-related quality of life, disease and treatment-related symptoms, health state utility, and health status.1
About Sarclisa
Sarclisa is a monoclonal antibody that binds to a specific epitope on the CD38 receptor on multiple myeloma (MM) cells, inducing distinct antitumor activity. It is designed to work through multiple mechanisms of action including programmed tumor cell death (apoptosis) and immunomodulatory activities. CD38 is highly and uniformly expressed on the surface of MM cells, making it a potential target for antibody-based therapeutics such as Sarclisa.
Based on the phase 3 ICARIA-MM study, Sarclisa is approved in >50 countries, including the U.S. and EU, in combination with pomalidomide and dexamethasone for the treatment of certain patients with relapsed refractory MM (RRMM) who have received ≥2 prior therapies, including lenalidomide and a proteasome inhibitor and who progressed on last therapy. Based on the phase 3 IKEMA study, Sarclisa is also approved in 50 countries in combination with carfilzomib and dexamethasone, including in the U.S. for the treatment of patients with RRMM who have received 1–3 prior lines of therapy and in the European Union for patients with MM who have received at least 1 prior therapy. In the U.S., the generic name for Sarclisa is isatuximab-irfc, with irfc as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. Food and Drug Administration (FDA).
Sarclisa continues to be evaluated in multiple ongoing phase 3 clinical studies in combination with current standard treatments across the MM treatment continuum. It is also under investigation for the treatment of other hematologic malignancies, and its safety and efficacy have not been evaluated by any regulatory authority outside of its approved indication.
For more information on Sarclisa clinical studies, please visit www.clinicaltrials.gov.
About multiple myeloma
Multiple myeloma (MM) is the second most common hematologic malignancy,2 with more than 180,000 new diagnoses of MM worldwide yearly.3 Despite available treatments, MM remains an incurable malignancy with an estimated 52% five-year survival rate for newly diagnosed patients.4 Since MM does not have a cure, most patients will relapse. Relapsed MM is the term for when the cancer returns after treatment or a period of remission. Refractory MM refers to when the cancer does not respond or no longer responds to therapy.
What is SARCLISA?
SARCLISA is a prescription medicine used in combination with:
- The medicines pomalidomide and dexamethasone, to treat adults who have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor to treat multiple myeloma.
- The medicines carfilzomib and dexamethasone, to treat adults with multiple myeloma who have already received 1 to 3 lines of treatment and they did not work or are no longer working.
It is not known if SARCLISA is safe and effective in children.
Please see full Prescribing Information, including Patient Information.
About Sanofi
We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people’s lives. Our team, across the world, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of our ambitions.
Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY
Sanofi's Sarclisa gets accepted for FDA priority review for treatment of multiple myeloma
May 27, 2024 2:50 AM ET
By: Sinchita Mitra, SA News Editor
- Sanofi (NASDAQ:SNY) said the FDA has accepted for priority review the supplemental Biologics License Application for the investigational use of Sarclisa in combination with bortezomib, lenalidomide and dexamethasone for the treatment of patients with transplant-ineligible newly diagnosed multiple myeloma.
- https://seekingalpha.com/news/4110523-sanofis-sarclisa-gets-accepted-for-fda-priority-review-for-treatment-of-multiple-myeloma
- Sanofi (SNY) Stock
- https://www.sanofi.us/en
- https://www.sarclisa.com/
ELAHERE® (mirvetuximab soravtansine-gynx)
ELAHERE® (mirvetuximab soravtansine-gynx)
Sarclisa (isatuximab-irfc) in combination with bortezomib
May 28, 2024
AbbVie Showcases Robust Solid Tumor Pipeline at ASCO 2024 with New Data from Its Innovative Antibody-Drug Conjugate (ADC) Platform
- Open a printable version of this page
- Email the URL of this page to a friend
- New safety and efficacy data in heavily pre-treated patients with metastatic colorectal cancer (CRC), from a Phase 1 study of ABBV-400, a next-generation, potential best-in-class c-Met directed ADC.
- Data from a first-in-human study of ABBV-706, a potential best-in-class SEZ6 directed ADC, in small cell lung cancer (SCLC), high-grade central nervous system (CNS) tumors and high-grade neuroendocrine neoplasms (NENs).
- Data from the primary analysis of the Phase 2 LUMINOSITY trial evaluating Telisotuzumab vedotin (Teliso-V), a potential first-in-class c-Met directed ADC, in advanced non-small cell lung cancer (NSCLC).
NORTH CHICAGO, Ill., May 28, 2024 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced that new data from its innovative antibody-drug conjugate (ADC) platform will be showcased across three oral presentations at the upcoming American Society of Clinical Oncology (ASCO) Annual Meeting (May 31 - June 4, 2024). AbbVie's ADCs are designed to target unique protein biomarkers such as c-Met (MET protein) and SEZ6 (seizure-related homolog 6 protein), which are over-expressed across various tumor types. By utilizing these biomarkers as targets, ADCs are designed to deliver potent cancer cell death-inducing agents called 'payloads' to the tumor.
"Building upon our strong commitment to patients and existing leadership in hematological malignancies, we are rapidly advancing a differentiated pipeline in solid tumors," said Daejin Abidoye, M.D., vice president, head of solid tumors, oncology development, AbbVie. "Our ADC platform allows us to utilize selected biomarkers such as c-Met and SEZ6 to induce targeted cancer cell death by delivering potent anti-cancer agents. The data we are presenting at ASCO demonstrate the clinical potential of this approach across a wide range of difficult-to-treat tumors."
Data from the dose-escalation and colorectal cancer (CRC) dose-expansion cohort of an ongoing first-in-human Phase 1 study (NCT05029882) of ABBV-400, a potential best-in-class c-Met directed ADC, will be presented in an oral presentation. The preliminary data show that among 122 heavily pre-treated advanced CRC patients, promising antitumor activity was observed at 2.4 and 3.0 mg/kg doses administered once every 3 weeks, with confirmed objective response rate (ORR) of 18% (n=40) and 24% (n=41) respectively in those groups. In patients with higher c-Met expression, ORR was enriched to >35% at doses ≥2.4 mg/kg. The most common Gr≥3 treatment-emergent adverse events (TEAEs) were anemia (35%), neutropenia (7%) and febrile neutropenia (6%). TEAEs leading to discontinuation occurred in 25 (20.5%) patients. Additional data will be presented at the meeting.
ABBV-400 is also being evaluated in a Phase 1b basket study (NCT06084481) in advanced solid tumors as a monotherapy and a Phase 2 study (NCT06107413) in second line metastatic CRC in combination with fluorouracil, folinic acid, and bevacizumab.
"c-Met overexpression, found in the majority of patients with metastatic CRC, has been reported to be associated with poor prognosis. However, there are no approved therapies specific for c-Met–overexpressing CRCs, making it an attractive cancer biomarker to target," said Manish Sharma, M.D., Co-Director of Clinical Research at START Midwest (Grand Rapids, MI) and Principal Investigator on the ABBV-400 trial. "Results from this Phase 1 study show preliminary evidence of efficacy for ABBV-400 in patients with heavily pre-treated colorectal cancer and are supportive of further exploration of this novel ADC in CRC and other solid tumors".
In addition, early data from the monotherapy dose escalation part of a first-in-human study of ABBV-706, a potential best-in-class SEZ6 directed ADC, will be presented at an oral presentation. The data demonstrate that among a total of 48 efficacy-evaluable patients (23 SCLC and 25 NEN), the overall confirmed objective response rate was 43.8%. Within the SCLC group, the confirmed objective response rate was 60.9%. Among all the 53 enrolled patients at the time of data cut-off, the most common ≥3 TEAEs were neutropenia (42%), anemia (42%), and leukopenia (28%). The ongoing study (NCT05599984) is evaluating ABBV-706 as monotherapy or in combination with budigalimab (a programmed cell death 1 inhibitor), carboplatin, or cisplatin, in patients with advanced solid tumors, including SCLC and other NENs. Additional data will be presented at the meeting.
Both ABBV-400 and ABBV-706 utilize a novel, AbbVie proprietary topoisomerase 1 inhibitor (Top1i) payload. Top1i is an anticancer agent that induces cell death by interrupting DNA replication. ABBV-400 and ABBV-706 are designed to specifically deliver Top1i to cells expressing c-Met and SEZ6 respectively.
AbbVie will also present data from the primary analysis of the Phase 2 LUMINOSITY non-small cell lung cancer (NSCLC) trial evaluating telisotuzumab vedotin (Teliso-V), a potential first-in-class c-Met directed ADC utilizing a microtubule polymerization inhibitor, monomethyl auristatin E (MMAE) payload, in patients with previously treated c-Met-overexpressing, non-squamous, epidermal growth factor receptor (EGFR) wild type, advanced NSCLC. AbbVie previously announced positive topline results from the study in November 2023.
Other presentations from AbbVie's ADC platform include safety and efficacy data in an older population (≥ 65) from the Phase 3 MIRASOL trial of mirvetuximab soravtansine (MIRV) vs investigator's choice chemotherapy in patients with platinum-resistant ovarian cancer (PROC) and high folate receptor-alpha (FRα) expression, and a retrospective, exploratory pooled analysis characterizing long-term survivors from four clinical trials examining patients with folate receptor alpha-positive recurrent ovarian cancer treated with MIRV monotherapy.
Further information on AbbVie clinical trials is available at https://www.clinicaltrials.gov/.
ABOUT ELAHERE® (mirvetuximab soravtansine-gynx)
ELAHERE is a first-in-class ADC comprising a folate receptor alpha-binding antibody, cleavable linker, and the maytansinoid payload DM4, a potent tubulin inhibitor designed to kill the targeted cancer cells. Patients requiring access support may call 1-833-ELAHERE or visit www.elahere.com.
The Marketing Authorization Application (MAA) for ELAHERE in Europe has been accepted by the European Medicines Agency (EMA). Regulatory submissions for ELAHERE are also under review in multiple other countries.
INDICATION
ELAHERE is indicated for the treatment of adult patients with folate receptor-alpha (FRα) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. Select patients for therapy based on an FDA-approved test.
Please see full Prescribing Information, including BOXED WARNING
About AbbVie in Oncology
At AbbVie, we are committed to transforming standards of care for patients living with difficult-to-treat cancers. We are advancing a dynamic pipeline of investigational therapies across a range of cancer types in both blood cancers and solid tumors. We are focusing on creating targeted medicines that either impede the reproduction of cancer cells or enable their elimination. We achieve this through various, targeted treatment modalities including Antibody Drug Conjugates (ADCs), Immuno-Oncology, bi-specific antibody and CAR-T platforms. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potential breakthrough medicines.
Today, our expansive oncology portfolio comprises of approved and investigational treatments for a wide range of blood and solid tumors. We are evaluating more than 20 investigational medicines in multiple clinical trials across some of the world's most widespread and debilitating cancers. As we work to have a remarkable impact on people's lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit http://www.abbvie.com/oncology.
About AbbVie
AbbVie's mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas – immunology, oncology, neuroscience, and eye care – and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on LinkedIn, Facebook, Instagram, X (formerly Twitter), and YouTube.
SOURCE AbbVie
https://seekingalpha.com/symbol/ABBV
https://www.nasdaq.com/market-activity/stocks/abbv/dividend-history
Rilzabrutinib
ELAHERE® (mirvetuximab soravtansine-gynx)
Omvoh™ (mirikizumab-mrkz)
- 2024-05-22-17-15-00-2886776
Media Update: New results from rilzabrutinib phase 2 study show potential to be first advanced oral treatment for moderate-to-severe asthma
May 22, 2024
New results from rilzabrutinib phase 2 study show potential to be first advanced oral treatment for moderate-to-severe asthma
- Late-breaking data presented at ATS show that treatment with rilzabrutinib led to a numerical reduction in loss of asthma control events, improvement in symptoms and was well-tolerated with no new safety signals observed
- Results support the further development and advancement into a phase 3 program
- Rilzabrutinib is one of 12 potential blockbusters in Sanofi’s robust immunology pipeline and a testament to Sanofi’s ability to successfully accelerate and build a portfolio of next-generation potentially transformative treatments for immune diseases
- Rilzabrutinib is currently being studied in multiple indications, including recently reported positive results from a phase 3 study in ITP with regulatory submission in H2 2024 and positive results from a phase 2 study in CSU
Paris, May 22, 2024. Encouraging results from a phase 2 study showed that treatment with oral rilzabrutinib at both high dose and low doses led to a numerical reduction in loss of asthma control (LOAC) events (the primary endpoint) and improvements in symptoms in adult patients with uncontrolled moderate-to-severe asthma. These results were presented today as a late-breaking poster at the 2024 American Thoracic Society (ATS) International Conference in San Diego and will support the phase 3 program where a twice-daily dose of rilzabrutinib will be studied for moderate-to-severe asthma.
Asthma is one of the most common chronic respiratory diseases affecting millions of people worldwide. Despite standard-of-care treatment, about 50% of patients with asthma remain uncontrolled with a high symptom burden that impacts their quality of life.
Tanya M. Laidlaw, MD
Director of Translational Research in Allergy Brigham and Women's Hospital, Boston, MA
“Many of my patients with asthma who are treated with standard of care inhaled therapies, even those with infrequent asthma attacks, still suffer from asthma symptoms and their activities are limited because of it. These patients may not qualify for a biologic medicine today but could benefit from an oral therapy that intervenes earlier in the disease. These results are encouraging as they show an improvement in asthma symptoms and a numerical reduction in Loss of Asthma Control events – important parameters in the treatment of this chronic respiratory condition that can significantly impact our patients’ daily lives.”
In this proof-of-concept study, treatment with high and low dose rilzabrutinib resulted in a 36% [OR: 0.584 (0.253, 1.349)] and 25% [OR:0.570 (0.202, 1.608)] relative risk reduction in loss of asthma control (LOAC) events, respectively, at week 12 (primary endpoint). Nominally significant and clinically meaningful improvements in asthma symptoms were also observed with a -0.54/-0.59 LS mean difference in asthma control questionnaire, ACQ-5. Improvements in ACQ-5 were seen as early as week 2.
Rilzabrutinib high and low doses were well tolerated over 12 weeks of treatment with no events of cytopenia, hemorrhagic events, or atrial fibrillation and no imbalance in liver function tests. Treatment-emergent adverse events (TEAEs) occurring with higher frequency with rilzabrutinib versus placebo were diarrhea (10.9% and 9.4% with rilzabrutinib high and low dose, versus 0% and 3.1% with matching placebo, respectively).
Houman Ashrafian
Executive Vice President, Head of Research and Development, Sanofi
“We are incredibly encouraged by the reduction in loss of asthma control events and improvements in asthma symptoms and look forward to advancing rilzabrutinib into a broader phase 3 clinical development program to further explore its potential in this disease. Advanced oral therapies have the potential to change the treatment paradigm for diseases like asthma, and we remain committed to exploring disruptive mechanisms of action for people living with uncontrolled chronic inflammatory diseases.”
Rilzabrutinib is currently under clinical investigation, and its safety and efficacy have not been evaluated by any regulatory authority.
About the study
This phase 2 study is a randomized, double-blind, placebo-controlled, parallel-group, 12-week proof-of-concept study to assess the efficacy, safety, and tolerability of rilzabrutinib in participants with moderate-to-severe asthma who are not well controlled on inhaled corticosteroid (ICS) plus long-acting β2 adrenergic agonist (LABA) therapy. Two doses of rilzabrutinib, 800 mg daily and 1200 mg daily, were studied. Patients were randomized 1:1 to receive either rilzabrutinib or placebo to be added to a background therapy of ICS/LABA which was withdrawn during the 12-week treatment period.
The primary endpoint was reduction in LOAC events. Secondary endpoints included asthma control (measured by the asthma control questionnaire, ACQ-5) and asthma quality of life (measured by the asthma quality of life questionnaire, AQLQ) or lung function (measured by FEV1).
About rilzabrutinib
Rilzabrutinib is an oral, reversible, covalent BTK inhibitor that has the potential to be a first- and/or best-in-class treatment for several immune-mediated diseases. BTK, expressed in B cells and mast cells, plays a critical role in multiple immune-mediated disease processes. With the application of Sanofi’s TAILORED COVALENCY® technology, rilzabrutinib can selectively inhibit the BTK target while potentially reducing the risk of off-target side effects.
Rilzabrutinib is being studied across a variety of immune-mediated diseases, including immune thrombocytopenia (ITP), asthma, chronic spontaneous urticaria, prurigo nodularis, IgG4-related disease, and warm autoimmune hemolytic anemia.
About Sanofi
We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people’s lives. Our team, across the world, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of our ambitions.
Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY
Sanofi says asthma candidate rilzabrutinib buoyed by phase 2 results
May 22, 2024 3:41 PM ET
By: Jonathan Block, SA News Editor
- Sanofi (NASDAQ:SNY) said that new phase 2 data indicates that its candidate rilzabrutinib led to a significant decline in loss of asthma control events compared to placebo.
- Results showed that at week 12, high and low dose rilzabrutinib led to, respectively, a 36% and 25% relative risk reduction in loss of asthma control events.
- In addition, other improvements in asthma symptoms were seen. There were no instances of cytopenia, hemorrhagic events, or atrial fibrillation, and no imbalance in liver function tests.
- https://seekingalpha.com/news/4109534-sanofi-says-asthma-candidate-rilzabrutinib-buoyed-phase-2-results
- Sanofi (SNY) Stock
- https://www.sanofi.com/en
- https://www.sanofi.com/en/our-science/our-pipeline
Omvoh™ (mirikizumab-mrkz)
ELAHERE® (mirvetuximab soravtansine-gynx)
Omvoh™ (mirikizumab-mrkz)
More than one-half of patients with Crohn's disease treated with Lilly's mirikizumab achieved clinical remission at one year, including patients with previous biologic failure
May 21, 2024
Nearly one-half of patients on mirikizumab achieved endoscopic response at 52 weeks; most of these patients were also in clinical remission
INDIANAPOLIS, May 21, 2024 /PRNewswire/ -- In Eli Lilly and Company's (NYSE: LLY) pivotal Phase 3 VIVID-1 study, patients with moderately to severely active Crohn's disease, with or without previous biologic failure, achieved statistically significant and clinically meaningful improvements across multiple clinical and endoscopic endpoints at one year with mirikizumab compared to placebo. Data from this study – the first Phase 3 treat-through data reported for an IL23p19 antibody – will be presented at Digestive Disease Week® (DDW), held in Washington, D.C. from May 18-21.
"Crohn's disease is a complex condition that, if untreated, may result in irreversible damage to the digestive tract. Mirikizumab patients achieved high rates of combined clinical remission and endoscopic response, two important treatment targets that are difficult to achieve in the same patient, at one year. This is particularly impressive for patients with previous biologic failure who are generally considered hard-to-treat," said Bruce Sands, M.D., M.S., Dr. Burrill B. Crohn Professor of Medicine and Chief of the Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai.* "Consistent results across patient populations underscore the potential impact of mirikizumab in individuals living with this condition."
Crohn's disease is a chronic, inflammatory bowel disease associated with progressive bowel damage, disability and decreased health-related quality of life. If not adequately controlled, it may lead to complications that require hospitalization and surgical intervention. A substantial proportion of patients do not experience adequate treatment outcomes, have secondary loss of response to maintenance therapy or do not tolerate existing therapies, including biologic agents. Patients with previous biologic failure may be more difficult to treat.
As previously reported, mirikizumab achieved both co-primary endpoints and all major secondary endpoints at Week 52 compared to placebo (p<0.000001), including:
- Proportion of participants achieving clinical response by patient reported outcomes (PRO)** at Week 12 and clinical remission (defined as a Crohn's Disease Activity Index [CDAI] Total Score <150) at Week 52 compared to placebo
- Proportion of participants achieving clinical response by PRO at Week 12 and endoscopic response (defined as ≥50% reduction from baseline in Simple Endoscopic Score – Crohn's Disease [SES-CD] Total Score) at Week 52 compared to placebo
Consistent response rates and treatment effects were observed in patients with no prior biologic failure (bio-naïve) and harder-to-treat patients with previous biologic failure:
- 39.3% of bio-naïve and 36.7% of bio-failed patients taking mirikizumab achieved composite Week 12 PRO clinical response and Week 52 endoscopic response compared to 11.8% and 6.2% of placebo, respectively
- 47.3% of bio-naïve and 43.4% of bio-failed patients taking mirikizumab achieved composite Week 12 PRO clinical response and Week 52 clinical remission by CDAI, compared to 26.5% and 12.4% of placebo, respectively
At one year, clinical remission and endoscopic response were achieved by 54.1% and 48.4% of patients on mirikizumab, respectively. Notably, of the patients who received mirikizumab, 56.7% of bio-naïve and 51.2% of bio-failed patients achieved clinical remission at Week 52.
Patients taking mirikizumab achieved combined Week 52 clinical remission and endoscopic response at nominally statistically significant higher rates compared to patients on ustekinumab (34.4% versus 27.9%), with greater difference among those patients with previous biologic failure. At multiple time points, including Week 52, mirikizumab also achieved nominal statistical significance compared to ustekinumab in decreasing fecal calprotectin and C-reactive protein, two key biomarkers for inflammation. Superiority to ustekinumab was not achieved for endoscopic response.
Additionally, in the population with previous biologic failure, numerically greater rates were observed with mirikizumab compared to ustekinumab for endoscopic response, endoscopic remission (SES-CD total score ≤4, a ≥2-point reduction from baseline and no subscore >1 in any individual variable), and corticosteroid-free CDAI clinical remission at Week 52. These observed differences were not statistically significant.
The overall safety profile of mirikizumab in patients with moderately to severely active Crohn's disease was consistent with the known safety profile in patients with ulcerative colitis. The frequency of serious adverse events was greater in placebo than mirikizumab. The most common adverse events were COVID-19, anemia, arthralgia, headache, upper respiratory tract infection, nasopharyngitis and injection site reaction.
"After one year of treatment, more than one-half of patients treated with mirikizumab achieved clinical remission and nearly one-half achieved endoscopic response. Remarkably, the majority of patients who achieved either of these endpoints, achieved both together," said Mark Genovese, M.D., senior vice president of Lilly Immunology development. "Lilly is committed to developing innovative treatments, like mirikizumab, that may improve upon the standard of care for people impacted by inflammatory bowel disease and immune-mediated diseases."
Lilly submitted a supplemental Biologics License Application for mirikizumab in Crohn's disease to the U.S. Food and Drug Administration and European Medicines Agency this year. Additional global regulatory submissions are planned.
Lilly is committed to finding solutions to elevate care and improve treatment outcomes for people living with inflammatory bowel diseases. Lilly has ongoing studies to evaluate the efficacy and safety of mirikizumab in other populations with Crohn's disease, including a Phase 3 study in pediatric patients (NCT05509777) and a long-term extension study of patients with moderately to severely active Crohn's disease (NCT04232553). Omvoh™ (mirikizumab-mrkz) is approved for the treatment of moderately to severely active ulcerative colitis (UC) in adults and has additional ongoing trials in UC, including a study in pediatric patients (NCT05784246) and a study to evaluate the long-term efficacy and safety of mirikizumab in adults (NCT03519945). Lilly is continuing to lead the science with an open-label UC trial studying two new endpoints in the assessment of bowel urgency with frequency and deferral time, both of which impact the quality of life for patients (NCT05767021).
* Disclosure: Dr. Sands is a paid consultant for Lilly. He has not been compensated for any media work.
About the VIVID-1 Clinical Trial Program
VIVID-1 was a Phase 3, randomized, double-blind, treat-through study that evaluated the safety and efficacy of mirikizumab compared with placebo and an active control (ustekinumab) in adults with moderately to severely active Crohn's disease. Patients randomized to mirikizumab were administered 900 mg of mirikizumab intravenously every four weeks from Week 0-12, then 300 mg subcutaneously every four weeks from Weeks 12-52. In this study, 49% of patients taking mirikizumab or placebo had experienced a prior biologic failure.
** Clinical response by PRO is defined as ≥30% decrease in stool frequency and/or abdominal pain, and neither score worse than baseline.
Indications and Usage for Omvoh™ (mirikizumab-mrkz) (in the United States)
Omvoh™ is indicated for the treatment of moderately to severely active ulcerative colitis in adults.
https://omvoh.lilly.com/what-is-omvoh
Please click for Prescribing Information and Medication Guide for Omvoh. Please click for Instructions for Use included with the device.
About Omvoh™
Omvoh (mirikizumab-mrkz) is an interleukin-23p19 antagonist indicated for the treatment of moderately to severely active ulcerative colitis in adults. Omvoh selectively targets the p19 subunit of IL-23 and inhibits the IL-23 pathway. Inflammation due to over-activation of the IL-23 pathway plays a critical role in the pathogenesis of ulcerative colitis. Treatment of ulcerative colitis with Omvoh starts with 300-mg IV infusions, once every four weeks for a total of three infusions, and transitions to two, 100-mg subcutaneous injections every four weeks during maintenance treatment.
Omvoh™ and its delivery device base are trademarks owned by Eli Lilly and Company.
About Lilly
Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help more than 51 million people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news, or follow us on Facebook, Instagram and LinkedIn. P-LLY
About Digestive Disease Week®
Digestive Disease Week® (DDW) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW is an in-person and online meeting from May 18-21, 2024. The meeting showcases more than 5,600 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology. More information can be found at www.ddw.org.
View original content to download multimedia:https://www.prnewswire.com/news-releases/more-than-one-half-of-patients-with-crohns-disease-treated-with-lillys-mirikizumab-achieved-clinical-remission-at-one-year-including-patients-with-previous-biologic-failure-302150721.html
SOURCE Eli Lilly and Company
Seladelpar
NEXLETOL (bempedoic acid) tablets
Seladelpar
May 18, 2024
Investigational Seladelpar Demonstrates Significant Improvements in Liver Disease Progression and Reduced Itching in Primary Biliary Cholangitis
- 70% of Patients Receiving Seladelpar 10mg Achieved the Clinically Meaningful Composite Endpoint and 37% Achieved ALP Normalization at 12 Months -
- Reduction in Patient-Reported Pruritus (Itching) was Rapid and Durable in Patients with Moderate to Severe Symptoms -
- Positive Interim Results are Highly Consistent with Results from the Phase 3 RESPONSE Study of Seladelpar -
FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD), following the recent acquisition of CymaBay Therapeutics, Inc., today announced interim results from the ongoing ASSURE study demonstrating treatment with seladelpar, an investigational PPAR delta agonist, led to improvements in markers of cholestasis and reduced inflammation. Additional findings demonstrate that seladelpar can help reduce pruritus (itch) in people living with primary biliary cholangitis (PBC). There are currently no treatments indicated to treat PBC-related pruritis. This data will be shared in an oral presentation during the Presidential Plenary of the Digestive Disease Week® 2024 Conference in Washington, DC.
ASSURE is an open-label study evaluating the long-term safety and efficacy of seladelpar, a once daily potent and selective peroxisome proliferator-activated receptor (PPAR) delta agonist, or delpar. ASSURE enrolled adult patients with PBC who previously participated in a study of seladelpar where a key eligibility criterion included having an inadequate response or intolerance to ursodeoxycholic acid (UDCA). This interim data analysis did not include patients from the Phase 3 RESPONSE study, which will be reported separately. Of the 174 patients included, the majority had a gap of one year or more between completion of the respective primary study (seladelpar or placebo) and enrollment into ASSURE. Enrolled patients received an open-label oral dose of 10 mg seladelpar once daily, with the majority (97%) also receiving UDCA treatment.
Most patients enrolled in ASSURE were female (94%), with a mean age of 59 years. Baseline characteristics included mean alkaline phosphatase (ALP) 270.5 U/L and total bilirubin (TB) 0.75 mg/dL; 19% of enrolled patients met the criteria for cirrhosis. The study evaluated several prespecified biochemical endpoints, including the composite response of an alkaline phosphatase (ALP) below 1.67 x upper limit of normal (ULN), a decrease in ALP of at least 15%, and a total bilirubin (TB) below the ULN. Endpoints were evaluated over an interim observation period extending from enrollment through a data cutoff date of June 29, 2023, with the majority of those (85%) having at least 12 months of continuous treatment with seladelpar. Seventy percent of the 148 patients who completed 12 months of treatment achieved the clinically meaningful composite response endpoint. Among those receiving seladelpar, 37% experienced ALP normalization, with a mean ALP change from baseline of -44% (-144.4 U/L). Of the 20 patients who completed 24 months of treatment, 70% achieved the composite response endpoint and 25% experienced ALP normalization. Seladelpar also reduced other important biomarkers of liver injury including TB, gamma-glutamyl transferase (GGT) and alanine aminotransferase (ALT) levels by 9%, 36%, and 25% from baseline, respectively. There were no treatment-related serious adverse events in the study, as determined by the study investigators. Seladelpar was generally well tolerated, with discontinuation due to adverse events occurring in 4.6% of patients.
“We are encouraged by these positive interim results from ASSURE, which are highly consistent with those observed in the Phase 3, double-blind placebo-controlled RESPONSE study of seladelpar in people with an inadequate response or intolerance to UDCA,” said Cynthia Levy, M.D., Professor of Medicine, University of Miami and presenter of the study. “Seladelpar continues to demonstrate a significant impact on PBC disease in the liver, helps a significant proportion of patients achieve normalization of their ALP and importantly reduces pruritus, which is often a debilitating and unrelenting comorbidity. The safety and tolerability profile of seladelpar is consistent with previous studies in PBC and underscores its potential as a promising therapeutic option for people living with PBC.”
Patient-reported pruritus was monitored throughout the study using the numerical rating scale (NRS; 0-10). In the 60 patients with moderate-to-severe pruritus at baseline with an NRS score of ≥4, a rapid improvement in pruritus was observed at Month 1. By Month 6 the patients reported a mean reduction of 3.5 points, and this impact was sustained through Month 12.
“The initial data from ASSURE further support the efficacy and safety profile of seladelpar observed across the robust development program and continue to indicate that seladelpar has the potential to be a best-in-class therapy that could help transform treatment for people living with primary biliary cholangitis,” said Merdad Parsey, Chief Medical Officer, Gilead Sciences. “The PBC community has been waiting for new treatments that help slow the progression of their liver disease as well as address difficult symptoms like pruritus that can have a significant impact on their quality of life. We are excited to offer a new option for this community as we work to bring seladelpar to people living with PBC, if approved.”
Additional results from ASSURE, including the long-term study of patients rolled over from RESPONSE to the ASSURE study, will be available at a future medical meeting.
A New Drug Application (NDA) for seladelpar for the treatment of PBC, including pruritus, in adults without cirrhosis or with compensated cirrhosis (Child Pugh A) who are inadequate responders or intolerant to UDCA, has been accepted for priority review by the U.S. Food and Drug Administration (FDA) with an anticipated decision in August 2024. Seladelpar has also been accepted for review by the UK Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA).
About ASSURE (NCT03301506)
ASSURE is an open label study to evaluate the long-term safety and tolerability of seladelpar in people with primary biliary cholangitis (PBC) who have already participated in other PBC clinical trials of seladelpar. The study is currently enrolling up to 500 people living with PBC from across 160 sites around the world. ASSURE will also address the long-term efficacy of seladelpar and its impact on important patient reported outcomes such as pruritus, or severe itch, which can have a significant impact on the quality of life of people living with PBC.
Interim results of ASSURE (Session #2060), titled “Efficacy and Safety of Seladelpar in Patients with Primary Biliary Cholangitis in the ASSURE Study: Interim Results,” will be presented Dr. Cynthia Levy on behalf of the ASSURE Study investigators during the DDW 2024 Presidential Plenary on May 18, 2024, from 8:00 am to 9:30 am EDT.
About Seladelpar
Seladelpar, an investigational treatment for people with PBC, is a first-in-class oral, selective PPAR-delta agonist, or delpar. PPAR-delta has been shown to regulate critical metabolic and liver disease pathways. Preclinical and clinical data support its ability to regulate genes involved in bile acid synthesis, inflammation, fibrosis and lipid metabolism, storage, and transport. Seladelpar is not approved by the FDA or any other regulatory authority globally and has not been determined to be safe or efficacious for any use.
About PBC
PBC is a rare, chronic inflammatory liver disease primarily affecting women (1 in 1,000 women over the age of 40 or about 130,000 total people in the U.S.). PBC is characterized by impaired bile flow (known as cholestasis) and the accumulation of toxic bile acids in the liver, leading to inflammation and destruction of the bile ducts within the liver and causing increased levels of ALP, ALT, and GGT, enzymes found primarily in the liver, as well as total bilirubin. The most common early symptoms of PBC are pruritus (itching) and fatigue, which can be debilitating for some patients. Progression of PBC is associated with an increased risk of liver-related mortality.
About CymaBay
CymaBay Therapeutics Inc. was acquired by Gilead Sciences in March 2024. CymaBay Therapeutics, a Gilead Company, is a clinical-stage biopharmaceutical company focused on improving the lives of people with liver and other chronic diseases that have high unmet medical need. Our deep understanding of the underlying mechanisms of liver inflammation and fibrosis, and the unique targets that play a role in their progression, helped CymaBay receive breakthrough therapy designation and orphan drug status from the U.S. Food and Drug Administration for seladelpar, a first-in-class investigational treatment for people with PBC.
About Gilead Sciences in Liver Disease
For decades, Gilead has pioneered the way forward to improve the lives of people living with liver disease around the world. We have helped to transform hepatitis C from a chronic condition into one that can be cured for millions of people. For people living with hepatitis B or D, our focus on advancing our medicines drives hope that today’s research will turn into tomorrow’s cures. Beyond viral hepatitis, we’re working to deliver advanced treatments for people living with primary biliary cirrhosis (PBC). But our commitment doesn’t stop there. Through our ground-breaking science and collaborative partnerships, we strive to create healthier futures for everyone living with liver disease. We are committed to a future without liver disease.
About Gilead Sciences
Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19 cancer and inflammation. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California.
Gilead and the Gilead logo are trademarks of Gilead Sciences, Inc. or its related companies.
For more information on Gilead’s commitment in Liver Disease please visit www.gilead.com .
For more information on investigational seladelpar and ASSURE please visit www.cymabay.com
Source: Gilead Sciences, Inc.
Gilead touts additional data on liver disease asset seladelpar ahead of PDUFA date
May 20, 2024 12:37 PM ET
Gilead Sciences, Inc. (GILD) Stock
By: Jonathan Block, SA News Editor
- Gilead Sciences (NASDAQ:GILD) said that interim results from an open-label trial of seladelpar, its candidate for the liver disease primary biliary cholangitis, led to improvements in markers of cholestasis and reduced inflammation.
- Results from the ASSURE study
- https://seekingalpha.com/news/4108439-gilead-touts-additional-data-liver-disease-asset-seladelpar-ahead-pdufa-date?mailingid=35440091&messageid=2900&serial=35440091.1584&utm_campaign=rta-stock-news&utm_content=link-1&utm_medium=email&utm_source=seeking_alpha&utm_term=35440091.1584
- Gilead Sciences, Inc. (GILD) Stock
- https://www.gilead.com/
Azeliragon
NEXLETOL (bempedoic acid) tablets
Seladelpar
20 MAY CANTEX PHARMACEUTICALS RECEIVES FDA ORPHAN DRUG DESIGNATION FOR AZELIRAGON FOR THE TREATMENT OF PANCREATIC CANCER
WESTON, FL, May 20, 2024 –
Cantex Pharmaceuticals, Inc., a clinical-stage pharmaceutical company focused on developing transformative therapies for cancer and other life-threatening medical conditions for which new treatments are urgently needed, announced today that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to Cantex’ azeliragon, a well-tolerated once-a-day pill, for the treatment of pancreatic cancer. This new azeliragon orphan drug designation adds to azeliragon’s previous orphan drug designation for the treatment of glioblastoma, received in early 2023.
Pancreatic cancer, unless controlled at its earliest stages, often spreads to local tissues and to distant organs. Although surgery can be curative if pancreatic cancer is diagnosed at its very earliest stages, once the cancer has spread to distant organs, the current treatment has some, although limited, efficacy. New treatments are clearly needed.
Cantex has an ongoing clinical trial studying the safety and efficacy of azeliragon in patients refractory to first-line treatment of metastatic pancreatic cancer. This clinical trial is enrolling metastatic pancreatic cancer patients in several world-class cancer treatment centers in the U.S.
“Receiving FDA orphan drug status for azeliragon for the treatment of pancreatic cancer underscores the significant unmet need for novel treatment options for patients with pancreatic cancer, particularly for those patients with locally advanced, unresectable, or metastatic disease,” commented Stephen G. Marcus, M.D., Chief Executive Officer of Cantex. “This designation strengthens our continued commitment to developing new azeliragon treatment options for patients with pancreatic cancer, as well as for other cancers and their complications, including glioblastoma, brain metastasis and breast cancer.”
FDA Orphan Drug Designation provides Cantex with seven years of azeliragon marketing exclusivity from the time of product launch for the orphan indication, and several other important benefits, including assistance in the drug development process, tax credits for clinical costs, and exemptions from certain FDA fees.
About Azeliragon
Azeliragon is an orally administered capsule, taken once daily, that inhibits interactions of the receptor for advanced glycation end products (known as RAGE) with certain ligands, including HMGB1 and S100 proteins in the tumor microenvironment. Azeliragon was discovered by and originally under development for Alzheimer’s disease by vTv Therapeutics Inc. (NASDAQ: VTVT) from which Cantex licensed worldwide rights to azeliragon. Clinical safety data from these trials, involving more than 2000 individuals dosed for periods up to 18 months, indicate that azeliragon is very well tolerated.
Cantex has ongoing Phase 2 clinical trials in pancreatic cancer, glioblastoma, brain metastasis, breast cancer, and a Phase 3 trial in hospitalized patients with pneumonia. These trials are based on azeliragon’s robust preclinical data as well as its extensive clinical safety information from randomized placebo-controlled clinical trials.
About Cantex Pharmaceuticals, Inc.
Cantex Pharmaceuticals, Inc. is a privately held, clinical stage pharmaceutical company focused on developing transformative therapies for cancer and other life-threatening medical conditions for which new treatments are urgently needed. For more information, please visit www.cantex.com.
About vTv Therapeutics Inc.
vTv Therapeutics Inc. is a clinical stage biopharmaceutical company focused on developing oral, small molecule drug candidates, led by cadisegliatin (TTP399), a potentially transformative treatment for the reduction of hypoglycemic episodes in type 1 diabetes patients. To learn more please visit vtvtherapeutics.com.
Cantex Pharmaceuticals receives FDA Orphan Drug Designation for its pancreatic cancer treatment
May 20, 2024 1:27 PM ET
vTv Therapeutics Inc. (VTVT) Stock
By: Nilanjana Basu, SA News Editor
- Cantex Pharmaceuticals announced that the FDA has granted Orphan Drug Designation to Cantex' azeliragon for the treatment of pancreatic cancer.
- This new azeliragon orphan drug designation adds to azeliragon's previous orphan drug designation for the treatment of glioblastoma, received in early 2023.
- https://seekingalpha.com/news/4108464-cantex-pharmaceuticals-receives-fda-orphan-drug-designation-for-its-pancreatic-cancer-treatment
- vTv Therapeutics Inc. (VTVT) Stock
- https://vtvtherapeutics.com/pipeline/
- https://cantex.com/
- https://vtvtherapeutics.com/
NEXLETOL (bempedoic acid) tablets
NEXLETOL (bempedoic acid) tablets
NEXLETOL (bempedoic acid) tablets
Bempedoic Acid Met Primary Endpoint of Phase 3 Trial in Japan for the Treatment for Hypercholesterolemia
May 20, 2024
ANN ARBOR, Mich., May 20, 2024 (GLOBE NEWSWIRE) -- Esperion (Nasdaq: ESPR) and Otsuka Pharmaceutical Co., Ltd (Otsuka) announced today that the primary endpoint was achieved in the Phase 3 trial in Japan for bempedoic acid as a potential treatment for patients with hypercholesterolemia. The trial demonstrated statistically significant outcomes on the primary endpoint for bempedoic acid and highlighted its potential future value to patients in Japan.
Bempedoic acid, created by Esperion Therapeutics, Inc. (Esperion), has a novel mechanism of action that inhibits a cholesterol synthesis pathway by acting on ATP (adenosine triphosphate) citrate lyase, a citrate-degrading enzyme in the liver. Bempedoic acid is marketed for the treatment of hypercholesterolemia and cardiovascular risk reduction in several regions of the world, including the United States and Europe. In 2020, Otsuka acquired exclusive development and commercialization rights for bempedoic acid in Japan from Esperion and is currently developing it domestically.
(https://www.otsuka.co.jp/en/company/newsreleases/2020/20200420_1.html)
This Phase 3 trial (NCT05683340) was conducted as a placebo-controlled, randomized, multicenter, double-blind, parallel-group comparative study in 96 patients with high LDL cholesterol and in whom satins have insufficient effect or cannot be tolerated. Trial participants were administered either 180 mg of bempedoic acid or a placebo, orally, once a day, for 12 weeks to evaluate the efficacy and safety of bempedoic acid.
In the preliminary results, the percentage change from baseline in LDL-C at Week 12, the primary endpoint, was -25.25%% in the group receiving bempedoic acid placebo group and -3.46% in the placebo group, demonstrating positive outcomes with statistical significance compared to placebo (p<0.01). Furthermore, the safety and tolerability of bempedoic acid were consistent with findings from previous trials, and no serious adverse events were observed.
Further data analysis will be conducted, and Otsuka plans to announces the results at a professional conference. Based on the results of this trial, Otsuka plans to submit an New Drug Application (NDA) in Japan in the latter half of 2024.
INDICATION
NEXLIZET and NEXLETOL are indicated:
- The bempedoic acid component of NEXLIZET and NEXLETOL is indicated to reduce the risk of myocardial infarction and coronary revascularization in adults who are unable to take recommended statin therapy (including those not taking a statin) with:
- established cardiovascular disease (CVD), or
- at high risk for a CVD event but without established CVD.
- As an adjunct to diet:
- NEXLIZET, alone or in combination with other LDL-C lowering therapies, to reduce LDL-C in adults with primary hyperlipidemia, including HeFH.
- NEXLETOL, in combination with other LDL-C lowering therapies, or alone when concomitant LDL-C lowering therapy is not possible, to reduce LDL-C in adults with primary hyperlipidemia, including HeFH.
- https://www.nexlizet.com/
Esperion Therapeutics
At Esperion, we discover, develop, and commercialize innovative medicines to help improve outcomes for patients with or at risk for cardiovascular and cardiometabolic diseases. The status quo is not meeting the health needs of millions of people with high cholesterol – that is why our team of passionate industry leaders is breaking through the barriers that prevent patients from reaching their goals. Providers are moving toward reducing LDL-cholesterol levels as low as possible, as soon as possible; we provide the next steps to help get patients there. Because when it comes to high cholesterol, getting to goal is not optional. It is our life’s work. For more information, visit esperion.com and esperionscience.com and follow us on X at twitter.com/EsperionInc.
Esperion's late stage trial of high cholesterol treatment met main goal
May 20, 2024 8:33 AM ET
Esperion Therapeutics, Inc. (ESPR) Stock
By: Nilanjana Basu, SA News Editor
- Esperion (Nasdaq: ESPR) and Otsuka Pharmaceutical announced that the primary endpoint was achieved in the Phase 3 trial in Japan for bempedoic acid as a potential treatment for patients with hypercholesterolemia.
- https://seekingalpha.com/news/4108266-esperions-late-stage-trial-of-hypercholesterolemia-treatment-met-main-goal
- Esperion Therapeutics, Inc. (ESPR) Stock
- https://www.nexlizet.com/
Sotyktu (deucravacitinib)
IMDELLTRA™ (TARLATAMAB-DLLE)
NEXLETOL (bempedoic acid) tablets
New Four-Year Sotyktu (deucravacitinib) Data Demonstrate Durable Response Rates and Consistent Safety in Moderate-to-Severe Plaque Psoriasis
05/16/2024
CATEGORY:
Following four years of continuous Sotyktu treatment, clinical response was maintained in more than seven out of 10 patients for Psoriasis Area and Severity Index (PASI) 75 in the POETYK PSO long-term extension trial
No new safety signals observed at Year 4 in the POETYK PSO long-term extension trial, consistent with the established Sotyktu safety profile
PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE:BMY) today announced new four-year results from the POETYK PSO long-term extension (LTE) trial of Sotyktu (deucravacitinib) treatment in adult patients with moderate-to-severe plaque psoriasis. After four years of continuous treatment, Week 208 responses for Psoriasis Area and Severity Index (PASI) 75 and 90 were 71.7% and 47.5%, respectively, and 57.2% for static Physician’s Global Assessment (sPGA) 0/1 (clear/almost clear), using modified nonresponder imputation (mNRI). The safety profile of Sotyktu at Year 4 remained consistent with the established safety profile, with no new safety signals identified.
These data were presented at the European Academy of Dermatology and Venereology (EADV) Spring Symposium in St. Julian’s, Malta taking place May 16-18, 2024.
“These four-year results further validate the safety profile, efficacy and key role of once-daily Sotyktu, the first and only TYK2 inhibitor available, for adults with moderate-to-severe plaque psoriasis,” said April Armstrong, MD, MPH, clinical investigator in the POETYK PSO clinical trial program and professor and chief of dermatology at the University of California, Los Angeles. “Many patients and their healthcare providers are looking for an efficacious, convenient oral treatment option that provides sustained relief from this chronic disease, allowing patients to prioritize other aspects of their daily lives. These findings further reinforce that we are able to offer a potential oral standard of care to meet patients’ needs.”
The efficacy analysis included 513 patients who received continuous Sotyktu treatment from Day 1 in the pivotal POETYK PSO-1 and POETYK PSO-2 trials and transitioned to the POETYK PSO-LTE trial. Clinical efficacy outcomes were maintained in patients who were continuously treated with Sotyktu from baseline through Year 4, with sustained response rates for PASI 75 of 71.7% at Year 4 (Year 1, 72.0%; Year 3, 73.8%), PASI 90 of 47.5% (Year 1, 45.6%; Year 3, 49.0%) and sPGA 0/1 of 57.2% (Year 1, 57.7%; Year 3, 55.2%).
The safety analysis included 1,519 patients who received at least one dose of Sotyktu across POETYK PSO-1, POETYK PSO-2 and POETYK PSO-LTE. Cumulative exposure from parent trial randomization was 4,392.8 patient-years (PYs) for the safety analyses. With increased exposure to Sotyktu, the exposure-adjusted incidence rates (EAIRs)/100 PYs at Year 4 decreased or remained the same as those at Year 1 for adverse events (AEs) (Year 1, 229.2; Year 4, 131.7), serious AEs (Year 1, 5.7; Year 4, 5.0), discontinuation due to AEs (Year 1, 4.4; Year 4, 2.2), herpes zoster (Year 1, 0.8; Year 4, 0.6), malignancies (Year 1, 1.0; Year 4, 0.9), major adverse cardiovascular events (Year 1, 0.3; Year 4, 0.3), venous thromboembolism (Year 1, 0.2; Year 4, 0.1) and deaths (Year 1, 0.2; Year 4, 0.3). EAIRs/100 PYs were calculated as the number of patients with an AE over the total exposure time for all patients at risk (time to an initial AE occurrence for patients with an AE and time of total exposure for patients without an AE).
“The data from our robust POETYK PSO clinical program continue to reinforce the potential of the first-in-class Sotyktu as an oral standard of care for individuals living with moderate-to-severe plaque psoriasis,” said Alyssa Johnsen, MD, PhD, senior vice president and head of clinical development, Immunology, Cardiovascular and Neuroscience, Bristol Myers Squibb. “Our leadership in TYK2 innovation highlights our transformational science that is advancing care for immune-mediated diseases.”
Bristol Myers Squibb thanks the patients and investigators involved in the POETYK PSO clinical trial program.
About the POETYK PSO Clinical Trial Program
PrOgram to Evaluate the efficacy and safety of Sotyktu (deucravacitinib), a selective TYK2 inhibitor (POETYK) PSO-1 (NCT03624127) and POETYK PSO-2 (NCT03611751) were global Phase 3 studies designed to evaluate the efficacy of Sotyktu compared to placebo and Otezla® (apremilast), and the safety of Sotyktu, in patients with moderate-to-severe plaque psoriasis. Both POETYK PSO-1, which enrolled 666 patients, and POETYK PSO-2, which enrolled 1,020 patients, were multicenter, randomized, double-blind trials that evaluated Sotyktu (6 mg once daily) compared to placebo and Otezla (30 mg twice daily). POETYK PSO-2 included a randomized withdrawal and retreatment period after Week 24.
The co-primary endpoints of both POETYK PSO-1 and POETYK PSO-2 were the percentage of patients who achieved Psoriasis Area and Severity Index (PASI) 75 response and those who achieved static Physician's Global Assessment (sPGA) score of 0 or 1 (clear/almost clear) at Week 16 versus placebo. Key secondary endpoints of the trials included the percentage of patients who achieved PASI 75 and sPGA 0/1 compared to Otezla at Week 16 and other measures evaluating Sotyktu versus placebo and Otezla.
Across both clinical trials and timepoints, significantly more Sotyktu-treated patients achieved a sPGA score of 0/1, PASI 75 response and PASI 90 response. Responses persisted through Week 52, as 82% (187/228) of patients who achieved PASI 75 with Sotyktu at Week 24 maintained their response at Week 52 in POETYK PSO-1. In POETYK PSO-2, 80% (119/148) of patients who continued Sotyktu maintained PASI 75 response compared to 31% (47/150) of patients who were withdrawn from Sotyktu.
Following the 52-week POETYK PSO-1 and POETYK PSO-2 trials, patients could enroll in the ongoing POETYK PSO long-term extension (LTE) trial (NCT04036435) and receive open-label Sotyktu 6 mg once-daily. In the LTE trial, 1,221 patients were enrolled and received at least one dose of Sotyktu. Efficacy was analyzed utilizing treatment failure rules (TFR) method of imputation, along with sensitivity analyses using modified non-responder imputation and as-observed analysis, which have been used in similar analyses with other agents.
In addition to POETYK PSO-1, POETYK PSO-2 and POETYK PSO-LTE, Bristol Myers Squibb has evaluated Sotyktu in two other Phase 3 studies in psoriasis: POETYK PSO-3 (NCT04167462) and POETYK PSO-4 (NCT03924427).
About Psoriasis
Psoriasis is a widely prevalent, chronic, systemic immune-mediated disease that substantially impairs patients’ physical health, quality of life and work productivity. Psoriasis is a serious global problem, with at least 100 million people worldwide impacted by some form of the disease, including around 14 million people in Europe and approximately 7.5 million people in the United States. Nearly one-quarter of people with psoriasis have cases that are considered moderate-to-severe. Up to 90 percent of patients with psoriasis have psoriasis vulgaris, or plaque psoriasis, which is characterized by distinct round or oval plaques typically covered by silvery-white scales. Despite the availability of effective systemic therapy, many patients with moderate-to-severe plaque psoriasis remain undertreated or even untreated and are dissatisfied with current treatments. People with psoriasis report an impact on their emotional well-being, straining both personal and professional relationships and causing a reduced quality of life. Psoriasis is associated with multiple comorbidities that may impact patients’ well-being, including psoriatic arthritis, cardiovascular disease, metabolic syndrome, obesity, diabetes, inflammatory bowel disease and depression.
About Sotyktu (deucravacitinib)
Sotyktu (deucravacitinib) is an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor with a unique mechanism of action, representing a new class of small molecules. It is the first selective TYK2 inhibitor in clinical studies across multiple immune-mediated diseases. Bristol Myers Squibb scientists designed Sotyktu to selectively target TYK2, thereby inhibiting signaling of interleukin (IL)-23, IL-12 and Type 1 interferons (IFN), key cytokines involved in the pathogenesis of multiple immune-mediated diseases. Sotyktu achieves a high degree of selectivity by binding to the regulatory domain of TYK2, resulting in allosteric inhibition of TYK2 and its downstream functions. Sotyktu selectively inhibits TYK2 at physiologically relevant concentrations. At therapeutic doses, Sotyktu does not inhibit JAK1, JAK2 or JAK3.
Bristol Myers Squibb: Pioneering Paths Forward in Immunology to Transform Patients’ Lives
Bristol Myers Squibb is inspired by a single vision – transforming patients’ lives through science. For people living with immune-mediated diseases, the debilitating reality of enduring chronic symptoms and disease progression can take a toll on their physical, emotional and social well-being, making simple tasks and daily life a challenge. Driven by our deep understanding of the immune system that spans over 20 years of experience, and our passion to help patients, the company continues to pursue pathbreaking science with the goal of delivering meaningful solutions that address unmet needs in rheumatology, gastroenterology, dermatology and pulmonology. We follow the science, aiming to tailor therapies to individual needs, improve outcomes and expand treatment options by working to identify mechanisms with the potential to achieve long-term remission – and perhaps even cures – in the future. By building partnerships with researchers, patients and caregivers to deliver innovative treatments, Bristol Myers Squibb strives to elevate patient care to new standards and deliver what matters most – the promise of living a better life.
SOTYKTU U.S. INDICATION
SOTYKTU™ (deucravacitinib) is indicated for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.
Limitations of Use:
SOTYKTU is not recommended for use in combination with other potent immunosuppressants.
Please see U.S. Full Prescribing Information, including Medication Guide, for SOTYKTU.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.
Otezla® (apremilast) is a registered trademark of Amgen Inc.
Source: Bristol Myers Squibb
Multimedia Files:
Download:Download original 99 KB 1497 x 206Download thumbnail 5 KB 200 x 28Download lowres 15 KB 480 x 66Download square 8 KB 250 x 250
Dividend History
Bristol-Myers Squibb Company Common Stock (BMY) Dividend History
https://www.nasdaq.com/market-activity/stocks/bmy/dividend-history
NVL-655
IMDELLTRA™ (TARLATAMAB-DLLE)
IMDELLTRA™ (TARLATAMAB-DLLE)
Nuvalent Receives U.S. FDA Breakthrough Therapy Designation for NVL-655
CAMBRIDGE, Mass., May 16, 2024 /PRNewswire/ -- Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, today announced that the U.S. Food and Drug Administration (FDA) has granted breakthrough therapy designation (BTD) to NVL-655 for the treatment of patients with locally advanced or metastatic ALK-positive non-small cell lung cancer (NSCLC) who have been previously treated with two or more ALK tyrosine kinase inhibitors (TKIs).
ALK rearrangements occur in up to approximately 5% of metastatic NSCLCs. At the time of diagnosis, up to 40% of these patients present with accompanying brain metastases, and approximately 50% of patients develop resistance mutations following treatment with currently available first- or second-generation ALK TKIs. There remains no clear standard of care for patients who have been previously treated with two or more ALK TKIs.
NVL-655 is a novel brain-penetrant ALK-selective TKI created with the aim to simultaneously overcome the clinical challenges of emergent treatment resistance, brain metastases, and off-target central nervous system (CNS) adverse events associated with inhibition of the structurally-related tropomyosin receptor kinase (TRK) family.
"Today's announcement of FDA breakthrough therapy designation for NVL-655 marks another important milestone for our ALK program and the second breakthrough designation granted to our pipeline of novel kinase inhibitors this year," said Darlene Noci, A.L.M., Chief Development Officer at Nuvalent. "Our team is committed to expeditiously advancing NVL-655 in recognition of the continued need for innovation for patients with ALK-positive NSCLC who have exhausted available therapies. We expect to provide an update from the ALKOVE-1 trial of NVL-655 at a medical meeting in the second half of this year."
BTD is designed to expedite the development and review of therapies intended to treat a serious or life-threatening condition and whose preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on one or more clinically significant endpoints over existing available therapies. Under the designation, the FDA provides intensive guidance, organizational commitment involving senior managers, and eligibility for rolling review and other actions to expedite review.
The BTD for NVL-655 is based on the preliminary safety and activity of NVL-655 in heavily pretreated patients with advanced ALK-positive NSCLC in the Phase 1 portion of the Phase 1/2 ALKOVE-1 clinical trial. Enrollment in the Phase 2 portion of the trial is ongoing, and the company expects to share updated data from the trial at a medical meeting in the second half of 2024.
About NVL-655
NVL-655 is a novel brain-penetrant ALK-selective inhibitor created with the aim to overcome limitations observed with currently available ALK inhibitors. NVL-655 is designed to remain active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumors with single or compound treatment-emergent ALK mutations such as G1202R. In addition, NVL-655 is designed for central nervous system (CNS) penetrance to improve treatment options for patients with brain metastases, and to avoid inhibition of the structurally related tropomyosin receptor kinase (TRK) family. Together, these characteristics have the potential to avoid TRK-related CNS adverse events seen with dual TRK/ALK inhibitors and to drive deep, durable responses for patients across all lines of therapy. NVL-655 has received orphan drug designation for ALK-positive non-small cell lung cancer (NSCLC) and is currently being investigated in the ALKOVE-1 clinical trial (NCT05384626), a first-in-human Phase 1/2 clinical trial for patients with advanced ALK-positive NSCLC and other solid tumors.
About Nuvalent
Nuvalent, Inc. (Nasdaq: NUVL) is a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for patients with cancer, designed to overcome the limitations of existing therapies for clinically proven kinase targets. Leveraging deep expertise in chemistry and structure-based drug design, we develop innovative small molecules that have the potential to overcome resistance, minimize adverse events, address brain metastases, and drive more durable responses. Nuvalent is advancing a robust pipeline with investigational candidates for ROS1-positive, ALK-positive, and HER2-altered non-small cell lung cancer, and multiple discovery-stage research programs.
SOURCE Nuvalent, Inc.
Nuvalent gains breakthrough therapy status for non-small cell lung cancer candidate
May 16, 2024 4:18 PM ET
By: Jonathan Block, SA News Editor
- The U.S. FDA has granted breakthrough therapy designation to Nuvalent's (NASDAQ:NUVL) non-small cell lung cancer candidate, NVL-655.
- The status is for patients with an ALK-positive form of the disease who were previously treated with at least two ALK tyrosine kinase inhibitors (TKIs).
- https://seekingalpha.com/news/4107719-nuvalent-gains-breakthrough-therapy-status-non-small-cell-lung-cancer-candidate
- https://clinicaltrials.gov/study/NCT05384626
- https://nuvalent.com/
- https://nuvalent.com/pipeline/
IMDELLTRA™ (TARLATAMAB-DLLE)
IMDELLTRA™ (TARLATAMAB-DLLE)
IMDELLTRA™ (TARLATAMAB-DLLE)
FDA APPROVES IMDELLTRA™ (TARLATAMAB-DLLE), THE FIRST AND ONLY T-CELL ENGAGER THERAPY FOR THE TREATMENT OF EXTENSIVE-STAGE SMALL CELL LUNG CANCER
Breakthrough DLL3-Targeting Therapy Regimen for a Major Solid Tumor
IMDELLTRA Demonstrated Impressive 40% Objective Response Rate, 9.7 Month Median Duration of Response and 14.3 Month Median Overall Survival in Pivotal DeLLphi-301 Study
Amgen to Host Webcast Investor Call on May 20, 2024 at 1:00 p.m. PT
THOUSAND OAKS, Calif., May 16, 2024 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced that the U.S. Food and Drug Administration (FDA) has approved IMDELLTRA™ (tarlatamab-dlle) for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy. IMDELLTRA has received accelerated approval based on the encouraging response rate and duration of response (DoR) observed in clinical studies. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Experience the full interactive Multichannel News Release here: https://www.multivu.com/players/English/9246451-fda-approves-imdelltra-tarlatamab-dlle-the-first-and-only-t-cell-engager-therapy-for-the-treatment-of-extensive-stage-small-cell-lung-cancer/
"The FDA's approval of IMDELLTRA marks a pivotal moment for patients battling ES-SCLC. This DLL3-targeting therapy in ES-SCLC comprises a transformative option demonstrating long-lasting responses in pretreated patients," said Jay Bradner, M.D., executive vice president, Research and Development, and chief scientific officer at Amgen. "This approval further demonstrates our commitment to addressing aggressive cancers through our second FDA-approved Bispecific T-cell Engager (BiTE®) molecule. IMDELLTRA offers these patients who are in urgent need of new innovative therapies hope, and we're proud to deliver this long-awaited effective treatment to them."
"Lung cancer is a complex and devastating disease, and less than 3% of patients with ES-SCLC live longer than five years," said David P. Carbone, M.D., Ph.D., professor of internal medicine and director of the James Thoracic Oncology Center at the Ohio State University Medical Center.1 "In the DeLLphi-301 trial, the median overall survival was 14.3 months, with 40% of patients responding to treatment with tarlatamab. These responses were remarkably durable, representing a major advancement in the SCLC treatment paradigm."
IMDELLTRA is the first and only DLL3-targeting Bispecific T-cell Engager therapy that activates the patient's own T cells to attack DLL3-expressing tumor cells.2
"After decades of minimal advancements in the SCLC treatment landscape, there is now an effective and innovative treatment option available," said Laurie Fenton Ambrose, co-founder, president, and CEO of GO2 for Lung Cancer. "Today's FDA approval marks a significant milestone for the SCLC community as the availability of a targeted bispecific therapy brings forward new possibilities to those living with this aggressive disease."
The FDA accelerated approval of IMDELLTRA is based on results from the Phase 2 DeLLphi-301 clinical trial that evaluated IMDELLTRA in patients with SCLC who had failed two or more prior lines of treatment, and who had received the 10 mg every two weeks dosing (Q2W) regimen. Results from the study found that IMDELLTRA at the 10 mg Q2W dose (N=99) demonstrated a robust objective response rate (ORR) of 40% (95% Confidence Interval [CI]: 31, 51) and median DoR of 9.7 months (CI: 2.7, 20.7+). The median overall survival (mOS) was 14.3 months, with final and complete survival data yet to mature.3
The IMDELLTRA label includes a Boxed Warning for cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), in addition to warnings and precautions for cytopenias, infections, hepatotoxicity, hypersensitivity, and embryo-fetal toxicity. The most common (> 20%) adverse reactions reported among patients were CRS (55%), fatigue (51%), pyrexia (36%), dysgeusia (36%), decreased appetite (34%), musculoskeletal pain (30%), constipation (30%), anemia (27%), and nausea (22%). Permanent discontinuations due to treatment-emergent adverse events (TEAEs) were infrequent (7%). CRS was largely confined to the first and second dose, predominantly grade 1 or 2, and was generally managed with supportive care. Details of the Important Safety Information are included below.
Amgen's Commitment to Patient Support
Amgen is committed to supporting patients with ES-SCLC and to helping ensure appropriate patients with access to IMDELLTRA. Patients, caregivers, and physicians who need support, tools, or resources can contact Amgen® SupportPlus. Amgen also provides patient assistance for its medicines marketed in the U.S. in a variety of ways, including for uninsured or under-insured patients through the Amgen Safety Net Foundation, a nonprofit patient assistance program sponsored by Amgen that helps qualifying patients access Amgen medicines at no cost.
Amgen to Webcast Investor Call on IMDELLTRA FDA Approval
Amgen will host a webcast call for the investment community on Monday, May 20, 2024 at 1:00 p.m. PT (4:00 p.m. ET). Jay Bradner, M.D., executive vice president, Research and Development, and chief scientific officer at Amgen, Murdo Gordon, executive vice president of Global Commercial Operations, and other members of the Amgen team will participate.
Live audio of the investor call will be simultaneously broadcast over the internet and will be available to members of the news media, investors, and the general public.
The webcast, as with other selected presentations regarding developments in Amgen's business given by management at certain investor and medical conferences, can be found on Amgen's website, www.amgen.com, under Investors. Information regarding presentation times, webcast availability, and webcast links are noted on Amgen's Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.
About IMDELLTRA™ (tarlatamab-dlle)
IIMDELLTRA is a first-in-class immunotherapy engineered by Amgen researchers that binds to both DLL3 on tumor cells and CD3 on T cells, activating T cells to kill DLL3-expressing SCLC cells. This results in the formation of a cytolytic synapse with lysis of the cancer cell.2,4 DLL3 is a protein that is expressed on the surface of SCLC cells in ~85-96% of patients with SCLC, but is minimally expressed on healthy cells, making it an exciting target.3,5
IMDELLTRA™ (tarlatamab-dlle) U.S. Indication
IMDELLTRA™ (tarlatamab-dlle) is indicated for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy.
This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Please see IMDELLTRA™ full Prescribing Information, including BOXED WARNINGS.
About Small Cell Lung Cancer (SCLC)
SCLC is one of the most aggressive and devastating solid tumor malignancies, with a median survival of approximately 12 months following initial therapy and a 3% five-year relative survival rate for ES-SCLC.1,6,7 Current second-line treatments impart a short duration of response (median DoR: 3.3–5.3 months) and limited survival (median OS: 5.8-9.3 months), while current third-line treatments for SCLC, which consist primarily of chemotherapy, yield a short median DoR of 2.6 months and a median OS of 4.4-5.3 months.8-12 SCLC comprises ~15% of the 2.4 million plus patients diagnosed with lung cancer worldwide each year.13-15 Despite initial high response rates to first-line platinum-based chemotherapy, most patients quickly relapse within months and require subsequent treatment options.13
About Tarlatamab Clinical Trials
Amgen's robust tarlatamab development program includes the DeLLphi clinical trials, which evaluate tarlatamab as both a monotherapy and in combination regimens in earlier lines of SCLC, and DeLLpro clinical trials, which evaluate the efficacy and safety of tarlatamab in neuroendocrine prostate cancer.
In the Phase 1 DeLLphi-300 study, tarlatamab showed responses in 23.4% of patients with encouraging durability in heavily pre-treated patients with SCLC.16 In the Phase 2 DeLLphi-301 study, tarlatamab administered as 10 mg dose every two weeks demonstrated an ORR of 40% in patients with advanced SCLC who had failed two or more prior lines of treatment. In the DeLLphi-301 Phase 2 trial, the most frequent treatment-related adverse events seen with 10 mg Q2W dosing regimen were CRS (51%), pyrexia (32%), and decreased appetite (23%). CRS events were predominantly grade 1 or 2 and occurred most often after the first or second dose.2 Treatment discontinuation for adverse events occurred in 4-7% of patients in the two trials.3,16
Tarlatamab is being investigated in multiple studies including DeLLphi-303, a Phase 1b study investigating tarlatamab in combination with standard of care therapies in first-line ES-SCLC; DeLLphi-304, a randomized Phase 3 trial comparing tarlatamab monotherapy with standard of care chemotherapy in second-line treatment of SCLC; DeLLphi-305, a randomized Phase 3 trial comparing tarlatamab in combination with durvalumab versus durvalumab alone as first-line maintenance treatment in ES-SCLC; DeLLphi-306, a randomized placebo-controlled Phase 3 trial of tarlatamab following concurrent chemoradiotherapy in limited-stage SCLC; and DeLLpro-300, a Phase 1b study of tarlatamab in de novo or treatment-emergent neuroendocrine prostate cancer.17
For more information, please visit www.tarlatamabclinicaltrials.com.
About Bispecific T-Cell Engager (BiTE®) Technology
BiTE technology is a targeted immuno-oncology platform that is designed to engage a patient's own T cells to any tumor-specific antigen, activating the cytotoxic potential of T cells to eliminate detectable cancer. The BiTE immuno-oncology platform has the potential to treat different cancer types through tumor-specific antigens. The BiTE platform has a goal of leading to off-the-shelf solutions, which have the potential to make innovative T cell treatment available to all providers when their patients need it. For more than a decade, Amgen has been advancing this innovative technology, which has demonstrated strong efficacy in hematological malignancies and now a solid tumor with the approval of IMDELLTRA. Amgen remains committed to progressing multiple BiTE molecules across a broad range of hematologic and solid tumor malignancies, paving the way for additional applications in more tumor types. Amgen is further investigating BiTE technology with the goal of enhancing patient experience and therapeutic potential. To learn more about BiTE technology, visit BiTE® Technology 101.
About Amgen
Amgen discovers, develops, manufactures and delivers innovative medicines to help millions of patients in their fight against some of the world's toughest diseases. More than 40 years ago, Amgen helped to establish the biotechnology industry and remains on the cutting-edge of innovation, using technology and human genetic data to push beyond what's known today. Amgen is advancing a broad and deep pipeline that builds on its existing portfolio of medicines to treat cancer, heart disease, osteoporosis, inflammatory diseases and rare diseases.
In 2024, Amgen was named one of the "World's Most Innovative Companies" by Fast Company and one of "America's Best Large Employers" by Forbes, among other external recognitions Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average®, and it is also part of the Nasdaq-100 Index®, which includes the largest and most innovative non-financial companies listed on the Nasdaq Stock Market based on market capitalization.
For more information, visit Amgen.com and follow Amgen on X, LinkedIn, Instagram, TikTok, YouTube and Threads.
View original content:https://www.prnewswire.com/news-releases/fda-approves-imdelltra-tarlatamab-dlle-the-first-and-only-t-cell-engager-therapy-for-the-treatment-of-extensive-stage-small-cell-lung-cancer-302148431.html
SOURCE Amgen
Amgen wins FDA nod for new lung cancer therapy
May 16, 2024 3:40 PM ET
By: Dulan Lokuwithana, SA News Editor7 Comments
The U.S. Food and Drug Administration (FDA) on Thursday approved Amgen’s (NASDAQ:AMGN) targeted cancer therapy, Imdelltra, as a late-line option for adults with advanced small cell lung cancer (SCLC).
According to the FDA, the drug will be approved in the U.S. under its accelerated pathway for adults with extensive-stage SCLC who have undergone prior platinum-based chemotherapy.
biotecHOPE™ 2024
Sipavibart (formerly AZD3152)
Vepdegestrant in Combination with Palbociclib (IBRANCE®)
Vepdegestrant in Combination with Palbociclib (IBRANCE®)
SUPERNOVA Phase III trial of sipavibart long-acting antibody met primary endpoints in preventing COVID-19 in immunocompromised patient population
PUBLISHED16 May 2024
Positive high-level results from the SUPERNOVA Phase III COVID-19 pre-exposure prophylaxis (prevention) trial showed AstraZeneca’s sipavibart (formerly AZD3152), an investigational long-acting antibody (LAAB), demonstrated a statistically significant reduction in the incidence of symptomatic COVID‑19 compared to control (tixagevimab/cilgavimab or placebo) in an immunocompromised patient population.
The trial met both dual primary endpoints; the first one being the relative risk reduction of symptomatic COVID-19 caused by any SARS-CoV-2 variant and the second being the relative risk reduction of infections caused by SARS-CoV-2 variants not containing the F456L mutation. SUPERNOVA demonstrated the potential benefit of sipavibart in an evolving variant landscape in which COVID-19 cases captured over the course of the trial were caused by several different SARS-CoV-2 variants.
SUPERNOVA is a large Phase III global trial providing the only efficacy data in immunocompromised patients, demonstrating the potential benefit of a COVID-19 antibody against recent SARS-CoV-2 variants. Immunocompromised patients include those with blood cancer, organ transplant recipients, patients with end-stage renal disease requiring dialysis, patients receiving B-cell depleting therapy within the past year, and those taking immunosuppressive medications. Despite accounting for approximately 4% of the population, immunocompromised patients make up about 25% of COVID-19 hospitalisations, ICU admissions, and deaths, even after multiple doses of COVID-19 vaccines.1-6
Ghady Haidar, M.D., UPMC (University of Pittsburgh Medical Center) transplant infectious diseases physician, medical director of the translational research program at UPMC’s division of infectious diseases and SUPERNOVA trial primary investigator, said: “COVID-19 still represents a significant and disproportionate risk for immunocompromised patients, with infection often leading to serious and protracted illness. By delivering infection-fighting antibodies directly to patients who often don’t respond adequately to vaccines, the data support that sipavibart has the potential to provide much-needed protection against COVID-19 in this highly vulnerable population.”
Iskra Reic, Executive Vice President, Vaccines and Immune Therapies, AstraZeneca, said: “Immunocompromised patients currently have limited or no options for COVID-19 protection and continue to face a significant burden of disease, despite often being fully vaccinated. Sipavibart has the potential to prevent COVID-19 in the immunocompromised and we will now work with regulatory authorities globally to bring sipavibart to these vulnerable patients.”
Sipavibart was well tolerated in the trial and preliminary analyses show adverse events were balanced between the control and sipavibart arms.
The data will be presented at a forthcoming medical meeting. AstraZeneca is in dialogue with regulatory authorities on potential authorisation or approval pathways.
Notes
SUPERNOVA
SUPERNOVA is a Phase III, global, randomised, double-blind, placebo-controlled trial assessing the safety and efficacy of sipavibart compared to control (tixagevimab/cilgavimab or placebo) for the prevention of COVID-19. The trial was conducted at 197 sites in the US, UK, EU and Asia. Participants were randomised in a 1:1 ratio to receive either a 300mg intramuscular dose of sipavibart or comparator, with 1,669/3,335 participants receiving sipavibart and 1,666/3,335 receiving comparator. A second dose of sipavibart or comparator was given approximately six months after initial receipt of study product.
The trial had dual primary efficacy endpoints. The first evaluated the efficacy of sipavibart against any confirmed SARS-CoV-2 positive symptomatic illness occurring post dose prior to day 181 caused by any variant (i.e., all cases regardless of if the variant has the F456L mutation or not, which sipavibart is not expected to neutralise). The second dual primary efficacy analysis was conducted using only the confirmed COVID-19 cases in the trial where the variant causing the COVID-19 cases did not have the F456L mutation, referred to as a “matched” variant analysis.
Participants were individuals 12 years of age and over who would benefit from prevention with the investigational LAAB, defined as having increased risk for inadequate response to active immunisation (predicted poor responders to vaccines or intolerant of vaccine). Participants at the time of screening had a negative point-of-care SARS-CoV-2 serology test. Participants will be followed for 15 months, with SARS-CoV-2 neutralising antibodies assessed at one, three and six months.
All participants in the trial had an immunocompromising condition and/or were on immunosuppressive treatments, which put them at risk to mount an inadequate immune response to vaccination and at high risk of developing severe COVID-19. This included patients with hematologic malignancies, solid organ transplant recipients, hematopoietic stem cell transplants, end stage kidney disease/dialysis and being within one year of receipt of B cell depleting therapy, among others. Across the treatment groups, demographic and baseline characteristics were generally well balanced.
Sipavibart
Sipavibart (formerly AZD3152) is an investigational long-acting monoclonal antibody (LAAB) against COVID-19. Sipavibart was designed to provide broad and potent coverage across Omicron and ancestral viral variants by neutralising spike protein interaction with the host receptor ACE2.7
Sipavibart was derived from B-cells donated by convalescent patients after SARS-CoV-2 infection. Sipavibart has been engineered using the same antibody scaffold as Evusheld and was optimised with the same half-life extension and reduced Fc effector function and complement C1q binding platform.7 The reduced Fc effector function aims to minimise the risk of antibody-dependent enhancement of disease - a phenomenon in which virus-specific antibodies promote, rather than inhibit, infection and/or disease.
Sipavibart was licensed by AstraZeneca in May 2022 from RQ Biotechnology.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Social Media @AstraZeneca.
AstraZeneca COVID therapy succeeds in late-stage study for the vulnerable
May 16, 2024 10:11 AM ET
By: Dulan Lokuwithana, SA News Editor
AstraZeneca (NASDAQ:AZN) announced Thursday that its monoclonal antibody sipavibart reached primary goals as a treatment for COVID-19 prevention in a Phase 3 trial for immunologically weaker individuals.
The company said its global trial, SUPERNOVA, for individuals aged 12 and above with immunocompromising conditions such as blood cancer and kidney conditions, achieved dual primary endpoints.
SUPERNOVA was designed to evaluate sipavibart against two comparators, tixagevimab/cilgavimab, a monoclonal antibody AstraZeneca (AZN) had previously marketed as Evusheld for COVID prevention and placebo.
As for its first primary endpoint, sipavibart, formerly known as AZD3152, outperformed comparators with a statistically significant effect on reducing the risk of symptomatic COVID-19.
Vepdegestrant in Combination with Palbociclib (IBRANCE®)
Vepdegestrant in Combination with Palbociclib (IBRANCE®)
Vepdegestrant in Combination with Palbociclib (IBRANCE®)
Arvinas and Pfizer Announce Updated Clinical Data from Phase 1b Trial of Vepdegestrant in Combination with Palbociclib (IBRANCE®)
Thursday, May 16, 2024 - 06:00am
– After six months of additional follow-up, clinical benefit rate (63%), overall response rate (41.9%), median progression-free survival (11.2 months), and safety profile of vepdegestrant in combination with palbociclib were consistent with data previously reported at SABCS in December 2023 –
– At the recommended Phase 3 dose of 200 mg vepdegestrant in combination with palbociclib, patients achieved a median progression-free survival of 13.9 months (95% CI: 8.1-NR) –
– Across all vepdegestrant dose groups, circulating tumor DNA analyses showed marked reduction in tumor fraction after one treatment cycle, regardless of ESR1 gene mutation status; at the 200 mg vepdegestrant dose, robust on-treatment decreases in mutant ESR1 circulating tumor DNA were sustained through multiple treatment cycles –
NEW HAVEN, Conn. and NEW YORK, May 16, 2024 – Arvinas, Inc. (Nasdaq: ARVN) and Pfizer Inc. (NYSE: PFE) today announced updated clinical data from a Phase 1b combination cohort evaluating vepdegestrant, an investigational oral PROteolysis TArgeting Chimera (PROTAC®) estrogen receptor (ER) degrader, in combination with palbociclib (IBRANCE®). After six months of additional follow-up, these data are consistent with data presented at the San Antonio Breast Cancer Symposium (SABCS) in December 2023, and show that vepdegestrant plus palbociclib continue to demonstrate encouraging clinical activity in heavily pre-treated patients with a median of four lines of prior therapy with locally advanced or metastatic ER positive (ER+)/human epidermal growth factor 2 (HER2) negative (ER+/HER2-) breast cancer. These updated data were presented at the 2024 European Society for Medical Oncology (ESMO) Breast Cancer Annual Congress.
“We're encouraged by the clinical activity and safety profile observed with vepdegestrant in combination with palbociclib in patients being treated for advanced ER+/HER2- breast cancer,” said Noah Berkowitz, M.D., Ph.D., Chief Medical Officer at Arvinas. “The median progression-free survival and duration of response data suggest a promising therapeutic benefit for these patients regardless of ESR1 mutation status.”
Vepdegestrant is an investigational PROTAC ER degrader designed to harness the body’s natural protein disposal system to specifically target and degrade the estrogen receptor. Vepdegestrant is being co-developed by Arvinas and Pfizer and is being evaluated as a monotherapy in the second-line setting in the ongoing Phase 3 VERITAC-2 trial and in the first-line setting in combination with palbociclib in the ongoing study lead-in cohort of the Phase 3 VERITAC-3 trial.
“Pfizer is focused on advancing the next generation of treatment breakthroughs for people with breast cancer,” said Roger Dansey, M.D., Chief Development Officer, Oncology, Pfizer. “With vepdegestrant, we hope to establish a new standard-of-care endocrine therapy backbone for patients with ER+/HER2- breast cancer, and the data shared at ESMO Breast Cancer continue to reinforce its potential.”
“This study evaluating vepdegestrant in combination with palbociclib among heavily pre-treated patients with advanced ER+/HER2- metastatic breast cancer is consistent with the clinical activity, safety, and tolerability outcomes reported at SABCS 2023,” said Erika Hamilton, M.D., Director Breast Cancer Research and Executive Chair, Breast Cancer Research Executive Committee, Sarah Cannon Research Institute in Nashville, Tennessee, and a lead investigator in the vepdegestrant clinical program and presenting author on the data presentation at ESMO Breast Cancer. “The data show promise that vepdegestrant could be a potential addition to current treatment options for this patient population, where there are significant unmet needs.”
Vepdegestrant + Palbociclib Phase 1b Study
The Phase 1b cohort of the ARV-471-mBC-101 study (NCT04072952) is designed to assess the safety, tolerability, and anti-tumor activity of vepdegestrant in combination with palbociclib among 46 patients with heavily pre-treated locally advanced or metastatic ER+/HER2- breast cancer. Patients in the study received a median of four prior therapies (median of three in the metastatic setting); 87% were previously treated with a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor; 80% were previously treated with fulvestrant; and 78% were previously treated with chemotherapy, including 48% in the metastatic setting.
Patients were treated once daily with oral doses of vepdegestrant at 180 mg (n=2), the recommended Phase 3 dose (RP3D) of 200 mg (n=21), 400 mg (n=3) or 500 mg (n=20), plus 125 mg of palbociclib given orally once daily for 21 days, followed by seven days off treatment in 28-day cycles. Initial data were presented at SABCS 2023 based on a data cutoff of June 6, 2023.
After six months of additional follow-up with a data cutoff of December 18, 2023, updated data from the study continue to demonstrate an encouraging clinical benefit rate, objective response rate and progression-free survival, and a consistent safety profile as previously reported at SABCS 2023.
Data presented at the 2024 ESMO Breast Cancer Annual Congress:
Clinical Benefit Rate (CBR):
- CBR, defined as the rate of confirmed complete response, partial response, or stable disease ≥24 weeks across all dose levels (n = 46) was 63% (95% CI: 47.5 - 76.8), with a CBR of 72% in patients with mutant ESR1 (n=29; 95% CI: 52.8 - 87.3) and a CBR of 53% in patients with wild-type ESR1 (n=15; 95% CI: 26.6 – 78.7).
- CBR in patients dosed at the RP3D of 200 mg (n=21) was 67% (95% CI: 43.0 - 85.4) with a CBR of 79% in patients with mutant ESR1 (n=14; 95% CI: 49.2 - 95.3) and a CBR of 43% in patients with wild-type ESR1 (n=7; 95% CI: 9.9 - 81.6)
Objective Response Rate (ORR) and Duration of Response (DOR):
- The ORR in evaluable patients with measurable disease at baseline (n=31) was 42% (95% CI: 24.5 - 60.9) with a median DOR in 13 responders of 14.6 months (95% CI: 9.5 – not reached). At the RP3D of 200 mg (n=15), the ORR was 53% (95% CI: 25.6 – 78.7).
- ORR in patients with mutant ESR1 (n=17): 47% (95% CI: 23.0 - 72.2).
- ORR at the RP3D of 200 mg (n=10): 60% (95% CI: 26.2 - 87.8).
- ORR in patients with wild-type ESR1 (n=12): 42% (95% CI: 15.2 - 72.3).
- ORR at the RP3D of 200 mg (n=5): 40% (95% CI: 5.3 - 85.3).
- ORR in patients with mutant ESR1 (n=17): 47% (95% CI: 23.0 - 72.2).
Progression-free Survival (PFS):
- Median PFS (mPFS) based on 27 (59%) events across all dose levels was 11.2 months (95% CI: 8.2 – 16.5) with a mPFS of 13.7 months (95% CI: 8.2 - NR) in patients with ESR1 mutation (n=29) and mPFS of 11.1 months (95% CI: 2.8 - 19.3) in patients with wild-type ESR1 (n=15).
- mPFS in patients dosed at the RP3D of 200 mg (n=21) based on 12 events (57%) was 13.9 months (95% CI: 8.1 - NR) with a mPFS of 13.9 months (95% CI: 8.1 - NR) in patients with ESR1 mutation (n=14) and mPFS of 11.2 months (95% CI: 1.8 - NR) in patients with wild-type ESR1 (n=7).
Circulating Tumor DNA (ctDNA):
- Exploratory ctDNA analyses found marked reduction (median change, −98.9%) in tumor fraction after one treatment cycle (all dose groups) regardless of ESR1 mutant status and robust on-treatment decreases in mutant ESR1 ctDNA levels sustained through cycle 7 (evaluated in patients in 200 mg dose cohort), as presented in the poster session.
About Vepdegestrant
Vepdegestrant is an investigational, orally bioavailable PROTAC protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with ER positive (ER+)/human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) breast cancer. Vepdegestrant is being developed as a potential monotherapy and as part of combination therapy across multiple treatment settings for ER+/HER2- metastatic breast cancer.
In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialization of vepdegestrant; Arvinas and Pfizer will share worldwide development costs, commercialization expenses, and profits.
The U.S. Food and Drug Administration (FDA) has granted vepdegestrant Fast Track designation as a monotherapy in the treatment of adults with ER+/HER2- locally advanced or metastatic breast cancer previously treated with endocrine-based therapy.
About IBRANCE® (palbociclib) 125 mg tablets and capsules
IBRANCE is an oral inhibitor of CDKs 4 and 6,1 which are key regulators of the cell cycle that trigger cellular progression. 2,3 In the U.S., IBRANCE is a prescription medicine indicated for the treatment of adults with HR+, HER2- advanced or metastatic breast cancer in combination with an aromatase inhibitor as the first hormonal based therapy; or with fulvestrant in people with disease progression following hormonal therapy.
The full U.S. Prescribing Information for the IBRANCE tablets and the IBRANCE capsules can be found here and here.
About Arvinas
Arvinas is a clinical-stage biotechnology company dedicated to improving the lives of patients suffering from debilitating and life-threatening diseases through the discovery, development, and commercialization of therapies that degrade disease-causing proteins. Arvinas uses its proprietary PROTAC® Discovery Engine platform to engineer proteolysis targeting chimeras, or PROTAC® targeted protein degraders, that are designed to harness the body’s own natural protein disposal system to selectively and efficiently degrade and remove disease-causing proteins. In addition to its robust preclinical pipeline of PROTAC protein degraders against validated and “undruggable” targets, the company has four investigational clinical-stage programs: vepdegestrant for the treatment of patients with locally advanced or metastatic ER+/HER2- breast cancer; ARV-766 and bavdegalutamide for the treatment of men with metastatic castration-resistant prostate cancer; and ARV-102 for the treatment of patients with neurodegenerative disorders. For more information, visit www.arvinas.com.
About Pfizer Oncology
At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and bispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives.
About Pfizer: Breakthroughs That Change Patients’ Lives
At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For 175 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.pfizer.com. In addition, to learn more, please visit us on www.pfizer.com and follow us on X at @Pfizer and @Pfizer_News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.
https://www.arvinas.com/research-and-development/estrogen-receptor/
Insulin efsitora alfa (efsitora)
Vepdegestrant in Combination with Palbociclib (IBRANCE®)
Insulin efsitora alfa (efsitora)
With Once-a-Week Dosing, Insulin Efsitora Alfa Delivers A1C Reduction and Safety Profile Consistent with Daily Insulin
May 16, 2024
Efsitora met the primary endpoint in both QWINT-2 and QWINT-4 with once-a-week dosing regimen for people living with type 2 diabetes
Efsitora was equally safe and effective among adults naïve to insulin therapy currently using and not using GLP-1 receptor agonists
INDIANAPOLIS, May 16, 2024 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced positive topline results from the QWINT-2 and QWINT-4 phase 3 clinical trials evaluating once-weekly insulin efsitora alfa (efsitora) in adults with type 2 diabetes using insulin for the first time (insulin naïve) and those who require multiple daily insulin injections. In the treat-to-target clinical trials, efsitora showed non-inferior A1C reduction compared to the most commonly used daily basal insulins globally.
"The results of QWINT-2 and QWINT-4 are a significant milestone for the diabetes community and demonstrate that efsitora as a weekly insulin provides blood sugar control equivalent to daily basal insulins," said Jeff Emmick, MD, Ph.D., senior vice president, product development, Lilly. "With efsitora, we have an opportunity to provide an innovative once-weekly solution that safely achieves and maintains A1C control, reduces treatment burden of traditional daily injections and potentially improves adherence for people with diabetes."
QWINT-2 evaluated the efficacy and safety of once-weekly efsitora compared to once-daily insulin degludec for 52 weeks. The trial randomized insulin-naïve adults with type 2 diabetes to receive efsitora once weekly or insulin degludec once daily and was also designed to assess efficacy in patients using and not using GLP-1 receptor agonists.
The trial met its primary endpoint of non-inferior A1C reduction with efsitora compared to insulin degludec at week 52. For the efficacy estimand1,2, efsitora reduced A1C by 1.34% compared to 1.26% for insulin degludec resulting in an A1C of 6.87% and 6.95% respectively3. In a key secondary endpoint, efsitora was non-inferior to insulin degludec in A1C change among participants using and not using GLP-1 receptor agonists. Further, participants taking efsitora spent 45 minutes more time in range4 and 37 minutes more in tight range5 without additional time in hypoglycemia (blood glucose <54 mg/dL) in comparison to insulin degludec.
QWINT-4 evaluated the efficacy and safety of efsitora compared to insulin glargine for 26 weeks in adults with type 2 diabetes who have previously been treated with basal insulin and at least two injections per day of mealtime insulin. The trial randomized participants to receive efsitora once weekly or insulin glargine once daily, both of which were administered with insulin lispro.
The trial met its primary endpoint of non-inferior A1C reduction with efsitora compared to insulin glargine at week 26. For the efficacy estimand, both efsitora and insulin glargine reduced A1C by 1.07% resulting in an A1C of 7.12% and 7.11%, respectively6,7.
In both QWINT-2 and QWINT-4, efsitora was safe and well-tolerated with estimated combined rates of severe or clinically significant (blood glucose <54 mg/dL) hypoglycemic events per patient-year of exposure of 0.58 with efsitora vs. 0.45 with insulin degludec (QWINT-2) and 6.6 with efsitora vs. 5.9 with insulin glargine (QWINT-4).
Detailed results from QWINT-2 will be presented at the European Association for the Study of Diabetes (EASD) Annual Meeting 2024. Topline readouts from QWINT-1, QWINT-3 and QWINT-5 are anticipated later this year.
About the QWINT clinical trial program
The QWINT phase 3 global clinical development program for insulin efsitora alfa (efsitora) in diabetes began in 2022 and has enrolled more than 4,000 people living with type 1 or type 2 diabetes across five global registration studies.
QWINT-2 (NCT05362058) was a parallel-design, open-label, treat-to-target, randomized controlled clinical trial comparing the efficacy and safety of efsitora as a once-weekly basal insulin to insulin degludec for 52 weeks in insulin-naïve adults with type 2 diabetes. The trial randomized 928 participants across the U.S., Brazil, Canada, China, Czechia (Czech Republic), Germany, Greece, Japan, Korea, Mexico and Puerto Rico to receive efsitora once weekly or insulin degludec once daily administered subcutaneously. The primary objective of the trial was to demonstrate non-inferiority in reducing A1C at week 52 with efsitora compared to insulin degludec. The trial was also designed to assess efficacy and safety for patients using and not using GLP-1 receptor agonists.
QWINT-4 (NCT05462756) was a parallel-design, open-label, treat-to-target, randomized controlled clinical trial comparing the efficacy and safety of efsitora as a weekly basal insulin to insulin glargine for 26 weeks in adults with type 2 diabetes who have previously been treated with basal insulin and at least two injections per day of mealtime insulin. The trial randomized 730 participants across the U.S., Argentina, Germany, India, Italy, Mexico, Puerto Rico and Spain to receive efsitora once weekly or insulin glargine once daily, both of which were administered subcutaneously along with insulin lispro. The primary objective of the trial was to demonstrate non-inferiority in reducing A1C at week 26 with efsitora compared to insulin glargine.
About insulin efsitora alfa
Insulin efsitora alfa (efsitora) is a once-weekly basal insulin, a fusion protein that combines a novel single-chain variant of insulin with a human IgG2 Fc domain. It is specifically designed for once-weekly subcutaneous administration, and with its low peak-to-trough ratio, it has the potential to provide more stable glucose levels (less glucose variability) throughout the week. Efsitora is in phase 3 development for adults with type 1 and 2 diabetes.
About Lilly
Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help more than 51 million people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news, or follow us on Facebook, Instagram and LinkedIn.
P-LLY
View original content to download multimedia:https://www.prnewswire.com/news-releases/with-once-a-week-dosing-insulin-efsitora-alfa-delivers-a1c-reduction-and-safety-profile-consistent-with-daily-insulin-302147034.html
SOURCE Eli Lilly and Company
Eli Lilly once-weekly insulin hits main goal in late-stage trials
May 16, 2024 7:21 AM ET
Eli Lilly and Company (LLY) Stock
By: Dulan Lokuwithana, SA News Editor
Eli Lilly (NYSE:LLY) announced Thursday that its once-weekly insulin therapy, efsitora, met its main goals in two Phase 3 trials for adults with type 2 diabetes, indicating a safety and efficacy profile in line with daily insulin injections.
Citing topline data from its QWINT-2 and QWINT-4 trials, the Indiana-based drugmaker said efsitora led to a reduction of the blood glucose biomarker A1C, comparable to daily insulin, reaching the main goals of both studies.
https://seekingalpha.com/news/4107209-eli-lilly-weekly-insulin-hits-main-goal-late-stage-trials
CT-388
LEQEMBI® (LECANEMAB-IRMB)
Insulin efsitora alfa (efsitora)
[Ad hoc announcement pursuant to Art. 53 LR] Roche reports positive Phase Ib results for its dual GLP-1/GIP receptor agonist CT-388 in people with obesity
May 16, 2024
- Over 24 weeks, a once-weekly subcutaneous injection of CT-388 achieved a clinically meaningful and statistically significant mean placebo-adjusted weight loss of 18.8% (p < 0.001)
- At week 24, 100% of CT-388 treated participants achieved >5% weight loss, 70% achieved >15% and 45% achieved >20% weight loss
- In a subgroup with pre-diabetes at baseline, CT-388 treatment normalised glycemia in all patients, indicating its strong impact on glucose homeostasis
- No new or unexpected safety signals were detected. Overall, CT-388 demonstrated a safety and tolerability profile consistent with its drug class
Basel, 16 May 2024 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today positive results from the Phase I clinical trial of CT-388, a dual GLP-1/GIP receptor agonist being developed for the treatment of obesity and type 2 diabetes. The study found that a once-weekly subcutaneous injection of CT-388 over 24 weeks resulted in significant weight loss in healthy adults with obesity compared to placebo. The weight loss achieved with CT-388 was clinically meaningful, with a mean placebo-adjusted weight loss of 18.8% (p-value < 0.001). At week 24, 100% of CT-388 treated participants achieved a weight loss of >5%, 85% achieved >10%, 70% achieved >15%, and 45% achieved >20%. The treatment was well tolerated, with mild to moderate gastrointestinal-related adverse events being the most common, consistent with the incretin class of medicines that CT-388 belongs to. All participants with a pre-diabetes status at baseline became normoglycemic after 24 weeks of CT-388 treatment, whereas glycemic status of participants treated with placebo remained largely unchanged during this period.
“We are very pleased to see the significant and clinically meaningful weight loss in people treated with CT-388,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “The results are highly encouraging for further development of CT-388 for both obesity and type 2 diabetes and underscore its potential to become a best-in-class therapy with durable weight loss and glucose control.”
Obesity is one of the most urgent health challenges in the world with extensive comorbidities, such as type 2 diabetes, cardiovascular diseases, steatohepatitis and chronic kidney disease. Over four billion people - about 50% of the world’s population - are estimated to be impacted by obesity or being overweight by 2035. The growing number puts an incredible strain on societies and healthcare systems around the world.
CT-388 belongs to the class of incretin-based medicines that aim to regulate blood sugar and reduce appetite. It selectively targets and activates two specific receptors in the body, known as GLP-1 and GIP, which integrate nutrient-derived signals to control food intake, energy absorption and assimilation. It is hypothesised that the dual targeting effect of CT-388 could result in a meaningful durable glucose reduction and weight loss, in addition to a favourable safety profile.
An additional cohort from the ongoing placebo-controlled Phase I trial of CT-388 will evaluate obese patients (BMI>30 kg/m2) with type 2 diabetes over a 12-week treatment duration. Roche expects data from this additional cohort in the second half of 2024.
About the CT-388 study
The CT-388-101 trial is a multi-arm, multi-cohort Phase I randomised, double-blind, placebo-controlled study designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of CT-388 in otherwise-healthy adult participants with overweight or obesity and in participants with obesity and type-2 diabetes mellitus.
The primary endpoint of the trial is safety and tolerability of CT-388; secondary endpoints include its effect on body weight and glucose homeostasis. Pharmacokinetics and other pharmacodynamic effects of CT-388 were also assessed.
About CT-388
CT-388 is a once-weekly subcutaneous injectable, dual GLP-1/GIP receptor agonist being developed for the treatment of obesity and type 2 diabetes (T2D). CT-388 was designed to have potent activity on both the GLP-1 and GIP receptors but with minimal to no ß-arrestin recruitment on either receptor. This biased signalling significantly minimises receptor internalisation and consequent desensitisation, which is expected to lead to prolonged pharmacological activity. It is currently being studied in a multi-part, multi-cohort Phase 1 clinical trial in people with overweight/obesity with and without T2D.
About Roche
Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice.
In recognising our endeavour to pursue a long-term perspective in all we do, Roche has been named one of the most sustainable companies in the pharmaceuticals industry by the Dow Jones Sustainability Indices for the fifteenth consecutive year. This distinction also reflects our efforts to improve access to healthcare together with local partners in every country we work.
Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan.
For more information, please visit www.roche.com.
All trademarks used or mentioned in this release are protected by law.
Roche obesity therapy leads to ~19% weight loss in Phase 1 trial
May 16, 2024 6:48 AM ET
Roche Holding AG (RHHBY) Stock, RHHBF StockAMGN, PFE, NVO, LLY, AZN, ALT, VKTX, GPCR
By: Dulan Lokuwithana, SA News Editor2 Comments
Roche (OTCQX:RHHBY) announced Thursday that its gut-hormone-mimicking obesity therapy, CT-388, caused 18.8% of weight loss on average over 24 weeks compared to placebo in a Phase 1 trial for healthy adults with obesity.
The results were clinically meaningful and statistically significant, the Swiss drugmaker added. The results were clinically meaningful and statistically significant, the Swiss drugmaker added. Roche (OTCQX:RHHBF) added CT-388 into its pipeline with its $2.7B acquisition of Berkeley, California-based biotech Carmot Therapeutics this year.
https://seekingalpha.com/news/4107185-roche-obesity-therapy-causes-19-weight-loss
LEQEMBI® (LECANEMAB-IRMB)
LEQEMBI® (LECANEMAB-IRMB)
LEQEMBI® (LECANEMAB-IRMB)
EISAI INITIATES ROLLING BIOLOGICS LICENSE APPLICATION TO US FDA FOR LEQEMBI® (LECANEMAB-IRMB) FOR SUBCUTANEOUS MAINTENANCE DOSING FOR THE TREATMENT OF EARLY ALZHEIMER'S DISEASE UNDER THE FAST TRACK STATUS
TOKYO and CAMBRIDGE, Mass., May 14, 2024 /PRNewswire/ -- Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") and Biogen Inc. (Nasdaq: BIIB, Corporate headquarters: Cambridge, Massachusetts, CEO: Christopher A. Viehbacher, "Biogen") announced today that Eisai has initiated the rolling submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for lecanemab-irmb (U.S. brand name: LEQEMBI®) subcutaneous autoinjector for weekly maintenance dosing after it was granted Fast Track designation by the FDA. LEQEMBI is indicated for the treatment of Alzheimer's disease (AD) in patients with Mild Cognitive Impairment (MCI) or mild dementia stage of disease (collectively referred to as early AD).
The BLA is based on data from the Clarity AD (Study 301) open-label extension (OLE) and modeling of observed data. If approved by the FDA, the LEQEMBI autoinjector could be used to administer LEQEMBI at home or at medical facilities. The injection process requires less time than the IV formulation. As part of the subcutaneous autoinjector 360 mg weekly maintenance regimen under review, patients who have completed the biweekly IV initiation phase would receive weekly doses that maintain effective drug concentrations to sustain the clearance of highly toxic protofibrils* which can continue to cause neuronal injury even after the amyloid-beta (Aβ) plaque has been cleared from the brain.
AD is an ongoing neurotoxic process that begins before and continues after plaque deposition. Data suggest that early and continuing treatment may prolong the benefit even after plaque is cleared from the brain. This SC autoinjector is easier for patients and their care partners to use, and may reduce the need for hospital visits and nursing care compared to intravenous (IV) administration. In addition to potentially maintaining the clinical and biomarker benefits, subcutaneous maintenance dosing may be more convenient for patients and their care partners to continue the treatment.
LEQEMBI is now approved in the U.S., Japan and China, and applications have been submitted for review in the European Union, Australia, Brazil, Canada, Hong Kong, Great Britain, India, Israel, Russia, Saudi Arabia, South Korea, Taiwan, Singapore and Switzerland. Eisai submitted to the FDA a Supplemental Biologics License Application (sBLA) for monthly LEQEMBI intravenous (IV) maintenance dosing in March 2024.
Eisai serves as the lead for lecanemab's development and regulatory submissions globally with both companies co-commercializing and co-promoting the product and Eisai having final decision-making authority.
* Protofibrils are believed to contribute to the brain injury that occurs with AD and are considered to be the most toxic form of Aβ, having a primary role in the cognitive decline associated with this progressive, debilitating condition.1 Protofibrils cause injury to neurons in the brain, which in turn, can negatively impact cognitive function via multiple mechanisms, not only increasing the development of insoluble Aβ plaques but also increasing direct damage to brain cell membranes and the connections that transmit signals between nerve cells or nerve cells and other cells. It is believed the reduction of protofibrils may prevent the progression of AD by reducing damage to neurons in the brain and cognitive dysfunction.2
INDICATION
LEQEMBI® [(lecanemab-irmb) 100 mg/mL injection for intravenous use] is indicated for the treatment of Alzheimer's disease (AD). Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment (MCI) or mild dementia stage of disease, the population in which treatment was initiated in clinical trials.
Please see full Prescribing Information for LEQEMBI, including Boxed WARNING.
1. About lecanemab (LEQEMBI®)
Lecanemab is the result of a strategic research alliance between Eisai and BioArctic. It is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibril) and insoluble forms of amyloid-beta (Aβ).3 Lecanemab is approved in the U.S.,4 Japan,5 and China.6. In the U.S., Japan and China, the indications are as follows:
- U.S.: For the treatment of Alzheimer's disease (AD). It should be initiated in patients with MCI or mild dementia stage of disease.3,7
- Japan: For slowing progression of MCI and mild dementia due to AD.5
- China: For the treatment of MCI due to AD and mild AD dementia.6
LEQEMBI's FDA approval was based on Phase 3 data from Eisai's, global Clarity AD clinical trial, in which it met its primary endpoint and all key secondary endpoints with statistically significant results.3 The primary endpoint was the global cognitive and functional scale, Clinical Dementia Rating Sum of Boxes (CDR-SB). In the Clarity AD clinical trial, treatment with lecanemab reduced clinical decline on CDR-SB by 27% at 18 months compared to placebo.3 The mean CDR-SB score at baseline was approximately 3.2 in both groups. The adjusted least-squares mean change from baseline at 18 months was 1.21 with lecanemab and 1.66 with placebo (difference, −0.45; 95% confidence interval [CI], −0.67 to −0.23; P<0.001).3 In addition, the secondary endpoint from the AD Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL), which measures information provided by people caring for patients with AD, noted a statistically significant benefit of 37% compared to placebo.3 The adjusted mean change from baseline at 18 months in the ADCS-MCI-ADL score was −3.5 in the lecanemab group and −5.5 in the placebo group (difference, 2.0; 95% CI, 1.2 to 2.8; P<0.001).3 The ADCS MCI-ADL assesses the ability of patients to function independently, including being able to dress, feed themselves and participate in community activities. The most common adverse events (>10%) in the lecanemab group were infusion reactions, ARIA-H (combined cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis), ARIA-E (edema/effusion), headache, and fall.3
Eisai has also submitted applications for approval of lecanemab in 14 countries and regions, including the European Union (EU).
Since July 2020 the Phase 3 clinical study (AHEAD 3-45) for individuals with preclinical AD, meaning they are clinically normal and have intermediate or elevated levels of amyloid in their brains, is ongoing. AHEAD 3-45 is conducted as a public-private partnership between the Alzheimer's Clinical Trial Consortium that provides the infrastructure for academic clinical trials in AD and related dementias in the U.S, funded by the National Institute on Aging, part of the National Institutes of Health, Eisai and Biogen. Since January 2022, the Tau NexGen clinical study for Dominantly Inherited AD (DIAD), that is conducted by Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU), led by Washington University School of Medicine in St. Louis, is ongoing and includes lecanemab as the backbone anti-amyloid therapy.
2. About the Collaboration between Eisai and Biogen for AD
Eisai and Biogen have been collaborating on the joint development and commercialization of AD treatments since 2014. Eisai serves as the lead of lecanemab development and regulatory submissions globally with both companies co-commercializing and co-promoting the product and Eisai having final decision-making authority.
3. About the Collaboration between Eisai and BioArctic for AD
Since 2005, Eisai and BioArctic have had a long-term collaboration regarding the development and commercialization of AD treatments. Eisai obtained the global rights to study, develop, manufacture and market lecanemab for the treatment of AD pursuant to an agreement with BioArctic in December 2007. The development and commercialization agreement on the antibody lecanemab back-up was signed in May 2015.
4. About Eisai Co., Ltd.
Eisai's Corporate Concept is "to give first thought to patients and people in the daily living domain, and to increase the benefits that health care provides." Under this Concept (also known as human health care (hhc) Concept), we aim to effectively achieve social good in the form of relieving anxiety over health and reducing health disparities. With a global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to create and deliver innovative products to target diseases with high unmet medical needs, with a particular focus in our strategic areas of Neurology and Oncology.
In addition, we demonstrate our commitment to the elimination of neglected tropical diseases (NTDs), which is a target (3.3) of the United Nations Sustainable Development Goals (SDGs), by working on various activities together with global partners.
For more information about Eisai, please visit www.eisai.com (for global headquarters: Eisai Co., Ltd.), and connect with us on X, LinkedIn and Facebook. For audiences based in the UK and Europe, please visit www.eisai.eu and Eisai EMEA LinkedIn.
5. About Biogen
Founded in 1978, Biogen is a leading biotechnology company that pioneers innovative science to deliver new medicines to transform patients' lives and to create value for shareholders and our communities. We apply deep understanding of human biology and leverage different modalities to advance first-in-class treatments or therapies that deliver superior outcomes. Our approach is to take bold risks, balanced with return on investment to deliver long-term growth.
The company routinely posts information that may be important to investors on its website at www.biogen.com. Follow Biogen on social media – Facebook, LinkedIn, X, YouTube.
SOURCE Eisai Inc.
Biogen partner Eisai begins FDA submissions for injectable Alzheimer’s therapy
May 15, 2024 7:44 AM ET
Biogen Inc. (BIIB) Stock, ESALF Stock, ESAIY Stock
By: Dulan Lokuwithana, SA News Editor
Biogen (NASDAQ:BIIB) and its partner Eisai (OTCPK:ESALF) (OTCPK:ESAIY) announced Wednesday the beginning of data submissions to the FDA on a rolling basis to obtain U.S. approval for an injectable version of their Alzheimer’s therapy, Leqembi.
The Japanese drugmaker, which leads global development and regulatory submissions for the anti-amyloid therapy, said it started the rolling submission of a Biologics License Application (BLA) for the treatment known as lecanemab-irmb.
https://seekingalpha.com/news/4106396-eisai-begins-fda-submissions-injectable-alzheimers-drug
Mim8
LEQEMBI® (LECANEMAB-IRMB)
LEQEMBI® (LECANEMAB-IRMB)
11:49 13 May 2024
Novo Nordisk A/S: Once-weekly and once-monthly Mim8 demonstrate superior reduction of treated bleeding episodes compared to on-demand and prior prophylaxis treatment in people with haemophilia A in the Frontier 2 trial
Bagsværd, Denmark, 13 May 2024 – Novo Nordisk today announced the headline results from the FRONTIER 2 trial, a pivotal phase 3a, 26-week open-label, randomised, controlled, multi-arm trial in 254 people. The trial investigated the efficacy and safety of once-weekly and once-monthly subcutaneous Mim8 versus no prophylaxis and versus prior coagulation factor prophylaxis treatment in people aged 12 years or older with haemophilia A with or without inhibitors.
The trial achieved its co-primary endpoints by demonstrating a statistically significant and superior reduction of treated bleeding episodes with both once-weekly and once-monthly Mim8 versus no prophylaxis treatment and prior coagulation factor prophylaxis treatment.
In people with no prior prophylaxis treatment, once-weekly and once-monthly Mim8 demonstrated superior reductions of 97% and 99% in treated bleeds, respectively, compared to those who received no prophylaxis treatment. In addition, 86% of people treated with once-weekly Mim8 and 95% of those treated with once-monthly Mim8 experienced zero treated bleeds, compared to 0% of those treated with no prophylaxis.
In the intra-patient analysis in people with prior coagulation factor prophylaxis, once-weekly and once-monthly Mim8 demonstrated superior reductions of 48% and 43% in treated bleeds, respectively, compared to prior coagulation factor prophylaxis (during run-in period of 26-52 weeks prior to initiation of Mim8 treatment). Additionally, 66% of people treated with once-weekly Mim8 and 65% of people treated with once-monthly Mim8 experienced zero treated bleeds.
In the trial, Mim8 appeared to have a safe and well-tolerated profile in line with previous trials. No deaths or thromboembolic events were reported in the trial.
“We are very pleased with the positive results from the FRONTIER 2 clinical trial. These data demonstrate the ability of Mim8 to prevent bleeding episodes effectively and safely in people with haemophilia A, regardless of their dosing frequency,” said Martin Holst Lange, executive vice president for Development at Novo Nordisk. “Given the differing needs of people living with haemophilia A, a convenient once-weekly or once-monthly dosing provides optionality and flexibility for people living with haemophilia A with or without inhibitors.”
Contingent on regulatory interactions, Novo Nordisk aims to submit Mim8 for the first regulatory approval towards the end of 2024. Data from the phase 3 FRONTIER programme, including FRONTIER 2 will be disclosed at upcoming congresses and in publications in 2024 and 2025.
About Haemophilia
Haemophilia is a rare inherited bleeding disorder that impairs the body’s ability to make blood clots, a process needed to stop bleeding. It is estimated to affect approximately 1,125,000 people worldwide, and haemophilia A is estimated to account for 80-85% of all haemophilia cases. Due to the nature of haemophilia being a rare x-linked recessive disorder, it often presents differently in males compared to females, with ~ 88% of people diagnosed with haemophilia worldwide being male. There are different types of haemophilia, which are characterised by the type of clotting factor protein that is defective or missing. Haemophilia A is caused by a missing or defective clotting Factor VIII (FVIII). Some people with haemophilia may also develop inhibitors, which are an immune system response to the clotting factors in replacement therapy that cause treatment to stop working. Currently, it is estimated that up to 30% of people living with haemophilia A have inhibitors.
About Mim8
Mim8 is a next-generation FVIIIa mimetic bispecific antibody delivering sustained haemostasis for once-weekly or once-monthly prophylaxis for people living with haemophilia A, with and without inhibitors. Administered subcutaneously, Mim8 bridges Factor IXa/X (FIXa/FX) together upon activation, thereby replacing missing FVIII, which effectively restores the body’s thrombin generation capacity, helping blood to clot.
About the FRONTIER Programme
The FRONTIER clinical development programme investigates Mim8 as a preventative treatment for people with haemophilia A, with or without inhibitors. The phase 3 programme includes:
FRONTIER 2 – a 52-week efficacy and safety phase 3 trial, with a 26-52-week run-in period comparing once-weekly and once-monthly Mim8 versus no prophylaxis, and versus prior coagulation factor prophylaxis treatment prior to enrolment in people aged 12 years and over with haemophilia A, with or without inhibitors. Following the completion of the 26-week main phase of the trial, a 26-week extension phase is ongoing.
FRONTIER 3 – a 52-week safety and efficacy phase 3 trial in paediatric patients with haemophilia A, with or without inhibitors (1-11 years). People will receive once-weekly Mim8 during the first 26 weeks and may subsequently choose to receive once-monthly Mim8.
FRONTIER 4 – an open-label extension following participation in the FRONTIER phase 2 and phase 3 studies. The study allows the collection of long-term safety data.
FRONTIER 5 – a 26-week phase 3 trial investigating pharmacokinetics, pharmacodynamics and safety of switching from previous emizicumab to Mim8 in adults and adolescents with haemophilia A, with or without inhibitors.
About Novo Nordisk
Novo Nordisk is a leading global healthcare company, founded in 1923 and headquartered in Denmark. Our purpose is to drive change to defeat serious chronic diseases, built upon our heritage in diabetes. We do so by pioneering scientific breakthroughs, expanding access to our medicines, and working to prevent and ultimately cure disease. Novo Nordisk employs about 66,000 people in 80 countries and markets its products in around 170 countries. Novo Nordisk's B shares are listed on Nasdaq Copenhagen (Novo-B). Its ADRs are listed on the New York Stock Exchange (NVO). For more information, visit novonordisk.com, Facebook, Instagram, X, LinkedIn and YouTube.
Novo Nordisk hemophilia candidate Mim8 meets primary goals in phase 3 trial
May 13, 2024 2:28 PM ET
By: Jonathan Block, SA News Editor
- Novo Nordisk (NVO) said that top-line data from a phase 3a trial of its experimental hemophilia A treatment Mim8 met co-primary endpoints when given both weekly and once a month.
- https://seekingalpha.com/news/4105364-novo-nordisk-hemophilia-candidate-mim8-meets-primary-goals-phase-3-trial
- Novo Nordisk A/S (NVO) Stock
- https://www.novonordisk.com/science-and-technology/r-d-pipeline.html
anitocabtagene autoleucel (anito-cel) with SOC
anitocabtagene autoleucel (anito-cel) with SOC
anitocabtagene autoleucel (anito-cel) with SOC
May 09, 2024
Kite and Arcellx Continue Momentum with Advances in Anito-Cel Multiple Myeloma Program
-- The companies share design of global Phase 3 trial, iMMagine-3; will evaluate anito-cel in patients exposed to both an immunomodulatory (lMiD) drug and an anti-CD38 monoclonal antibody --
-- Anito-cel will be manufactured from Kite’s Frederick, Maryland facility for iMMagine-3 as the successful technical transfer is complete --
-- Remain on track to present preliminary data from the iMMagine-1 trial by end of the year --
REDWOOD CITY, Calif. & SANTA MONICA, Calif.--(BUSINESS WIRE)-- Kite, a Gilead Company (NASDAQ: GILD), and Arcellx, Inc. (NASDAQ: ACLX) today announced several key operational updates on their partnered anitocabtagene autoleucel (anito-cel) multiple myeloma program. Anito-cel is the first BCMA CAR T to be investigated in multiple myeloma that utilizes Arcellx’s novel and compact D-Domain binder.
The companies shared the design of a global, Phase 3 randomized controlled clinical trial, iMMagine-3, which Kite expects to start in the second half of this year. The trial will compare the efficacy and safety of anito-cel randomized against the standard of care (SOC) in patients with relapsed and/or refractory multiple myeloma (rrMM) who have received one to three prior lines of therapy, including an immunomodulatory drug (lMiD) and an anti-CD38 monoclonal antibody.
Kite’s facility in Frederick, Maryland will manufacture anito-cel for this trial. This follows the completion of the technical transfer from a third-party contract manufacturing organization to Kite, as well as the transfer of the Investigational New Drug (IND) application for anito-cel, which has been cleared by the U.S. Food and Drug Administration.
“We are pleased to start the Phase 3 pivotal trial, iMMagine-3, in the second half of this year given the tremendous unmet need that remains in patients with relapsed and/or refractory multiple myeloma,” said Cindy Perettie, Executive Vice President, Kite. “As we prepare for this pivotal program, we look forward to leveraging our manufacturing expertise to further position anito-cel as a potential best-in-class cell therapy. We know manufacturing quality, reliability and speed are critically important as every day matters for these patients.”
“Our global iMMagine-3 trial will evaluate anito-cel as a second through fourth line treatment in patients with multiple myeloma who were previously exposed to both an immunomodulatory drug and an anti-CD38 monoclonal antibody,” said Rami Elghandour, Arcellx’s Chairman and Chief Executive Officer. “The iMMagine-3 study allows us to maximize the impact of anito-cel as it captures what will become the largest second line patient population based on the current treatment paradigm, as anti-CD38 therapies move to front line treatment. This population represents an emerging significant unmet clinical need allowing us to provide access to a unique patient population. In addition, the completion of the technical transfer to Kite allowed us to accelerate our development program and launch iMMagine-3 globally, which will enable broader and earlier patient access to anito-cel.”
About iMMagine-3 Global Phase 3 Randomized Controlled Clinical Trial
iMMagine-3 is a phase 3, randomized controlled trial designed to compare the efficacy and safety of anitocabtagene autoleucel (anito-cel) with SOC in patients with relapsed and/or refractory multiple myeloma (rrMM) who have received one to three prior lines of therapy, including an immunomodulatory drug (lMiD) and an anti-CD38 monoclonal antibody.
iMMagine-3 will enroll approximately 450 adult patients. Prior to randomization, investigator’s choice of SOC regimens include: pomalidomide, bortezomib, and dexamethasone (PVd); daratumumab, pomalidomide, and dexamethasone (DPd); carfilzomib, daratumumab and dexamethasone (KDd); or carfilzomib and dexamethasone (Kd). Patients in the anito-cel arm will undergo leukapheresis and optional bridging therapy (with the SOC regimen selected by the investigator prior to randomization) followed by lymphodepleting chemotherapy (fludarabine 30 mg/m2/d and cyclophosphamide 300 mg/m2/d for 3 days) and one infusion of anito-cel (115×106 CAR+ T cells) on Day 1.
The primary endpoint is progression free survival (PFS) per blinded independent review according to the 2016 IMWG uniform response criteria for MM with the hypothesis that anito-cel will prolong PFS compared to SOC. Key secondary endpoints include complete response rate (CR/sCR), minimal residual disease negativity, overall survival, and safety.
The iMMagine-3 trial is expected to initiate in the second half of 2024 at ~130 study sites across North America, Europe, and rest of world.
About Arcellx and Kite Collaboration
Arcellx and Kite, a Gilead Company, formed a global strategic collaboration to co-develop and co-commercialize Arcellx's anito-cel candidate for the treatment of patients with relapsed or refractory multiple myeloma currently in a pivotal Phase 2 trial. Kite and Arcellx will jointly develop and commercialize the anito-cel asset in the United States, and Kite will commercialize the product outside the United States.
About anitocabtagene autoleucel (anito-cel)
Anito-cel is a BCMA CAR T that utilizes a novel binder (or CAR) known as the D-Domain. Its small size (8kDa) facilitates high T-cell transduction and expression, resulting in more CAR positive cells and more CARs expressed per T-cell.
Anito-cel has been granted Fast Track, Orphan Drug, and Regenerative Medicine Advanced Therapy designations by the U.S. Food and Drug Administration.
About Kite
Kite, a Gilead Company, is a global biopharmaceutical company based in Santa Monica, California, focused on cell therapy to treat and potentially cure cancer. As the global cell therapy leader, Kite has treated more patients with CAR T-cell therapy than any other company. Kite has the largest in-house cell therapy manufacturing network in the world, spanning process development, vector manufacturing, clinical trial production and commercial product manufacturing.
About Gilead Sciences
Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California. Gilead acquired Kite in 2017.
About Arcellx, Inc.
Arcellx, Inc. is a clinical-stage biotechnology company reimagining cell therapy by engineering innovative immunotherapies for patients with cancer and other incurable diseases. Arcellx believes that cell therapies are one of the forward pillars of medicine and Arcellx's mission is to advance humanity by developing cell therapies that are safer, more effective, and more broadly accessible. Arcellx's lead product candidate, anito-cel (formerly CART-ddBCMA), is being developed for the treatment of relapsed or refractory multiple myeloma (rrMM) in a Phase 2 pivotal trial.
Arcellx is also developing its dosable and controllable CAR T therapy, ARC-SparX, through two Phase 1 programs, ACLX-001 for rrMM and ACLX-002 in relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome. For more information on Arcellx, please visit www.arcellx.com. Follow Arcellx on X (Twitter) at @arcellx and LinkedIn.
Source: Gilead Sciences, Inc.
Gilead's Kite, Arcellx share phase 3 trial design for CAR-T multiple myeloma asset
May 09, 2024 5:13 PM ET
Gilead Sciences, Inc. (GILD) Stock, ACLX Stock
By: Jonathan Block, SA News Editor
- Kite, a division of Gilead Sciences (NASDAQ:GILD), and Arcellx (NASDAQ:ACLX) will begin a phase 3 study of their CAR-T multiple myeloma treatment anitocabtagene autoleucel (anito-cel) in the H2 2024 with preliminary data expected by the end of the year.
- The trial, iMMagine-3, will be rendomized and compare anito-cel against the standard of care in individuals with relapsed/refractory multiple myeloma who have received one to three prior lines of treatment.
- https://seekingalpha.com/news/4104222-gilead-kite-arcellx-share-phase-3-trial-design-car-t-multiple-myeloma-asset
- Gilead Sciences, Inc. (GILD) Stock, ACLX Stock
- https://www.gilead.com/
- https://www.arcellx.com/
Mazdutide
anitocabtagene autoleucel (anito-cel) with SOC
anitocabtagene autoleucel (anito-cel) with SOC
Head-to-head Superiority to High-dose Dulaglutide: Innovent’s First Phase 3 Clinical Trial of Mazdutide in Chinese Patients with Type 2 Diabetes Met Study Endpoints
Published on: May 9th, 2024
SAN FRANCISCO, U.S. and SUZHOU, China, May 9, 2024, - Innovent Biologics, Inc. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, autoimmune, cardiovascular and metabolic, ophthalmology and other major diseases, announces that the Phase 3 clinical trial (DREAMS-2) of mazdutide (Innovent R&D code: IBI362), a glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) dual agonist, in Chinese subjects with type 2 diabetes (T2D) met the primary endpoint. The study results suggested that mazdutide was superior compared with dulaglutide for glycaemic control, and mazdutide also showed multiple cardiometabolic benefits in T2D patients including weight loss, blood lipid, blood pressure, serum uric acid, liver enzymes, etc.
DREAMS-2 (ClinicalTrials.gov, NCT05606913) is a multi-center, randomized Phase 3 clinical study to compare the efficacy and safety of mazdutide and dulaglutide in Chinese subjects with T2D who have inadequate glycemic control with metformin monotherapy or combination therapy of metformin with other oral drugs. The study enrolled 731 subjects to receive either mazdutide 4.0 mg, mazdutide 6.0 mg or dulaglutide 1.5 mg for 28 weeks. The primary endpoint was the change from baseline to week 28 in glycated hemoglobin (HbA1c) levels. The study used a non-inferiority design, and further superiority testing was performed after non-inferiority was achieved.
The primary endpoint was successfully met, showing a robust glucose-lowering efficacy of mazdutide
After 28 weeks of treatment, mazdutide 4.0 mg and mazdutide 6.0 mg showed non-inferiority to dulaglutide 1.5 mg in terms of improvement in HbA1c level from baseline. Based on these results, the superiority test was further performed, and both mazdutide 4.0 mg and 6.0 mg achieved superiority to dulaglutide 1.5 mg.
The key secondary endpoints showed mazdutide’s superior benefits in both glucose-lowering and weight loss
Statistical superiority was achieved in the following endpoints in both mazdutide 4.0 mg and mazdutide 6.0 mg groups after 28 weeks of treatment, including the change from baseline in HbA1c (superiority), percent change from baseline in body weight, proportion of subjects with HbA1c < 7.0% and weight loss of ≥ 5%, and proportion of subjects with HbA1c < 7.0%*.
Mazdutide showed comprehensive benefits beyond glucose-lowering and weight loss in multiple cardiometabolic indicators (blood pressure, blood lipids, serum uric acid, and liver enzymes)
Mazdutide also showed significant advantages compared with dulaglutide in various indicators, including the proportion of subjects with HbA1c ≤ 6.5%, changes in fasting blood glucose and seven-point fingerstick blood glucose from baseline, the proportion of subjects with body weight loss of ≥ 5% and ≥ 10%, absolute change in body weight from baseline, waist circumference, body mass index (BMI), systolic blood pressure (SBP), triglyceride (TG), serum uric acid (UA), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), etc.
Favorable safety and tolerability profile
- Gastrointestinal adverse reactions were the most common adverse events, most were mild to moderate in severity , transient, and mainly occurred during the first 12-week titration period.
- No severe hypoglycemia occurred; the incidence of moderate or severe hypoglycemia was comparable to that of dulaglutide; and the incidence of hypoglycemia was lower in indirect comparison to reported in registrational studies of other GLP-1 drugs.
- No signal of increased cardiovascular risk throughout the treatment period, similar to dulaglutide.
- The overall safety profile was consistent with that observed in previous clinical studies of mazdutide and no new safety signals observed.
Mazdutide is the first GLP-1R/GCGR dual agonist in the regulatory review status, with the first new drug application (NDA) for chronic weight management under review by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA). DREAMS-2, as one of the registrational clinical studies of mazdutide, will provide high-quality evidence of mazdutide for Chinese population with T2D. Innovent plans to read out the results of another DREAMS-1 Phase 3 clinical study in mid-2024 and submit to the CDE an NDA for the treatment of T2D with mazdutide. Detailed data from the DREAMS-1 and DREAMS-2 studies will be further analyzed and published at academic congresses or in clinical journals.
Professor Lixin Guo, the principal investigator of the clinical study, Department of Endocrinology in Beijing Hospital, said: “In China, T2D patients often have a variety of chronic diseases as comorbidities, such as obesity, hyperlipidemia, coronary heart disease, hypertension and so on. Therefore, the management of T2D should take into consideration the improvements in blood glucose, blood lipid, blood pressure and other aspects. In endocrine and CVM areas, GLP-1-based drugs are the hotspot of research and development for the healthcare industry as well as for clinicians, especially multi-target drugs that are potentially more efficacious and can provide more metabolic benefits. DREAMS-2 is the first Phase 3 clinical study head-to-head with dulaglutide in China, which has high clinical significance and academic value. The results of this study showed that mazdutide, compared with dulaglutide, has a stronger glycaemic lowering effect and favorable safety profile. More importantly, mazdutide provided more comprehensive benefits in weight loss, blood lipid, blood pressure, blood uric acid, liver enzymes and other aspects. I look forward to the NDA submission of mazdutide in T2D, and wish it to benefit hundreds of millions of diabetic patients in China.”
Professor Yang Wenying, the principal investigator of the clinical study, Department of Endocrinology in China Japan Friendship Hospital, said: “China has the largest number of T2D patients in the world, and the prevalence of T2D among adults in China has reached 11.9%. Together with other investigators of the DREAMS-2 study, I am pleased to see that mazdutide, as a new generation of GLP-1R/GCGR dual target agonist, has met the primary endpoint and demonstrated superiority in change from baseline in HbA1c and multiple metabolic benefits compared with dulaglutide. DREAMS-2 is a landmark study as it is the first successful registrational study of a GLP-1R/GCGR dual target agonist in T2D. I believe that in the near future, mazdutide will provide a new and better choice for the treatment of type 2 diabetes in China.”
Dr. Lei Qian, Vice President of Clinical Development of Innovent, said: “There is a huge population of diabetes in China. Innovative drugs that are more effective, safer and more convenient are urgently needed. In the DREAMS-2 study, mazdutide showed comprehensive superiority to dulaglutide, one of the most-described glucose-lowering drugs in the world. We will further analyze the study data, and strive to submit an NDA for T2D as soon as possible this year, so as to help more Chinese T2D patients to achieve target blood glucose levels and acquire metabolic benefits. At the same time, we look forward to the performance of mazdutide in the DREAMS-3 study, a head-to-head study with semaglutide.”
About Diabetes
According to the global overview of diabetes published by the International Diabetes Federation in 2021, China ranks first in the number of patients with diabetes globally, with an estimated number of more than 140 million in 2021 and 174 million in 2045 [1]. Poor glycemic control can lead to irreversible microvascular and macrovascular complications, such as decreased visual acuity, blindness, renal dysfunction, peripheral neuropathy, myocardial infarction, stroke and amputation [2]. The high incidence of diabetes, with serious complications, are of serious threat to human health. At present, there are many therapeutic regimens for diabetes. In addition to effectively controlling blood glucose, the development of new hypoglycemic drugs has begun to include the additional benefits of weight loss, cardiovascular risk reduction and kidney protection for patients with diabetes [3].
About Mazdutide (IBI362)
Innovent entered into an exclusive license agreement with Eli Lilly and Company (Lilly) for the development and potential commercialization of OXM3 (also known as mazdutide), a GLP-1R and GCGR dual agonist, in China. As a mammalian oxyntomodulin (OXM) analogue, in addition to the effects of GLP-1 receptor agonists on promoting insulin secretion, lowering blood glucose and reducing body weight, mazdutide may also increase energy expenditure and improve hepatic fat metabolism through the activation of glucagon receptor. Mazdutide has demonstrated robust weight loss and glucose-lowering effects in clinical studies, as well as multiple cardio-metabolic benefits, including reducing waist circumference, blood lipids, blood pressure, blood uric acid, liver enzymes, liver fat content and improving insulin sensitivity. Currently, a total of five Phase 3 registrational studies are underway, including GLORY-1 (4 mg and 6 mg) in Chinese overweight or obese subjects, GLORY-2 (9 mg) in Chinese obese subjects, DREAMS-1, DREAMS-2, and DREAMS-3 (mazdutide in subjects with type 2 diabetes). Among them, GLORY-1 study and DREAMS-2 study have reached the endpoints.
About Innovent
Innovent is a leading biopharmaceutical company founded in 2011 with the mission to provide high-quality biologics that are affordable to all. The company discovers, develops, manufactures and commercializes innovative medicines that treat some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has 10 products in the market, 3 new drug applications under the NMPA review, 5 assets in Phase III or pivotal clinical trials and 18 more molecules in early clinical stage. Innovent partners with over 30 global healthcare leaders, including Eli Lilly, Roche, Sanofi, Adimab, Incyte and MD Anderson Cancer Center.
Guided by the motto, "Start with Integrity, Succeed through Action," Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit www.innoventbio.com, or follow Innovent on Facebook and LinkedIn.
Statement: Innovent does not recommend the use of any unapproved drug (s)/indication (s).
* Note: This is based on efficacy estimand. The study used efficacy estimand and treatment-regimen estimand for statistical analysis, and they showed a high degree of concordance in the conclusions.
Lilly next-generation diabetes drug mazdutide meets primary goal in phase 3 trial
May 09, 2024 12:40 PM ET
Eli Lilly and Company (LLY) StockIVBIY, IVBXF
By: Jonathan Block, SA News Editor1 Comment
- A phase 3 trial in China of Eli Lilly's (NYSE:LLY) glucagon-like peptide-1 receptor (GLP-1) and glucagon receptor (GCGR) dual agonist mazdutide met its primary endpoint in a type 2 diabetes trial.
- Data indicated that mazdutide bested Lilly's Trulicity dulaglutide in terms of glycemic control. Also, those on mazdutide demonstrated weight loss, as well as improvements in blood lipid levels, blood pressure, serum uric acid, and liver enzymes.
- After 28 weeks of treatment, mazdutide 4 mg and 6 mg showed non-inferiority to dulaglutide 1.5 mg in improvement in HbA1c level from baseline. A superiority test indicated both doses of mazdutide were superior to dulaglutide.
- https://seekingalpha.com/news/4103883-lilly-next-generation-diabetes-drug-mazdutide-meets-primary-goal-phase-3-trial?mailingid=35323124&messageid=2900&serial=35323124.1443&utm_campaign=rta-stock-news&utm_content=link-1&utm_medium=email&utm_source=seeking_alpha&utm_term=35323124.1443
- Eli Lilly and Company (LLY) StockIVBIY, IVBXF
- https://www.lilly.com/
- https://www.innoventbio.com/
- https://www.innoventbio.com/ScienceAndProducts/Pipeline
- https://www.hkex.com.hk/Market-Data/Securities-Prices/Equities/Equities-Quote?sym=1801&sc_lang=en
Cretostimogene Grenadenorepvec
anitocabtagene autoleucel (anito-cel) with SOC
Cretostimogene Grenadenorepvec
Cretostimogene Monotherapy Demonstrated 75.2% Complete Response Rate in High-Risk, BCG-Unresponsive Non-Muscle Invasive Bladder Cancer
May 03, 2024
- Phase 3 BOND-003 study results showed sustained, durable complete responses over 12 months with novel investigational oncolytic immunotherapy -
- Company will hold an investor conference call today at 4:30pm EDT -
IRVINE, Calif., May 03, 2024 (GLOBE NEWSWIRE) -- CG Oncology, Inc. today announced that data from the Phase 3 BOND-003 study evaluating the efficacy and safety of cretostimogene monotherapy in patients with high-risk Non-Muscle Invasive Bladder Cancer (NMIBC) unresponsive to Bacillus Calmette Guerin (BCG), showed that 75.2% of patients (79 out of 105 [95% confidence interval (CI), 65-83]) achieved a complete response (CR) at any time, as of the cutoff date of April 1, 2024. These data were featured today at the Paradigm-Shifting, Practice-Changing Clinical Trials in Urology Plenary Session as an oral presentation (Abstract #24-11358) by Dr. Mark D. Tyson, Urologic Oncologist at Mayo Clinic, at the 2024 American Urological Association (AUA) Annual Meeting, in San Antonio, TX. In addition, cretostimogene has shown durable responses over time with twenty-nine patients maintaining a complete response for 12 months or more, pending evaluation and assessment of ongoing responses in twenty-two patients as of the data cutoff. Median duration of response (DOR) was not reached. 92.4% cystectomy-free survival was observed and none of the patients with a complete response had undergone radical cystectomy or showed nodal or metastatic progression.
Cretostimogene is an investigational oncolytic immunotherapy which has shown selective oncolysis and potent anti-tumor immune response, and is being evaluated in BOND-003 (NCT04452591), a single-arm, Phase 3, monotherapy clinical trial for the treatment of patients with high-risk BCG-unresponsive NMIBC with carcinoma in-situ (CIS) with or without Ta or T1 papillary tumors. The fully enrolled global trial with a total of 112 patients is currently ongoing in North America and the Asia-Pacific region. The primary endpoint of the study is CR at any time, with DOR measured as a secondary endpoint. The highly pre-treated study population includes patients with prior intravesical chemotherapy and systemic immunotherapy.
There were no Grade 3 or higher treatment-related adverse events (TRAEs) or deaths reported, and two patients (1.8%) had serious TRAEs (Grade 2). No treatment-related discontinuation of cretostimogene was observed. 94.5% of patients completed all expected treatments. TRAEs occurred in 70 patients (62.5%). The most common TRAEs (≥10%) were bladder spasm, pollakiuria, dysuria, micturition urgency, and hematuria, as of the safety cutoff date of January 31, 2024.
“The positive 12-month BOND-003 data presented at AUA 2024, with a notable duration of response, reinforces cretostimogene monotherapy as a potential backbone therapy in the NMIBC treatment landscape for BCG-unresponsive patients. This innovative immunotherapy candidate may, if approved, emerge as a favored option for patients over the surgical extraction of their bladder, as they face limited options,” said Gary D. Steinberg, M.D., Professor, Department of Urology at Rush University Medical Center. “Cretostimogene reported remarkable interim efficacy results, with over half of the patients experiencing complete responses upon repeat induction. There continues to be a need for new options for patients with bladder cancer.”
“We’re thrilled to present today’s updated data which reinforces cretostimogene’s potential as a bladder-sparing therapeutic that could materially improve both patient outcomes and quality of life,” said Ambaw Bellete, President & Chief Operating Officer, CG Oncology. “Importantly, with topline data expected from BOND-003 by the end of 2024, we look forward to a regulatory approval submission.”
Last December, the U.S. Food and Drug Administration (FDA) granted both Fast Track Designation and Breakthrough Therapy Designation for cretostimogene in high-risk BCG-unresponsive NMIBC with carcinoma in-situ with or without Ta or T1 papillary tumors.
Investor Conference Call
CG Oncology will host a conference call and live webcast at 4:30pm EDT today on May 3, 2024. Individuals interested in listening to the live conference call may do so by using the webcast link in the “Investor Relations" section of the company's website at https://ir.cgoncology.com. A webcast replay will be available in the investor relations section on the company's website following the completion of the call.
About Cretostimogene Grenadenorepvec
Cretostimogene is an investigational, intravesically delivered oncolytic immunotherapy being evaluated in BOND-003, a Phase 3 clinical trial for the treatment of patients with high-risk Non-Muscle Invasive Bladder Cancer (NMIBC) who are unresponsive to Bacillus Calmette Guerin (BCG) therapy. Cretostimogene was previously evaluated in a Phase 2 clinical trial (CORE-001) in combination with pembrolizumab in the same indication and is also being evaluated in a Phase 3 monotherapy clinical trial (PIVOT-006) in intermediate-risk NMIBC patients. In addition, cretostimogene is being evaluated in an investigator-sponsored clinical trial in combination with nivolumab for the treatment of muscle invasive bladder cancer.
About the BOND-003 Clinical Study
BOND-003 (NCT04452591) is a single-arm, open-label, Phase 3 clinical trial evaluating cretostimogene as monotherapy in patients with high-risk NMIBC unresponsive to BCG therapy. The study fully enrolled 112 evaluable patients with BCG-unresponsive NMIBC across North America and the Asia-Pacific region.
About Bladder Cancer
More than 83,000 people are estimated to be diagnosed with bladder cancer in 2024. NMIBC is the most common form of bladder cancer, representing approximately 75% of newly diagnosed cases. Bladder cancer is the sixth most common form of cancer in the United States, and men account for three quarters of newly diagnosed cases.
About CG Oncology
CG Oncology is a late-stage clinical biopharmaceutical company focused on developing and commercializing a potential backbone bladder-sparing therapeutic for patients afflicted with bladder cancer. CG Oncology sees a world where urologic cancer patients may benefit from our innovative immunotherapies to live with dignity and have an enhanced quality of life. To learn more, please visit: www.cgoncology.com.
CG Oncology reports data from Phase 3 bladder cancer study
May 03, 2024 5:23 PM ET
CG Oncology, Inc. (CGON) Stock
By: Val Brickates Kennedy, SA News Editor
CG Oncology (NASDAQ:CGON), which went public in late January, reported data for its drug cretostimogene as a monotherapy in the treatment of a certain type of bladder cancer.
The biotech company said the Phase 3 study showed 75.2% of patients, or 79 out of 105, achieved a complete response at any time, the primary endpoint of the study.
https://seekingalpha.com/news/4099973-cg-oncology-reports-data-from-phase-3-bladder-cancer-study
SIRTURO® (bedaquiline)
MNKD-101 (Clofazimine Inhalation Suspension)
Cretostimogene Grenadenorepvec
Johnson & Johnson Receives Positive CHMP Opinion Recommending Full Approval for SIRTURO® (bedaquiline) for Treatment of Multidrug-Resistant Tuberculosis
CHMP recommends Conditional Marketing Authorisation be converted into standard Marketing Authorisation
Recommendation supported by results from the Phase 3 STREAM Stage 2 study, which show bedaquiline-containing regimens offer significant improvement compared to other available therapies
APRIL 29, 2024
Beerse, Belgium, (April 29, 2024) – Johnson & Johnson announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended the approval of a Type II variation for SIRTURO® (bedaquiline) and the conversion of the medicine’s Conditional Marketing Authorisation into a standard Marketing Authorisation. SIRTURO® is currently indicated for use as part of an appropriate combination regimen for pulmonary multidrug-resistant tuberculosis (MDR TB) in adult and pediatric patients (5 years to less than 18 years of age and weighing at least 15 kg) when an effective treatment regimen cannot otherwise be composed for reasons of resistance or tolerability. i The approved indication may vary per country. The Company’s continued support for bedaquiline reflects its longstanding commitment to patients affected by MDR-TB.
The positive CHMP recommendation is supported by data from the Phase 3 STREAM Stage 2 study (NCT02409290), the first large-scale, randomized, multi-country clinical study to evaluate the efficacy and safety of an all-oral bedaquiline-containing regimen for treatment of MDR-TB. Results from the study showed bedaquiline-containing regimens offered a significant improvement over other therapies, confirm the positive risk-benefit of treatment with bedaquiline and were published in The Lancet in November 2022.ii
SIRTURO® was first granted accelerated approval by the U.S. Food and Drug Administration (FDA) in December 2012 and conditional approval by the EMA in March 2014 following positive Phase 2 study data.iii,iv In addition to the Type II variation filed with EMA, a supplemental New Drug Application was submitted to the FDA in August 2023 to support the transition to full approval in the U.S., and is currently under review.v
Johnson & Johnson’s Commitment to TB Patients
Johnson & Johnson has long been committed to helping end tuberculosis. When Johnson & Johnson introduced SIRTURO®, it was the first targeted medicine for TB with a novel mechanism of action to be introduced in over 40 years. Today, it is a core component of World Health Organization-recommended treatment guidelines for drug-resistant TB, and three of every four MDR-TB patients on treatment are receiving a bedaquiline-containing regimen. More than 800,000 courses of the medicine have been shipped to 159 countries.
In 2023, Johnson & Johnson granted the Stop TB Partnership’s Global Drug Facility (GDF) a license that enabled GDF to tender, procure and supply generic versions of SIRTURO® (bedaquiline) for the majority of low-and middle-income countries and confirmed its intent to not to enforce patents it owns and controls for SIRTURO® in 134 low- and middle-income countries.vi
In collaboration with partners, Johnson & Johnson has spent the decade since the introduction of the medicine investing in critical TB systems capacity, such as healthcare professional training, resistance testing and surveillance, and supply chain security, to help ensure the medicine is accessible. These efforts include supporting community-centered efforts to help bring more people living with TB into treatment, further expand access to TB medicines and achieve the global goal of ending TB.
About SIRTURO®
EU
For a full list of adverse events and information on dosage and administration, contraindications and other precautions when using bedaquiline, please refer to the Summary of Product Characteristics.
About Johnson & Johnson
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at https://www.jnj.com/.
© Janssen-Cilag International NV. All rights reserved.
EU regulators recommend full approval for J&J TB drug Sirturo
Apr. 29, 2024 11:20 AM ET
By: Val Brickates Kennedy, SA News Editor
Johnson & Johnson (NYSE:JNJ) has received a positive recommendation from the European Medicines Agency’s Committee for Medicinal Products for Human Use for full approval of the company’s drug Sirturo for the treatment of certain patients with pulmonary multidrug-resistant tuberculosis.
V116
MNKD-101 (Clofazimine Inhalation Suspension)
MNKD-101 (Clofazimine Inhalation Suspension)
Merck Announces Positive Data for V116, an Investigational, 21-Valent Pneumococcal Conjugate Vaccine Specifically Designed for Adults
April 29, 2024 9:00 am ET
Late-breaker Phase 3 STRIDE-10 trial presented as an oral presentation at European Society of Clinical Microbiology and Infectious Diseases
Results build on the data supporting the clinical profile of V116 for adults
RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced results from STRIDE-10, a Phase 3 trial evaluating V116, the company’s investigational, adult-specific 21-valent pneumococcal conjugate vaccine, at the 34th European Society of Clinical Microbiology and Infectious Diseases (ESCMID Global) in Barcelona, Spain. The trial evaluated the immunogenicity, tolerability and safety of V116 compared to PPSV23 (pneumococcal vaccine, polyvalent [23-valent]) in adults 50 years of age and older who had not previously received a pneumococcal vaccine.
Key results from the study include:
- V116 elicited immune responses that were noninferior compared to PPSV23 for the 12 serotypes (or strains) common to both vaccines, as measured by serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) at Day 30.
- Immune responses elicited by V116 were superior for the nine serotypes included in V116 but not PPSV23, as measured by OPA GMT ratios at Day 30, and superior for eight of nine serotypes unique to V116 compared to PPSV23, as measured by the proportions of participants with ≥4-fold rise in immune responses.
- V116 had a safety profile comparable to PPSV23.
These data build upon Phase 3 trial results that were presented at this year’s Meeting of the International Society of Pneumonia and Pneumococcal Diseases and the 2023 World Vaccine Congress West Coast.
“Invasive pneumococcal disease and pneumococcal pneumonia represent significant public health challenges, particularly among older adult populations and those with risk conditions,” said Dr. Walter Orenstein, professor emeritus of medicine, epidemiology, global health and pediatrics at Emory University and member of Merck’s Scientific Advisory Committee. “These positive results show that V116 has the potential to help prevent invasive pneumococcal disease among adult populations.”
“Even with the availability of current pneumococcal conjugate vaccines for adults, gaps in serotype coverage for invasive pneumococcal disease persist,” said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. “These data add to the evidence supporting the potential for V116 to become an important new preventative option for adults, with results showing V116 elicited immune responses to the serotypes responsible for the majority of adult invasive pneumococcal disease.”
In addition to the clinical data on V116, Merck also presented findings that suggest V116 may help to reduce the health and economic burden associated with invasive pneumococcal disease and non-bacteremic pneumococcal pneumonia among adults in France, Sweden, Spain, and the Netherlands.
V116 is currently under review by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The FDA granted V116 priority review with a Prescription Drug User Fee Act (PDUFA), or target action date, of June 17, 2024. V116 is specifically designed to help protect adults from invasive pneumococcal disease; the serotypes in V116 account for approximately 83% of adult invasive pneumococcal disease in individuals 65 and older, according to U.S. Centers for Disease Control and Prevention data from 2018-2021. An overview of the V116 late-stage development program is available here.
Summary of Findings from Select Studies Presented at ESCMID
Data from STRIDE-10 (Abstract #353)
STRIDE-10 (NCT05569954) is a Phase 3, randomized, double-blind, active comparator-controlled study evaluating the immunogenicity, tolerability and safety of V116 compared to PPSV23 in adults 50 years of age and older who had not previously received pneumococcal vaccine (n=1,484). Participants were randomized to receive a single dose of either V116 or PPSV23.
The primary objectives included serotype-specific OPA GMTs 30 days post-vaccination and percentage of participants with greater than or equal to four-fold rise from baseline in serotype-specific OPAs. Serotype-specific OPA responses were measured at baseline and 30 days post-vaccination. Safety was evaluated as the proportion of participants with adverse events (AEs). Results demonstrated that:
- V116 elicited noninferior immune responses for the 12 serotypes (or strains) shared with PPSV23 (3, 7F, 8, 9N, 10A, 11A, 12F, 17F, 19A, 20A, 22F, 33F), as measured by serotype-specific OPA GMTs 30 days post-vaccination;
- V116 elicited superior immune responses for the nine serotypes only covered by V116 and not PPSV23 (6A, 15A, 15C, 16F, 23A, 23B, 24F, 31, 35B), as assessed by serotype-specific OPA GMT ratios 30 days post-vaccination;
- The proportion of patients with ≥4-fold rise in OPA GMT ratios from Day 1 to Day 30 for serotype-specific OPA for V116 was superior to PPSV23 for eight out of nine serotypes unique to V116 compared to PPSV23;
- V116 had a comparable safety profile to PPSV23.
Data from Health and Economic Burden of Disease Studies (Abstract #7201, Abstract #2784, Abstract #2738, and Abstract #2843)
Four studies were conducted to quantify the health and economic burden of invasive pneumococcal disease and non-bacteremic pneumococcal pneumonia attributable to V116 and PCV20 (pneumococcal 20-valent conjugate vaccine) serotypes among adults in France, Sweden, Spain, and the Netherlands. Across the studies, results showed that when compared with PCV20, V116 serotypes were associated with considerably higher health and economic burden in France, Sweden, Spain, and the Netherlands––the difference is driven largely by the eight unique V116 serotypes not in any currently approved pneumococcal vaccine, suggesting V116 may help reduce the health and economic burden associated with invasive pneumococcal disease and non-bacteremic pneumococcal pneumonia among adults in these countries.
About V116
V116 is an investigational, 21-valent pneumococcal conjugate vaccine in Phase 3 development for the prevention of invasive pneumococcal disease and pneumococcal pneumonia in the adult population. V116 is specifically designed to address Streptococcus pneumoniae serotypes predominantly responsible for adult pneumococcal disease, including eight unique serotypes not in any currently approved pneumococcal vaccine (15A, 15C, 16F, 23A, 23B, 24F, 31 and 35B) which account for approximately 30% of adult invasive pneumococcal disease, according to CDC data from 2018-2021. The serotypes covered by V116 are responsible for approximately 83% of invasive pneumococcal disease in individuals 65 years of age and older, based on the same CDC data. V116 is designed to be administered as a single dose to help prevent invasive pneumococcal disease and pneumococcal pneumonia in adults.
The V116 Phase 3 program includes multiple studies, including STRIDE-3 (NCT05425732), STRIDE-4 (NCT05464420), STRIDE-5 (NCT05526716), STRIDE-6 (NCT05420961), STRIDE-7 (NCT05393037), STRIDE-8 (NCT05696080), STRIDE-9 (NCT05633992) and STRIDE-10 (NCT05569954).
Indication for PNEUMOVAX 23 (Pneumococcal Vaccine Polyvalent)
PNEUMOVAX 23 is a vaccine indicated for active immunization for the prevention of pneumococcal disease caused by the 23 serotypes contained in the vaccine (1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F and 33F).
PNEUMOVAX 23 is approved for use in persons 50 years of age or older and persons aged ≥2 years who are at increased risk for pneumococcal disease.
PNEUMOVAX 23 will not prevent disease caused by capsular types of pneumococcus other than those contained in the vaccine.
Select Safety Information for PNEUMOVAX 23
PNEUMOVAX 23 is contraindicated in individuals with a history of a hypersensitivity reaction to any component of PNEUMOVAX 23.
Do not administer PNEUMOVAX 23 to individuals with a history of a hypersensitivity reaction to any component of the vaccine.
Defer vaccination with PNEUMOVAX 23 in persons with moderate or severe acute illness.
Use caution and appropriate care in administering PNEUMOVAX 23 to individuals with severely compromised cardiovascular and/or pulmonary function in whom a systemic reaction would pose a significant risk.
Available human data from clinical trials of PNEUMOVAX 23 in pregnancy have not established the presence or absence of a vaccine-associated risk.
Since elderly individuals may not tolerate medical interventions as well as younger individuals, a higher frequency and/or a greater severity of reactions in some older individuals cannot be ruled out.
Persons who are immunocompromised, including persons receiving immunosuppressive therapy, may have a diminished immune response to PNEUMOVAX 23.
PNEUMOVAX 23 may not be effective in preventing pneumococcal meningitis in patients who have chronic cerebrospinal fluid (CSF) leakage resulting from congenital lesions, skull fractures or neurosurgical procedures.
The most common adverse reactions, reported in >10% of subjects vaccinated with PNEUMOVAX 23 for the first time in a clinical trial, were: injection-site pain/soreness/tenderness, injection-site swelling/induration, headache, injection-site erythema, asthenia and fatigue, and myalgia.
For subjects aged 65 years or older in a clinical study, systemic adverse reactions which were determined by the investigator to be vaccine-related were higher following revaccination than following initial vaccination.
Vaccination with PNEUMOVAX 23 may not offer 100% protection from pneumococcal infection.
About Pneumococcal Disease
Pneumococcal disease is an infection caused by a bacteria called Streptococcus pneumoniae. There are more than 100 different types (referred to as serotypes) of pneumococcal bacteria, which can affect adults differently than children. Certain serotypes threaten to put more people at risk for invasive pneumococcal illnesses, such as bacteremia (infection in the bloodstream); bacteremic pneumonia (pneumonia with bacteremia); and meningitis (infection of the coverings of the brain and spinal cord), as well as non-invasive pneumonia (when pneumococcal disease is confined to the lungs).
While healthy adults can suffer from pneumococcal disease, patient populations particularly vulnerable to infection include older adults and those with certain chronic or immunocompromising health conditions (including diabetes, HIV, or heart, lung and liver diseases). Mortality from invasive pneumococcal disease is highest among adults 50 years of age and older.
Merck’s Commitment to Pneumococcal Disease Protection
Merck has been at the forefront of pneumococcal disease prevention through vaccination for more than four decades and remains committed to helping to protect people of all ages from this disease. Merck’s ongoing pneumococcal vaccine development program is designed to provide options that address the specific needs of different populations, including infants and children, healthy adults and at-risk sub-groups. This approach recognizes that disease burden in pediatric and adult populations is often driven by different bacterial strains, or serotypes, and aims to address unmet needs by offering vaccine options that target serotypes posing the greatest global risk to each population. To learn more about Merck’s pipeline, visit www.merck.com.
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.
Source: Merck & Co., Inc.
Merck late-stage data strengthens profile of pneumonia vaccine candidate
Apr. 29, 2024 10:20 AM ET
Merck & Co., Inc. (MRK) StockPFE
By: Jonathan Block, SA News Editor
- New data from a phase 3 study of Merck's (NYSE:MRK) experimental pneumococcal conjugate vaccine, V116, found that immune responses were non-inferior to serotypes in common to the company's older Pneumovax23 (PPSV23) vaccine.
- https://seekingalpha.com/news/4095517-merck-late-stage-data-strengthens-profile-pneumonia-vaccine-candidate?mailingid=35195205&messageid=2900&serial=35195205.29077&utm_campaign=rta-stock-news&utm_content=link-1&utm_medium=email&utm_source=seeking_alpha&utm_term=35195205.29077
- Merck & Co., Inc. (MRK) Stock
- https://www.merck.com/
- https://www.cdc.gov/vaccines/vpd/pneumo/hcp/who-when-to-vaccinate.html
- https://www.merck.com/product/usa/pi_circulars/p/pneumovax_23/pneumovax_pi.pdf
MNKD-101 (Clofazimine Inhalation Suspension)
MNKD-101 (Clofazimine Inhalation Suspension)
MNKD-101 (Clofazimine Inhalation Suspension)
MannKind Announces IND Clearance From U.S. FDA to Start Phase 3 Study of Clofazimine Inhalation Suspension for Nontuberculous Mycobacterial (NTM) Lung Disease
04/29/24
DANBURY, Conn. and WESTLAKE VILLAGE, Calif., April 29, 2024 (GLOBE NEWSWIRE) --
MannKind Corporation
(Nasdaq: MNKD), a company focused on the development and commercialization of innovative inhaled therapeutic products and devices for patients with endocrine and orphan lung diseases, announced today that the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) application for MNKD-101 (Clofazimine Inhalation Suspension), enabling the initiation of a Phase 3 study for the treatment of nontuberculous mycobacterial (NTM) lung disease.
“Oral clofazimine has been utilized as a treatment option for patients living with NTM lung disease and we believe that by reducing the dose and administering it directly to the lung we can demonstrate improved dosing, tolerability and safety,” said Michael Castagna, PharmD, Chief Executive Officer of MannKind Corporation. “Advancing this program to a Phase 3 trial, we are encouraged that MNKD-101 could potentially address a serious unmet need that is on the rise globally – particularly in the U.S. and the Asia Pacific region.”
This single registrational study, identified as ICoN-1, anticipates getting underway by end of 2Q 2024 in the U.S., and internationally in the second half of 2024. ICoN-1 is a multi-national, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of Clofazimine Inhalation Suspension when added to guideline-based therapy in adults with refractory NTM lung disease caused by Mycobacterium Avium Complex (MAC), followed by an open-label extension.
“Current regimens for patients living with NTM lung disease require the use of multiple medications that are often associated with significant adverse reactions and safety concerns, prolonged periods of administration, and suboptimal outcomes both short-term and long-term,” said Dr. Burkhard Blank, Executive Vice President, Research & Development and Chief Medical Officer of MannKind Corporation. “Patients living with NTM deserve safe, well-tolerated, convenient, and effective options to treat this serious respiratory disease.”
Pulmonary NTM infection is recognized as a major global health concern due to its rising prevalence worldwide, association with shortened life span and significant impact on patients’ daily living. NTM is a group of bacteria naturally found in our environment, including water and soil, that can lead to cough, fatigue, a reduction in lung function, and poor quality of life. While most people are exposed to NTM daily, the organisms generally do no harm. Individuals with underlying conditions such as COPD, asthma, and bronchiectasis are prone to NTM getting established in the lungs creating an infection and progressive worsening of lung function.
NTM lung disease is more common in women over the age of 65, with a predominance in those of Caucasian and Asian descent. In 2022, there were approximately 122,000 and 159,000 patients living with NTM in the U.S. and Japan, respectively, with as much as 20% of those cases being refractory. The disease state is on the rise, with an estimated annual growth rate averaging 8%.
About MannKind
MannKind Corporation (Nasdaq: MNKD) focuses on the development and commercialization of innovative inhaled therapeutic products and devices to address serious unmet medical needs for those living with endocrine and orphan lung diseases.
We are committed to using our formulation capabilities and device engineering prowess to lessen the burden of diseases such as diabetes, nontuberculous mycobacterial (NTM) lung disease, pulmonary fibrosis, and pulmonary hypertension. Our signature technologies – dry-powder formulations and inhalation devices – offer rapid and convenient delivery of medicines to the deep lung where they can exert an effect locally or enter the systemic circulation, depending on the target indication.
With a passionate team of Mannitarians collaborating nationwide, we are on a mission to give people control of their health and the freedom to live life.
Please visit mannkindcorp.com to learn more, and follow us on LinkedIn, Facebook, X or Instagram.
MNKD-101 is an investigational product that is not approved for any use in any country.
MANNKIND is a registered trademark of MannKind Corporation.
Source: MannKind
MannKind rises as FDA advances rare lung disease therapy to Phase 3 trial
Apr. 29, 2024 6:34 AM ET
MannKind Corporation (MNKD) Stock
By: Preeti Singh, SA News Editor
MannKind (NASDAQ:MNKD) shares rose 13% premarket on Monday after the U.S. drug regulator cleared its clofazimine inhalation suspension (MNKD 101) for a Phase 3 study to treat nontuberculous mycobacterial (NTM) lung disease.
The U.S. Food and Drug Administration (FDA) cleared MannKind’s (MNKD) investigational new drug application for MNKD-101, enabling the initiation of a Phase 3 study.
biotecHOPE™ 2024
Efanesoctocog alfa [Antihemophilic Factor (Recombinant)
Efanesoctocog alfa [Antihemophilic Factor (Recombinant)
Efanesoctocog alfa [Antihemophilic Factor (Recombinant)
Sobi® receives positive CHMP opinion recommending approval of efanesoctocog alfa for once-weekly treatment of haemophilia A
26 April, 2024 13:35
Sobi® today announced the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has issued a positive opinion recommending approval of efanesoctocog alfa, for the treatment and prevention of bleeds and perioperative prophylaxis in haemophilia A. Efanesoctocog alfa is a once-weekly and high-sustained factor VIII replacement therapy for patients of all ages and any disease severity.
Efanesoctocog alfa provides children, adolescents and adults with normal to near-normal factor VIII activity levels (above 40%) for a significant part of the week with once-weekly dosing, reaching trough levels of 15% in adults and adolescents at day 7. This results in significantly improved protection from bleeds compared to existing factor VIII prophylaxis. The CHMP positive opinion will now be submitted to the European Commission for a marketing authorisation decision.
“Today’s announcement marks a major milestone in haemophilia care and moves us one step closer to bringing efanesoctocog alfa to patients in the EU. Efanesoctocog alfa sustains high factor VIII activity levels throughout the week, giving patients confidence in the protection it can provide to prevent bleeds, manage surgery, and resolve bleeds. With the potential to significantly improve treatment outcomes and quality of life for people living with haemophilia A, we are excited about the positive impact this treatment could have around the world,” said Lydia Abad-Franch, MBA, Head of Research, Development, and Medical Affairs, and Chief Medical Officer at Sobi.
Haemophilia A is a rare, lifelong genetic condition in which the body does not produce enough, or makes dysfunctional, factor VIII – a protein that is essential for blood clotting. It occurs in about one in 5,000 male births annually, and more rarely in females. People with haemophilia can experience bleeding episodes that can cause pain, irreversible joint damage and life-threatening haemorrhages. Clinical outcomes have improved over time thanks to significant advances in the treatment options available, however important unmet clinical and social needs still exist for those living with the condition.
The recommendation from the CHMP is based on the results from the pivotal phase 3 studies: XTEND-1 in adults and adolescents and XTEND-Kids in children, which evaluated the efficacy and safety of efanesoctocog alfa. These studies demonstrated that once-weekly efanesoctocog alfa prophylaxis (50 IU/kg) provided significant bleed protection (mean ABR <1 and 80-88% of patients free from spontaneous bleeds) in people with severe haemophilia A of any age. The data also showed substantial improvement in joint health, physical health, pain and overall quality of life when comparing week 52 and baseline measurements.1 No factor VIII inhibitors were observed in the efanesoctocog alfa clinical program.
Efanesoctocog alfa was first approved in the US in February 2023 by the US Food and Drug Administration (FDA). The FDA previously granted efanesoctocog alfa Breakthrough Therapy designation in May 2022 — the first factor VIII therapy to receive this designation, Fast Track designation in February 2021, and Orphan Drug designation in 2017.
References
- von Drygalski. A., Chowdary. P., Kulkarni. R., et al. Efanesoctocog Alfa Prophylaxis for Patients with Severe Haemophilia A. N Engl J Med 2023; 388:310-318.
About XTEND-1
XTEND-1 was an open-label, non-randomized interventional study with two parallel assignment arms. Participants in the prophylaxis arm received a weekly prophylactic dose of efanesoctocog alfa for 52 weeks. Participants in on-demand arm received efanesoctocog alfa on demand for 26 weeks followed by a switch to weekly prophylaxis for another 26 weeks. XTEND-1 evaluated efficacy, safety and pharmacokinetics in 159 previously treated patients ≥12 years of age with severe haemophilia A.
About XTEND-Kids
XTEND-Kids was an open-label, non-randomised interventional, single-arm study. Participants received a weekly prophylactic dose of efanesoctocog alfa for 52 weeks. XTEND-Kids evaluates efficacy, safety, and pharmacokinetics in 74 previously treated patients <12 years of age with severe haemophilia A.
About efanesoctocog alfa
Efanesoctocog alfa [Antihemophilic Factor (Recombinant), Fc-VWF-XTEN Fusion Protein] (formerly BIVV001) is a new class of recombinant factor VIII therapy with the potential to deliver near-normal factor activity levels for a significant part of the week, improving bleed protection in a once-weekly dose for people with haemophilia A. Efanesoctocog alfa builds on the innovative Fc fusion technology by adding a region of von Willebrand factor and XTEN® polypeptides to extend its time in circulation. It is the only therapy that has been shown to break through the von Willebrand factor ceiling, which imposes a half-life limitation on current factor VIII therapies. It is approved and marketed as ALTUVIIIO™ [Antihemophilic Factor (Recombinant), Fc-VWF-XTEN Fusion Protein-ehtl] by Sanofi in the United States, Japan, and Taiwan. The European Commission granted Orphan Drug designation in June 2019.
About the Sanofi and Sobi collaboration
Sobi and Sanofi collaborate on the development and commercialisation of Alprolix® and Elocta®/Eloctate®. The companies also collaborate on the development and commercialisation of efanesoctocog alfa, or ALTUVIIIO™ in the US. Sobi has final development and commercialisation rights in the Sobi territory (essentially Europe, North Africa, Russia, and most Middle Eastern markets). Sanofi has final development and commercialisation rights in North America and all other regions in the world excluding the Sobi territory.
About Sanofi
We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people’s lives. Our team, across some 100 countries, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the centre of our ambitions. Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY
Sobi®
Sobi® is a specialised international biopharmaceutical company transforming the lives of people with rare and debilitating diseases. Providing reliable access to innovative medicines in the areas of haematology, immunology, and specialty care, Sobi has approximately 1,800 employees across Europe, North America, the Middle East, Asia, and Australia. In 2023, revenue amounted to SEK 22.1 billion. Sobi's share (STO:SOBI) is listed on Nasdaq Stockholm. More about Sobi at sobi.com and LinkedIn
Sobi® receives positive CHMP opinion recommending approval of efanesoctocog alfa for once-weekly treatment of haemophilia A
Apr. 26, 2024 8:02 AM ET
Q1: 2024-04-25 Earnings Summary
Transcript
SlidesPress Release
EPS of $0.95 beats by $0.01 | Revenue of $11.23B (-0.38% Y/Y) beats by $298.54M
STOCKHOLM, April 26, 2024 /PRNewswire/ -- Sobi® today announced the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has issued a positive opinion recommending approval of efanesoctocog alfa, for the treatment and prevention of bleeds and perioperative prophylaxis in haemophilia A. Efanesoctocog alfa is a once-weekly and high-sustained factor VIII replacement therapy for patients of all ages and any disease severity.
BEQVEZ™ (fidanacogene elaparvovec-dzkt)
Efanesoctocog alfa [Antihemophilic Factor (Recombinant)
Efanesoctocog alfa [Antihemophilic Factor (Recombinant)
U.S. FDA Approves Pfizer’s BEQVEZ™ (fidanacogene elaparvovec-dzkt), a One-Time Gene Therapy for Adults with Hemophilia B
Friday, April 26, 2024 - 06:45am
- A one-time dose of BEQVEZ has reduced bleeds post-treatment compared to standard of care with a median of zero bleeds (range 0 to 19) after up to three years of follow-up, providing sustained bleed protection and potentially avoiding years of treatment burden with prophylaxis for many patients
NEW YORK--(BUSINESS WIRE)-- Pfizer Inc. (NYSE: PFE)announced today that the U.S. Food and Drug Administration (FDA) has approved BEQVEZ™ (fidanacogene elaparvovec-dzkt) for the treatment of adults with moderate to severe hemophilia B who currently use factor IX (FIX) prophylaxis therapy, or have current or historical life-threatening hemorrhage, or have repeated, serious spontaneous bleeding episodes, and do not have neutralizing antibodies to adeno-associated virus serotype Rh74var (AAVRh74var) capsid as detected by an FDA-approved test. BEQVEZ is a one-time treatment that is designed to enable people living with hemophilia B to produce FIX themselves rather than the current standard of care, which requires regular intravenous infusions of FIX that are often administered multiple times a week or multiple times a month.1,2
“Many people with hemophilia B struggle with the commitment and lifestyle disruption of regular FIX infusions, as well as spontaneous bleeding episodes, which can lead to painful joint damage and mobility issues,” said Adam Cuker, M.D., M.S., Director, Penn Comprehensive and Hemophilia Thrombosis Program. “A one-time treatment with BEQVEZ has the potential to be transformative for appropriate patients by reducing both the medical and treatment burden over the long term.”
Hemophilia B is a rare genetic bleeding disorder that prevents normal blood clotting because of a deficiency in FIX that causes those with the disease to bleed more frequently and longer than others.3,4 The standard of care for hemophilia B treatment is prophylactic infusions of FIX replacement therapy that temporarily replace or supplement low levels of blood-clotting factor.2,4 Despite prophylaxis and regular intravenous infusions, many people living with moderate to severe hemophilia B are at risk of spontaneous bleeding episodes.5,6,7 The current standard of care also places strain on healthcare systems’ budgets and resource utilization.6,8,9,10 According to the World Federation of Hemophilia, more than 38,000 people worldwide are living with hemophilia B.11
“This milestone is a testament to Pfizer’s continued effort to advance the standard of care for people living with hemophilia, with the delivery of a medicine that has the potential to offer both long-term bleed protection and value to the healthcare system because of its one-time administration,” said Aamir Malik, Chief U.S. Commercial Officer and Executive Vice President, Pfizer. “We are leveraging our expertise that comes with more than 40 years of experience in the hemophilia space, and are proactively working with treatment centers, payers, and the hemophilia community to appropriately help ensure the healthcare system is prepared to readily deliver BEQVEZ to the patients who can benefit from it.”
With BEQVEZ now approved for use, Pfizer is launching an innovative warranty program based on durability of patient response to treatment. The goal of the warranty is to provide greater certainty to payers, maximize access for eligible patients who receive BEQVEZ, and offer financial protection by insuring against the risk of efficacy failure.
“For people living with hemophilia, disease management can interfere with many aspects of their lives. A one-time infusion of BEQVEZ may allow eligible patients more time for the things they love,” said Kim Phelan, Chief Operating Officer, The Coalition for Hemophilia B. “We are excited to have BEQVEZ as a promising treatment option for eligible people living with hemophilia B. We look forward to learning more and celebrating with the community and with Pfizer at our annual conference that is currently taking place.”
BEQVEZ is currently under review with the European Medicines Agency (EMA), and the treatment recently received regulatory approval in Canada. In addition to BEQVEZ, Pfizer currently has two other Phase 3 programs investigating gene therapy in populations where there is a high unmet need: hemophilia A (giroctocogene fitelparvovec) and Duchenne muscular dystrophy (fordadistrogene movaparvovec). Additionally, a Phase 3 trial is investigating marstacimab, a novel, investigational anti-tissue factor pathway inhibitor for the treatment of people with hemophilia A and B with and without inhibitors. A Biologics License Application and European Marketing Authorization Application for marstacimab are currently under review with the FDA and EMA, respectively.
About BEQVEZ (fidanacogene elaparvovec-dzkt)
BEQVEZ is an adeno-associated virus (AAV)-based gene therapy designed to introduce in the transduced cells a functional copy of the FIX gene encoding a high-activity FIX variant. For eligible patients living with hemophilia B, the goal of this gene therapy is to enable them to produce FIX themselves via this one-time treatment rather than having to receive frequent infusions of FIX, as is the current standard of care.1,2,4 It is currently approved in the U.S. for the treatment of adults with moderate to severe hemophilia B (congenital factor IX deficiency) who:
- Currently use factor IX prophylaxis therapy, or
- Have current or historical life-threatening hemorrhage, or
- Have repeated, serious spontaneous bleeding episodes, and,
- Do not have neutralizing antibodies to adeno-associated virus serotype Rh74var (AAVRh74var) capsid as detected by an FDA-approved test.
For eligible patients who are prescribed BEQVEZ, Pfizer offers personalized patient support services including financial assistance resources and logistical support through the Pfizer Gene Together program. More information is available on www.PfizerGeneTogether.com.
In December 2014, Pfizer licensed BEQVEZ from Spark Therapeutics. Under the agreement, Pfizer assumed responsibility for pivotal studies, any regulatory activities, and potential global commercialization of this gene therapy.
About BENEGENE-2
The FDA approval is based on the results from the pivotal BENEGENE-2 study, a Phase 3, open-label, single-arm study to evaluate the efficacy and safety of BEQVEZ in adult male participants (age 18–65) with moderately severe to severe hemophilia B (defined as FIX circulating activity of 2% or less). The main objective of the study is to evaluate the annualized bleeding rate (ABR) for participants treated with gene therapy versus FIX prophylaxis replacement regimen, administered as part of usual care.
The study enrolled 45 participants. Eligible study participants have completed a minimum of six months of routine FIX prophylaxis therapy during the lead-in study (NCT03587116) and received a single intravenous infusion of BEQVEZ at a dose of 5 x 1011 vg/kg of body weight. Clinical trial participants will be followed for up to a total of 15 years, including six years in the BENEGENE-2 study and an additional nine years as part of a separate Phase 3 study (NCT05568719) to learn about the long-term safety and efficacy of BEQVEZ.
BENEGENE-2 met its primary endpoint of non-inferiority in the ABR of total bleeds post-BEQVEZ infusion versus prophylaxis regimen with FIX, administered as part of usual care. A mean ABR of 2.5 was observed among patients who received BEQVEZ in the efficacy evaluation period – defined as between week 12 and data cutoff (median 1.8 years of follow-up) – after receiving the one-time dose compared to a mean ABR of 4.5 during the lead-in pre-treatment period of at least six months (median 1.2 years of follow-up). Bleeds were eliminated in 60% of patients compared to 29% in the prophylaxis arm. A median ABR of zero (range of 0 to 19) was observed during the efficacy evaluation period compared to the prophylaxis arm in which a median ABR of 1.3 (range of 0 to 53.9) was observed.
BEQVEZ was generally well-tolerated in patients who received it. The most common adverse reaction (incidence ≥5%) reported in Phase 3 and 1/2 clinical studies was an increase in transaminases. No deaths, serious adverse events related to treatment or associated with infusion reactions, thrombotic events, or FIX inhibitors were reported. Elevated transaminases were observed in 26 out of 60 patients treated at the recommended dose and 31 out of 60 patients received corticosteroids.
In addition to the Phase 3 trial, BEQVEZ patients have been followed up to six years in a Phase 1/2a study and its corresponding Phase 2a long-term follow-up study. Pfizer is continuing to monitor for long-term treatment durability and safety in its clinical program over the course of 15 years.
About Hemophilia B
Hemophilia is a rare genetic bleeding disorder that prevents normal blood clotting because of a deficiency in one of several blood clotting factors and is predominately found in males.3,4 People with hemophilia are at risk for excessive and recurrent spontaneous and/or post-traumatic bleeding, which can be life-threatening, particularly in those with severe hemophilia.3,4 People with severe hemophilia often bleed spontaneously into their muscles or joints, or rarely into other critical closed spaces such as the intracranial space, where bleeding can be fatal.3,4
According to the World Federation of Hemophilia, more than 38,000 people worldwide are living with hemophilia B.11 People with hemophilia B have a deficiency in clotting FIX, a specific protein in the blood. Hemophilia B is also called congenital FIX deficiency or Christmas disease. The current standard of care requires recurrent intravenous infusions of either plasma-derived or recombinant FIX to control and prevent bleeding episodes.1,2,4
BEQVEZ (fidanacogene elaparvovec-dzkt) U.S. Important Safety Information
What is BEQVEZ?
BEQVEZ is a one-time gene therapy used for the treatment of adults with moderate to severe hemophilia B who are receiving routine prophylaxis, have a current life-threatening bleed or a history of life-threatening bleeds, or have repeated serious spontaneous bleeds.
Before treatment with BEQVEZ, your healthcare professional will conduct a blood test to check for antibodies to the AAVRh74var virus. The results of this testing will help determine if you may receive BEQVEZ.
Before receiving BEQVEZ, tell your healthcare professional about all your medical conditions, including if you:
- Have kidney or liver problems, including hepatitis
- Have factor IX inhibitors or a history of factor IX inhibitors
- Have an active infection
About Pfizer: Breakthroughs That Change Patients’ Lives
At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For 175 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.Pfizer.com. In addition, to learn more, please visit us on www.Pfizer.com and follow us on X at @Pfizer and @Pfizer_News, LinkedIn, YouTube and like us on Facebook at www.facebook.com/Pfizer/.
View source version on businesswire.com: https://www.businesswire.com/news/home/20240425269649/en/
Source: Pfizer Inc.
Pfizer gets FDA approval for hemophilia B gene therapy Beqvez
Apr. 26, 2024 12:38 PM ET
By: Val Brickates Kennedy, SA News Editor8 Comments
Pfizer (NYSE:PFE) said it has received FDA approval for its one-time gene therapy Beqvez for the treatment of certain adults with hemophilia B.
The drugmaker said the therapy is aimed at enabling patients to produce factor IX in their own bodies rather than relying on regular intravenous transfusions of the blood-clotting protein.
Pfizer said it is also launching a warranty program for the therapy based on durability of patient response. The warranty is intended to provide greater certainty about the treatment to payers and financial protection against efficacy failure.
https://seekingalpha.com/news/4095010-pfizer-gets-fda-approval-for-hemophila-b-gene-therapy-beqvez
CTX-009 in Combination with Paclitaxel
Efanesoctocog alfa [Antihemophilic Factor (Recombinant)
CTX-009 in Combination with Paclitaxel
Compass Therapeutics Receives FDA Fast Track Designation for the Investigation of CTX-009 in Combination with Paclitaxel for the Treatment of Patients with Metastatic or Locally Advanced Biliary Tract Tumors That Have Been Previously Treated
Apr 25, 2024 at 8:00 AM EDT
- CTX-009, the Company’s bispecific DLL4/VEGF-A antibody, in combination with paclitaxel, has shown promising clinical responses in patients with advanced biliary tract cancer (BTC) in its Phase 2 study
- Top-line data readout for COMPANION-002, the Company’s randomized Phase 2/3 BTC U.S. study, is expected by the end of 2024
BOSTON, April 25, 2024 (GLOBE NEWSWIRE) -- Compass Therapeutics, Inc. (Nasdaq: CMPX), a clinical-stage, oncology-focused biopharmaceutical company developing proprietary antibody-based therapeutics to treat multiple human diseases, today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation (FTD) to CTX-009, the Company’s bispecific DLL4/VEGF-A antibody, in combination with paclitaxel for the treatment of patients with metastatic or locally advanced BTC that have been previously treated.
“We are delighted that CTX-009 has received FDA Fast Track Designation highlighting the large unmet need in patients with advanced BTC where current therapies have low, single digit response rates, and limited effect on patient survival,” said Thomas Schuetz, MD, PhD, Co-founder, President of R&D, and Vice Chairman of the Compass board. “Our current study is evaluating the combination of CTX-009 with paclitaxel following the observation of nine partial responses in 24 patients treated in our Phase 2 study, leading to an overall response rate of 37.5% (n= 9/24), a median progression free survival of 9.4 months and a median overall survival of 12.5 months. Compass remains on track to complete enrollment by mid-year and reporting top-line data by year end.”
About CTX-009
CTX-009 is a bispecific antibody that simultaneously blocks Delta-like ligand 4 (DLL4) and vascular endothelial growth factor A (VEGF-A) signaling pathways, which are critical to angiogenesis and tumor vascularization. Preclinical and early clinical data of CTX-009 suggest that blockade of both pathways provides robust anti-tumor activity across several solid tumors, including colorectal, gastric, cholangiocarcinoma, pancreatic and non-small cell lung cancer. Partial responses to CTX-009 as a monotherapy have been observed in heavily pre-treated patients with cancer who were resistant to approved anti-VEGF therapies.
About Biliary Tract Cancers
Biliary tract cancers (BTC) are a group of aggressive gastrointestinal (GI) cancers that form in the cells of the bile ducts (cholangiocarcinoma), gallbladder, or ampulla of Vater (where the bile duct and pancreatic duct connect to the small intestine).
In the United States approximately 23,000 cases of BTC are diagnosed annually,1 including cholangiocarcinoma, gallbladder, and ampullary subtypes. Only 10% of these patients present at an early stage when they would be candidates for surgical resection. The vast majority present with locally advanced or metastatic BTC, for which there are very few therapeutic options.2
1Marcano-Bonilla, L. et al, Chin Clin Oncol. 2016 Oct; 5(5):61, p.1-31.
2cancer.gov/types/liver/patient/bile-duct-treatment-pdq#_66.
About FDA Fast Track Designation
FTD is designed to help drugs reach patients faster by facilitating the development and expediting the review of drugs with the potential to fill an unmet medical need by treating a serious or life-threatening condition. Fast Track addresses a broad range of serious conditions. Programs that receive FTD benefit from early and frequent interactions with the FDA during the clinical development process, more frequent written communication from the FDA, and, if relevant criteria are met, the FDA may consider reviewing portions of a marketing application before the sponsor submits the complete biologics license application.
About Compass Therapeutics
Compass Therapeutics, Inc. is a clinical-stage oncology-focused biopharmaceutical company developing proprietary antibody-based therapeutics to treat multiple human diseases. Compass’s scientific focus is on the relationship between angiogenesis, the immune system, and tumor growth. The company pipeline of novel product candidates is designed to target multiple critical biological pathways required for an effective anti-tumor response. These include modulation of the microvasculature via angiogenesis-targeted agents, induction of a potent immune response via activators on effector cells in the tumor microenvironment, and alleviation of immunosuppressive mechanisms used by tumors to evade immune surveillance. Compass plans to advance its product candidates through clinical development as both standalone therapies and in combination with proprietary pipeline antibodies based on supportive clinical and nonclinical data. The company was founded in 2014 and is headquartered in Boston, Massachusetts. For more information, visit the Compass Therapeutics website at https://www.compasstherapeutics.com.
Compass gains FDA Fast Track status for biliary tract cancer candidate
Apr. 25, 2024 12:07 PM ET
Compass Therapeutics, Inc. (CMPX) Stock
By: Jonathan Block, SA News Editor
- The U.S. FDA has granted Fast Track designation to Compass Therapeutics' (NASDAQ:CMPX) CTX-009 in combination with paclitaxel for previously treated advanced biliary tract cancer.
- The candidate is currently in phase 3 with top-line data expected by the end of this year.
- https://seekingalpha.com/news/4094258-compass-gains-fda-fast-track-status-biliary-tract-cancer-candidate
- Compass Therapeutics, Inc. (CMPX) Stock
- https://www.compasstherapeutics.com/
- https://www.compasstherapeutics.com/pipeline/
Bentrio® nasal spray
ANKTIVA (N-803, or nogapendekin alfa inbakicept-pmln) plus Bacillus Calmette-Guérin (BCG)
CTX-009 in Combination with Paclitaxel
Altamira Therapeutics Announces Publication of Positive Results from Bentrio Trial in Seasonal Allergic Rhinitis in Top Peer Reviewed Journal
April 24, 2024
Hamilton, Bermuda, April 24, 2024 (GLOBE NEWSWIRE) --
- Detailed results from randomized controlled Bentrio® trial in seasonal allergic rhinitis published in Allergy journal
- Study met primary efficacy endpoint of improvement in nasal symptoms (p = 0.013)
- Corroborated by statistically significant improvement in health-related quality of life and reduced need for relief medication
- Study outcomes support plans for further international expansion
HAMILTON, BERMUDA -- April 24, 2024 -- Altamira Therapeutics Ltd. (“Altamira” or the “Company”) (Nasdaq:CYTO), a company dedicated to developing and commercializing RNA delivery technology for targets beyond the liver, today announced the publication of the detailed results from the NASAR clinical trial with Bentrio® nasal spray in seasonal allergic rhinitis (SAR). The peer-reviewed article appeared in Allergy,1 which is published by the European Academy of Allergy and Clinical Immunology and recognizes as one of the highest-ranking journals in the field of allergology. Bentrio (AM-301) is a drug-free and preservative-free nasal spray designed to help protect against airborne allergens such as pollen or house dust mites.
The NASAR trial enrolled 100 patients during two allergy seasons in Australia who were randomized at a 1:1 ratio to receive either Bentrio or saline nasal spray, the current standard of care in drug-free SAR management. Study participants self-administered the treatment for two weeks three times per day. The primary efficacy endpoint was the reduction in the mean daily reflective Total Nasal Symptom Score (rTNSS; ANCOVA model).
Bentrio-treated patients achieved a significantly lower rTNSS than the saline group (least square means difference -1.1, p = 0.013) with improvement observed across all individual nasal symptoms. Health-related quality of life, as measured by the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), was significantly improved as well (p < 0.001). Patients and investigators rated the efficacy of treatment as significantly better with Bentrio compared to saline control (both p < 0.001). Both treatments showed similarly good safety and tolerability. With Bentrio, fewer patients used relief medication and more enjoyed symptom-free days compared to saline treatment.
“We are thrilled to see the detailed results from our pivotal Australian trial published in one the leading medical journals in allergology,” commented Thomas Meyer, Altamira’s founder, Chairman, and CEO. “The study provided a wealth of additional evidence for the protective effects of Bentrio as well as its good safety and tolerability. In addition, we are very encouraged to see that Bentrio helps to manage not only mild allergy symptoms, but also more severe ones, and appears to reduce the need for the use of drug-based relief treatments. We would like to thank all participating patients and study sites for their contributions to the NASAR trial and look forward to making Bentrio available in additional countries and helping patients who have to deal with the daily burden and discomfort associated with allergic rhinitis.”
Bentrio is marketed by Altamira Medica AG, an associate company of Altamira Therapeutics, primarily through distributors. From 2024 onwards, Altamira Medica expects sales to grow significantly, mainly driven by the launch of Bentrio in additional countries. The Company expects to conclude partnering discussions and negotiations for distribution in the US, Europe and other key markets in the course of 2024.
About Altamira Therapeutics
Altamira Therapeutics (Nasdaq: CYTO) is developing and supplying peptide-based nanoparticle technologies for efficient RNA delivery to extrahepatic tissues (OligoPhore™ / SemaPhore™ platforms). The Company currently has two flagship siRNA programs using its proprietary delivery technology: AM-401 for KRAS driven cancer and AM-411 for rheumatoid arthritis, both in preclinical development beyond in vivo proof of concept. The versatile delivery platform is also suited for mRNA and other RNA modalities and made available to pharma or biotech companies through out-licensing. In addition, Altamira holds a 49% stake (with additional economic rights) in Altamira Medica AG, its commercial-stage legacy asset Bentrio®, an OTC nasal spray for allergic rhinitis. Further, the Company is in the process of partnering / divesting its inner ear legacy assets. Founded in 2003, Altamira is headquartered in Hamilton, Bermuda, with its main operations in Basel, Switzerland. For more information, visit: https://altamiratherapeutics.com/
Altamira reports publication of positive results from NASAR clinical trial with Bentrio
Apr. 24, 2024 10:11 AM ET
Altamira Therapeutics Ltd. (CYTO) Stock
By: Arundhati Sarkar, SA News Editor
- Altamira Therapeutics (NASDAQ:CYTO) Wednesday announced the publication of the detailed results from the NASAR clinical trial with Bentrio nasal spray in seasonal allergic rhinitis.
- Bentrio (AM-301) is a drug-free and preservative-free nasal spray designed to help protect against airborne allergens such as pollen or house dust mites.
- https://seekingalpha.com/news/4093184-altamira-therapeutics-reports-positive-results-from-nasar-clinical-trial-with-bentrio
- Altamira Therapeutics Ltd. (CYTO) Stock
- https://altamiratherapeutics.com/
- https://bentrio.com/
NBI-1065845
ANKTIVA (N-803, or nogapendekin alfa inbakicept-pmln) plus Bacillus Calmette-Guérin (BCG)
ANKTIVA (N-803, or nogapendekin alfa inbakicept-pmln) plus Bacillus Calmette-Guérin (BCG)
Neurocrine Biosciences Reports Positive Phase 2 Data for NBI-1065845 in Adults with Major Depressive Disorder
04/23/24
- SAVITRI™ Study Met Primary Endpoint with Statistically Significant Reduction in Montgomery Åsberg Depression Rating Scale (MADRS) Total Score at Day 28
- Met Key Secondary Endpoints, Including Statistically Significant Reduction in MADRS Score at Day 56
- NBI-1065845 Was Generally Well-Tolerated
SAN DIEGO, April 23, 2024 /PRNewswire/ -- Neurocrine Biosciences, Inc.
(Nasdaq: NBIX),
today announced positive topline data for its Phase 2 SAVITRI™ study. This randomized, double-blind, placebo-controlled dose-finding study assessed the efficacy and safety of NBI-1065845 in adult subjects with major depressive disorder (MDD). NBI-1065845 is an investigational alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) positive allosteric modulator (PAM) in development as a potential treatment for patients with MDD who have not benefited from treatment with at least one antidepressant in their current episode of depression.
The study met its primary and key secondary endpoints, demonstrating that once-daily, oral administration of NBI-1065845 produced a statistically significant change from baseline in Montgomery Åsberg Depression Rating Scale (MADRS) total score at both Day 28 (primary) and Day 56 (secondary). In the full analysis data set, the least squares (LS) mean differences from baseline in MADRS total score for NBI-1065845 were:
- One of the doses demonstrated an improvement over placebo of -4.3 (p-value = 0.0159) and -7.5 (p-value = 0.0016) at Day 28 and Day 56, respectively.
- The other dose also demonstrated a trend toward improvement over placebo of -3.0 (p-value = 0.0873) and -3.6 (p-value = 0.1082) at Day 28 and Day 56, respectively.
NBI-1065845 was generally well tolerated. The most common adverse event was headache. The adverse event profile for both doses of NBI-1065845 were comparable to placebo. There were no deaths or serious adverse events. The discontinuation rates were low throughout the study.
"Many millions of people living with major depressive disorder do not benefit fully from currently available treatments and experience persistent debilitating symptoms," said Eiry W. Roberts, M.D., Chief Medical Officer at Neurocrine Biosciences. "NBI-1065845 has the potential to be a first-in-class treatment to alleviate many of these symptoms of MDD. The Phase 2 data from the SAVITRI study are very encouraging, and we look forward to meeting with the FDA to discuss a path into Phase 3 studies."
Additional data from the SAVITRI study will be shared at a future scientific conference.
About the Phase 2 SAVITRI™ Study
The Phase 2 SAVITRI™ study is a double-blind, placebo-controlled study designed to assess the efficacy and safety of investigational NBI-1065845 in adult subjects with major depressive disorder (MDD). The study enrolled 183 adults with a primary diagnosis of MDD and who had inadequate response to current antidepressant treatment.
About NBI-1065845
NBI-1065845 is a potential first-in-class, investigational alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) positive allosteric modulator (PAM) in development as a potential treatment for patients with inadequate response to treatment in MDD.
About the Collaboration with Takeda
In 2020, Neurocrine Biosciences and Takeda (TSE:4502/NYSE:TAK) entered into a strategic collaboration to develop and commercialize compounds in Takeda's early-to-mid-stage psychiatry pipeline, including an exclusive license to NBI-1065845 (TAK-653). Under the terms of the agreement, Neurocrine Biosciences is responsible for developing and commercializing all compounds included in the collaboration and for compounds other than NBI-1065845 and NBI-1065846, Takeda is eligible to receive development or commercial milestone payments and royalties. For NBI-1065845 and NBI-1065846, Takeda may elect to opt out of a 50:50 profit share at certain development events on a program-by-program basis. Until such time Takeda elects to opt out of either profit share arrangement, it will not be eligible to receive development or commercial milestone payments.
About Major Depressive Disorder
Major depressive disorder (MDD) is a mental health disorder characterized by a persistently depressed mood, loss of interest, lack of enjoyment in daily activities, poor concentration, and decreased energy. MDD is one of the leading causes of disability. More than 21 million people in the U.S. live with major depressive disorder. It is estimated that roughly 1/3 of people living with major depressive disorder do not respond to available antidepressants.
About Neurocrine Biosciences
Neurocrine Biosciences is a leading neuroscience-focused, biopharmaceutical company with a simple purpose: to relieve suffering for people with great needs, but few options. We are dedicated to discovering and developing life-changing treatments for patients with under-addressed neurological, neuroendocrine and neuropsychiatric disorders. The company's diverse portfolio includes FDA-approved treatments for tardive dyskinesia, chorea associated with Huntington's disease, endometriosis* and uterine fibroids*, as well as a robust pipeline including multiple compounds in mid- to late-phase clinical development across our core therapeutic areas. For three decades, we have applied our unique insight into neuroscience and the interconnections between brain and body systems to treat complex conditions. We relentlessly pursue medicines to ease the burden of debilitating diseases and disorders, because you deserve brave science. For more information, visit neurocrine.com, and follow the company on LinkedIn, X (formerly Twitter), and Facebook.
(*in collaboration with AbbVie)
NEUROCRINE BIOSCIENCES, NEUROCRINE, and YOU DESERVE BRAVE SCIENCE are registered trademarks of Neurocrine Biosciences, Inc. The Neurocrine logo and SAVITRI are trademarks of Neurocrine Biosciences, Inc.
View original content to download multimedia:https://www.prnewswire.com/news-releases/neurocrine-biosciences-reports-positive-phase-2-data-for-nbi-1065845-in-adults-with-major-depressive-disorder-302123889.html
SOURCE Neurocrine Biosciences, Inc.
Neurocrine succeeds in mid-stage trial for Takeda-partnered depression drug
Apr. 23, 2024 2:22 PM ET
Neurocrine Biosciences, Inc. (NBIX) Stock, TAK Stock
By: Dulan Lokuwithana, SA News Editor
Neurocrine Biosciences (NASDAQ:NBIX) announced Tuesday that its Phase 2 SAVITRI trial for depression therapy NBI-1065845, developed in partnership with Takeda Pharmaceutical (NYSE:TAK), reached its main goals in adults with major depressive disorder.
SAVITRI, designed to test two dose levels of NBI-1065845 (TAK-653) as a late-line option in adults with MDD, reached its primary and key secondary endpoints, the San Diego, California-based biotech said.
ANKTIVA (N-803, or nogapendekin alfa inbakicept-pmln) plus Bacillus Calmette-Guérin (BCG)
ANKTIVA (N-803, or nogapendekin alfa inbakicept-pmln) plus Bacillus Calmette-Guérin (BCG)
ANKTIVA (N-803, or nogapendekin alfa inbakicept-pmln) plus Bacillus Calmette-Guérin (BCG)
ImmunityBio Announces FDA Approval of ANKTIVA®, First-in-Class IL-15 Receptor Agonist for BCG-Unresponsive Non-Muscle Invasive Bladder Cancer
Apr 22, 2024
- Designated an FDA Breakthrough Therapy, the novel immunotherapy ANKTIVA activates the body’s natural killer (NK) and killer T-cell immune system to attack tumor cells
- Therapy stimulates memory T cells, leading to long duration of complete response exceeding 47 months and ongoing to date, with a median duration of response yet to be determined
- The percentage of patients with durable responses at 12 and 24 months exceeded the benchmark for magnitude of clinically meaningful results established by experts at the International Bladder Cancer Group (IBCG)
- ANKTIVA in combination with BCG is approved for maintenance therapy for up to 37 months with tolerable side effects ranging from 0% to 3% Grade 3/4 adverse events
- ANKTIVA is expected to be available in the U.S. by mid-May 2024
- Conference call and webcast are expected to be held April 26 at 11:00 am EDT
CULVER CITY, Calif., April 22, 2024 — ImmunityBio, Inc. (NASDAQ: IBRX), an immunotherapy company, today announced that the U.S. Food and Drug Administration (FDA) has approved ANKTIVA (N-803, or nogapendekin alfa inbakicept-pmln) plus Bacillus Calmette-Guérin (BCG) for the treatment of patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without papillary tumors.
“The FDA’s approval of ANKTIVA marks our launch of a next-generation immunotherapy beyond checkpoint inhibitors,” said Patrick Soon-Shiong, M.D., Executive Chairman and Global Chief Scientific and Medical Officer at ImmunityBio. “ANKTIVA not only proliferates and activates the patient’s own NK cells and CD8+ killer T cells, but also activates CD4+ T helper cells, thus enhancing the proliferation of memory killer T cells. This novel mechanism of action, which mimics the biology of the dendtritic cell, begins the evolution of immunotherapy beyond T cells alone. The combination of the proliferation of key cancer-killing immune cells, together with the activation of T cells with memory, results in durable complete responses. The ‘triangle offense’ of tumor cell killing by the body’s immune system with long-term memory is the foundation of our efforts to develop a therapeutic cancer vaccine across multiple tumor types, regardless of the site of origin.”
ANKTIVA, a first-in-class IL-15 agonist immunotherapy for NMIBC, received Breakthrough Therapy Designation and approval from the FDA based on the safety and efficacy outcome of complete responses (CR) and duration of complete response (DOR). The 77 evaluable patients in this single-arm, multicenter trial received ANKTIVA with BCG maintenance therapy for up to 37 months. The tumor status was assessed with cystoscopy and urine cytology and will continue for up to five years after each patient began their participation in the trial.
The CR rate for the 77 evaluable patients was 62% with the upper end of the confidence interval being 73%. The duration of complete response as of the November 2023 cut-off was more than 47 months and is ongoing to date. These prolonged duration of complete response results beyond 24 months with ANKTIVA and BCG exceed the benchmark for the magnitude of meaningful clinical results suggested by a panel of experts at the IBCG.
“We are pleased that treatment with ANKTIVA now exceeds the clinically meaningful benchmarks established by the IBCG in 2016 for durable complete response,” said Roger Buckley, with the IBCG. “We look forward to the global availability of ANKTIVA to potentially reduce the need for cystectomy in many patients worldwide with NMIBC.”
The duration of response is ongoing, so the final median duration of response has yet to be determined. Fifty-eight percent (58%) of patients with CR had a DOR ≥ 12 months and 40% had a DOR ≥ 24 months.
“The long duration of complete response ranging over 47 months is a game changer for NMIBC patients and provides further clinical evidence of ANKTIVA’s effectiveness for patients who historically have faced high rates of recurrence and significantly diminished quality of life due to radical surgeries,” said Karim Chamie, M.D., Associate Professor of Urology at UCLA and principal investigator for the QUILT 3.032 study. “With this approval, ANKTIVA could represent a new standard of care for patients with NMIBC and has the potential to change the way we treat bladder cancer.”
ANKTIVA is expected to be available in the U.S. by mid-May 2024.
New Hope for Patients
Bladder cancer is the 10th most commonly-diagnosed cancer globally,1 and in the U.S., the American Cancer Society estimates there will be 83,190 new cases and 16,840 deaths from bladder cancer in 2024.2 At the time of diagnosis, about 80% of cases are non-muscle invasive bladder cancer (NMIBC), wherein the cancer is found only on the inner layer of the bladder wall.3 The standard therapy for NMIBC is intravesical instillation (delivery to the bladder via a catheter) of bacillus Calmette-Guerin (BCG).4,5 BCG is a benign bacteria that induces an immune response in the bladder in proximity to the cancer cells, leading to clearance of the cancer in many patients. In ~30-40% of patients, however, BCG will fail, and in ~50% that initially respond, cancer will recur.6
“A new immunotherapy that builds upon our knowledge and experience with BCG as an immune stimulant is exciting to see,” said Ashish Kamat, M.D., MBBS, an Endowed Professor of Urologic Oncology and Cancer Research at University of Texas MD Anderson Cancer Center. “While patients have had limited options in the past after failure of BCG, nogapendekin alfa inbakicept-pmln, with its reported safety and efficacy, now offers them yet another choice in their quest to avoid a radical cystectomy. This is a big win for NMIBC patients everywhere.”
With the approval of ANKTIVA in combination with BCG, NMIBC patients who would otherwise face highly invasive surgery with life-long consequences have an important new therapeutic option with a long-term durable complete response.
“ANKTIVA enhances natural killer cell recruitment as well as T cell stimulation. By doing this and stimulating the innate immune memory response, we get an improved ability to kill tumor cells,” said Sam S. Chang, M.D., Professor of Urology and Chief Surgical Officer of the Vanderbilt Ingram Cancer Center, and a principal investigator for the QUILT 3.032 study. “It’s a potent and exciting combination.”
“NMIBC has a high rate of recurrence that sometimes results in major surgery to remove the bladder to prevent further disease progression,” said Andrea Maddox-Smith, CEO of the Bladder Cancer Advocacy Network (BCAN). “The addition of ANKTIVA to BCG gives NMIBC patients and their physicians a much-needed, new option to effectively treat the disease and offers an important non-surgical alternative to a cystectomy.”
ANKTIVA was well-tolerated with adverse events consistent with that of BCG alone. Studies of ANKTIVA in BCG-unresponsive and BCG-naive patients are ongoing. Reports of 82 subjects of high risk CIS NMIBC were reported in NEJM Evidence and previously presented.
The co-authors of an expert commentary on the published findings for ANKTIVA plus BCG in European Urology —Drs. Peter Black, Jonathan Suderman, and Marie-Pier St-Laurent—from the University of British Columbia, Vancouver, stated, “This appears to be a major advance in disease control in this patient population, especially when the low rate of serious adverse events is considered.” They further stated, “One could make the argument that NAI [ANKTIVA] should now become the standard of care given its more rigorous clinical trial data.”
Further updates on the ongoing analysis of QUILT-3.032 (NCT03022825) will be presented by Dr. Soon-Shiong at the upcoming American Urological Association’s annual conference on May 3, 2024.
“Today’s approval of ANKTIVA for patients with NMIBC marks an important milestone in our quest to develop cancer vaccines, and preventative vaccines for patients with genetic predisposition to developing cancer such as in Lynch syndrome,” said Soon-Shiong. “We believe that by orchestrating the innate and adaptive immune system and driving long-term complete remission, ANKTIVA has the potential to play a key role as the immunotherapy beyond checkpoints in multiple tumor types in the years to come.”
ANKTIVA has been studied in more than 700 patients in multiple Phase 1 and 2 trials in both liquid and solid tumors. In addition to trials in NMIBC, it is currently being studied in trials for non-small-cell lung cancer, colorectal cancer, non-Hodgkin’s lymphoma, glioblastoma, solid tumors, and HIV. Future studies are planned for platinum-resistant ovarian cancer and acute myeloid leukemia.
How ANKTIVA (N-803) Works
The cytokine interleukin-15 (IL-15) plays a crucial role in the immune system by affecting the development, maintenance, and function of key immune cells—NK and CD8+ killer T cells—that are involved in killing cancer cells.
ANKTIVA is a novel IL-15 superagonist complex consisting of an IL-15 mutant (IL-15N72D) fused with an IL-15 receptor alpha, which binds with high affinity to IL-15 receptors on NK, CD4, and CD8 T cells. This mimics the natural biological properties of dendritic cells, and drives the generation of memory killer T cells that have specifically been trained to recognize the cancer cells, resulting in activation and proliferation of these killing cells with durable complete response. ANKTIVA has improved pharmacokinetic properties, longer persistence in lymphoid tissues, and enhanced anti-tumor activity compared to native, non-complexed IL-15 in vivo.
Selected Safety Information for ANKTIVA (N-803)
The most common (≥15%) adverse reactions, including laboratory test abnormalities, are increased creatinine, dysuria, hematuria, urinary frequency, micturition urgency, urinary tract infection, increased potassium, musculoskeletal pain, chills, and pyrexia.
Patient Assistance Program
ImmunityBio is committed to helping patients access ANKTIVA and will be offering services to overcome access barriers. ImmunityBio’s Patient Assistance Program will be operational in mid May. This program is designed to help those in need, ensuring access to ImmunityBio’s innovative treatment. More information for patients and healthcare professionals will be available on Anktiva.com.
Conference Call and Webcast Information
ImmunityBio management will discuss FDA approval of ANKTIVA in combination with BCG for the treatment of BCG-unresponsive NMIBC via a conference call and webcast on Fri., April 26, 2024 at 11 am EDT. The conference call registration details will be available in the IR section of the ImmunityBio website.
About ImmunityBio
ImmunityBio is a vertically-integrated biotechnology company developing next-generation therapies and vaccines that bolster the natural immune system to defeat cancers and infectious diseases. The company’s range of immunotherapy and cell therapy platforms, alone and together, act to drive and sustain an immune response with the goal of creating durable and safe protection against disease. We are applying our science and platforms to treating cancers, including the development of potential cancer vaccines, as well as developing immunotherapies and cell therapies that we believe sharply reduce or eliminate the need for standard high-dose chemotherapy. These platforms and their associated product candidates are designed to be more effective, accessible, and easily administered than current standards of care in oncology and infectious diseases.
ImmunityBio stock jumps as FDA clears bladder cancer therapy
Apr. 23, 2024 5:57 AM ET
ImmunityBio, Inc. (IBRX) Stock
By: Preeti Singh, SA News Editor10 Comments
Shares of ImmunityBio (NASDAQ:IBRX) jumped around 33% premarket on Tuesday after the U.S. drug regulator cleared the company’s combination therapy for a type of bladder cancer.
The U.S. Food and Drug Administration (FDA) approved ImmunityBio’s ANKTIVA, an IL-15 agonist immunotherapy, in combination with the Bacillus Calmette-Guérin (BCG) vaccine for the treatment of patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ, with or without papillary tumors.
https://seekingalpha.com/news/4092292-immunitybio-stock-jumps-as-fda-clears-bladder-cancer-therapy
ImmunityBio, Inc. (IBRX) Stock
https://immunitybio.com/pipeline/
FDA approves bladder cancer treatment by Culver City company
https://www.latimes.com/business/story/2024-04-22/fda-approves-immunitybios-bladder-cancer-treatment
Rilzabrutinib
EMBLAVEO® (aztreonam-avibactam)
EMBLAVEO® (aztreonam-avibactam)
Press Release: Rilzabrutinib LUNA 3 phase 3 study met primary endpoint in immune thrombocytopenia
April 23, 2024
Rilzabrutinib LUNA 3 phase 3 study met primary endpoint in immune thrombocytopenia
- Pivotal data from the first phase 3 study of a BTKi in immune thrombocytopenia (ITP) underscore the potential of rilzabrutinib to provide a clinically meaningful benefit to patients living with ITP
- Regulatory submissions in the US and EU anticipated by year-end
- Rilzabrutinib is one of 12 potential medicines and vaccines in Sanofi’s robust immunology pipeline and a testament to Sanofi’s ability to successfully accelerate and build a portfolio of next-generation transformative treatments for immune diseases
- In addition to ITP, rilzabrutinib is being studied across a variety of immune-mediated diseases including asthma, chronic spontaneous urticaria, prurigo nodularis, IgG4-related disease and warm autoimmune hemolytic anemia
Paris, April 23, 2024.
Positive results from the LUNA 3 phase 3 study demonstrated that rilzabrutinib 400 mg twice daily orally achieved the primary endpoint of durable platelet response in adult patients with persistent or chronic immune thrombocytopenia (ITP). The safety profile of rilzabrutinib was consistent with that reported in previous studies.
LUNA 3 study met its primary endpoint demonstrating a significantly higher proportion of patients receiving rilzabrutinib achieved the primary endpoint of durable platelet response versus placebo. This clinically and statistically significant result was achieved in a population of patients with primary ITP that had been refractory to prior therapy. Overall, study participants had a median of four prior ITP therapies and a median baseline platelet count of 15,000/μL (normal platelet count levels typically range from 150,000-450,000/μL). Positive results on key secondary endpoints also underscore the potential for rilzabrutinib to deliver clinically meaningful benefits for patients living with persistent and chronic ITP.
Rilzabrutinib was granted Fast Track Designation by the US Food and Drug Administration (FDA) for the treatment of ITP in November 2020 and was previously granted Orphan Drug Designation.
Houman Ashrafian
Executive Vice President, Head of Research and Development, Sanofi
“The results of this study reinforce rilzabrutinib’s potential to be a first-in-class oral, reversible BTK inhibitor that can provide clinically meaningful improvements for people living with severe immune-mediated diseases like ITP. These pivotal results are a testament to our commitment and expertise in rare blood diseases and ability to build a portfolio of next-generation small-molecule inhibitors that are both more selective and optimized to deliver robust efficacy and safety outcomes as compared to existing therapies.”
ITP is a serious, acquired autoimmune blood disorder characterized by autoantibody-mediated platelet destruction and impaired platelet production, leading to thrombocytopenia (low platelet counts of less than 100,000/μL) and an increased risk of life-threatening bleeding episodes (like intracranial hemorrhage). In addition, patients with ITP often experience significant quality-of-life impairments such as fatigue and cognitive dysfunction. With its dual mechanisms of action that reduce production of pathogenic autoantibodies and decrease macrophage mediated platelet destruction, rilzabrutinib could address the underlying mechanisms responsible for a wide range of ITP complications.
About LUNA 3
LUNA 3 (NCT04562766) is a randomized, multicenter, phase 3 study evaluating the efficacy and safety of rilzabrutinib vs placebo in adult and adolescent patients with persistent or chronic ITP. Patients received either oral rilzabrutinib 400 mg twice a day or placebo through a 12- to 24-week double-blind treatment period, followed by a 28-week open-label treatment, and then a 4-week safety follow-up or long-term extension period. The adolescent part of the study is ongoing and still recruiting.
The primary endpoint is durable platelet response defined as the proportion of participants able to achieve platelet counts at or above 50,000/μL for for at least 8 out of the last 12 weeks of the 24-week blinded treatment period in the absence of rescue therapy. Secondary endpoints include the number of weeks with and time to platelet responses, rescue therapy use, and physical fatigue and bleeding score.
Detailed results of the LUNA 3 phase 3 study will be presented at a medical congress later this year.
Rilzabrutinib is currently under clinical investigation, and its safety and efficacy have not been evaluated by any regulatory authority.
About Rilzabrutinib
Rilzabrutinib is an oral, reversible, covalent BTK inhibitor that has the potential to be a first- or best-in-class treatment of several immune-mediated diseases. BTK, expressed in B cells, mast cells and other cells from the innate immune system, plays a critical role in inflammatory pathways and multiple immune-mediated disease processes. With the application of Sanofi’s TAILORED COVALENCY® technology, rilzabrutinib can selectively inhibit the BTK target.
Rilzabrutinib is being studied across a variety of immune-mediated diseases, including immune thrombocytopenia (regulatory submission in H2 2024), asthma (phase 2), chronic spontaneous urticaria (phase 3 start in 2024), prurigo nodularis (phase 3 start in 2024), IgG4-related disease (phase 2b results in H2 2024), and warm autoimmune hemolytic anemia (phase 2b results in H2 2024).
About Sanofi
We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people’s lives. Our team, across the world, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of our ambitions.
Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY
Attachment
Sanofi succeeds in late-stage trial for blood disorder candidate
Apr. 23, 2024 9:44 AM ET
Sanofi (SNY) Stock, GCVRZ Stock, SNYNF Stock
By: Dulan Lokuwithana, SA News Editor
Sanofi (NASDAQ:SNY) announced Tuesday that rilzabrutinib, an oral therapy for an autoimmune blood disorder called immune thrombocytopenia (ITP), reached the primary endpoint in a Phase 3 trial.
The study, named LUNA 3, enrolled adults and adolescents with persistent or chronic ITP who had been unresponsive to prior therapy.
They received rilzabrutinib 400 mg or placebo over a 12- to 24-week period, followed by a 28-week open-label phase and a 4-week follow-up.
EMBLAVEO® (aztreonam-avibactam)
EMBLAVEO® (aztreonam-avibactam)
EMBLAVEO® (aztreonam-avibactam)
European Commission Approves Pfizer’s EMBLAVEO® for Patients with Multidrug-Resistant Infections and Limited Treatment Options
Monday, April 22, 2024 - 08:08am
- EMBLAVEO® is the first β-lactam/β-lactamase inhibitor antibiotic combination approved in the European Union for treating serious infections in adult patients caused by multidrug-resistant Gram-negative bacteria, including metallo-β-lactamase-producing bacteria
- EMBLAVEO® was reviewed under European Medicines Agency accelerated assessment procedure, used when a pharmaceutical product is of major interest for public health and therapeutic innovation
NEW YORK--(BUSINESS WIRE)-- Pfizer Inc. (NYSE: PFE) today announced that the European Commission (EC) has granted marketing authorization for EMBLAVEO® (aztreonam-avibactam) for the treatment of adult patients with complicated intra-abdominal infections (cIAI), hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP), and complicated urinary tract infections (cUTI), including pyelonephritis. It is also indicated for the treatment of infections due to aerobic Gram-negative organisms in adult patients with limited treatment options.
“For healthcare teams treating patients with serious Gram-negative bacterial infections, the prospect of running out of effective treatment options is a daunting but very real threat,” said Yehuda Carmeli, Head, National Institute for Antibiotic Resistance and Infection Control, Tel Aviv Medical Center, Israel, and an investigator in the REVISIT study. “The approval of EMBLAVEO is welcome news for the infectious disease community and provides new hope to critically ill patients affected by antimicrobial resistance.”
Antimicrobial resistance (AMR) – when bacteria, viruses, fungi, and parasites change and find ways to resist the effects of antimicrobial drugs – is recognized as one of the biggest threats to global health.1 If AMR continues to rise unchecked, minor infections could become life-threatening, and many routine medical procedures such as caesarean sections and hip replacements could become too risky to perform.1 Multidrug-resistant Gram-negative bacteria are of particular concern due to the high rates of morbidity and mortality they cause.2,3 Metallo-β-lactamases (MBLs) are a type of enzyme produced by certain bacteria that can result in resistance to antibiotics, and MBL-producing Gram-negative bacteria are on the rise globally.4 Developing new treatments for infections caused by Gram-negative bacteria has been prioritized by the World Health Organization (WHO) as a critical area of focus due to their increasing spread.1,5
“The European Medicines Agency’s accelerated review of EMBLAVEO reflects the urgent need for new treatments to address the threat of antimicrobial resistance,” said Alexandre de Germay, Chief International Commercial Officer, Executive Vice President, Pfizer. “With this approval, Pfizer is proud to take another step forward in its commitment to developing and bringing breakthrough health solutions to patients impacted by serious infectious diseases around the world.”
This approval is based on results from the previously reported Phase 3 program comprising the REVISIT (NCT03329092) and ASSEMBLE (NCT03580044) studies evaluating the efficacy, safety, and tolerability of EMBLAVEO in treating serious bacterial infections due to Gram-negative bacteria, including MBL-producing multidrug-resistant pathogens for which there are limited or no treatment options.6,7 Data support that EMBLAVEO is effective and well-tolerated, with no new safety findings and a similar safety profile to aztreonam alone.8
The marketing authorization of EMBLAVEO is valid in all 27 European Union (EU) member states, as well as in Iceland, Liechtenstein, and Norway. Marketing authorization applications for EMBLAVEO are planned for submission in other countries.
About EMBLAVEO® (aztreonam-avibactam)
EMBLAVEO® is indicated for the treatment of adult patients with complicated intra-abdominal infections (cIAI), hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP), complicated urinary tract infections (cUTI), including pyelonephritis, and infections due to aerobic Gram-negative organisms with limited treatment options. It combines aztreonam, a monobactam β-lactam, with avibactam, a recent broad-spectrum β-lactamase inhibitor.9,10 MBLs are a class of β-lactamase enzymes that are not inhibited by current β-lactamase inhibitors and hydrolyze nearly all β-lactam antibiotics, with an exception being monobactams such as aztreonam. However, monobactams are degraded by other β-lactamases that are frequently co-produced with MBLs, limiting the clinical usefulness of aztreonam monotherapy.9
The combination of aztreonam with avibactam restores aztreonam’s activity against bacteria that co-produce MBLs and other β-lactamases and provides a well-tolerated and effective treatment option against multidrug-resistant Gram-negative bacteria.9 These multidrug-resistant Gram-negative bacteria include MBL-producing Enterobacterales, which have been highlighted as a critical priority pathogen by the WHO, and S. maltophilia.4,11 EMBLAVEO is the first β-lactam/β-lactamase inhibitor combination for treating serious bacterial infections in adult patients caused by multidrug-resistant Gram-negative bacteria, including MBL-producing bacteria, approved for use in the EU.
EMBLAVEO was jointly developed with AbbVie. Pfizer holds the global rights to commercialize this therapy outside of the U.S. and Canada, where the rights are held by AbbVie. Development of EMBLAVEO was also supported by public-private partnerships between Pfizer and the U.S. Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA) under OTA number HHSO100201500029C; and through the EU’s Innovative Medicines Initiative (IMI) – a partnership between the EU and the European pharmaceutical industry – under a project called COMBACTE-CARE (Combatting Bacterial Resistance in Europe – Carbapenem Resistance). The COMBACTE-CARE consortium is a unique public-private collaboration that unites the knowledge and capabilities of leading drug-resistant bacterial infection experts and is supported by the COMBACTE pan-European clinical and laboratory networks.
About Pfizer: Breakthroughs That Change Patients’ Lives
At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development, and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For 175 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.Pfizer.com.In addition, to learn more, please visit us on www.Pfizer.com and follow us on X at @Pfizer and @Pfizer_News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer/.
View source version on businesswire.com: https://www.businesswire.com/news/home/20240417715308/en/
Source: Pfizer Inc.
EU regulators approve Pfizer antibiotic Emblaveo
Apr. 22, 2024 10:14 AM ET
Pfizer Inc. (PFE) Stock, ABBV Stock
By: Val Brickates Kennedy, SA News Editor3 Comments
EU regulators have approved Pfizer (NYSE:PFE) and AbbVie’s (NYSE:ABBV) antibiotic product Emblaveo for the treatment of serious infections due to multi-drug resistant Gram-negative bacteria.
Pfizer said the European Commission has approved the drug for adults with complicated intra-abdominal infections, hospital-acquired pneumonia, and complicated urinary tract infections, including pyelonephritis. The EC also approved the product for the treatment of infections due to aerobic Gram-negative organisms in adults with limited options.
Emblaveo is a combination of the drugs aztreonam and avibactam. The product was co-developed by AbbVie and Pfizer. AbbVie holds commercial rights to the product in the US and Canada, with Pfizer holding the remaining worldwide rights.
PREVYMIS® (letermovir)
EMBLAVEO® (aztreonam-avibactam)
PREVYMIS® (letermovir)
Health Canada Approves New Indication for Merck’s PREVYMIS® (letermovir) for Prevention of Cytomegalovirus (CMV) Disease in High-Risk Adult Kidney Transplant Recipients
KIRKLAND, QC, April 19, 2024 – Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced that Health Canada has approved a new indication for PREVYMIS® (letermovir) for the prophylaxis of cytomegalovirus (CMV) disease in adult kidney transplant recipients at high risk (Donor CMV-seropositive/Recipient CMV-seronegative [D+/R-]).
“We are pleased that PREVYMIS® has received Health Canada approval to help prevent CMV disease in high-risk adult kidney transplant patients.” said Philippe Houle, Executive Director of Infectious Diseases and Specialty Medicines at Merck Canada. “Our focus remains solely on providing innovative medicines to address the unmet needs of all Canadians.”
Phase 3 study for PREVYMIS in high-risk adult kidney transplant recipients [CMV D+/R-]
Health Canada’s approval of PREVYMIS® for CMV disease prophylaxis in adult kidney transplant recipients was supported by a Phase 3, randomized, multicenter, double-blind, active comparator-controlled non-inferiority trial (P002, NCT03443869) in 589 adult kidney transplant recipients at high risk (CMV D+/R-). Participants were randomized (1:1) to receive either PREVYMIS® concomitantly with acyclovir (n=292), or valganciclovir concomitantly with a placebo to acyclovir (n=297). Study drug was initiated between Day 0 and Day 7 post-kidney transplant and continued through Week 28 (~200 days) post-transplant. Study drug was administered either orally or IV; the dose of PREVYMIS® was the same regardless of the route of administration.
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information about our operations in Canada, visit www.merck.ca and connect with us on YouTube and X (formally known as Twitter) @MerckCanada.
Please see the product monograph for PREVYMIS® (letermovir) at: PREVYMIS-PM_E.pdf (merck.ca)
FXR314
Lomecel-B™
PREVYMIS® (letermovir)
Organovo Announces Positive Phase 2 Results for FXR314 in Metabolic Dysfunction-Associated Steatohepatitis (MASH) Showing Both Reduction in Liver Fat Content and Strong Safety and Tolerability Compared to Placebo
April 15, 2024 at 8:05 AM EDT
SAN DIEGO, April 15, 2024 (GLOBE NEWSWIRE) -- Organovo Holdings, Inc. (Nasdaq:ONVO), a clinical stage biotechnology company focused on developing novel treatment approaches based on demonstration of clinical promise in three-dimensional (3D) human tissues, today released the complete details of its 16-week, randomized, placebo-controlled, multi-center Phase 2 study of the non-steroidal, non-bile acid FXR agonist FXR314 for the treatment of metabolic function-associated steatohepatitis (MASH). Study results demonstrated statistically significant reduction in liver fat content from baseline in patients receiving FXR314 compared to placebo.
Study subjects receiving FXR314 achieved statistically significant reduction in liver fat content from baseline, with LS mean percent reduction at end of treatment of 22.8% (p=0.0010) with 3 mg and 17.5% (p=0.0267) with 6 mg doses of FXR314 compared to 6.1% in the placebo group. The proportion of subjects with >30% magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) reduction was 29.2% (p=0.0023) and 32.2% (p=0.0020) for 3 mg and 6 mg FXR314, respectively, compared to 9.5% with placebo. Investigators observed improvements in hepatocellular damage and liver function based on serological measures, with no evidence of worsening of liver fibrosis.
FXR314 was also found to be safe and well tolerated. Treatment-emergent adverse events were mostly mild to moderate in severity, with incidence comparable between FXR314 3 mg, 6 mg, and placebo. Drug-related treatment discontinuation was minimal and similar across groups. There was also no evidence with FXR314 of adverse events considered common in the FXR class, including measures of pruritus (3 mg 2.8%, 6 mg 4.2% and placebo 2.8%) and LDL-C levels (change from baseline of 1.5%, 4.5% and -3.6% for 3mg, 6mg, and placebo groups respectively).
“The key findings of this study are that once daily oral FXR314 demonstrated statistically significant liver fat reduction and excellent tolerability. Whereas other FXR agonists have had challenges in providing clear benefit without significant pruritus or other adverse events, or have had lack of efficacy potentially related to lack of sustained exposure, we are pleased to note FXR314’s data demonstrate it clearly rises above previous problems seen with the class,” stated Keith Murphy, Organovo’s Executive Chairman. “Given these exciting findings, we believe the data are supportive of further clinical development of FXR314 in MASH.”
The clinical trial evaluated the safety, tolerability, and pharmacological activity of FXR314, as measured by reductions in liver fat content with magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF), changes in liver enzymes, low-density lipoprotein cholesterol (LDL-C) levels, and incidence of pruritus. The treatment population were MASH patients diagnosed via biopsy, magnetic resonance elastography (MRE), or transient elastography (TE FibroScan), and who had liver fat content ≥ 10% as measured by MRI-PDFF. A total of 214 patients were randomized in a 1:1:1 ratio to either 3 mg or 6 mg of FXR314, or placebo. Treatment was administered orally once daily for 16 weeks. The Company expects that detailed findings of this study (Clinical trial registry NCT047773964) will be presented at an upcoming conference.
About Organovo
Organovo is a clinical stage biotechnology company that is developing drugs that are demonstrated to be effective in three-dimensional (3D) human tissues as candidates for drug development. The company’s lead molecule, FXR314, is on the path for Phase 2 investigation in inflammatory bowel disease and has applications in metabolic liver disease and oncology. The company has proprietary technology used to build 3D human tissues that mimic key aspects of native human tissue composition, architecture, function, and disease. For more information visit Organovo's website at www.organovo.com.
Source: Organovo, Inc.
Organovo reports positive mid-stage results for FXR314 in metabolic dysfunction-associated steatohepatitis
Apr. 15, 2024 8:51 AM ET
Organovo Holdings, Inc. (ONVO) Stock
By: Nilanjana Basu, SA News Editor
- Organovo Holdings (NASDAQ:ONVO) said that results from Phase 2 study of its metabolic function-associated steatohepatitis treatment demonstrated statistically significant reduction in liver fat content from baseline in patients receiving FXR314 compared to placebo.
- https://seekingalpha.com/news/4089580-organovo-reports-positive-mid-stage-results-for-fxr314-in-metabolic-dysfunction-associated-steatohepatitis
- Organovo Holdings, Inc. (ONVO) Stock
- https://organovo.com/
- https://organovo.com/pipeline/
MarVax™
Lomecel-B™
Lomecel-B™
FDA Grants Soligenix Orphan Drug Designation for the Prevention and Post-Exposure Prophylaxis Against Marburg Marburgvirus Infection
Provides MarVax™ Heat Stable Vaccine Seven Years of U.S. Market Exclusivity Upon FDA Approval
PRINCETON, N.J., April 15, 2024 /PRNewswire/ -- Soligenix, Inc. (Nasdaq: SNGX) (Soligenix or the Company), a late-stage biopharmaceutical company focused on developing and commercializing products to treat rare diseases where there is an unmet medical need, announced today that the Office of Orphan Products Development of the United States (U.S.) Food and Drug Administration (FDA) has granted orphan drug designation to the active ingredient in MarVax™, the subunit protein vaccine of recombinantly expressed Marburg marburgvirus (MARV) glycoprotein, for "the prevention and post-exposure prophylaxis against MARV infection."
The U.S. Orphan Drug Act is intended to assist and encourage companies to develop safe and effective therapies for the treatment of rare diseases and disorders, defined as one that affects fewer than 200,000 people in the U.S. In addition to providing a seven-year term of market exclusivity upon final FDA approval, orphan drug designation also positions Soligenix to be able to leverage a wide range of financial and regulatory benefits, including government grants for conducting clinical trials, waiver of expensive FDA user fees for the potential submission of a Biologics License Application (BLA), and certain tax credits.
"Marburg marburgvirus causes Marburg Virus Disease, a highly related disease to the more commonly known Ebola Virus Disease. Although MARV has caused fewer outbreaks, they remain highly fatal and a significant risk in continental Africa, with the most recent outbreak occurring in 2023. There is no approved vaccine for MARV, and the only approved vaccines for filovirus type disease is specific to Zaire ebolavirus. Unlike the approved vaccines, which depend on using a different inactive or attenuated virus to stimulate the immune system, MarVax™ is a heat stable subunit vaccine with adjuvant. Subunit vaccines are a gold standard technology for safety and are also broadly applicable across the population, especially when combined with an effective adjuvant," stated Christopher J. Schaber, PhD, President and Chief Executive Officer of Soligenix. "Elements of this subunit vaccine platform have been utilized in our ricin toxin, filovirus and COVID-19 vaccine candidates, indicating its broad applicability. We have also demonstrated the ability to package more than one vaccine antigen in a single vaccine, particularly against MARV and Sudan ebolavirus where there are currently no available vaccines. The FDA's decision to grant orphan drug designation to both the MARV and Sudan ebolavirus vaccine candidates signifies an important step for Soligenix as we continue to advance the program and adds significantly to the existing patent estate surrounding this novel technology and the filovirus program."
About MarVax™
MarVax™ is a subunit protein vaccine of recombinantly expressed Marburg marburgvirus (MARV) glycoprotein, developed in partnership with Dr. Axel Lehrer at the University of Hawaiʽi at Mānoa. The vaccine includes a protein found on the surface of MARV, to engender an appropriate immune response without posing a risk of infection, as well as a novel adjuvant which stimulates both humoral and cell mediated immune responses, in combination with Generally Regarded as Safe (GRAS) excipients that enable lyophilization (i.e., freeze-drying) of the vaccine. The resulting product is manufactured as a heat stable powder in a vial which is reconstituted with generically available water for injection immediately prior to use. Stability studies have demonstrated that MarVax™ is heat stable for at least 2 years at temperatures of at least 40 degrees Celsius (104 degrees Fahrenheit). MarVax™ has demonstrated 100% protection of non-human primates exposed to a lethal injection of MARV.
Manufacture of the recombinant protein utilized in MarVax™ utilizes a robust protein manufacturing process, developed and tested in other subunit vaccines advanced through clinical testing. Similarly, the selected adjuvant, while novel, has also been independently tested in Phase 1 and Phase 2 clinical studies. MarVax™ can also be expressed as part of a multivalent vaccine, in combination with antigens against Sudan ebolavirus for example.
About Marburg marburgvirus Infection
Marburg Virus Disease is caused by MARV, a member of the Filoviridae family that also includes Sudan ebolavirus (causing Sudan Virus Disease) and Zaire ebolavirus (causing Ebola Virus Disease). Filoviruses are believed to be harbored in various animal species in Africa, particularly bats, although the specific reservoir host for many of these viruses is still unknown. There have been several known Ebola (both Sudan and Zaire) and Marburg Virus Disease outbreaks since 1967 with the most recent MARV outbreaks occurring in February – June 2023 in Equatorial Guinea and in March – May 2023 in Tanzania, with no relationship between the two outbreaks, according to the Centers for Disease Control and Prevention (CDC). Cases of Marburg Virus Disease were also recorded in Ghana in 2022 and 2021.
Transmission of filoviruses requires direct contact with bodily fluids from an infected person or contact with infected animals. The mortality rates following filovirus infections are extremely high, and, in the absence of wide availability of effective therapeutics, are affected by the quality of supportive care available with a focus on early initiation of treatment. Resolution of the disease largely depends on the patient's own immune system. While there are limited treatment options for disease caused by Zaire ebolavirus, there are no available treatments or vaccines available for Marburg Virus Disease. The approved vaccines for Ebola virus (Zaire ebolavirus) utilize a viral vector approach which has contraindications for some individuals and require stringent ultra-low cold-chain storage, inhibiting their broad use in challenging conditions where power supply can be uncertain and ambient temperature can be very high.
About Soligenix, Inc.
Soligenix is a late-stage biopharmaceutical company focused on developing and commercializing products to treat rare diseases where there is an unmet medical need. Our Specialized BioTherapeutics business segment is developing and moving toward potential commercialization of HyBryte™ (SGX301 or synthetic hypericin sodium) as a novel photodynamic therapy utilizing safe visible light for the treatment of cutaneous T-cell lymphoma (CTCL). With successful completion of the second Phase 3 study, regulatory approvals will be sought to support potential commercialization worldwide. Development programs in this business segment also include expansion of synthetic hypericin (SGX302) into psoriasis, our first-in-class innate defense regulator (IDR) technology, dusquetide (SGX942) for the treatment of inflammatory diseases, including oral mucositis in head and neck cancer, and (SGX945) in Behçet's Disease.
Our Public Health Solutions business segment includes development programs for RiVax®, our ricin toxin vaccine candidate, as well as our vaccine programs targeting filoviruses (such as Marburg and Ebola) and CiVax™, our vaccine candidate for the prevention of COVID-19 (caused by SARS-CoV-2). The development of our vaccine programs incorporates the use of our proprietary heat stabilization platform technology, known as ThermoVax®. To date, this business segment has been supported with government grant and contract funding from the National Institute of Allergy and Infectious Diseases (NIAID), the Defense Threat Reduction Agency (DTRA) and the Biomedical Advanced Research and Development Authority (BARDA).
For further information regarding Soligenix, Inc., please visit the Company's website at
and follow us on LinkedIn and Twitter at @Soligenix_Inc.
SOURCE SOLIGENIX, INC.
Soligenix stock soars 106% on FDA orphan drug status
Apr. 15, 2024 10:13 AM ET
By: Val Brickates Kennedy, SA News Editor
Soligenix (SNGX) stock soared 106% in early trading Monday after the company said it received orphan drug designation from the FDA for the active ingredient in its Marburg vaccine, MarVax.
Lomecel-B™
Lomecel-B™
Lomecel-B™
Longeveron’s CLEAR MIND Randomized Phase 2a Clinical Trial Evaluating Lomecel-B™ in Mild Alzheimer’s Disease Accepted for Featured Research Session Oral Presentation at the 2024 Alzheimer’s Association International Conference (AAIC)
04/15/2024
MIAMI, April 15, 2024 (GLOBE NEWSWIRE) -- Longeveron Inc.
(NASDAQ: LGVN), a clinical stage biotechnology company developing regenerative medicines, today announced that it has been accepted for a Featured Research Oral Presentation to present the Company’s CLEAR MIND Phase 2a study results. CLEAR-MIND is a Phase 2a randomized clinical trial evaluating Lomecel-BTM in mild Alzheimer’s Disease. In addition to the clinical study results, the Company has been accepted for a poster presentation at the 2024 Alzheimer’s Association International Conference (AAIC), to be held July 28 – August 1, 2024 in Philadelphia, PA, USA and online.
“We are extremely excited to share the full study results of our CLEAR-MIND trial at the AAIC meeting this year, and have the opportunity to present at the leading forum for Alzheimer’s disease clinical investigation,” said Wa’el Hashad, CEO of Longeveron.
Oral PresentationDate:
Sunday, July 28, 2024Time:4:15pm – 5:45pm EDTSession:Featured Research Session, 1-32-FRS-BTitle:“Results from a Phase 2a Proof-of-Concept Double-Blind, Randomized, Placebo-Controlled Trial of Lomecel-BTM in Mild Alzheimer’s Disease Dementia” Longeveron’s Kevin N. Ramdas, MD, MPH, Director of Clinical Operations, was invited to chair this Featured Research Session.
Poster PresentationDate:
Tuesday, July 30, 2024Time:7:30am – 4:15pm EDTSession:In-Person Posters Tuesday; Drug DevelopmentTopic:MRI Imaging results in the CLEAR MIND phase 2a clinical trial of Lomecel-BTM
Longeveron previously announced top-line results for the CLEAR MIND Phase 2a clinical trial on October 5, 2023, and reported additional clinical data and imaging biomarker results from CLEAR MIND on December 20, 2023.
About Longeveron Inc.
Longeveron is a clinical stage biotechnology company developing regenerative medicines to address unmet medical needs. The Company’s lead investigational product is Lomecel-B™ an allogeneic Mesenchymal Stem Cell (MSC) formulation sourced from the bone marrow of young, healthy adult donors. Lomecel-B™ has multiple potential mechanisms of action that promote tissue repair and healing with broad potential applications across a spectrum of disease areas. The underlying mechanism(s) of action that may lead to the tissue repair programs include the stimulation of new blood vessel formation, modulation of the immune system, reduction in tissue fibrosis, and the stimulation of endogenous cells to divide and increase the numbers of certain specialized cells in the body. Longeveron is currently pursuing three pipeline indications: Hypoplastic Left Heart Syndrome, Alzheimer’s disease, and Aging-related Frailty. For more information, visit www.longeveron.com or follow Longeveron on LinkedIn, X, and Instagram.
Source: Longeveron
Longeveron stock rallies 85% on Alzheimer's presentation (update)
Apr. 15, 2024 9:55 AM ET
By: Val Brickates Kennedy, SA News Editor
Shares of Longeveron (NASDAQ:LGVN) rallied 85% early Monday after the biotech company announced it will present results from its Phase 2a CLEARMIND study for its therapy Lomecel-B in the treatment of mild Alzheimer’s disease at the Alzheimer’s Association International Conference in July.
https://seekingalpha.com/news/4089636-longeveron-stock-rallies-pre-market-on-alzheimers-data-update
biotecHOPE™ 2024
nanatinostat in combination with valganciclovir
nanatinostat in combination with valganciclovir
nanatinostat in combination with valganciclovir
Viracta Therapeutics Announces Positive Topline Nana-val Results from Stage 1 of the NAVAL-1 Trial in Patients with Relapsed or Refractory Epstein-Barr Virus-Positive (EBV+) Peripheral T-Cell Lymphoma-
Patients in the Nana-val (nanatinostat in combination with valganciclovir) treatment arm achieved clinically meaningful anti-tumor responses with an overall response rate of 50% and a complete response rate of 20% in the intent-to-treat population (71% and 29% in the efficacy-evaluable population) with a generally manageable safety profile -- Nana-val demonstrated substantially greater efficacy than nanatinostat monotherapy, further validating its ‘Kick and Kill’ mechanism of action -- Data were presented in an oral presentation at the 2024 Joint Annual Congress of Taiwan Society of Blood and Marrow Transplantation and The Hematology Society of Taiwan -
San Diego, April 15, 2024 – Viracta Therapeutics, Inc. (Nasdaq: VIRX), a clinical-stage precision oncology company focused on the treatment and prevention of virus-associated cancers that impact patients worldwide, today reported positive topline results from Stage 1 of the pivotal Phase 2 NAVAL-1 trial from both arms of the relapsed or refractory (R/R) Epstein-Barr virus-positive (EBV+) peripheral T-cell lymphoma (PTCL) cohort. Patients were randomized to either nanatinostat monotherapy (n=10) or to nanatinostat in combination with valganciclovir (Nana-val, n=10). These data were featured in an oral presentation during the 2024 Joint Annual Congress of Taiwan Society of Blood and Marrow Transplantation and The Hematology Society of Taiwan.
“Nana-val demonstrated an impressive clinical response in patients with relapsed or refractory EBV-positive PTCL with a generally manageable safety profile, including one patient who was able to proceed to allogeneic stem-cell transplant and remains in response for over 8 months to date,” said Hung Chang, M.D., Professor of Hematology, Linkou Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan and principal investigator in the NAVAL-1 trial. “The substantially greater clinical efficacy of Nana-val relative to nanatinostat monotherapy suggests that both agents in the combination regimen are contributing to its anti-tumor activity as predicted by their mechanisms of action. Nana-val is emerging as a promising, generally well-tolerated, convenient all-oral treatment for patients with relapsed or refractory EBV-positive PTCL.”
Darrel P. Cohen, M.D., Ph.D., Chief Medical Officer of Viracta added, “Patients with relapsed or refractory EBV-positive PTCL have a very poor prognosis, worse than those with EBV-negative disease, yet there are presently no EBV-targeted treatment options available. We are encouraged by the Stage 1 data from patients with relapsed or refractory EBV-positive PTCL in the pivotal Phase 2 NAVAL-1 trial that further validates Nana-val’s differentiated ‘Kick and Kill’ mechanism of action. Building on these promising clinical outcomes emerging from the NAVAL-1 trial, which are consistent with those from our preceding Phase 1b/2 study, we will continue to advance Nana-val in this lead indication through regulatory approval as quickly as possible. We look forward to engaging with the FDA on a potential accelerated approval pathway midyear and sharing topline results from Stage 2 together with additional data from Stage 1 in the third quarter of 2024.”
Key takeaways from the pivotal Phase 2 NAVAL-1 trial in patients with R/R EBV+ PTCL: Nana-val (nanatinostat in combination with valganciclovir) demonstrated greater efficacy than nanatinostat monotherapy and was generally well-tolerated. The median duration of response continues to mature.
- Overview: A total of 20 patients with primarily Stage III-IV disease (who had received ≥1 [median of 2] prior systemic PTCL therapies) were randomized (1:1) to receive nanatinostat (20 mg orally once daily, 4 days/week) alone or as Nana-val in combination with valganciclovir (900 mg orally once daily, 7 days/week). Patients who did not respond to nanatinostat monotherapy after 6 weeks of treatment were offered the opportunity to cross over to receive Nana-val.
- Efficacy was evaluated as of the February 7, 2024 data cutoff date.
- In the Nana-val arm, the overall response rate (ORR) was 50% and the complete response rate (CRR) was 20% in the intent-to-treat (ITT) population (N=10); the ORR was 71% and the CRR was 29% in the efficacy-evaluable population (N=7).
- In the nanatinostat monotherapy arm, the ORR and CRR were 10% and 0%, respectively, in the ITT population (N=10), and the ORR was 13% in the efficacy-evaluable population (N=8).
- Five nanatinostat monotherapy patients crossed over to receive Nana-val, two of whom remain on Nana-val treatment with stable disease as of the data cutoff.
- Safety was also evaluated as of the February 7, 2024 data cutoff date.
- The most common treatment-related adverse events in both treatment arms were thrombocytopenia, anemia, fatigue, decreased appetite, nausea, diarrhea, and weight loss.
- These adverse events were primarily mild to moderate in severity and generally manageable or reversible.
- The most common treatment-related adverse events in both treatment arms were thrombocytopenia, anemia, fatigue, decreased appetite, nausea, diarrhea, and weight loss.
A copy of the data presentation is accessible under the “Events and Presentations” section of Viracta’s website at www.viracta.com.
About the NAVAL-1 Trial
NAVAL-1 (NCT05011058) is a global, multicenter, clinical trial of Nana-val in patients with relapsed or refractory (R/R) Epstein-Barr virus-positive (EBV+) lymphoma. This Phase 2 trial employs a Simon two-stage design where, in Stage 1, participants are enrolled into one of three indication cohorts based on EBV+ lymphoma subtype. If two objective responses are achieved within a lymphoma subtype in Stage 1 (n=10), then additional patients will be enrolled in Stage 2 for a total of 21 patients. EBV+ lymphoma subtypes demonstrating promising anti-tumor activity in Stage 2 may be further expanded following discussion with regulators to potentially support registration.
About Nana-val (Nanatinostat and Valganciclovir)
Nanatinostat is an orally available histone deacetylase (HDAC) inhibitor being developed by Viracta. Nanatinostat is selective for specific isoforms of Class I HDACs, which are key to inducing viral genes that are epigenetically silenced in Epstein-Barr virus (EBV)-associated malignancies. Nanatinostat is currently being investigated in combination with the antiviral agent valganciclovir as an all-oral combination therapy, Nana-val, in various subtypes of EBV-associated malignancies. Ongoing trials include a pivotal, global, multicenter, open-label, Phase 2 basket trial in multiple subtypes of relapsed or refractory (R/R) EBV+ lymphoma (NAVAL-1) as well as a multinational Phase 1b/2 clinical trial in patients with recurrent or metastatic (R/M) EBV+ NPC and other advanced EBV+ solid tumors.
About Peripheral T-Cell Lymphoma
T-cell lymphomas comprise a heterogeneous group of rare and aggressive malignancies, including peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL). There are approximately 5,600 newly diagnosed T-cell lymphoma patients and approximately 2,600 newly diagnosed PTCL-NOS and AITL patients in the U.S. annually. Approximately 70% of these patients are either refractory to first-line therapy, or eventually experience relapse of their disease. Clinical trials are currently recommended for all lines of PTCL therapy, and most patients with R/R PTCL have poor outcomes, with median progression-free survival and median overall survival times reported to be 3.7 and 6.5 months, respectively. Approximately 40% to 65% of PTCL is associated with EBV, the incidence of EBV+ PTCL varies by geography, and reported outcomes for patients with EBV+ PTCL are inferior to those whose disease is EBV-negative. There is no approved targeted treatment specific for EBV+ PTCL, and therefore this represents a high unmet medical need.
About EBV-Associated Cancers
Approximately 90% of the world's adult population is infected with EBV. Infections are commonly asymptomatic or associated with mononucleosis. Following infection, the virus remains latent in a small subset of cells for the duration of the patient's life. Cells containing latent virus are increasingly susceptible to malignant transformation. Patients who are immunocompromised are at an increased risk of developing EBV-positive (EBV+) lymphomas. EBV is estimated to be associated with approximately 2% of the global cancer burden including lymphoma, nasopharyngeal carcinoma (NPC), and gastric cancer.
About Viracta Therapeutics, Inc.
Viracta is a clinical-stage precision oncology company focused on the treatment and prevention of virus-associated cancers that impact patients worldwide. Viracta’s lead product candidate is an all-oral combination therapy of its proprietary investigational drug, nanatinostat, and the antiviral agent valganciclovir (collectively referred to as Nana-val). Nana-val is currently being evaluated in multiple ongoing clinical trials, including a pivotal, global, multicenter, open-label Phase 2 basket trial for the treatment of multiple subtypes of relapsed or refractory (R/R) Epstein-Barr virus-positive (EBV+) lymphoma (NAVAL-1), as well as a multinational, open-label Phase 1b/2 clinical trial for the treatment of patients with recurrent or metastatic (R/M) EBV+ nasopharyngeal carcinoma (NPC) and other advanced EBV+ solid tumors. Viracta is also pursuing the application of its “Kick and Kill” approach in other virus-related cancers.
For additional information, please visit www.viracta.com.
SOURCE Viracta Therapeutics, Inc.
Viracta Therapeutics reports positive results from stage 1 of phase 2 trial for lymphoma treatment
Apr. 15, 2024 8:40 AM ET
Viracta Therapeutics, Inc. (VIRX) StockITT
By: Nilanjana Basu, SA News Editor
- Viracta Therapeutics (NASDAQ:VIRX) reported positive topline results from Stage 1 of the Phase 2 NAVAL-1 trial from both arms of the relapsed or refractory Epstein-Barr virus-positive peripheral T-cell lymphoma cohort.
- https://seekingalpha.com/news/4089565-viracta-therapeutics-reports-positive-results-from-stage-1-of-phase-2-trial-for-lymphoma-treatment
- Viracta Therapeutics, Inc. (VIRX) Stock
- https://www.viracta.com/
- https://www.viracta.com/pipeline/
Tamibarotene (formerly SY-1425)
nanatinostat in combination with valganciclovir
nanatinostat in combination with valganciclovir
Syros Receives Fast Track Designation from the FDA for Tamibarotene for the Treatment of Newly Diagnosed Unfit AML with RARA gene overexpression
APRIL 09, 2024
CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Syros Pharmaceuticals (NASDAQ:SYRS), a biopharmaceutical company committed to advancing new standards of care for the frontline treatment of hematologic malignancies, today announced that the United States Food and Drug Administration (FDA) has granted Fast Track Designation to tamibarotene in combination with azacitidine and venetoclax for the treatment of newly diagnosed acute myeloid leukemia (AML) with RARA overexpression as detected by an FDA approved test in adults who are over age 75 years or who have comorbidities that preclude the use of intensive induction chemotherapy. Tamibarotene, an oral first-in-class selective retinoic acid receptor alpha (RARα) agonist, is currently being evaluated in combination with venetoclax and azacitidine for the treatment of newly diagnosed AML patients with RARA gene overexpression.
“We are pleased to receive Fast Track designation for tamibarotene for the treatment of AML. This designation reflects the tremendous need for a safe and effective therapy, which can improve the clinical outcomes and prognosis among people diagnosed with AML, many of whom cannot tolerate intensive treatment,” said David A. Roth, M.D., Chief Medical Officer of Syros Pharmaceuticals. “We are particularly encouraged to secure Fast Track designation following initial randomized data from a prespecified interim analysis of our ongoing SELECT-AML-1 clinical trial, in which treatment with our RARα agonist, tamibarotene, in combination with venetoclax and azacitidine resulted in a 100% CR/CRi rate compared with a 70% CR/CRi rate for the comparator of venetoclax and azacitidine. Additionally, tamibarotene in combination with venetoclax and azacitidine demonstrated no added toxicity relative to venetoclax and azacitidine alone. We look forward to sharing additional data from SELECT-AML-1 later this year, and to potentially accelerate the delivery of tamibarotene as a new frontline option for the approximately 30% of AML patients who are positive for RARA overexpression.”
Fast Track is a process designed by the FDA to facilitate the development and expedite the review of drug candidates intended to treat serious conditions and for which nonclinical or clinical data demonstrate the potential to address unmet medical need. The purpose is to facilitate development and expedite review of drugs to treat serious and life-threatening conditions, to bring the approved products to patients earlier. A therapeutic candidate that receives Fast Track designation may be eligible for more frequent interactions with the FDA to discuss the therapeutic candidate’s development plan. Therapeutic candidates with Fast Track designation may also be eligible for priority review and accelerated approval if supported by clinical data.
Syros is evaluating tamibarotene in combination with venetoclax and azacitidine in newly diagnosed, unfit AML patients with RARA overexpression in the ongoing SELECT-AML-1 Phase 2 trial. In December 2023, Syros announced initial randomized data from SELECT-AML-1, demonstrating a 100% CR/CRi (complete response/complete response with incomplete hematologic recovery) rate in response-evaluable patients (nine of nine) treated with the triplet regimen of tamibarotene, venetoclax and azacitidine, as compared to 70% among patients (seven of ten) treated with venetoclax and azacitidine alone, with corresponding CR rates of 78% vs 30%, respectively. The median time to CR/CRi response was rapid; all patients treated with the triplet regimen achieved a CR/CRi by the end of cycle one. Consistent with prior clinical experience, tamibarotene in combination with approved doses of venetoclax and azacitidine was generally well tolerated, and the overall safety profile demonstrated no additive toxicities or new safety signals, and no evidence of increased myelosuppression compared to treatment with the doublet combination of venetoclax and azacitidine. Syros expects to report additional data from SELECT-AML-1 in 2024.
Syros is also evaluating tamibarotene in combination with azacitidine in newly diagnosed higher-risk myelodysplastic syndrome (MDS) patients with RARA overexpression in the SELECT-MDS-1 Phase 3 trial. As recently announced, enrollment to support the pivotal primary efficacy analysis was completed in the first quarter of 2024, and pivotal complete response data is expected by the middle of the fourth quarter of 2024. In January 2023, the FDA granted Fast Track Designation to tamibarotene for the treatment of HR-MDS patients with RARA overexpression.
About Syros Pharmaceuticals
Syros is committed to developing new standards of care for the frontline treatment of patients with hematologic malignancies. Driven by the motivation to help patients with blood disorders that have largely eluded other targeted approaches, Syros is developing tamibarotene, an oral selective RARα agonist in frontline patients with higher-risk myelodysplastic syndrome and acute myeloid leukemia with RARA gene overexpression. For more information, visit www.syros.com and follow us on Twitter (@SyrosPharma) and LinkedIn.
View source version on businesswire.com: https://www.businesswire.com/news/home/20240409254657/en/
Source: Syros Pharmaceuticals
Released April 9, 2024
Syros jumps on FDA fast track tag for leukemia drug
Apr. 09, 2024 11:00 AM ET
By: Dulan Lokuwithana, SA News Editor
Shares of Syros Pharmaceuticals (NASDAQ:SYRS) traded higher on Tuesday on the news that the U.S. Food and Drug Administration (FDA) granted its fast-track designation for the company’s leukemia candidate, tamibarotene.
The designation covers the use of tamibarotene for newly diagnosed patients with acute myeloid leukemia aged 75 years and older.
Olezarsen
nanatinostat in combination with valganciclovir
NEXLETOL® (bempedoic acid) Tablets
Ionis presents positive results from Phase 3 Balance study of olezarsen for familial chylomicronemia syndrome
April 7, 2024 at 9:48 AM EDT
– Olezarsen met the primary endpoint with statistically significant reduction of fasting triglycerides and showed substantial, clinically meaningful reduction in acute pancreatitis events –
– Results demonstrate olezarsen may represent a novel treatment option for this rare, life-threatening disease, for which there are no approved treatments in the U.S. –
– Data presented today at ACC 2024 and published in The New England Journal of Medicine –
– Ionis to host webcast on Monday, April 8 at 10:00 am ET –
CARLSBAD, Calif., April 7, 2024 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) today announced full results from the Phase 3 Balance study of Ionis' lead independent investigational medicine, olezarsen, for the treatment of adults with familial chylomicronemia syndrome (FCS). The olezarsen 80 mg monthly dose met the primary endpoint of significantly reducing triglycerides (TGs) in patients with genetically validated FCS at six months. In addition, olezarsen demonstrated robust and sustained reductions in TGs and serum apolipoprotein C-III (apoC-III) levels. Importantly, olezarsen reduced the incidence of acute pancreatitis (AP) events over the 12-month treatment period compared to placebo. Olezarsen also demonstrated a favorable safety and tolerability profile. These results were presented in an oral presentation at the 2024 American College of Cardiology (ACC) Annual Meeting in Atlanta, Georgia and published simultaneously in The New England Journal of Medicine (NEJM). Based on these data, Ionis is pursuing regulatory approval of olezarsen as a potential breakthrough treatment for adults with FCS.
"As a physician who has seen first-hand the struggles of people living with FCS and its serious complications, there is significant need for an effective therapy to lower triglycerides and reduce acute pancreatitis events," said Erik Stroes, M.D., professor of medicine, Amsterdam University Medical Centers, and a principal investigator of the Balance study. "Olezarsen represents a potentially life-changing new medicine for these patients who experience debilitating chronic symptoms, including abdominal pain and cognitive symptoms, as well as hospitalizations associated with potentially fatal acute pancreatitis events."
Balance Study Results
In the study, patients were treated with olezarsen 80 mg (n=22), 50 mg (n=21) or placebo (n=23) once every four weeks.
- In the 80 mg group, olezarsen met the primary endpoint, with a statistically significant placebo-adjusted reduction in TG levels from baseline to six months (44%, p<0.001).
- Reductions from six to 12 months were sustained, with olezarsen 80 mg achieving a placebo-adjusted 59% reduction in TGs.
- ApoC-III placebo-adjusted reductions were robust and sustained at six and 12 months (74% and 81% reductions, respectively).
- In the 50 mg group, olezarsen reduced TG levels, however this difference was not statistically significant at six months compared to placebo (22%, p=0.078).
- Reductions from six to 12 months were improved, with olezarsen 50 mg achieving a placebo-adjusted 44% reduction in TGs.
- Olezarsen-treated patients had markedly fewer AP events during the 12-month period, compared to placebo.
- Eleven episodes of AP occurred in the placebo group versus one episode in the 80 mg olezarsen group and one episode in the 50 mg group.
- Furthermore, there was a substantially greater time to the first event with olezarsen compared to placebo (one year (80 mg) and 102 days (50 mg), vs. nine days for placebo).
- Olezarsen-treated patients experienced a placebo-adjusted 84% reduction in all-cause hospitalizations between baseline and 12 months.
- A favorable safety and tolerability profile was observed, with a higher number of treatment-emergent adverse events (TEAEs) in the placebo group. There were no serious TEAEs related to olezarsen.
- The most common AEs were COVID-19, abdominal pain and diarrhea, none of which were more frequent in patients treated with either dose of olezarsen versus placebo.
- Serious AEs occurred in 14% of patients treated with olezarsen 80 mg, 19% treated with olezarsen 50 mg, and 39% treated with placebo.
"Balance is the first clinical study to validate the association of reduced triglyceride levels with reduced incidence of acute pancreatitis events in patients with severely elevated triglycerides. This important finding supports the potential for olezarsen to be the standard of care for patients with FCS, if approved. These data further strengthen our confidence for a successful outcome in the ongoing Phase 3 CORE studies evaluating olezarsen in the much more prevalent severe hypertriglyceridemia patient population," said Brett P. Monia, Ph.D., chief executive officer of Ionis. "Our team looks forward to working closely with the FDA to advance the first potential treatment for FCS in the U.S., and to successfully delivering Ionis' first independent commercial launch later this year, assuming priority review. We offer our sincerest gratitude to the patients and investigators who participated in this pivotal study."
The ACC Balance presentation can be found on Ionis' website after today's presentation at 10:08 am ET.
In addition to the Balance data, a late-breaking abstract entitled, "Efficacy and Safety of Olezarsen in Patients with Hypertriglyceridemia and High Cardiovascular Risk: Primary Results of the Bridge-TIMI 73a Trial" was also presented at ACC and published in NEJM.
Webcast
Ionis will host a webcast to discuss the detailed results from the Balance study on Monday, April 8 at 10:00 am ET. Interested parties may access the webcast here. A webcast replay will be available for a limited time.
About the Balance Study
The global, multicenter, randomized, double-blind, placebo-controlled Phase 3 Balance study (NCT04568434) enrolled 66 patients aged 18 and older with confirmed FCS. Patients in the study received background therapies including statins, fibrates and omega-3 fatty acids. Patients were randomized in a 1:1:1 ratio to receive olezarsen 80 mg or 50 mg or placebo via subcutaneous injection once every four weeks for 53 weeks. The primary endpoint was the percent change from baseline in fasting triglyceride levels at six months compared to placebo. Secondary endpoints included percent changes in triglyceride levels at 12 months, percent changes in other lipid parameters, and adjudicated acute pancreatitis event rates over the treatment period.
About Olezarsen
Olezarsen is an RNA-targeted investigational LIgand Conjugated Antisense (LICA) medicine being evaluated for people at risk of disease due to elevated triglyceride levels, including those with familial chylomicronemia syndrome (FCS). Olezarsen is designed to inhibit the body's production of apoC-III, a protein produced in the liver that regulates triglyceride metabolism in the blood.1,2 The U.S. FDA granted olezarsen Fast Track designation for the treatment of FCS in January 2023, as well as Orphan Drug designation and Breakthrough Therapy designation in February 2024. In addition to FCS, Ionis is evaluating olezarsen for the treatment of severe hypertriglyceridemia (sHTG) in Phase 3 clinical trials.
Olezarsen is an investigational medicine that has not been reviewed or approved for the treatment of any disease by any regulatory authority.
About FCS
FCS is a rare, genetic disease characterized by extremely elevated triglyceride levels. It is caused by impaired function of the enzyme lipoprotein lipase (LPL).3 Because of limited LPL production or function, people with FCS cannot effectively break down chylomicrons, lipoprotein particles that are 90% triglycerides.3,4 FCS is estimated to impact one to 13 people per million in the U.S.5,6,7 People living with FCS are at high risk of acute pancreatitis (AP) in addition to other chronic health issues such as fatigue and severe, recurrent abdominal pain.3,8,9 People living with FCS are sometimes unable to work, adding to the burden of disease.9
Currently, there are no U.S. FDA-approved therapies for the treatment of FCS and standard triglyceride lowering therapies are generally ineffective in patients with FCS.10,11 People living with this condition currently rely solely on nutrition management through extremely restrictive and difficult to manage diets to navigate the health risks associated with FCS.11,12
About Ionis Pharmaceuticals, Inc.
For three decades, Ionis has invented medicines that bring better futures to people with serious diseases. Ionis currently has five marketed medicines and a leading pipeline in neurology, cardiology, and other areas of high patient need. As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in RNA therapies in addition to advancing new approaches in gene editing. A deep understanding of disease biology and industry-leading technology propels our work, coupled with a passion and urgency to deliver life-changing advances for patients. To learn more about Ionis, visit Ionispharma.com and follow us on X (Twitter) and LinkedIn.
View original content to download multimedia:https://www.prnewswire.com/news-releases/ionis-presents-positive-results-from-phase-3-balance-study-of-olezarsen-for-familial-chylomicronemia-syndrome-302109871.html
SOURCE Ionis Pharmaceuticals, Inc.
Ionis experimental drug meets key goal in familial chylomicronemia study
Apr. 08, 2024 10:16 AM ET
Ionis Pharmaceuticals, Inc. (IONS) Stock
By: Preeti Singh, SA News Editor1 Comment
Ionis Pharmaceuticals (NASDAQ:IONS) on Sunday announced positive results from a late-stage study of its lead investigational drug, olezarsen.
Olezarsen is an RNA-targeted Ligand Conjugated Antisense medicine being evaluated for people at risk of disease due to elevated triglyceride levels, including those with familial chylomicronemia syndrome (FCS).
Ionis Pharmaceuticals, Inc. (IONS) Stock
NEXLETOL® (bempedoic acid) Tablets
LIVMARLI (maralixibat oral solution)
NEXLETOL® (bempedoic acid) Tablets
Esperion Presents Important New Data from CLEAR Outcomes at ACC.24 Highlighting Value of NEXLETOL® (bempedoic acid) Tablets in Diverse Populations Including Women, Hispanics/Latinx and Patients with Obesity
April 7, 2024
– Patients With Obesity Who Took NEXLETOL Were 23% Less Likely to Experience a Major Adverse Cardiovascular Event (MACE-4) Compared to Placebo –
– NEXLETOL Demonstrated Clinical Benefit in Historically Underrepresented Groups: Women and Hispanic/Latinx Patients With and Without Cardiovascular Disease (CVD) –
– CLEAR Outcomes Sets New Standards for Diversity and Inclusion with Enrollment of 48% Women and 17% Hispanic/Latinx Patients –
ANN ARBOR, Mich., April 07, 2024 (GLOBE NEWSWIRE) -- Esperion (Nasdaq: ESPR) today announced the presentation of results from three pre-specified subgroups from CLEAR Outcomes at the 2024 American College of Cardiology’s Annual Scientific Sessions (ACC.24): women, Hispanic/Latinx, and patients with obesity. These results align with the American College of Cardiology’s robust diversity, equity and inclusion programs to drive cultural change across the profession and ensure that the cardiovascular care team is as diverse as the patients they care for and that all patients are represented in cardiovascular research. The data also reinforce the mission of the ACC: transforming cardiovascular care for all.
“These analyses showcase the benefit of NEXLETOL and the bempedoic acid component of NEXLIZET® (bempedoic acid and ezetimibe) Tablets in several important yet often understudied populations,” said JoAnne Foody, MD, FACC, FAHA, Chief Medical Officer of Esperion. “Bempedoic acid is the only FDA approved non-statin LDL lowering therapy to demonstrate reductions in MACE in both primary prevention and secondary prevention patient populations. In women and Hispanic/Latinx patients with or at risk for CVD, bempedoic acid decreased LDL-cholesterol (LDL-C) and inflammatory markers, did not worsen glucose or weight, and in turn reduced the risk of major adverse cardiovascular events (MACE). These results continue to reinforce the importance of early and aggressive LDL-C lowering in order to reduce cardiovascular events, underscoring the paradigm of ‘even lower, even earlier is even better.’”
Harold Bays, MD, FOMA, FTOS, FACC, FNLA, FASPC, Louisville Metabolic and Atherosclerosis Research Center, University of Louisville School of Medicine, presented “Bempedoic Acid for Prevention of Cardiovascular Events in Patients with Obesity: A CLEAR Outcomes Subset Analysis.” Nearly 45% of patients in CLEAR Outcomes had obesity (body mass index greater than or equal to 30 kg/m2) at the start of the study. In this analysis, patients with obesity treated with bempedoic acid were 23% less likely to experience MACE-4 (cardiovascular (CV) death, nonfatal myocardial infarction (MI), nonfatal stroke, or coronary revascularization) compared to placebo. “Given that obesity is an epidemic and a risk factor for cardiovascular disease, clinicians and their patients can make more informed therapeutic decisions upon knowing the CVD outcomes among patients with obesity who receive specific cardiometabolic therapies,” said Dr. Bays.
Fatima Rodriguez, MD, MPH, Stanford Medicine, presented “Characteristics and Outcomes for Hispanic/Latinx Participants with Statin Intolerance Receiving Bempedoic Acid: Results from a CLEAR Outcomes Pre-Specified Subgroup Analysis.” Hispanic/Latinx patients represented almost 17% of those enrolled in the CLEAR Outcomes trial. The Hispanic population is the largest ethnic minority in the U.S., yet is a population historically underrepresented in clinical trials. This subgroup analysis showed a similar 21% lowering of LDL-C with bempedoic acid compared to placebo in Hispanic/Latinx and non-Hispanic/Latinx alike, confirming the CV risk reduction benefit of LDL-C lowering and the high tolerability of bempedoic acid, regardless of ethnicity. This analysis was published in the Journal of the American College of Cardiology (JACC).
Leslie Cho, MD, Cleveland Clinic, presented “Characteristics and Outcomes for Statin-Intolerant Women Receiving Bempedoic Acid in the CLEAR Outcomes Trial.” CLEAR Outcomes is notable for the highest percentage enrollment (48%) of females among contemporary lipid-lowering cardiovascular outcomes trials. In the CLEAR Outcomes trial, the risk of MACE-4 was similarly reduced for women treated with bempedoic acid compared to placebo, thus confirming its LDL-C lowering benefit on CV risk reduction, regardless of sex. This analysis was simultaneously published in Circulation.
INDICATION
NEXLIZET and NEXLETOL are indicated:
- The bempedoic acid component of NEXLIZET and NEXLETOL is indicated to reduce the risk of myocardial infarction and coronary revascularization in adults who are unable to take recommended statin therapy (including those not taking a statin) with:
- established cardiovascular disease (CVD), or
- at high risk for a CVD event but without established CVD.
- As an adjunct to diet:
- NEXLIZET, alone or in combination with other LDL-C lowering therapies, to reduce LDL-C in adults with primary hyperlipidemia, including HeFH.
- NEXLETOL, in combination with other LDL-C lowering therapies, or alone when concomitant LDL-C lowering therapy is not possible, to reduce LDL-C in adults with primary hyperlipidemia, including HeFH.
Esperion Therapeutics
At Esperion, we discover, develop, and commercialize innovative medicines to help improve outcomes for patients with or at risk for cardiovascular and cardiometabolic diseases. The status quo is not meeting the health needs of millions of people with high cholesterol – that is why our team of passionate industry leaders is breaking through the barriers that prevent patients from reaching their goals. Providers are moving toward reducing LDL-cholesterol levels as low as possible, as soon as possible; we provide the next steps to help get patients there. Because when it comes to high cholesterol, getting to goal is not optional. It is our life’s work. For more information, visit esperion.com and esperionscience.com and follow us on X at twitter.com/EsperionInc.
CLEAR Cardiovascular Outcomes Trial
CLEAR Outcomes is part of the CLEAR clinical research program for NEXLETOL® (bempedoic acid) Tablet and NEXLIZET® (bempedoic acid and ezetimibe) Tablet. The CLEAR Program seeks to generate important clinical evidence on the safety and efficacy of bempedoic acid, a first in a class ATP citrate lyase inhibitor contained in NEXLETOL and NEXLIZET and its potential role in addressing additional critical unmet medical needs. More than 60,000 people will have participated in the program by the time of its completion. The CLEAR Program includes 5 label-enabling Phase III studies as well as other key Phase IV studies with the potential to reach more than 70 million people with or at risk for CVD based on elevated LDL-C.
Esperion stock jumps as non-statin therapy shows clinical benefits across diverse patient groups
Apr. 08, 2024 6:16 AM ET
Esperion Therapeutics, Inc. (ESPR) Stock
By: Preeti Singh, SA News Editor3 Comments
Esperion Therapeutics (NASDAQ:ESPR) shares gained 7% premarket on Monday after the company touted clinical benefits of NEXLETOL (bempedoic acid) tablets in diverse populations, including women, Hispanic/Latinx, and patients with obesity.
Bempedoic acid is the only FDA-approved non-statin LDL lowering therapy to demonstrate reductions in major adverse cardiovascular events (MACE) in both primary prevention and secondary prevention patient populations.
KarXT (xanomeline-trospium)
LIVMARLI (maralixibat oral solution)
LIVMARLI (maralixibat oral solution)
Bristol Myers Squibb Presents New Pooled Interim Long-Term Safety and Metabolic Outcomes Data from the EMERGENT Program Evaluating KarXT in Schizophrenia at the 2024 Annual Congress of the Schizophrenia International Research Society
04/06/2024
CATEGORY:
KarXT demonstrated a favorable long-term metabolic profile where most patients experienced stability or improvements on metabolic parameters over 52 weeks of treatment
A majority of patients (65%) experienced reductions in weight over the course of the trial, with a mean weight decrease of 2.6kg observed at one year
Data show no significant changes related to prolactin or clinically meaningful changes in movement disorder scale scores over 52 weeks
KarXT was generally well tolerated, with a side effect profile consistent with prior trials of KarXT in schizophrenia
PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced interim long-term safety, tolerability and metabolic outcomes data from its Phase 3 EMERGENT program evaluating KarXT (xanomeline-trospium) in adults with schizophrenia. These data were presented in a poster titled, “Long-Term Safety of KarXT (Xanomeline and Trospium) in Schizophrenia” (Poster F74) and in the Oral Session “Long-Term Metabolic Outcomes Associated With KarXT (Xanomeline and Trospium): Interim Results From Pooled, Long-Term Safety Studies EMERGENT-4 and EMERGENT-5” at the Annual Congress of the Schizophrenia International Research Society (SIRS) being held April 3-7, 2024, in Florence, Italy.
“These long-term safety results and metabolic outcomes from the EMERGENT program are extremely encouraging, allowing us to further understand the tolerability profile of KarXT in people living with schizophrenia,” said Roland Chen, MD, senior vice president and head, Immunology, Cardiovascular and Neuroscience development, Bristol Myers Squibb. “It is promising to see that over one year of treatment, KarXT was not associated with burdensome side effects, specifically weight gain and metabolic dysfunction, as well as extrapyramidal symptoms, which underscores its potential to provide a meaningful and differentiated option for people living with schizophrenia.”
Pooled Interim Long-Term Metabolic Outcomes Associated with KarXT (EMERGENT-4 and EMERGENT-5)
The EMERGENT-4 and EMERGENT-5 trials are Phase 3, outpatient, 52-week, open-label trials evaluating the safety, tolerability, and efficacy of KarXT in adults with schizophrenia. At the time of the data cutoff of August 18, 2023, the interim pooled data analysis included 718 patients who received at least one dose of KarXT, with 134 patients having completed one year of treatment.
In the pooled analysis, KarXT demonstrated a favorable impact on weight and long-term metabolic profile where most patients experienced stability or improvements on key metabolic parameters over 52 weeks of treatment. The majority of patients (65%) experienced an overall reduction in weight over the course of the trial, with more patients (18%) experiencing potentially clinically significant (≥7% change) decreases in weight vs. 4% of patients experiencing increases in weight (≥7% change). In patients who completed 52 weeks of treatment with KarXT, an average reduction in weight of 2.6kg was observed, with a larger mean reduction in weight of 4.1kg observed in clinically obese patients (BMI > 30 kg/m2). Total cholesterol, triglyceride and HbA1c levels did not meaningfully change over one year of treatment.
Interim Long-Term Pooled Safety Outcomes Associated with KarXT (EMERGENT-4 and EMERGENT-5)
In the long-term studies, KarXT was generally well-tolerated across 52 weeks of treatment, with a side effect profile consistent with prior trials of KarXT in schizophrenia. The overall discontinuation rate in the trial was 53% and primary reasons for discontinuation included withdrawn consent (19%), treatment-related adverse events (15%), participant lost to follow-up (8%), and participant failed to adhere to protocol requirements (7%).
Across the long-term EMERGENT trials, 62% of participants reported at least one treatment-related adverse event. The most common treatment-related adverse events (≥5%) were nausea, vomiting, constipation, dry mouth, dyspepsia, dizziness, hypertension, and diarrhea, of which nearly all were mild or moderate in severity and transient in nature.
KarXT was not associated with significant changes related to prolactin or clinically meaningful changes in movement disorder scale scores over 52 weeks.
“People living with schizophrenia and their care partners have long carried the burden of the condition, with a lack of treatment options that adequately treat the symptoms of schizophrenia without common debilitating side effects. To see that the long-term tolerability profile of KarXT remains consistent with earlier studies, where the cholinergic side effects of KarXT remained mainly mild or moderate in severity, and were transient and resolving with continued treatment is very encouraging,” said Rishi Kakar, M.D., chief scientific officer and medical director of Segal Trials and investigator in the EMERGENT program. “These results are extremely promising and add to the growing body of data which suggest that, if approved, KarXT could provide a long-desired, differentiated treatment option for people living with schizophrenia.”
In additional interim long-term data presented at the congress, KarXT was associated with significant improvements in symptoms of schizophrenia across all efficacy measures at 52 weeks in the EMERGENT-4 trial. Improvements in symptoms of schizophrenia continued throughout the open-label extension regardless of whether participants were previously treated with KarXT or placebo during the acute trials, EMERGENT-2 or EMERGENT-3 (Poster F264).
About KarXT
KarXT (xanomeline-trospium) is an investigational muscarinic antipsychotic in development for the treatment of schizophrenia and psychosis related to Alzheimer’s disease. Through its novel mechanism of action, KarXT acts as a dual M1/M4 muscarinic acetylcholine receptor agonist in the central nervous system, which is thought to improve positive, negative, and cognitive symptoms of schizophrenia. Unlike existing treatments, KarXT does not directly block dopamine receptors, representing a potential new approach to treating schizophrenia.
About Schizophrenia
Schizophrenia is a persistent and often disabling mental illness impacting how a person thinks, feels, and behaves, and affects nearly 24 million people worldwide, including 2.8 million people in the U.S. It is characterized by three symptom domains: positive symptoms (hallucinations and delusions), negative symptoms (difficulty enjoying life and withdrawal from others), and cognitive impairment (deficits in memory, concentration, and decision-making). In part due to limitations with current treatments, people living with schizophrenia often struggle to maintain employment, live independently, and manage relationships. While current treatments can be effective in managing select symptoms, approximately 30% of people do not respond to therapy, with an additional 50% experiencing only a partial improvement in symptoms or unacceptable side effects.
Bristol Myers Squibb: Delivering Breakthrough Science for Meaningful Interventions in Neuroscience
Neurological conditions represent some of the greatest challenges of our time because of their impact on society, including patients, caregivers, families and healthcare systems. At Bristol Myers Squibb, we are committed to advancing our robust pipeline of potential medicines for neurological disorders with the goal of modifying disease and improving quality of life. Leveraging genetics, biomarkers and predictive sciences, we target key pathways involved in the initiation and progression of neurological diseases to develop therapies with the potential to optimize patient outcomes.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.
Source: Bristol Myers Squibb
Multimedia Files:
Download:Download original 99 KB 1497 x 206Download thumbnail 5 KB 200 x 28Download lowres 15 KB 480 x 66Download square 8 KB 250 x 250
Bristol-Myers highlights safety of KarXT schizophrenia therapy
Apr. 06, 2024 3:21 PM ET
Bristol-Myers Squibb Company (BMY) Stock
By: Dulan Lokuwithana, SA News Editor14 Comments
Bristol-Myers Squibb (NYSE:BMY) announced Saturday that its experimental schizophrenia therapy KarXT, acquired as part of its recent Karuna Therapeutics buyout, indicated a well-tolerated safety profile in a Phase 3 program.
Citing data from its EMERGENT-4 and EMERGENT-5 trials, the Princeton, New Jersey-based pharma giant said KarXT was not associated with weight gain, a side effect commonly seen with antipsychotic use in schizophrenia.
Bristol-Myers Squibb Company (BMY) Stock
LIVMARLI (maralixibat oral solution)
LIVMARLI (maralixibat oral solution)
LIVMARLI (maralixibat oral solution)
Mirum Pharmaceuticals’ LIVMARLI (maralixibat oral solution) Receives Positive Reimbursement Recommendation by Canada’s CADTH for Patients with Cholestatic Pruritus in Alagille Syndrome
Apr 2, 2024
- Positive HTA recommendation for reimbursement signifies an important milestone towards public funding to treat eligible patients with this rare liver disorder
- LIVMARLI is the first and only approved medication to treat cholestatic pruritus in patients with Alagille syndrome in Canada
FOSTER CITY, Calif.--(BUSINESS WIRE)-- Mirum Pharmaceuticals, Inc. (NASDAQ: MIRM) today announced that the Canadian Agency for Drugs and Technologies in Health (CADTH) Canadian Drug Expert Committee (CDEC) has recommended public reimbursement for LIVMARLI® (maralixibat oral solution) for the treatment of cholestatic pruritus in patients with Alagille Syndrome (ALGS), with certain conditions. This announcement follows Health Canada’s authorization of LIVMARLI in this indication in 2023.
“The positive reimbursement recommendation for LIVMARLI by CADTH is an important step forward for patients suffering from the debilitating effects of cholestatic pruritus related to Alagille syndrome,” said Chris Peetz, chief executive officer at Mirum. “Accelerating access in all provinces to this meaningful treatment is critical as it is the first and only approved therapy available in this setting in Canada. These patients suffer greatly from the debilitating and disruptive effects of Alagille syndrome, which often starts in early childhood.”
“CADTH’s recommendation of reimbursement for LIVMARLI provides a meaningful advancement in the treatment of cholestatic pruritus for patients with Alagille syndrome. I am pleased that LIVMARLI will now become more accessible in Canada, where I have seen the critical need for a treatment to address the itch caused by cholestasis,” said Dr. Binita Kamath, Director, Hepatology Program and Senior Associate Scientist at The Hospital for Sick Children (SickKids), Toronto, Canada.
“This recommendation is incredibly meaningful as it signifies hope for patients and their families who have suffered from the disruptive and painful effects of pruritus for far too long,” said Roberta Smith, president, Alagille Syndrome Alliance and mother of a daughter with ALGS. “We are grateful to CADTH for ensuring support of this new and important medication.”
The CADTH recommendation is based on data from the pivotal ICONIC study including six years of data across the LIVMARLI clinical program resulting in a robust body of evidence in patients with cholestatic pruritus in ALGS. Data from ICONIC demonstrated statistically significant and clinically meaningful reductions in pruritus compared to placebo, as well as significant reductions in serum bile acids, both of which were durably maintained over several years of treatment.
LIVMARLI is also approved for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) in the U.S. and Europe, and for Progressive Familial Intrahepatic Cholestasis (PFIC) in the U.S. and in Europe.
ALGS is a rare genetic disorder caused by abnormalities in bile ducts that can lead to progressive liver disease. Malformed or reduced bile ducts cause cholestasis, the accumulation of bile acids in the liver, which leads to inflammation and liver injury, and prevents the liver from working properly. Cholestasis in ALGS is associated with pruritus which is among the most common indications for liver transplant in ALGS.
About LIVMARLI® (maralixibat) oral solution
LIVMARLI® (maralixibat) oral solution is an orally administered, once-daily, ileal bile acid transporter (IBAT) inhibitor and the only approved medication by the U.S. Food and Drug Administration for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) three months of age and older and progressive familial intrahepatic cholestasis (PFIC) five years of age and older.
LIVMARLI is also the only approved IBAT inhibitor approved by the European Commission for the treatment of cholestatic pruritus in patients with ALGS two months and older, and by Health Canada for the treatment of cholestatic pruritus in ALGS. For more information for U.S. residents, please visit LIVMARLI.com.
Mirum has also submitted LIVMARLI for approval in Europe in PFIC for patients two months of age and older.
LIVMARLI has received Breakthrough Therapy designation for ALGS and PFIC type 2 and orphan designation for ALGS and PFIC. To learn more about ongoing clinical trials with LIVMARLI, please visit Mirum’s clinical trials section on the company’s website.
About Mirum Pharmaceuticals, Inc.
Mirum Pharmaceuticals, Inc. is a biopharmaceutical company dedicated to transforming the treatment of rare diseases affecting children and adults. Mirum has three approved medications: LIVMARLI® (maralixibat) oral solution, CHOLBAM® (cholic acid) capsules, and CHENODAL® (chenodiol) tablets.
LIVMARLI, an IBAT inhibitor, is approved for the treatment of two rare liver diseases affecting children and adults. It is approved for the treatment of cholestatic pruritus in patients with Alagille syndrome in the U.S. (three months and older), in Europe (two months and older), and in other regions globally. It is also approved in the U.S. in cholestatic pruritus in PFIC patients five years of age and older. Mirum has submitted for approval in Europe for the treatment of PFIC in patients two months of age and older. CHOLBAM is FDA-approved for the treatment of bile acid synthesis disorders due to single enzyme deficiencies and adjunctive treatment of peroxisomal disorders in patients who show signs or symptoms or liver disease. CHENODAL has received medical necessity recognition by the FDA to treat patients with cerebrotendinous xanthomatosis (CTX).
Mirum’s late-stage pipeline includes two investigational treatments for debilitating liver diseases. Volixibat, an IBAT inhibitor, is being evaluated in two potentially registrational studies including the Phase 2b VISTAS study for primary sclerosing cholangitis and Phase 2b VANTAGE study for primary biliary cholangitis. Lastly, CHENODAL, has been evaluated in a Phase 3 clinical study, RESTORE, to treat patients with CTX, with positive topline results reported in 2023.
To learn more about Mirum, visit mirumpharma.com and follow Mirum on Facebook, LinkedIn, Instagram and Twitter.
Source: Mirum Pharmaceuticals, Inc.
Mirum’s LIVMARLI receives positive reimbursement recommendation by Canada’s CADTH
Apr. 02, 2024 8:59 AM ET
Mirum Pharmaceuticals, Inc. (MIRM) StockFSV, BSEP, ALGS, IBAT
By: Nilanjana Basu, SA News Editor
- Mirum Pharmaceuticals (NASDAQ:MIRM) announced that the Canadian Agency for Drugs and Technologies in Health Canadian Drug Expert Committee has recommended public reimbursement for LIVMARLI for the treatment of cholestatic pruritus in patients with Alagille Syndrome, with certain conditions.
- This announcement follows Health Canada’s authorization of LIVMARLI in this indication in 2023.
- https://seekingalpha.com/news/4086233-mirums-livmarli-receives-positive-reimbursement-recommendation-by-canadas-cadth
- Mirum Pharmaceuticals, Inc. (MIRM) Stock
- https://mirumpharma.com/
- https://livmarli.com/
datopotamab deruxtecan (Dato-DXd)
datopotamab deruxtecan (Dato-DXd)
datopotamab deruxtecan (Dato-DXd)
Datopotamab deruxtecan Biologics License Application accepted in the US for patients with previously treated metastatic HR-positive, HER2-negative breast cancer
PUBLISHED
2 April 2024
Application based on results from the TROPION-Breast01 Phase III trial
Additional BLA under review in the US for AstraZeneca and Daiichi Sankyo’s datopotamab deruxtecan for patients with advanced nonsquamous non-small cell lung cancer
AstraZeneca and Daiichi Sankyo’s Biologics License Application (BLA) for datopotamab deruxtecan (Dato-DXd) has been accepted in the US for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior systemic therapy for unresectable or metastatic disease. The Prescription Drug User Fee Act date, the US Food and Drug Administration (FDA) action date for its regulatory decision, is during the first quarter of 2025.
The BLA is based on results from the pivotal TROPION-Breast01 Phase III trial in which datopotamab deruxtecan demonstrated a statistically significant and clinically meaningful improvement for the dual primary endpoint of progression-free survival (PFS) compared to investigator’s choice of chemotherapy in patients with unresectable or metastatic HR-positive, HER2-negative breast cancer previously treated with endocrine-based therapy and at least one systemic therapy. For the dual primary endpoint of overall survival (OS), interim results numerically favoured datopotamab deruxtecan over chemotherapy but were not mature at the time of data cut-off. The trial is ongoing and OS will be assessed at future analyses.
Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed by AstraZeneca and Daiichi Sankyo.
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “Despite marked progress in the treatment of HR-positive, HER2-negative breast cancer, most patients with advanced disease develop endocrine resistance and face the prospect of one or several lines of chemotherapy. If approved, datopotamab deruxtecan has the potential to provide these patients an efficacious and better tolerated alternative to conventional chemotherapy.”
Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo, said: “The FDA’s acceptance of the BLA brings us closer to providing patients with previously treated HR-positive, HER2-negative breast cancer an alternative option to conventional chemotherapy earlier in the metastatic setting. Following our recently accepted application for advanced nonsquamous non-small cell lung cancer in the US, along with additional regulatory reviews underway in China, the EU, Japan and other regions, we are working swiftly to bring datopotamab deruxtecan as a potential new treatment option to patients around the world.”
Results from TROPION-Breast01 were presented during a Presidential Symposium at the 2023 European Society for Medical Oncology Congress and in an oral presentation at the 2023 San Antonio Breast Cancer Symposium.
The safety profile of datopotamab deruxtecan was consistent with that observed in other ongoing trials with no new safety concerns identified.
An additional BLA for datopotamab deruxtecan based on results from the pivotal TROPION-Lung01 Phase III trial is under review in the US for the treatment of adult patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) who have received prior systemic therapy. Additional regulatory submissions for datopotamab deruxtecan in lung and breast cancer are underway globally.
Notes
HR-positive breast cancer
More than 275,000 breast cancer cases were diagnosed in the US in 2022.1 HR-positive, HER2-negative breast cancer is the most common subtype, accounting for more than 65% of diagnosed cases.2 Breast cancer is considered HR-positive, HER2-negative when tumours test positive for oestrogen and/or progesterone hormone receptors and negative for HER2 (measured as HER2 score of IHC 0, IHC 1+ or IHC 2+/ISH-).2,3 Standard initial treatment for this subtype of breast cancer is endocrine therapy but most patients with advanced disease will develop resistance, underscoring the need for additional options.4,5
TROP2 is a protein broadly expressed in HR-positive, HER2-negative breast cancer and is associated with increased tumour progression and poor survival.6,7
TROPION-Breast01
TROPION-Breast01 is a global, randomised, multicentre, open-label Phase III trial evaluating the efficacy and safety of datopotamab deruxtecan versus investigator’s choice of single-agent chemotherapy (eribulin, capecitabine, vinorelbine or gemcitabine) in patients with unresectable or metastatic HR-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have progressed on and are not suitable for endocrine therapy per investigator assessment and have received at least one additional systemic therapy for unresectable or metastatic disease.
The dual primary endpoints of TROPION-Breast01 are PFS as assessed by blinded independent central review and OS. Key secondary endpoints include objective response rate, duration of response, investigator-assessed PFS, disease control rate, time to first subsequent therapy and safety. TROPION-Breast01 enrolled more than 700 patients in Africa, Asia, Europe, North America and South America. For more information visit ClinicalTrials.gov.
Datopotamab deruxtecan (Dato-DXd)
Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, datopotamab deruxtecan is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programmes in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanised anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.
A comprehensive global clinical development programme is underway with more than 20 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple cancers, including NSCLC, triple-negative breast cancer (TNBC) and HR-positive, HER2-negative breast cancer.
Daiichi Sankyo collaboration
AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise Enhertu in March 2019 and datopotamab deruxtecan in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and datopotamab deruxtecan.
AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge, and redefine, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.
AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment.
With Enhertu (trastuzumab deruxtecan), a HER2-directed ADC, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive and HER2-low metastatic breast cancer and are exploring its potential in earlier lines of treatment and in new breast cancer settings.
In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines Faslodex and Zoladex (goserelin) and aims to reshape the HR-positive space with first-in-class AKT inhibitor, Truqap, and next-generation SERD and potential new medicine camizestrant. AstraZeneca is also collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan, in this setting.
PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in these settings and to explore its potential in earlier disease.
To bring much-needed treatment options to patients with TNBC, an aggressive form of breast cancer, AstraZeneca is evaluating the potential of datopotamab deruxtecan alone and in combination with immunotherapy Imfinzi (durvalumab), Truqap in combination with chemotherapy, and Imfinzi in combination with other oncology medicines, including Lynparza and Enhertu.
AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.
The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.
AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, Respiratory & Immunology and Vaccines & Immune Therapies. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca.
FDA accepts Daiichi Sankyo-AstraZeneca's breast cancer therapy for review
Apr. 02, 2024 8:16 AM ET
AstraZeneca PLC (AZN) Stock, DSNKY Stock, DSKYF Stock
By: Preeti Singh, SA News Editor
AstraZeneca (NASDAQ:AZN) and Daiichi Sankyo’s (OTCPK:DSNKY) (OTCPK:DSKYF) biologics license application (BLA) for datopotamab deruxtecan (Dato-DXd) has been accepted in the U.S. for patients with previously treated metastatic HR-positive, HER2-negative breast cancer, with a target action date set for the first quarter of 2025.
The BLA is based on results from the pivotal TROPION-Breast01 Phase III trial in which datopotamab deruxtecan showed a statistically significant and clinically meaningful improvement for the dual primary endpoint of progression-free survival compared to investigator’s choice of chemotherapy in patients with unresectable or metastatic HR-positive, HER2-negative breast cancer.
Povorcitinib
datopotamab deruxtecan (Dato-DXd)
datopotamab deruxtecan (Dato-DXd)
Incyte And CMS Announce Collaboration And License Agreement For Povorcitinib, An Oral JAK1 Inhibitor, In Mainland China, Hong Kong, Macau, Taiwan And Southeast Asia
April 1, 2024 at 8:30 AM EDT
Povorcitinib, a selective oral JAK1 inhibitor discovered by Incyte, is an investigational medicine being evaluated for the treatment of non-segmental vitiligo, hidradenitis suppurativa (HS), prurigo nodularis (PN), asthma and chronic spontaneous urticaria
WILMINGTON, Del. and HONG KONG--(BUSINESS WIRE)--Apr. 1, 2024-- Incyte (Nasdaq:INCY) (“Incyte”) and China Medical System Holdings Limited (“CMS” or the “Group”) are pleased to announce that on March 31, 2024, Incyte and CMS, through a wholly-owned dermatology medical aesthetic subsidiary of the Company (“CMS Skinhealth”), entered into a Collaboration and License Agreement for the development and commercialization of povorcitinib (the “Product”), a selective oral JAK1 inhibitor, to research, develop, register and commercialize the Product in Mainland China, Hong Kong, Macao, Taiwan Region and eleven Southeast Asian countries (the “Territory”) and a non-exclusive license to manufacture the Product in CMS’ Territory.
Under the terms of the agreement, CMS will make an upfront payment to Incyte and Incyte is eligible to receive additional potential development and commercial milestones and royalties on net sales of the licensed product in CMS’ territory.
CMS will receive an exclusive license to develop and commercialize and a non-exclusive license to manufacture povorcitinib in autoimmune and inflammatory dermatologic diseases, including non-segmental vitiligo, hidradenitis suppurativa (HS), prurigo nodularis (PN), asthma and chronic spontaneous urticaria, for patients in mainland China, Hong Kong, Macau, Taiwan and certain countries in Southeast Asia.
“We are excited to announce the addition of this collaboration for povorcitinib, expanding our relationship with CMS in the Dermatology space beyond ruxolitinib cream, to include two products with the potential to help patients with limited treatment options,” said Hervé Hoppenot, Chief Executive Officer, Incyte. “There remains a significant need for new, innovative treatment for vitiligo and other immune-mediated dermatologic conditions, and we look forward to working together with the CMS team to bringing these products to market in China.”
Mr. Huang Anjun, the general manager of CMS Skinhealth, stated that, “We expect that this collaboration will enhance CMS Skinhealth's portfolio of potential treatments for vitiligo that, if approved, will provide differentiated treatment options for vitiligo patients in China. Upon approval, povorcitinib is poised to synergize with the innovative drugs in the commercialization stage of our pipeline Ilumetri (tildrakizumab injection), original/drugs including Hirudoid (mucopolysaccharide polysulfate cream) and Aethoxysklerol (polidocanol injection) in terms of our network and market resources, which will help the Product to realize its clinical and commercial value.”
The transaction is effective immediately upon the execution of the Collaboration and License Agreement.
About Povorcitinib
Povorcitinib is a selective oral small-molecule JAK1 inhibitor, with compound and use patents in certain countries/regions in the Territory. Currently, povorcitinib is in Phase 3 clinical trials for non-segmental vitiligo and HS in multiple countries outside of China. Additionally, Phase 2 clinical studies of povorcitinib for PN, asthma and chronic spontaneous urticaria are also ongoing.
About Vitiligo
Vitiligo is a chronic autoimmune disease characterized by depigmentation of the skin, which results from the loss of pigment-producing cells known as melanocytes. Overactivity of the JAK signaling pathway is believed to drive inflammation involved in the pathogenesis and progression of vitiligo.
It is estimated that there are approximately 14 million vitiligo patients in China and 6.5 million in the eleven Southeast Asian countries respectively. Non-segmental vitiligo patients account for approximately 85% of them1. Vitiligo can occur at any age, although many patients with vitiligo will experience initial onset before the age of 302. Currently, therapeutic options for vitiligo are limited, and the condition is difficult to treat, especially for patients with moderate to severe extensive vitiligo.
About Hidradenitis Suppurativa (HS)
HS is a chronic recurrent inflammatory skin condition characterized by the presence of painful inflammatory nodules, abscesses, ruptures, as well as the formation of sinus tracts and scarring. Overactivity of the JAK signaling pathway is believed to drive inflammation involved in the pathogenesis and progression of HS3.
It is estimated that there are approximately 470 thousand HS patients in China, about 75% of whom are moderate to severe patients4. Additionally, it is estimated that there are approximately 13 thousand HS patients in the six Southeast Asian countries, comprising Thailand, Singapore, Malaysia, Philippine, Vietnam and Indonesia. HS has been included in the second batch of the Rare Disease List in China. Given the debilitating nature of condition, it can have a profoundly negative effect on patients’ quality of life. However, currently in China, there are no biologics or small molecule medicines approved by the National Medical Products Administration for the treatment of HS, creating an urgent need for effective therapeutic options5.
About Incyte
A global biopharmaceutical company on a mission to Solve On., Incyte follows the science to find solutions for patients with unmet medical needs. Through the discovery, development and commercialization of proprietary therapeutics, Incyte has established a portfolio of first-in-class medicines for patients and a strong pipeline of products in Oncology and Inflammation & Autoimmunity. Headquartered in Wilmington, Delaware, Incyte has operations in North America, Europe and Asia.
For additional information on Incyte, please visit Incyte.com or follow us on social media: LinkedIn, X, Instagram, Facebook, YouTube.
About CMS Skinhealth
CMS’s Dermatology and Medical Aesthetic Business "CMS Skinhealth" regards dermatology prescription products as its core, and extends to dermatology-grade skincare products and light medical aesthetic products, continually optimizing full lifecycle skin-health management solutions, and gradually moving toward becoming "the largest and most professional skin-health management company in China ". Relying on its strong clinical development and commercialization advantages, CMS will realize the commercialization of povorcitinib in the Territory as soon as possible to meet the clinical needs of oral vitiligo drugs with efficacy and benefit relevant patients.
About CMS
CMS is a platform company linking pharmaceutical innovation and commercialization with strong product lifecycle management capability, dedicated to providing competitive products and services to meet unmet medical needs.
CMS focuses on the global first-in-class (FIC) and best-in-class (BIC) innovative products, and efficiently promotes the clinical research, development and commercialization of innovative products, enabling the continuous transformation of scientific research into clinical practices to benefit patients.
CMS deeply engages in several specialty therapeutic fields, and has developed proven commercialization capabilities, extensive networks and expert resources, resulting in leading academic and market positions for its major marketed products. CMS continues to promote the in-depth development of its advantageous specialty fields and expand business boundaries. While strengthening the competitiveness of the cardio-cerebrovascular/gastroenterology business, CMS independently operates its dermatology and medical aesthetics business, and ophthalmology business, aiming to gain leading positions in specialty therapeutic fields, whilst enhancing the scale and efficiency. At the same time, CMS has expanded its business territory to the Southeast Asian market, striving to become a “bridgehead” for global pharmaceutical companies to enter the Southeast Asian market, further escorting the sustainable and healthy development of the Group.
View source version on businesswire.com: https://www.businesswire.com/news/home/20240401280916/en/
Source: Incyte
Incyte and CMS collaborate for povorcitinib in Mainland China, Hong Kong, Macau, Taiwan and SEA
Apr. 01, 2024 9:35 AM ET
Incyte Corporation (INCY) Stock
By: Nilanjana Basu, SA News Editor
- Incyte (NASDAQ:INCY) and China Medical System, through a wholly-owned dermatology medical aesthetic subsidiary of the company, entered into a collaboration and license agreement.
- Agreement is for the development and commercialization of povorcitinib, a selective oral JAK1 inhibitor, to research, develop, register and commercialize the product in Mainland China, Hong Kong, Macao, Taiwan Region and eleven Southeast Asian countries and a non-exclusive license to manufacture the product in CMS’ Territory.
- https://seekingalpha.com/news/4085608-incyte-and-cms-collaborate-for-povorcitinib-in-mainland-china-hong-kong-macau-taiwan-and-sea
- Incyte Corporation (INCY) Stock
- https://incyte.com/
- https://www.incytemi.com/document/Poster/EADV%202022%20-%20Povorcitinib%20in%20HS%20Ph2%20Efficacy%20and%20Safety.pdf
- https://web.cms.net.cn/en/home/
- https://web.cms.net.cn/en/investors/
Inaxaplin (VX-147)
datopotamab deruxtecan (Dato-DXd)
Inaxaplin (VX-147)
Apr 1, 2024
Vertex Advances Inaxaplin (VX-147) into Phase 3 Portion of Adaptive Phase 2/3 Clinical Trial for the Treatment of APOL1-Mediated Kidney Disease
– 45 mg once daily oral dose selected for Phase 3 –
– Results support trial expansion to lower age group and study will now include adolescents ages 10-17 years –
– If positive, pre-planned interim analysis at Week 48 may serve as the basis for accelerated approval in the U.S. –
BOSTON--(BUSINESS WIRE)--Apr. 1, 2024-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that inaxaplin (VX-147) has advanced into the Phase 3 portion of the global Phase 2/3 pivotal clinical trial in APOL1-mediated kidney disease (AMKD), where a 45 mg once daily oral dose will be compared to placebo, on top of standard of care. The clinical trial is designed to assess the impact of inaxaplin on kidney function and proteinuria for people living with proteinuric kidney disease mediated by two variants in the APOL1 gene, known as AMKD. In addition, the trial has been expanded to include adolescents with AMKD ages 10 to 17 years.
Previously reported Phase 2a proof-of-concept data demonstrated that inaxaplin led to a statistically significant and clinically meaningful mean reduction in the urine protein to creatinine ratio (UPCR) of 47.6% at 13 weeks of treatment compared to baseline, providing the first clinical evidence that an oral small molecule APOL1 inhibitor can decrease proteinuria in people with AMKD.
“Inaxaplin, a first-in-class molecule that addresses the underlying cause of APOL1-mediated kidney disease, has already shown impressive results in the Phase 2a proof-of-concept study,” said Carmen Bozic, M.D., Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex. “Advancing this trial into Phase 3 and broadening the trial to include younger patients is a critical step forward in bringing this potential therapy to patients who are waiting.”
“AMKD is a rapidly progressing condition and often remains silent until the disease reaches an advanced stage. We have no approved disease-specific therapies for this truly devastating condition, and inaxaplin has the potential to transform the care of AMKD and significantly improve the lives of patients,” noted Glenn M. Chertow, M.D., M.P.H., Professor of Medicine, Stanford University School of Medicine, and Chair of Vertex’s APOL1 Program Steering Committee. “The kidney community is strongly encouraged by inaxaplin’s potential, which energizes those of us caring for patients with AMKD.”
An Independent Data Monitoring Committee (IDMC) reviewed blinded and unblinded Phase 2 safety and efficacy data from the Phase 2/3 pivotal trial, which evaluated two different doses of inaxaplin compared to placebo for 12 weeks of treatment in patients ages 18 to 65 years and recommended the selection of a single inaxaplin dose of 45 mg once daily in the Phase 3 portion of the Phase 2/3 study. The IDMC also recommended enrolling adolescents with AMKD ages 10 to 17 years in the Phase 3 portion of the study.
The U.S. Food and Drug Administration (FDA) has granted inaxaplin Rare Pediatric Disease Designation (RPD) and Breakthrough Therapy Designation (BTD) for APOL1-mediated focal segmental glomerulosclerosis (FSGS). The European Medicines Agency (EMA) has also granted inaxaplin Priority Medicines (PRIME) and Orphan Drug designations for AMKD.
About the Phase 2/3 AMPLITUDE Study
Inaxaplin is a potential first-in-class, investigational small molecule inhibitor of APOL1 with the goal of targeting the underlying cause of APOL1-mediated kidney disease (AMKD).
The primary efficacy endpoint for the final analysis is estimated glomerular filtration rate (eGFR) slope in patients receiving inaxaplin compared to placebo. The secondary efficacy endpoint is time to composite clinical outcome, which will also be assessed at the final analysis and is defined as a sustained decline of ≥30% from baseline in the eGFR, the onset of end-stage kidney disease or death. The final study analysis will occur when subjects have at least two years of eGFR data and when approximately 187 composite clinical outcomes have occurred.
The study is also designed to have a pre-planned interim analysis at Week 48 evaluating eGFR slope, supported by a percent change from baseline in proteinuria in the inaxaplin arm versus placebo. If positive, the interim analysis may serve as the basis for Vertex to seek accelerated approval of inaxaplin in the U.S. for patients with AMKD.
Enrollment in the study is ongoing, with more than 200 sites open in the U.S. and internationally.
About APOL1-Mediated Kidney Disease
APOL1-mediated kidney disease (AMKD) is a form of chronic kidney disease caused by variants in the APOL1 gene. Approximately 100,000 people in the U.S. and Europe have two APOL1 genetic variants and proteinuric kidney disease. People who inherit two variants in the APOL1 gene have a course of disease that is far more aggressive than in the absence of APOL1 genetic variants. Inherited APOL1 genetic variants may lead to kidney cell injury, cell death and damage to the glomeruli (which filter blood in the kidney). This leads to protein in the urine (known as “proteinuria”) and decreased ability of the kidney to function, which can lead to dialysis, transplant or death.
About Vertex
Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has approved medicines that treat the underlying causes of multiple chronic, life-shortening genetic diseases — cystic fibrosis, sickle cell disease and transfusion-dependent beta thalassemia — and continues to advance clinical and research programs in these diseases. Vertex also has a robust clinical pipeline of investigational therapies across a range of modalities in other serious diseases where it has deep insight into causal human biology, including acute and neuropathic pain, APOL1-mediated kidney disease, autosomal dominant polycystic kidney disease, type 1 diabetes, myotonic dystrophy type 1 and alpha-1 antitrypsin deficiency.
Vertex was founded in 1989 and has its global headquarters in Boston, with international headquarters in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia, Latin America and the Middle East. Vertex is consistently recognized as one of the industry's top places to work, including 14 consecutive years on Science magazine's Top Employers list and one of Fortune’s 100 Best Companies to Work For. For company updates and to learn more about Vertex's history of innovation, visit www.vrtx.com or follow us on LinkedIn, Facebook, Instagram, YouTube and Twitter/X.
View source version on businesswire.com: https://www.businesswire.com/news/home/20240401112879/en/
Source: Vertex Pharmaceuticals Incorporated
Vertex Pharmaceuticals Incorporated (VRTX) Stock
KRAZATI (adagrasib)
LEQEMBI® (LECANEMAB-IRMB)
Inaxaplin (VX-147)
Apr 01, 2024
Zai Lab Partner Bristol Myers Squibb Announces Pivotal KRYSTAL-12 Confirmatory Trial Evaluating KRAZATI (adagrasib) Meets Primary Endpoint of Progression-Free Survival for Patients with Pretreated KRASG12C-Mutated Locally Advanced or Metastatic...
SHANGHAI & CAMBRIDGE, Mass.--(BUSINESS WIRE)--Apr. 1, 2024--
Zai Lab Partner Bristol Myers Squibb Announces Pivotal KRYSTAL-12 Confirmatory Trial Evaluating KRAZATI (adagrasib) Meets Primary Endpoint of Progression-Free Survival for Patients with Pretreated KRASG12C-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) partner Bristol Myers Squibb (NYSE: BMY) announced the pivotal Phase 3 KRYSTAL-12 study, evaluating KRAZATI® (adagrasib) as a monotherapy in patients with pretreated locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring a KRASG12C mutation, met the primary endpoint of progression-free survival (PFS) and the key secondary endpoint of overall response rate (ORR) as assessed by Blinded Independent Central Review (BICR) at final analysis for these endpoints. The study remains ongoing to assess the additional key secondary endpoint of overall survival. Results of the confirmatory trial showed that KRAZATI demonstrated a statistically significant and clinically meaningful benefit in PFS and ORR compared to standard-of-care chemotherapy as a second-line or later treatment for these patients. KRAZATI had no new safety signals and the safety data was consistent with the known safety profile.
“We are delighted to see these data underscoring the potential of adagrasib as a therapy for patients with KRASG12C mutated NSCLC in second or later line treatment,” said Rafael G. Amado, M.D., President, Head of Global Oncology Research and Development, Zai Lab. “Lung cancer is the most common cancer in China, and adagrasib is one of several important products in Zai Lab’s growing lung cancer pipeline. We are proud to have contributed to the KRYSTAL-12 study and are looking forward to bringing adagrasib to patients in need in China."
Bristol Myers Squibb will complete a full evaluation of the available data and will share the results with the scientific community at an upcoming medical conference as well as discuss the results with health authorities.
Zai Lab expects to submit the New Drug Application (NDA) for adagrasib to the National Medical Products Association (NMPA) for KRASG12C mutated NSCLC in second or later line treatment in China this year.
In addition to KRASG12C-mutated NSCLC, KRAZATI and KRAZATI-based combinations have shown encouraging meaningful benefit in Phase 2 clinical trials across several tumors, including advanced colorectal cancer, pancreatic cancer and other solid tumors. In February, the U.S. FDA accepted for priority review the supplemental new drug application (sNDA) for KRAZATI in combination with cetuximab for the treatment of patients with previously treated KRASG12C-mutated locally advanced or metastatic colorectal cancer (CRC). The FDA assigned a Prescription Drug User Fee Act (PDUFA) goal date of June 21, 2024.
Zai Lab thanks the patients and investigators involved in the KRYSTAL-12 clinical trial.
About NSCLC in China
According to the World Health Organization, the incidence of lung cancer in China in 2020 was 815,563 cases, with 714,699 deaths. Lung cancer consists of NSCLC in approximately 85% of cases and small cell lung cancer (SCLC) in approximately 15% of cases. KRASG12C is the most common KRAS mutation in NSCLC. The mutation is a biomarker of poor prognosis in Chinese patients with NSCLC.
ABOUT KRAZATI® (adagrasib)
KRAZATI (adagrasib) is highly selective and potent oral small-molecule inhibitor of KRASG12C that is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12C-mutated cancers, as the KRAS protein regenerates every 24-48 hours. In China, it is estimated that there are around 42,000 patients each year with KRASG12C-mutated NSCLC and colorectal cancer indications alone.
In 2022, KRAZATI was granted accelerated approval for treatment of adult patients with KRASG12C-mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, who have received at least one prior systemic therapy. This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial(s).
In 2023, Medicines and Healthcare products Regulatory Agency (MHRA) granted conditional marketing authorization for KRAZATI as a targeted treatment option for adult patients with KRASG12C-mutated advanced non-small cell lung cancer and disease progression after at least one prior systemic therapy followed by the European Commission (EC) in 2024.
KRAZATI continues to be evaluated as monotherapy and in combination with other anti-cancer therapies in patients with advanced KRASG12C-mutated solid tumors, including non-small cell lung cancer and colorectal cancer.
In 2022, the FDA granted breakthrough therapy designation for KRAZATI in combination with cetuximab in patients with KRASG12C-mutated advanced colorectal cancer whose cancer has progressed following prior treatment with chemotherapy and an anti-VEGF therapy.
For U.S. Prescribing Information, visit KRAZATI.
About KRYSTAL-12
KRYSTAL-12 is an open-label, multicenter, randomized Phase 3 study evaluating KRAZATI compared to standard-of-care chemotherapy alone, in patients with KRASG12C-mutated non-small cell lung cancer. The primary endpoint of the study is PFS as assessed by BICR. Secondary endpoints included overall survival (OS), overall response rate (ORR), duration of response (DOR), and safety.
About Zai Lab
Zai Lab (NASDAQ: ZLAB; HKEX: 9688) is an innovative, research-based, commercial-stage biopharmaceutical company based in China and the United States. We are focused on discovering, developing, and commercializing innovative products that address medical conditions with significant unmet needs in the areas of oncology, autoimmune disorders, infectious diseases, and neuroscience. Our goal is to leverage our competencies and resources to positively impact human health in China and worldwide.
For additional information about Zai Lab, please visit www.zailaboratory.com or follow us at www.twitter.com/ZaiLab_Global.
View source version on businesswire.com: https://www.businesswire.com/news/home/20240401347225/en/
Source: Zai Lab Limited
Zai Lab reports Krazati lung cancer study meets primary endpoint
Apr. 01, 2024 10:57 AM ET
Zai Lab Limited (ZLAB) Stock, BMY Stock
By: Val Brickates Kennedy, SA News Editor
Zai Lab (NASDAQ:ZLAB) said a confirmatory study for Bristol Myers’ (NYSE:BMY) drug Krazati has met its primary endpoint of progression-free survival in pretreated patients with KRASG12C-mutated locally advanced or metastatic non-small cell lung cancer, or NSCLC.
The study, called KRYSTAL-12, is still ongoing to assess a key secondary endpoint of overall survival. Zai plans to submit a market application later this year for Chinese regulatory approval of Krazati at a second or later line treatment for KRASG12C-mutated NSCLC.
Zai Lab Limited (ZLAB) Stock, BMY Stock
LEQEMBI® (LECANEMAB-IRMB)
LEQEMBI® (LECANEMAB-IRMB)
LEQEMBI® (LECANEMAB-IRMB)
EISAI COMPLETES SUBMISSION OF LEQEMBI® (LECANEMAB-IRMB) SUPPLEMENTAL BIOLOGICS LICENSE APPLICATION FOR IV MAINTENANCE DOSING FOR THE TREATMENT OF EARLY ALZHEIMER'S DISEASE TO THE U.S. FDA
TOKYO and CAMBRIDGE, Mass., March 31, 2024 /PRNewswire/ -- Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") and Biogen Inc. (Nasdaq: BIIB, Corporate headquarters: Cambridge, Massachusetts, CEO: Christopher A. Viehbacher, "Biogen") announced today that Eisai submitted to the U.S. Food and Drug Administration (FDA) a Supplemental Biologics License Application (sBLA) for monthly lecanemab-irmb (U.S. brand name: LEQEMBI®) intravenous (IV) maintenance dosing. LEQEMBI is indicated for the treatment of Alzheimer's disease (AD) in patients with mild cognitive impairment or mild dementia stage of disease (collectively referred to as early AD).
As part of the monthly IV maintenance regimen, the patients who have completed the biweekly IV initiation phase, exact period under discussion with the FDA, would receive a monthly IV dose that maintains effective drug concentration to sustain the clearance of highly toxic protofibrils* which can continue to cause neuronal injury even after the amyloid-beta (Aβ) plaque has been cleared from the brain. The sBLA is based on modeling of observed data from the Phase 2 study (Study 201) and its open-label extension (OLE) as well as Clarity AD study (Study 301) and its OLE study.
Eisai had aimed to submit a Biologics License Application (BLA) for weekly maintenance therapy using subcutaneous (SC) administration in March 2024. To respond to the FDA's recent requirement of additional three-month immunogenicity data at the proposed maintenance dose of 360 mg weekly, Eisai planned to initiate a rolling BLA for lecanemab SC maintenance in March 2024, under the existing Fast Track and Breakthrough Therapy designations. However, Eisai was recently informed by the FDA that a Fast Track designation specific for the SC formulation is needed to receive rolling review. Following the guidance, Eisai submitted a request for Fast Track designation for the SC formulation and will initiate a rolling submission should the FDA grant this designation. The Fast Track designation will be determined within 60 days from the March 2024 submission.
AD is an ongoing neurotoxic process that begins before and continues after plaque deposition. There is an urgency to treat early AD because early and ongoing treatment can slow the progression of AD and continuing treatment may prolong the benefit even after plaque is cleared from the brain. The earlier Mild Cognitive Impairment (MCI) due to AD and mild AD dementia are diagnosed and treated, the greater the opportunity for the patient to benefit. Continued maintenance dosing is intended to maintain the clinical and biomarker benefits with a dosing regimen that may be more convenient for some patients and their care partners.
LEQEMBI is now approved in the U.S., Japan and China, and applications have been submitted for review in the European Union, Australia, Brazil, Canada, Hong Kong, Great Britain, India, Israel, Russia, Saudi Arabia, South Korea, Taiwan, Singapore, and Switzerland. Eisai serves as the lead for lecanemab's development and regulatory submissions globally with both companies co-commercializing and co-promoting the product and Eisai having final decision-making authority.
* Protofibrils are believed to contribute to the brain injury that occurs with AD and are considered to be the most toxic form of Aβ, having a primary role in the cognitive decline associated with this progressive, debilitating condition.1 Protofibrils cause injury to neurons in the brain, which in turn, can negatively impact cognitive function via multiple mechanisms, not only increasing the development of insoluble Aβ plaques but also increasing direct damage to brain cell membranes and the connections that transmit signals between nerve cells or nerve cells and other cells. It is believed the reduction of protofibrils may prevent the progression of AD by reducing damage to neurons in the brain and cognitive dysfunction. 2
U.S. INDICATION AND IMPORTANT SAFETY INFORMATION
LEQEMBI (lecanemab-irmb) 100 mg/ml injection for intravenous (IV) use is indicated for the treatment of Alzheimer's disease. Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials.
Please see full Prescribing Information for LEQEMBI, including Boxed WARNING.
1. About lecanemab (Leqembi®)
Lecanemab is the result of a strategic research alliance between Eisai and BioArctic. It is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibril) and insoluble forms of amyloid-beta (Aβ).3 Lecanemab is approved in the U.S.,4 Japan,5 and China.6 In the U.S., Japan and China, the indications are as follows:
- U.S.: For the treatment of Alzheimer's disease (AD). It should be initiated in patients with mild cognitive impairment (MCI) or mild dementia stage of disease.4
- Japan: For slowing progression of MCI and mild dementia due to AD.5
- China: For the treatment of MCI due to AD and mild AD dementia.6
LEQEMBI's FDA approval was based on Phase 3 data from Eisai's, global Clarity AD clinical trial, in which it met its primary endpoint and all key secondary endpoints with statistically significant results.7 The primary endpoint was the global cognitive and functional scale, Clinical Dementia Rating Sum of Boxes (CDR-SB). In the Clarity AD clinical trial, treatment with lecanemab reduced clinical decline on CDR-SB by 27% at 18 months compared to placebo.7 The mean CDR-SB score at baseline was approximately 3.2 in both groups. The adjusted least-squares mean change from baseline at 18 months was 1.21 with lecanemab and 1.66 with placebo (difference, −0.45; 95% confidence interval [CI], −0.67 to −0.23; P<0.001).7 In addition, the secondary endpoint from the AD Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL), which measures information provided by people caring for patients with AD, noted a statistically significant benefit of 37% compared to placebo.7 The adjusted mean change from baseline at 18 months in the ADCS-MCI-ADL score was −3.5 in the lecanemab group and −5.5 in the placebo group (difference, 2.0; 95% CI, 1.2 to 2.8; P<0.001).7 The ADCS MCI-ADL assesses the ability of patients to function independently, including being able to dress, feed themselves and participate in community activities. The most common adverse events (>10%) in the lecanemab group were infusion reactions, ARIA-H (combined cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis), ARIA-E (edema/effusion), headache, and fall.7
Eisai has also submitted applications for approval of lecanemab in 14 countries and regions, including the European Union (EU).
2. About the Collaboration between Eisai and Biogen for AD
Eisai and Biogen have been collaborating on the joint development and commercialization of AD treatments since 2014. Eisai serves as the lead of lecanemab development and regulatory submissions globally with both companies co-commercializing and co-promoting the product and Eisai having final decision-making authority.
3. About the Collaboration between Eisai and BioArctic for AD
Since 2005, Eisai and BioArctic have had a long-term collaboration regarding the development and commercialization of AD treatments. Eisai obtained the global rights to study, develop, manufacture and market lecanemab for the treatment of AD pursuant to an agreement with BioArctic in December 2007. The development and commercialization agreement on the antibody lecanemab back-up was signed in May 2015.
4. About Eisai Co., Ltd.
Eisai's Corporate Concept is "to give first thought to patients and people in the daily living domain, and to increase the benefits that health care provides." Under this Concept (also known as human health care (hhc) Concept), we aim to effectively achieve social good in the form of relieving anxiety over health and reducing health disparities. With a global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to create and deliver innovative products to target diseases with high unmet medical needs, with a particular focus in our strategic areas of Neurology and Oncology.
In addition, we demonstrate our commitment to the elimination of neglected tropical diseases (NTDs), which is a target (3.3) of the United Nations Sustainable Development Goals (SDGs), by working on various activities together with global partners.
For more information about Eisai, please visit www.eisai.com (for global headquarters: Eisai Co., Ltd.), and connect with us on X, LinkedIn and Facebook. The website and social media channels are intended for audiences outside of the UK and Europe. For audiences based in the UK and Europe, please visit www.eisai.eu and Eisai EMEA LinkedIn.
5. About Biogen
Founded in 1978, Biogen is a leading biotechnology company that pioneers innovative science to deliver new medicines to transform patient's lives and to create value for shareholders and our communities. We apply deep understanding of human biology and leverage different modalities to advance first-in-class treatments or therapies that deliver superior outcomes. Our approach is to take bold risks, balanced with return on investment to deliver long-term growth.
The company routinely posts information that may be important to investors on its website at www.biogen.com. Follow Biogen on social media – Facebook, LinkedIn, X, YouTube.
SOURCE Eisai Inc.
Eisai submits sBLA for monthly maintenance dose of Alzheimer's drug Leqembi
Apr. 01, 2024 6:04 AM ET
Biogen Inc. (BIIB) Stock, ESALF Stock, ESAIY Stock
By: Jonathan Block, SA News Editor
- Eisai (OTCPK:ESALF) has submitted an sBLA to the U.S. FDA for a monthly maintenance dose of the Alzheimer's therapy Leqembi (lecanemab).
- The current recommended dose for the treatment, which is marketed with Biogen (NASDAQ:BIIB), is an intravenous infusion every two weeks.
- https://seekingalpha.com/news/4085471-eisai-submits-sbla-monthly-maintenance-dose-alzheimers-drug-leqembi?mailingid=34880396&messageid=2900&serial=34880396.6368&utm_campaign=rta-stock-news&utm_content=link-1&utm_medium=email&utm_source=seeking_alpha&utm_term=34880396.6368
- Biogen Inc. (BIIB) Stock, ESALF Stock, ESAIY Stock
- https://us.eisai.com/
- https://www.leqembi.com/
Revumenib
LEQEMBI® (LECANEMAB-IRMB)
LEQEMBI® (LECANEMAB-IRMB)
Syndax Announces FDA Priority Review of NDA for Revumenib for the Treatment of Relapsed/Refractory KMT2Ar Acute Leukemia
March 26, 2024
– PDUFA action date set for September 26, 2024 –
– NDA being reviewed under FDA's RTOR program –
WALTHAM, Mass., March 26, 2024 /PRNewswire/ -- Syndax Pharmaceuticals (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, today announced that the U.S. Food and Drug Administration (FDA) has granted Priority Review for its New Drug Application (NDA) for revumenib, the Company's first-in-class menin inhibitor, for the treatment of adult and pediatric relapsed or refractory (R/R) KMT2A-rearranged (KMT2Ar) acute leukemia. The NDA filing is being reviewed under the FDA's Real-Time Oncology Review Program (RTOR) and has been assigned a Prescription Drug User Fee Act (PDUFA) target action date of September 26, 2024. RTOR allows for a more efficient review and close engagement between the sponsor and the FDA throughout the submission process, which historically has led to earlier approvals.
"The receipt of Priority Review for the revumenib NDA filing is a significant milestone as we transition to a leading commercial-stage oncology company with the planned launches of two first- and best-in class drugs in 2024," said Michael A. Metzger, Chief Executive Officer. "With two regulatory filings now under FDA Priority Review, our team is focused on commercial preparations to enable Syndax's continued success as we enter this next stage of growth."
The NDA submission is supported by positive data from the pivotal AUGMENT-101 trial of revumenib in adult and pediatric patients with KMT2Ar acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). As previously reported, the trial met its primary endpoint at the protocol-defined interim analysis with a complete remission (CR) or a CR with partial hematological recovery (CRh) rate of 23% (13/57; 95% confidence interval [CI]: [12.7, 35.8, one-sided p-value = 0.0036]) among the 57 efficacy evaluable patients in the pooled KMT2Ar acute leukemia population. 70% of patients who achieved a CR/CRh and were assessed for minimal residual disease (MRD) were MRD negative. Additionally, 63% (36/57) of the efficacy-evaluable patients achieved an overall response, 39% (14/36) of whom underwent hematopoietic stem cell transplant (HSCT), with 50% (7/14) restarting revumenib as post-transplant maintenance at the time of the data cutoff.
About Revumenib
Revumenib is a potent, selective, small molecule inhibitor of the menin-KMT2A binding interaction that is being developed for the treatment of KMT2A-rearranged, also known as mixed lineage leukemia rearranged or MLLr, acute leukemias including ALL and AML, and NPM1-mutant AML. Positive topline results from the Phase 2 AUGMENT-101 trial in R/R KMT2Ar acute leukemia showing the trial met its primary endpoint were presented at the 65th American Society of Hematology Annual Meeting and data from the Phase 1 portion of AUGMENT-101 in acute leukemia was published in Nature. Revumenib was granted Orphan Drug Designation by the FDA and European Commission for the treatment of patients with AML and Fast Track designation by the FDA for the treatment of adult and pediatric patients with R/R acute leukemias harboring a KMT2A rearrangement or NPM1 mutation. Revumenib was granted Breakthrough Therapy Designation (BTD) by the FDA for the treatment of adult and pediatric patients with R/R acute leukemia harboring a KMT2A rearrangement.
About Real-Time Oncology Review (RTOR)
RTOR provides a more efficient review process for oncology drugs to ensure that safe and effective treatments are available to patients as early as possible, while improving review quality and engaging in early iterative communication with the applicant. Specifically, it allows for close engagement between the sponsor and the FDA throughout the submission process and it enables the FDA to review individual sections of modules of a drug application rather than requiring the submission of complete modules or a complete application prior to initiating review. Additional information about RTOR can be found at: https://www.fda.gov/about-fda/oncology-center-excellence/real-time-oncology-review-pilot-program
About Syndax
Syndax Pharmaceuticals is a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies. Highlights of the Company's pipeline include revumenib, a highly selective inhibitor of the menin–KMT2A binding interaction, and axatilimab, a monoclonal antibody that blocks the colony stimulating factor 1 (CSF-1) receptor. For more information, please visit www.syndax.com or follow the Company on X (formerly Twitter) and LinkedIn.
Cision View original content:https://www.prnewswire.com/news-releases/syndax-announces-fda-priority-review-of-nda-for-revumenib-for-the-treatment-of-relapsedrefractory-kmt2ar-acute-leukemia-302100145.html
SOURCE Syndax Pharmaceuticals, Inc.
FDA grants priority review for Syndax leukemia drug, sets action date
Mar. 26, 2024 5:11 PM ET
Syndax Pharmaceuticals, Inc. (SNDX) Stock
By: Val Brickates Kennedy, SA News Editor
Syndax Pharmaceuticals (NASDAQ:SNDX) said the FDA has granted Priority Review status for its New Drug Application for revumenib in the treatment of relapsed/refractory KMT2Ar acute leukemia.
The drug was previously granted Fast Track and Breakthrough Therapy status by the agency for the indication.
biotecHOPE™ 2024
Tumor Treating Fields (TTFields) therapy
Tumor Treating Fields (TTFields) therapy
Tumor Treating Fields (TTFields) therapy
METIS Phase 3 Clinical Trial Met Primary Endpoint, Demonstrating a Statistically Significant Extension in Time to Intracranial Progression for Patients with Brain Metastases from Non-Small Cell Lung Cancer
March 27, 2024
The METIS trial demonstrated 21.9 months median time to intracranial progression for patients treated with Tumor Treating Fields and supportive care compared to 11.3 months for patients treated with supportive care alone
Novocure to host investor conference call at 8 a.m. EDT
ROOT, Switzerland–(BUSINESS WIRE)– Novocure (NASDAQ: NVCR) today announced the phase 3 METIS clinical trial met its primary endpoint, demonstrating a statistically significant improvement in time to intracranial progression for adult patients treated with Tumor Treating Fields (TTFields) therapy and supportive care compared to supportive care alone in the treatment of patients with 1-10 brain metastases from non-small cell lung cancer (NSCLC) following stereotactic radiosurgery (SRS). Patients treated with TTFields therapy and supportive care exhibited a median time to intracranial progression of 21.9 months compared to 11.3 months in patients treated with supportive care alone for brain metastasis (n=298; hazard ratio=0.67; P=0.016). Median TTFields therapy treatment duration was 16 weeks and median usage was 67%. Consistent with previous studies, TTFields therapy was well-tolerated with sustained quality of life and neurocognitive function. Baseline characteristics were well balanced between arms.
“Patients with brain metastases from non-small cell lung cancer are frequently treated with radiosurgery but face a high likelihood of rapid brain relapse,” said Minesh Mehta, MD, Chief of Radiation Oncology and Deputy Director at Miami Cancer Institute, part of Baptist Health South Florida. “In this international, multicenter, phase 3 trial, the use of TTFields therapy significantly delayed time to brain relapse, with associated improvement in quality of life and stable cognition. This is a major benefit and is potentially practice changing.”
Preliminary analyses of key secondary endpoints (time to neurocognitive failure, overall survival, and radiological response rate) did not demonstrate statistical significance. Certain secondary endpoints showed positive trends in favor of treatment with TTFields therapy, including time to distant progression and quality of life. Full analysis of secondary endpoints is ongoing.
“Novocure’s willingness to pursue areas of considerable unmet need, like the patient population studied in METIS, is a point of pride for our company,” said Asaf Danziger, Novocure’s Chief Executive Officer. “We are so pleased with the positive outcome of this trial and encouraged by TTFields’ performance. I would like to thank everyone involved with METIS, especially our courageous patients and dedicated investigators, for their contributions to the trial and for meaningfully contributing to the evolution of treatment of brain metastases from NSCLC.”
Novocure intends to submit these data to regulatory authorities. Novocure also intends to publish these findings in a peer-reviewed scientific journal and share them at an upcoming scientific congress.
CONFERENCE CALL DETAILS
Novocure will host a conference call and webcast to discuss the METIS topline results at 8:00 a.m. EST today, March 27th. To access the conference call by phone, use the following conference call registration link and dial-in details will be provided. To access the webcast, use the following webcast registration link.
The webcast and slides presented during the webcast can be accessed live from the Investor Relations page of Novocure’s website, www.novocure.com/investor-relations, and will be available for at least 14 days following the call. Novocure has used, and intends to continue to use, its investor relations website as a means of disclosing material non-public information and for complying with its disclosure obligations under Regulation FD.
ABOUT METIS
METIS [NCT02831959] is a phase 3 trial of stereotactic radiosurgery with or without TTFields therapy for patients with 1-10 brain metastases from NSCLC. 298 adult patients were enrolled in the trial and randomized to receive either TTFields therapy with supportive care or supportive care alone following SRS. Supportive care consisted of, but was not limited to, treatment with steroids, anti-epileptic drugs, anticoagulants, pain control or nausea control medications. Patients in both arms of the study were eligible to receive systemic therapy for their NSCLC at the discretion of their treating physician. Patients with known tumor mutations for which targeted agents are available were excluded from the trial.
The primary endpoint of the METIS trial is time to first intracranial progression, as measured from the date of first SRS treatment to intracranial progression or neurological death (per RANO-BM criteria), whichever occurs first. Time to intracranial progression was calculated according to the cumulative incident function. Patient scans were evaluated by a blinded, independent radiologic review committee. Secondary endpoints include, but are not limited to, time to distant progression, time to neurocognitive failure, overall survival, time to second intracranial progression, quality of life and adverse events. Key secondary endpoints (time to neurocognitive failure, overall survival, and radiological response rate) were planned to be used in labeling claims, if successful. Patients were stratified by the number of brain metastases (1-4 or 5-10 metastases), prior systemic therapy, and tumor histology. Patients were allowed to crossover to the experimental TTFields therapy arm following confirmation of second intracranial progression.
ABOUT BRAIN METASTASES
Brain metastases are a secondary tumor formed when cancer cells break away from the primary tumor and travel through the blood or lymph system to form new tumors (or metastases) in the brain. Brain metastasis are a negative prognostic factor in NSCLC and adversely impact neurocognitive function and quality of life. Approximately 25% of patients with NSCLC have brain metastasis at diagnosis, and lifetime risk among patients with NSCLC is approximately 50%. Neurologic symptoms are present in approximately 60-75% of patients with brain metastasis, and seizures, focal neurologic deficits, headaches, and altered mental status are common. Treatment options for patients with brain metastasis from NSCLC are limited to neurosurgery, SRS, whole brain radiation therapy, or combinations of these options. However, given the neurotoxicity and significant decline in cognitive functioning, whole brain radiation therapy (WBRT) is an unfavorable treatment option. New therapeutic options are needed for greater intracranial control while minimizing the risk of neurocognitive adverse events.
ABOUT TUMOR TREATING FIELDS THERAPY
Tumor Treating Fields (TTFields) are electric fields that exert physical forces to kill cancer cells via a variety of mechanisms. TTFields do not significantly affect healthy cells because they have different properties (including division rate, morphology, and electrical properties) than cancer cells. The multiple, distinct mechanisms of TTFields therapy work together to selectively target and kill cancer cells. Due to its multimechanistic actions, TTFields therapy can be added to cancer treatment modalities in approved indications and demonstrates enhanced effects across solid tumor types when used with chemotherapy, radiotherapy, immune checkpoint inhibition, or PARP inhibition in preclinical models. TTFields therapy provides clinical versatility that has the potential to help address treatment challenges across a range of solid tumors. To learn more about Tumor Treating Fields therapy and its multifaceted effect on cancer cells, visit tumortreatingfields.com.
ABOUT NOVOCURE
Novocure is a global oncology company working to extend survival in some of the most aggressive forms of cancer through the development and commercialization of its innovative therapy, Tumor Treating Fields. Novocure’s commercialized products are approved in certain countries for the treatment of adult patients with glioblastoma and malignant pleural mesothelioma. Novocure has ongoing or completed clinical studies investigating Tumor Treating Fields in brain metastases, gastric cancer, glioblastoma, liver cancer, non-small cell lung cancer, pancreatic cancer and ovarian cancer.
Headquartered in Root, Switzerland and with a growing global footprint, Novocure has regional operating centers in Portsmouth, New Hampshire and Tokyo, as well as a research center in Haifa, Israel. For additional information about the company, please visit Novocure.com and follow @Novocure on LinkedIn and Twitter.
Source: Novocure
Novocure climbs after late-stage win for lung cancer therapy
Mar. 27, 2024 7:50 AM ET
NovoCure Limited (NVCR) Stock, ZLAB Stock
By: Dulan Lokuwithana, SA News Editor
Novocure (NASDAQ:NVCR) shares surged ~31% premarket Wednesday after the oncology company said that a Phase 3 trial for its cancer therapy Tumor Treating Fields (TTFields) reached its primary endpoint in patients with brain metastases resulting from lung cancer. Its Chinese partner, TTFields, Zai Lab (NASDAQ:ZLAB), traded flat after the announcement.
Citing topline data, Jersey-based Novocure (NVCR) said that the companies’ Phase 3 METIS trial met the primary endpoint with a statistically significant improvement in time to intracranial progression for those treated with TTFields therapy plus supportive care.
NovoCure Limited (NVCR) Stock, ZLAB Stock
Nipocalimab
Tumor Treating Fields (TTFields) therapy
Tumor Treating Fields (TTFields) therapy
Johnson & Johnson’s nipocalimab granted U.S. FDA Fast Track designation to reduce the risk of fetal neonatal alloimmune thrombocytopenia (FNAIT) in alloimmunized pregnant adults
FNAIT is a rare disease that occurs when a pregnant person’s immune system attacks fetal platelets, resulting in the risk of internal bleeding, which can be life threatening to the fetus or newborn
The Phase 3 FREESIA program is underway and nipocalimab is the only investigational therapy currently reported to be in clinical development for the treatment of FNAIT
MARCH 26, 2024
SPRING HOUSE, Pa. (March 26, 2024) – Johnson & Johnson announced today that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation (FTD) for nipocalimab to reduce the risk of FNAIT in alloimmunizeda pregnant adults during their current pregnancy. FNAIT is a rare and severe condition that occurs when the immune system of a pregnant person mistakenly attacks platelets in a developing fetus. This immune response can lead to impaired clotting ability and bleeding, posing a significant risk to the fetus or newborn.1 Nipocalimab, an investigational monoclonal antibody targeting FcRn, is the only investigational therapy currently reported to be in clinical development to address the needs of alloimmunized pregnant individuals at risk of FNAIT.
The FDA’s Fast Track program is designed to expedite development and review timelines of drugs that demonstrate the potential to treat serious conditions and address unmet medical needs for serious or life-threatening conditions. Fast Track designation supports close communication between the FDA and sponsor with the aim of delivering new therapeutics to patients more quickly.
“Receiving Fast Track designation for nipocalimab in FNAIT underscores the urgency to address the unmet need for safe, effective, and targeted treatments to prevent FNAIT, a condition that could carry severe health consequences and even be fatal for the fetus or newborn,” said Katie Abouzahr, M.D., Vice President, Autoantibody and Maternal Fetal Immunology Disease Area Leader, Johnson & Johnson. “We are committed to applying our decades of immunology leadership to pioneer innovative approaches to transform treatment for patients and their families affected by FNAIT and other alloantibody-driven diseases of pregnancy.”
Johnson & Johnson is conducting research and development for nipocalimab, an FcRn blocker, to address the significant unmet need in reducing the risk of FNAIT. Nipocalimab is believed to work by blocking the transfer of immunoglobulin G (IgG) alloantibodies from pregnant individuals to their babies through the placenta while not suppressing the broader immune systems of the pregnant individual or developing fetus.2 Johnson & Johnson is also proceeding with two Phase 3 trials focused on FNAIT. Nipocalimab was granted orphan drug designation by the U.S. FDA for FNAIT in December 2023.
Nipocalimab is additionally being studied in hemolytic disease of the fetus and newborn (HDFN), another alloimmune disease of pregnancy with a similar disease mechanism, often referred to as the red blood cell counterpart to FNAIT.3 After Phase 2 safety and efficacy results from the UNITY trial, Johnson & Johnson is additionally proceeding with Phase 3 trials focused on HDFN.4
Editor’s Notes:
a. Alloimmunized: an immune response to foreign antigens upon exposure to genetically different cells or tissues
About Fetal Neonatal Alloimmune Thrombocytopenia (FNAIT)
Fetal neonatal alloimmune thrombocytopenia (FNAIT) is a rare and potentially life-threatening alloimmune condition in which a pregnant person’s immune system develops antibodies against fetal or newborn platelet antigens, leading to thrombocytopenia (low platelet counts in the fetus or newborn).1
FNAIT can result in severe bleeding complications for a fetus or newborn and is characterized by organ bleeding in the gastrointestinal tract, lungs, or eyes, and may result in lifelong disability or death.1 If a severe bleed occurs in the brain, termed intracranial hemorrhage (ICH), death or life-long neurologic effects could occur.1 ICH occurs in up to 26 percent of untreated pregnancies with FNAIT.5
There are no approved targeted therapies for FNAIT management. FNAIT is not routinely screened for during pregnancy and firstborn children with FNAIT are often only diagnosed postnatally.1
About HDFN
Hemolytic disease of the fetus and newborn (HDFN) is a rare disease (and in its severe form, ultra rare) that arises in pregnancies with maternal-fetal incompatibility in certain red blood cell types.6 Alloantibodies produced by the maternal immune system against fetal red blood cells cross the placenta during pregnancy and attack fetal red blood cells causing fetal anemia or persist after birth in the neonate to cause neonatal hyperbilirubinemia and anemia.2 The symptoms of HDFN can range from mild jaundice, to neurotoxic hyperbilirubinemia in the newborn, to life-threatening fetal anemia requiring invasive intervention.7 The potential for in utero onset at an increasingly earlier GA with increasing risk of severe outcomes may occur with each incompatible pregnancy due to pregnancy-related alloimmunization.8 Currently there are no non-surgical interventions approved for pregnancies at high risk for severe HDFN.3 Pregnancies affected by severe HDFN may necessitate repeated intrauterine transfusions (IUTs), which are invasive, technically complex surgical procedures performed by specialists at specialized medical centers, and these procedures are associated with an increased rate of fetal mortality and premature birth.9,10,11 The most difficult to treat cases of HDFN are early onset severe HDFN (EOS-HDFN) that develops at ≤24 weeks gestational age (GA) and results in significant fetal/neonatal morbidity and mortality. According to the American Journal of Obstetrics and Gynecology, in the U.S., it is estimated that up to 80 of every 100,000 pregnancies are affected by HDFN each year.12
About Nipocalimab
Nipocalimab is an investigational, high-affinity, fully human, aglycosylated, effectorless, monoclonal antibody that aims to selectively block FcRn to reduce levels of circulating immunoglobulin G (IgG) antibodies, including autoantibodies and alloantibodies that underlie multiple conditions.13 Nipocalimab is the only FcRn blocker being studied across three key segments in the autoantibody space: Rare Autoantibody diseases (e.g., generalized myasthenia gravis in adults and children, chronic inflammatory demyelinating polyneuropathy, warm autoimmune hemolytic anemia, and idiopathic inflammatory myopathies); Maternal Fetal diseases mediated by maternal alloantibodies (e.g., hemolytic disease of the fetus and newborn and fetal and neonatal alloimmune thrombocytopenia); and Prevalent Rheumatology (e.g., rheumatoid arthritis, Sjögren’s disease, and systemic lupus erythematosus).14,15,16,17,18,19,20,21,22 Blockade of FcRn has the potential to reduce overall IgG including pathogenic alloantibody levels while preserving immune function without causing broad immunosuppression. Blockade of IgG binding to FcRn in the placenta is also believed to prevent transplacental transfer of maternal alloantibodies to the fetus.8,23
About Johnson & Johnson
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity.
Learn more at https://www.jnj.com/ or at www.janssen.com/johnson-johnson-innovative-medicine.
Follow us at @JanssenUS and @JNJInnovMed.
Janssen Research & Development, LLC and Janssen Biotech, Inc. are both Johnson & Johnson companies.
J&J experimental therapy gets FDA fast track status to reduce FNAIT in pregnancy
Mar. 26, 2024 8:24 AM ET
By: Preeti Singh, SA News Editor
- Johnson & Johnson (NYSE:JNJ) has received FDA fast track designation for its investigational monoclonal antibody, nipocalimab, to reduce the risk of fetal and neonatal alloimmune thrombocytopenia (FNAIT) in alloimmunized pregnant adults.
- https://seekingalpha.com/news/4083654-jj-experimental-therapy-gets-fda-fast-track-to-reduce-fnait-in-pregnancy?mailingid=34817559&messageid=2900&serial=34817559.26516&utm_campaign=rta-stock-news&utm_content=link-1&utm_medium=email&utm_source=seeking_alpha&utm_term=34817559.26516
- Johnson & Johnson (JNJ) Stock
- https://www.jnj.com/
WINREVAIR™ (sotatercept-csrk)
Tumor Treating Fields (TTFields) therapy
VK2735, a dual GLP-1 and GIP agonist
FDA Approves Merck’s WINREVAIR™ (sotatercept-csrk), a First-in-Class Treatment for Adults with Pulmonary Arterial Hypertension (PAH, WHO* Group 1)
March 26, 2024 6:21 pm ET
WINREVAIR is a breakthrough biologic for this rare, progressive disease
WINREVAIR on top of background therapy significantly improved exercise capacity and multiple important secondary outcome measures compared to background therapy alone
RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced today that the U.S. Food and Drug Administration (FDA) has approved sotatercept-csrk (U.S. Brand Name: WINREVAIR™, for injection, 45mg, 60mg) for the treatment of adults with pulmonary arterial hypertension (PAH, World Health Organization [WHO] Group 1) to increase exercise capacity, improve WHO functional class (FC), and reduce the risk of clinical worsening events. WINREVAIR was previously granted Breakthrough Therapy Designation by the FDA. WINREVAIR is the first FDA-approved activin signaling inhibitor therapy for PAH, representing a new class of therapy that works by improving the balance between pro- and anti-proliferative signaling to regulate vascular cell proliferation underlying PAH.
WINREVAIR logo (Graphic: Merck & Co., Inc.)
“Pulmonary arterial hypertension is a rare, progressive and ultimately life-threatening disease in which blood vessels in the lungs thicken and narrow, causing significant strain on the heart,” said Dr. Marc Humbert, Professor of Medicine and Director of the Pulmonary Hypertension Reference Center at the Université Paris-Saclay and investigator on the Phase 3 STELLAR study. “Based on the Phase 3 STELLAR trial, adding WINREVAIR to background PAH therapy demonstrated significant clinical benefits compared to background PAH therapy alone. This approval is an important milestone, as it offers healthcare providers a novel therapeutic option that targets a new PAH treatment pathway.”
The approval is based on the Phase 3 STELLAR trial, which compared WINREVAIR (n=163) to placebo (n=160), both in combination with background standard of care therapies in adult patients with PAH (WHO Group 1 FC II or III). Results showed adding WINREVAIR to background therapy increased six-minute walk distance from baseline by 41 meters (95% CI: 28, 54; p<0.001; placebo-adjusted) at Week 24 and significantly improved multiple important secondary outcome measures, including reducing the risk of death from any cause or PAH clinical worsening events by 84% versus background therapy alone (number of events: 9 vs 42, hazard ratio=0.16; 95% CI: 0.08, 0.35; p<0.001).
Healthcare providers should monitor hemoglobin and platelets before each dose of WINREVAIR for the first 5 doses, or longer if values are unstable, and periodically thereafter to determine if dose adjustments are required. WINREVAIR may increase hemoglobin and may lead to erythrocytosis, which if severe may increase the risk of thromboembolic events or hyperviscosity syndrome. WINREVAIR also may decrease platelet count and lead to severe thrombocytopenia, which may increase the risk of bleeding; thrombocytopenia occurred more frequently in patients also receiving prostacyclin infusion. Treatment should not be initiated if platelet count is <50,000/mm3. See additional Selected Safety Information below.
“The Pulmonary Hypertension Association welcomes the development of new therapies for those with PAH,” said Matt Granato, president and chief executive officer, Pulmonary Hypertension Association. “A diagnosis of PAH is a life-changing experience for patients and families due to its chronic, progressive nature. Patients with PAH experience limiting symptoms such as shortness of breath and fatigue. We are excited to see industry research leading to a better understanding of PAH and the development of a medicine in a novel treatment pathway that expands options for the patient community.”
“New treatment options continue to be needed for patients with pulmonary arterial hypertension that support important clinical goals, including increasing exercise capacity and improving functional class,” said Dr. Aaron Waxman, Executive Director of the Center for Pulmonary Heart Diseases at Brigham and Women’s Hospital and investigator on the Phase 3 STELLAR study. “Sotatercept added to background therapy has the potential to become a new standard of care option for patients with pulmonary arterial hypertension.”
WINREVAIR is given once every three weeks by subcutaneous injection and may be administered by appropriate patients or caregivers with guidance, training and follow-up from a healthcare provider. Healthcare providers and patients/caregivers should refer to the Instructions for Use for information on the proper preparation and administration of WINREVAIR. Merck estimates that WINREVAIR will be available for dispensing by select specialty pharmacies in the U.S. by the end of April.
“PAH remains a debilitating disease with high morbidity and mortality,” said Dr. Eliav Barr, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “This approval of WINREVAIR is an important milestone and a testament to our science-led strategy and focus on the development of innovations that can help people affected by rare diseases like PAH. We are proud to bring this novel medicine to patients.”
Merck offers support to patients who are prescribed WINREVAIR, including information about insurance coverage and help for eligible patients with out-of-pocket costs and co-pay assistance options, through the Merck Access Program. For additional information, healthcare providers and patients can call 1-888-637-2502 or visit www.merckaccessprogram-WINREVAIR.com in the coming days.
STELLAR Study Results
The primary efficacy endpoint in the STELLAR trial was the change from baseline at Week 24 in 6-Minute Walk Distance (6MWD). In the WINREVAIR treatment group, the placebo-adjusted median increase in 6MWD was 41 meters (95% CI: 28, 54; p<0.001, Hodges-Lehmann estimate). Additionally, patients who added WINREVAIR had statistically significantly greater improvements compared to placebo across multiple secondary endpoints:
- Treatment with WINREVAIR led to an improvement in FC from baseline at Week 24 in 29% of patients compared to 14% of patients treated with placebo (p<0.001).
- Treatment with WINREVAIR resulted in an 84% reduction in the occurrence of death or PAH clinical worsening events compared to placebo (median duration of exposure 33.6 weeks; number of events: 9/163 vs 42/160, hazard ratio=0.16; 95% CI: 0.08, 0.35; p<0.001).
- Treatment with WINREVAIR led to an improvement from baseline in pulmonary vascular resistance (PVR). The median treatment difference in PVR between WINREVAIR and placebo was -235 dynes*sec/cm5 (95% CI: -288, -181; p<0.001).
- Treatment with WINREVAIR led to an improvement from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. The median treatment difference in NT-proBNP between WINREVAIR and placebo was -442 pg/mL (95% CI: -574, -310; p<0.001).
About STELLAR
The STELLAR study (NCT04576988) was a global, double-blind, placebo-controlled, multicenter, parallel-group clinical trial in which 323 patients with PAH (WHO Group 1 FC II or III) were randomized 1:1 to WINREVAIR (target dose 0.7 mg/kg) (n=163) or placebo (n=160) plus stable background therapy administered subcutaneously once every 3 weeks.
The most common PAH etiologies were idiopathic PAH (59%), heritable PAH (18%), and PAH associated with connective tissue diseases (CTD) (15%). Most participants were receiving either three (61%) or two (35%) background drugs for PAH, and 40% were receiving prostacyclin infusions. The mean time from PAH diagnosis was 8.8 years. Patients had a WHO FC II (49%) or III (51%) at baseline.
About WINREVAIR™ (sotatercept-csrk) for injection, for subcutaneous use, 45 mg, 60 mg
WINREVAIR is FDA-approved for the treatment of adults with pulmonary arterial hypertension (PAH, WHO Group 1) to increase exercise capacity, improve WHO functional class (FC) and reduce the risk of clinical worsening events. WINREVAIR is the first activin signaling inhibitor therapy approved to treat PAH. WINREVAIR improves the balance between pro-proliferative and anti-proliferative signaling to modulate vascular proliferation. In preclinical models, WINREVAIR induced cellular changes that were associated with thinner vessel walls, partial reversal of right ventricular remodeling, and improved hemodynamics.
WINREVAIR is the subject of a licensing agreement with Bristol Myers Squibb.
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.
Please see Prescribing Information for WINREVAIR (sotatercept-csrk) at http://www.merck.com/product/usa/pi_circulars/w/winrevair/winrevair_pi.pdf, Patient Information for WINREVAIR at http://www.merck.com/product/usa/pi_circulars/w/winrevair/winrevair_ppi.pdf, and Instructions for Use for WINREVAIR (1-vial kit, 2-vial kit) at https://www.merck.com/product/usa/pi_circulars/w/winrevair/winrevair_ifu_1-vial_2-vial_kits.pdf.
Source: Merck & Co., Inc.
Merck wins FDA approval of sotatercept for rare lung disease
Mar. 26, 2024 5:48 PM ET
Merck & Co., Inc. (MRK) StockUTHR
By: Jonathan Block, SA News Editor8 Comments
- The U.S. FDA has approved Merck's (NYSE:MRK) sotatercept, a treatment or pulmonary arterial hypertension, a rare type of lung disease. It will be marketed under the name Winrevair.
- https://seekingalpha.com/news/4084059-merck-wins-fda-approval-sotatercept-rare-lung-disease?mailingid=34828756&messageid=2900&serial=34828756.7624&utm_campaign=rta-stock-news&utm_content=link-1&utm_medium=email&utm_source=seeking_alpha&utm_term=34828756.7624
- Merck & Co., Inc. (MRK) Stock
- https://www.merck.com/
VK2735, a dual GLP-1 and GIP agonist
VK2735, a dual GLP-1 and GIP agonist
VK2735, a dual GLP-1 and GIP agonist
Up to 3.3% Placebo-Adjusted Mean Weight Loss (5.3% from Baseline) Observed After 28 Days
VK2735 Shown to be Safe and Well-Tolerated in 28-Day Study with Low Rates of GI-Related Adverse Events
Phase 2 Trial in Obesity Planned for 2H24
Conference Call Scheduled for 8:00 a.m. ET Today
SAN DIEGO, March 26, 2024 /PRNewswire/ --
Viking Therapeutics, Inc. ("Viking") (NASDAQ: VKTX), a clinical-stage biopharmaceutical company focused on the development of novel therapies for metabolic and endocrine disorders, today announced positive results from the company's Phase 1 multiple ascending dose (MAD) clinical trial of an oral tablet formulation of VK2735, a dual agonist of the glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, in development for the potential treatment of metabolic disorders such as obesity. Based on these Phase 1 results, the company plans to initiate a Phase 2 trial with the oral formulation of VK2735 in obesity later this year.
Highlights from the study results include:
Body Weight Reductions
The 28-day MAD study results highlight positive signs of clinical activity following treatment with oral VK2735. Cohorts receiving VK2735 demonstrated dose-dependent reductions in mean body weight from baseline, ranging up to 5.3%. Cohorts receiving VK2735 also demonstrated reductions in mean body weight relative to placebo, ranging up to 3.3%. For doses ≥10 mg, placebo-adjusted reductions in mean body weight were maintained or improved at Day 34, six days after the last dose of VK2735 was administered, ranging up to 3.6% relative to placebo. An exploratory assessment of the proportion of subjects achieving at least 5% weight loss after 28 days demonstrated that up to 57% of VK2735-treated subjects achieved ≥5% weight loss, compared with 0% for placebo. Based on a preliminary evaluation of weight loss trajectory, the company believes that treatment duration beyond 28 days may provide further reductions in body weight.
"These Phase 1 results highlight VK2735's promising early weight loss and tolerability profile when dosed as an oral tablet," said Brian Lian, Ph.D., chief executive officer of Viking. "We believe these data indicate that longer treatment duration, at potentially higher doses, may result in additional weight loss. We are particularly pleased with the initial safety and tolerability data, which suggest a differentiated profile with minimal gastrointestinal-related side effects. We believe that an oral agent with good tolerability could represent an attractive potential treatment option for patients with obesity. We look forward to exploring longer treatment windows and potentially higher doses in an upcoming Phase 2 trial."
Notes: 1) Population includes all randomized subjects who received at least one dose of study drug and had at least one planned post-baseline body weight assessment. 2) Patients treated with VK2735 were titrated to final doses as indicated: 2.5 mg cohort = 2.5 daily x 4 weeks; 5 mg cohort = 2.5 mg daily x 1 wk, 5 mg daily x 3 wks; 10 mg cohort = 5 mg daily x 1 wk, 10 mg daily x 3 wks; 20 mg cohort = 15 mg daily x 1 wk, 20 mg daily x 3 wks; 40 mg cohort = 20 mg daily x 1 wk, 40 mg daily x 3 wks. 3) All subjects enrolled were required to have baseline BMI ≥30 kg/m2. 4) Least squares mean. 5) Two-sided t test using mixed model for repeated measures. 6) Fisher's exact test.
Safety and Tolerability
Oral VK2735 demonstrated encouraging safety and tolerability following 28 days of once-daily dosing. Among subjects receiving VK2735, all treatment emergent adverse events (TEAEs) reported to date have been mild or moderate, with the majority (76%) reported as mild. Similarly, all observed gastrointestinal (GI) adverse events have been reported as mild or moderate, with the majority (79%) reported as mild. Mild nausea was reported in five (14%) VK2735-treated subjects. Vomiting was not reported among any VK2735-treated subjects. Diarrhea was reported in one subject (3%) receiving VK2735 compared with two subjects (20%) receiving placebo. Overall, no clinically meaningful differences were reported for GI-related adverse events among subjects treated with VK2735 compared with placebo. In addition, no serious adverse events (SAEs) have been reported to date.
Notes: Safety population, includes all randomized subjects who received at least one dose of study drug or placebo.
Based on the encouraging weight loss, as well as the safety and tolerability results to date, the company has elected to continue further dose escalation in this study. Viking also plans to initiate a Phase 2 trial of oral VK2735 in patients with obesity in the second half of 2024.
The Phase 1 MAD study of oral VK2735 is an extension of the company's Phase 1 single ascending dose (SAD)/MAD trial of VK2735 administered subcutaneously. The oral portion of the trial is a randomized, double-blind, placebo-controlled study in healthy adults with a minimum body mass index of 30 kilograms per meter squared. The primary objective of the study was to evaluate the safety and tolerability of VK2735 administered as an oral tablet once daily for 28 days. Exploratory pharmacodynamic measures included assessments of changes in body weight and other metrics.
Conference Call
Management will host a conference call to discuss results from the company's Phase 1 trial of an oral formulation of VK2735 today at 8:00 am Eastern. To participate in the conference call, please dial (844) 850-0543 from the U.S. or (412) 317-5199 from outside the U.S. In addition, following the completion of the call, a telephone replay will be accessible until April 2, 2024, by dialing (877) 344-7529 from the U.S. or (412) 317-0088 from outside the U.S. and entering conference ID #6296711. Those interested in listening to the conference call live via the internet may do so by visiting the Webcasts page of Viking's website at http://ir.vikingtherapeutics.com/webcasts. An archive of the webcast will also be available on the Webcasts page of Viking's website for 30 days.
About GLP-1 and Dual GLP-1/GIP Agonists
Activation of the glucagon-like peptide 1 (GLP-1) receptor has been shown to decrease glucose, reduce appetite, lower body weight, and improve insulin sensitivity in patients with type 2 diabetes, obesity, or both. Semaglutide is a GLP-1 receptor agonist that has been approved by the U.S. Food and Drug Administration and is currently marketed in various dosage strengths and forms as Ozempic®, Rybelsus®, and Wegovy®. More recently, research efforts have explored the potential co-activation of the glucose-dependent insulinotropic peptide (GIP) receptor as a means of enhancing the therapeutic benefits of GLP-1 receptor activation. Tirzepatide is a dual GLP-1/GIP receptor agonist that has been approved by the U.S. Food and Drug Administration and is currently marketed in various dosage strengths and forms as Mounjaro® and Zepbound®.
About Viking Therapeutics, Inc.
Viking Therapeutics is a clinical-stage biopharmaceutical company focused on the development of novel first-in-class or best-in-class therapies for the treatment of metabolic and endocrine disorders, with three compounds currently in clinical trials. Viking's research and development activities leverage its expertise in metabolism to develop innovative therapeutics designed to improve patients' lives. The company's clinical programs include VK2809, a novel, orally available, small molecule selective thyroid hormone receptor beta agonist for the treatment of lipid and metabolic disorders, which is currently being evaluated in a Phase 2b study for the treatment of biopsy-confirmed non-alcoholic steatohepatitis (NASH) and fibrosis. In a Phase 2a trial for the treatment of non-alcoholic fatty liver disease (NAFLD) and elevated LDL-C, patients who received VK2809 demonstrated statistically significant reductions in LDL-C and liver fat content compared with patients who received placebo. The company is also developing VK2735, a novel dual agonist of the glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors for the potential treatment of various metabolic disorders. Data from a Phase 1 and a Phase 2 trial evaluating VK2735 (dosed subcutaneously) for obesity demonstrated an encouraging safety and tolerability profile as well as positive signs of clinical benefit. The company is also evaluating an oral formulation of VK2735 in a Phase 1 trial. In the rare disease space, the company is developing VK0214, a novel, orally available, small molecule selective thyroid hormone receptor beta agonist for the potential treatment of X-linked adrenoleukodystrophy (X-ALD). VK0214 is currently being evaluated in a Phase 1b clinical trial in patients with the adrenomyeloneuropathy (AMN) form of X-ALD. The company holds exclusive worldwide rights to a portfolio of five therapeutic programs, including VK2809 and VK0214, which are based on small molecules licensed from Ligand Pharmaceuticals Incorporated.
For more information about Viking Therapeutics, please visit www.vikingtherapeutics.com.
SOURCE Viking Therapeutics, Inc.
Viking Therapeutics gains on early data for oral weight loss therapy
Mar. 26, 2024 7:37 AM ET
Viking Therapeutics, Inc. (VKTX) StockAMGN, PFE, NVO, LLY, AZN, ALT, VTVT, RYTM, TERN, VTYX, BHVN, GPCR
By: Dulan Lokuwithana, SA News Editor23 Comments
Shares of Viking Therapeutics (NASDAQ:VKTX) gained ~15% premarket Tuesday after the company said its oral once-daily obesity therapy VK2735 caused up to ~5% of weight loss with a favorable safety profile in a Phase 1 trial.
Based on data from its multiple ascending dose (MAD) clinical trial, Viking (VKTX) noted that VK2735, a dual GLP-1 and GIP agonist, led to dose-dependent reductions in body weight.
While VK2735 recipients showed up to a 5.3% decline in mean body weight from the baseline, their mean body weight reduction compared to those on placebo reached up to 3.3%.
https://seekingalpha.com/news/4083623-viking-therapeutics-stock-gains-data-weight-loss-drug
OPSYNVI® (macitentan and tadalafil)
VK2735, a dual GLP-1 and GIP agonist
OPSYNVI® (macitentan and tadalafil)
U.S. FDA Approves OPSYNVI® (macitentan and tadalafil) as the First and Only Once-Daily Single-Tablet Combination Therapy for Patients with Pulmonary Arterial Hypertension (PAH)
OPSYNVI® combines two proven treatments with established efficacy and safety profiles into one tablet to be taken once daily, offering an option that helps to support the implementation of clinical guideline recommendations for early use of combination therapy.1
The comprehensive PAH portfolio at Johnson & Johnson now includes treatments that address all three foundational and guideline-recommended pathways for this rare, progressive disease.2
Approval is based on the results from the pivotal Phase 3 A DUE study, which met its co-primary endpoints, demonstrating significant pulmonary hemodynamic improvement.1
MARCH 22, 2024Share
RARITAN, NJ, March 22, 2024 – Johnson & Johnson today announced that the U.S. Food and Drug Administration (FDA) has approved OPSYNVI® – a single-tablet combination of macitentan, an endothelin receptor antagonist (ERA), and tadalafil, a phosphodiesterase 5 (PDE5) inhibitor – for the chronic treatment of adults with pulmonary arterial hypertension (PAH, World Health Organization [WHO] Group I) and WHO functional class (FC) II-III.1 OPSYNVI® may be used in patients with PAH who are treatment-naïve or who are already on an ERA, PDE5 inhibitor or both. OPSYNVI® may be used in patients who are currently treated concomitantly with stable doses of macitentan 10 mg and tadalafil 40 mg (20 mg x 2) as separate tablets.1
PAH is a rare, progressive and life-threatening blood vessel disorder characterized by the constriction of small pulmonary arteries and elevated blood pressure in the pulmonary circulation that eventually leads to right heart failure.2 An estimated 500 to 1,000 new cases of PAH are diagnosed each year in the U.S., classifying the disease as a rare condition.3
The 2022 European Society of Cardiology (ESC) / European Respiratory Society (ERS) clinical guidelines recommend initial combination therapy of an ERA and a PDE5 inhibitor for patients with idiopathic PAH, heritable drug-associated PAH, or PAH-associated with connective tissue disease without cardiopulmonary comorbidities at low or intermediate risk.2
“Clinical guidelines recommend treating patients with initial and sequential dual-combination therapy, regardless of risk at initial diagnosis and follow-up. Historically, this required patients to take multiple pills because no single-tablet combination therapy targeting two or more pathways was available,” said Kelly Chin, M.D., Professor of Internal Medicine and Director of the Pulmonary Hypertension Program at UT Southwestern Medical Center, and an investigator in the A DUE study.* “As administration of macitentan and tadalafil together are commonly prescribed for initial therapy for PAH, the introduction of a single tablet combining both is promising for clinicians treating patients as it may help bridge the gap between clinical guidelines and everyday clinical practice, while offering a patient-friendly approach to support initial combination therapy and rapid escalation for the appropriate patients.”
The FDA’s approval of OPSYNVI® is based on the results from the pivotal Phase 3 A DUE study, in which OPSYNVI® demonstrated greater reduction in Pulmonary Vascular Resistance (PVR) after 16 weeks versus tadalafil or macitentan monotherapy. OPSYNVI® has a Boxed Warning due to the risk of embryo-fetal toxicity and requires female patients to enroll in the Macitentan-Containing Products Risk Evaluation and Mitigation Strategy (REMS) program.1
With the approval, Johnson & Johnson now offers a PAH portfolio addressing all three foundational and guideline-recommended pathways – nitric oxide, endothelin, and prostacyclin.
“People with PAH often live with the burden of taking many pills each day, which can pose challenges,” said James F. List, M.D., Ph.D., Global Therapeutic Area Head, whose team oversees a portfolio of programs including Pulmonary Hypertension at Johnson & Johnson. “We’re thrilled to bring this single tablet combination therapy to patients, as it has the potential to optimize disease management and fulfill a significant unmet need in supporting recently updated treatment guidelines that call for initial or early combination treatment.”
About OPSYNVI®1
OPSYNVI® is a combination of macitentan, an endothelin receptor antagonist (ERA), and tadalafil, a phosphodiesterase 5 (PDE5) inhibitor indicated for the chronic treatment of pulmonary arterial hypertension (PAH, WHO Group I) in adult patients of WHO functional class (FC) II-III.
Individually, macitentan reduces the risk of clinical worsening events and hospitalization, and tadalafil improves exercise ability.
About the A DUE Study1,4
The A DUE study was a double-blind, randomized, active-controlled, multi-center, adaptive, parallel-group study designed to compare the efficacy and safety of OPSYNVI® to macitentan and tadalafil monotherapies in adult patients with PAH (WHO FC II or III). The three-arm trial enrolled patients from across 76 sites in 16 countries/territories worldwide who were treatment-naïve or on a stable dose of an endothelin receptor antagonist (ERA), or a phosphodiesterase 5 (PDE5) inhibitor, for at least three months. The primary endpoint was change from baseline in PVR at the end of double-blind treatment at 16 weeks and was considered met if macitentan and tadalafil fixed-dose combination (FDC) treatment was superior to both monotherapies. Following the treatment period, patients transitioned to the open-label treatment period for 24 months.
INDICATION
OPSYNVI® is the combination of macitentan and tadalafil indicated for the chronic treatment of adults with pulmonary arterial hypertension (PAH, WHO Group I and WHO Functional Class [FC] II-III).
Individually, macitentan reduces the risk of clinical worsening events and hospitalization, and tadalafil improves exercise ability.
Please read Important Safety Information and full Prescribing Information, including Boxed WARNING, for OPSYNVI®.
About Johnson & Johnson
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at https://www.jnj.com/ or at www.janssen.com/johnson-johnson-innovative-medicine. Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC and Actelion Pharmaceuticals US, Inc., are both Johnson & Johnson companies.
*Dr. Chin was compensated for her participation on the steering committee for the A DUE study.
J&J wins FDA nod for blood vessel disorder therapy, Opsynvi
Mar. 23, 2024 8:44 AM ET
By: Dulan Lokuwithana, SA News Editor
The U.S. Food and Drug Administration (FDA) has granted Johnson & Johnson (NYSE:JNJ) approval for its oral therapy combination, Opsynvi, as a treatment for adults with pulmonary arterial hypertension (PAH), a fatal blood vessel disorder.
Accordingly, Opsynvi, a single tablet comprising the endothelin receptor antagonist macitentan and the phosphodiesterase 5 (PDE5) inhibitor tadalafil, will be indicated in the U.S. for adults with certain types of PAH as a first-line or late-line option.
The FDA approval is based on the company’s Phase 3 A DUE study, in which Opsynvi outperformed tadalafil or macitentan monotherapy over 16 weeks in addressing pulmonary vascular resistance.
VX-407
VK2735, a dual GLP-1 and GIP agonist
OPSYNVI® (macitentan and tadalafil)
Mar 21, 2024
Vertex Announces FDA Clearance of Investigational New Drug Application for VX-407 for the Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD)
– ADPKD is the most common inherited kidney disease, with no treatments currently available that address the underlying cause of disease –
– Vertex to initiate a Phase 1 clinical trial in healthy volunteers this month –
– ADPKD is Vertex’s 10th disease area in the clinic, further expanding the company’s pipeline of potentially transformative medicines for serious diseases –
BOSTON--(BUSINESS WIRE)--Mar. 21, 2024-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug Application (IND) for VX-407, an investigational first-in-class small molecule corrector that targets the underlying cause of autosomal dominant polycystic kidney disease (ADPKD) in patients with a subset of PKD1 genetic variants. ADPKD is the most common inherited kidney disease, with an estimated 250,000 people in the U.S. and Europe living with ADPKD; however, there are no treatments currently available that address the underlying causal biology of the disease.
ADPKD is a life-shortening genetic kidney disease characterized by the growth of numerous kidney-enlarging cysts that impair kidney function and can ultimately lead to kidney failure, requiring dialysis or kidney transplantation, and premature death.
The majority of ADPKD cases are caused by variants in the PKD1 gene, which encodes the polycystin 1 (PC1) protein. These inherited variants lead to a loss of PC1 function that results in cyst growth. VX-407 is a first-in-class small molecule corrector that is designed to target the underlying cause of ADPKD in a subset of patients with PKD1 variants, estimated at ~25,000 (or ~10%) of the overall ~250,000 ADPKD patient population, by restoring function to the variant PC1 protein. Vertex plans to initiate a Phase 1 clinical trial of VX-407 in healthy volunteers this month.
“The advancement of VX-407, a first-in-class molecule for the treatment of ADPKD, into the clinic represents another important opportunity to transform the treatment of a serious disease,” said Carmen Bozic, M.D., Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex. “Just as our approach in cystic fibrosis allowed us to reach more patients over time, our goal here is to serially innovate to reach the 250,000 people suffering from ADPKD.”
About Autosomal Dominant Polycystic Kidney Disease (ADPKD)
ADPKD is the most common inherited kidney disease and one of the most common severe Mendelian genetic diseases, affecting approximately 250,000 diagnosed people in the U.S. and Europe. As an autosomal dominant disease, one affected parent can pass on the disease to their children.
In most cases, ADPKD is caused by variants in the PKD1 and PKD2 genes, which express proteins known as polycystins. The majority of ADPKD patients (~80%) have a variant in the PKD1 gene, resulting in a loss of function of polycystin 1 (PC1). This leads to the proliferation of kidney epithelial cells, increased fluid secretion and the formation and expansion of numerous fluid-filled cysts. The progressive cyst formation causes an increase in kidney size and decline in kidney function. Around half of patients with ADPKD experience kidney failure by the age of 60. Kidney cysts can also lead to severe abdominal pain, cyst infection, blood in the urine and kidney stones, all of which significantly impair quality of life.
About VX-407
VX-407 is a first-in-class small molecule corrector that is designed to treat ADPKD in patients with a subset of PKD1 variants, estimated at ~25,000 (or ~10%) of the overall ~250,000 ADPKD patient population, by correcting defective PC1 folding to restore function. In doing so, the aim is to stop growth of kidney cysts and reduce kidney volume, thereby preventing progression to kidney failure.
About Vertex
Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has approved medicines that treat the underlying causes of multiple chronic, life-shortening genetic diseases — cystic fibrosis, sickle cell disease and transfusion-dependent beta thalassemia — and continues to advance clinical and research programs in these diseases. Vertex also has a robust clinical pipeline of investigational therapies across a range of modalities in other serious diseases where it has deep insight into causal human biology, including acute and neuropathic pain, APOL1-mediated kidney disease, autosomal dominant polycystic kidney disease, type 1 diabetes, myotonic dystrophy type 1 and alpha-1 antitrypsin deficiency.
Vertex was founded in 1989 and has its global headquarters in Boston, with international headquarters in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia, Latin America and the Middle East. Vertex is consistently recognized as one of the industry's top places to work, including 14 consecutive years on Science magazine's Top Employers list and one of Fortune’s 100 Best Companies to Work For. For company updates and to learn more about Vertex's history of innovation, visit www.vrtx.com or follow us on LinkedIn, Facebook, Instagram, YouTube and Twitter/X.
View source version on businesswire.com: https://www.businesswire.com/news/home/20240321788878/en/
Source: Vertex Pharmaceuticals Incorporated
Vertex expands kidney disease research as FDA clears clinical trial
Mar. 21, 2024 8:28 AM ET
Vertex Pharmaceuticals Incorporated (VRTX) Stock
By: Dulan Lokuwithana, SA News Editor
Vertex Pharmaceuticals (NASDAQ:VRTX) said Thursday the U.S. Food and Drug Administration (FDA) greenlighted a clinical trial for its kidney disease candidate VX-407, further expanding its R&D work related to renal diseases.
Its investigational new drug (IND) application is related to investigations into the potential of VX-407 in autosomal dominant polycystic kidney disease (ADPKD), a hereditary form of kidney disease that can require dialysis and transplantation and can ultimately lead to death.
https://seekingalpha.com/news/4082015-vertex-pharma-stock-gains-fda-clears-trial
Awiqli® (once-weekly basal insulin icodec)
Awiqli® (once-weekly basal insulin icodec)
Awiqli® (once-weekly basal insulin icodec)
11:55 21 March 2024
Awiqli® (once-weekly basal insulin icodec) recommended for approval for the treatment of diabetes by the European regulatory authorities
Bagsværd, Denmark, 21 March 2024 – Novo Nordisk today announced that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion, recommending marketing authorisation for Awiqli® (the brand name for once-weekly basal insulin icodec) for treatment of diabetes in adults.
The positive CHMP opinion is based on results from the ONWARDS phase 3a clinical trial programme. Once-weekly basal insulin icodec achieved superior blood sugar reduction1 (measured by a change in HbA1c) and superior Time in Range2 (time spent within recommended blood sugar range), compared with daily basal insulin in people with type 2 diabetes. In people with type 2 diabetes who have not previously been treated with insulin, overall observed rates of clinically significant or severe hypoglycaemia3 were below one event per patient-year of exposure with both once-weekly basal insulin icodec and comparators. In people with type 1 diabetes, once-weekly basal insulin icodec demonstrated non-inferiority in reducing HbA1c with a statistically significant higher estimated rate of severe or clinically significant hypoglycaemia compared with insulin degludec4. Across the programme, once-weekly basal insulin icodec appeared to have a safe and well-tolerated profile.
“We believe that by reducing the number of basal insulin injections from seven to one per week, Awiqli® has the potential to have a significant impact and improve treatment for people living with diabetes,” said Martin Holst Lange, executive vice president for Development at Novo Nordisk. “We are committed to driving innovation in diabetes treatment, and Awiqli® has the potential to become the insulin of choice for people with type 2 diabetes initiating insulin treatment.”
Novo Nordisk expects to receive final marketing authorisation from the European Commission within approximately two months.
About Awiqli® (once-weekly basal insulin icodec) and the ONWARDS programme
Awiqli® is a once-weekly basal insulin analogue designed to cover the basal insulin requirements for a full week with a single subcutaneous injection.
The ONWARDS clinical development programme comprised six phase 3a global clinical trials, which investigated the efficacy and safety of once-weekly basal insulin icodec, involving more than 4,000 adults with type 1 or type 2 diabetes, including a trial with real-world elements.
Novo Nordisk is a leading global healthcare company, founded in 1923 and headquartered in Denmark. Our purpose is to drive change to defeat serious chronic diseases, built upon our heritage in diabetes. We do so by pioneering scientific breakthroughs, expanding access to our medicines, and working to prevent and ultimately cure disease. Novo Nordisk employs about 63,400 people in 80 countries and markets its products in around 170 countries. Novo Nordisk's B shares are listed on Nasdaq Copenhagen (Novo-B). Its ADRs are listed on the New York Stock Exchange (NVO). For more information, visit novonordisk.com, Facebook, Instagram, X, LinkedIn and YouTube.
Novo Nordisk's Awiqli gets positive recommendation from EU regulators
Mar. 21, 2024 2:30 PM ET
By: Val Brickates Kennedy, SA News Editor
Novo Nordisk (NVO) said its once-weekly basal insulin product Awiqli for the treatment of diabetes has been recommended for approval by an advisory panel of the European Medicines Agency.
The Danish drugmaker said it expects Awiqli to receive final marketing authorization by EU regulators within approximately two months.
https://www.novonordisk.com/science-and-technology/r-d-pipeline.html
Lonigutamab (anti-IGF-1R)
Awiqli® (once-weekly basal insulin icodec)
Awiqli® (once-weekly basal insulin icodec)
ACELYRIN, INC. Announces Positive Phase 1/2 Proof-Of-Concept Data For Lonigutamab, First Subcutaneous Anti-IGF-1R To Demonstrate Clinical Responses In Thyroid Eye Disease
March 20, 2024
Rapid improvements demonstrated for proptosis, clinical activity scores, and diplopia versus placebo with a favorable safety profile
Phase 2b/3 trial to be initiated in the second half of 2024
Conference call to review these data to be held at 8:30 a.m. ET today
LOS ANGELES, March 20, 2024 (GLOBE NEWSWIRE) -- ACELYRIN, INC. (Nasdaq: SLRN), a late-stage clinical biopharma company focused on accelerating the development and delivery of transformative medicines in immunology, today announced positive proof-of-concept data from an ongoing Phase 1/2 trial of lonigutamab in thyroid eye disease (TED). Lonigutamab is a subcutaneously (SC) delivered humanized IgG1 monoclonal antibody targeting the insulin-like growth factor-1 receptor (IGF-1R), a validated mechanism of action for the treatment for TED.
In the Phase 1/2 trial, lonigutamab demonstrated rapid improvements in proptosis and clinical activity score (CAS) at the first measurement – within three weeks after the first subcutaneous dose.
“These results are the first reported clinical data for the anti-IGF-1R mechanism delivered subcutaneously and demonstrating clinical benefit in thyroid eye disease patients. The data support our hypothesis that lonigutamab has the potential to optimize benefit-risk by enabling longer-term subcutaneous dosing to increase depth and durability of clinical response while attempting to limit safety liabilities by avoiding the high maximal concentrations resulting from IV administration, while maintaining optimal therapeutic levels,” said Shao-Lee Lin, MD, PhD, Founder and CEO of ACELYRIN. “Tackling thyroid eye disease has special meaning for our team, and we are thankful to the patients and investigators who have partnered with us. We are delighted to have achieved proof of concept for lonigutamab in TED and intend to advance clinical development with the potential to move patients toward resolution of their disease.”
Lonigutamab Phase 1/2 Study Results
This multi-center, dose-ranging Phase 1/2 clinical trial is evaluating the safety and efficacy of lonigutamab dosed in TED patients. Cohort 1 was placebo-controlled with six patients receiving lonigutamab and two receiving placebo. Cohort 2 is open label with data available from six patients at six weeks.
Overall, lonigutamab has been well-tolerated across our clinical experience to date. There have been no reports of hyperglycemia or hearing impairment and no serious adverse events.
“It is very encouraging to see the results of subcutaneous administration of an anti-IGF-1R therapy. The data shown suggest that there is a clinically meaningful response in patients as early as 3 weeks after a single subcutaneous dose of lonigutamab. In addition, it appears that the safety profile of medication through the subcutaneous route may be favorable when compared to standard of care,” said Shoaib Ugradar, MD, Department of Orbital and Oculoplastic Surgery, private practice, Beverly Hills, California. “It is important to note that this is preliminary data in a small group, however the positive results are highly promising. Given the growing body of evidence that suggests thyroid eye disease may have long-term sequelae, the convenience of a subcutaneous administered medication with a potentially favorable side effect profile becomes critical.”
A presentation of these data can be found on the “Events & Presentations” section of the ACELYRIN website via this link ACELYRIN.com. Further data from this ongoing trial will be presented at future scientific meetings.
Next Steps
With proof of concept achieved in Cohort 1, and Cohort 2 further validating these results, a Phase 2b/3 trial is planned to be initiated in the second half of 2024, designed to be the first of two registrational trials in TED.
Given the close proximity of the recent data announcements for izokibep and lonigutamab and today’s conference call, ACELYRIN will forego hosting a fiscal year 2023 earnings call. The company will instead announce its financial results in a press release and file the related 10-K report no later than April 1, 2024.
Conference Call Information
ACELYRIN will host a conference call and webcast today, March 20, 2024, at 8:30 a.m. ET to review these positive clinical data. A live webcast of the conference call can be accessed in the “Events & Presentations” section of ACELYRIN’s website at ACELYRIN.com. A recording of the webcast will be available approximately two hours after the event, and will be archived on the Company’s website for approximately 30 days.
About the Phase 1/2 Trial
The Phase 1/2 clinical trial (NCT05683496) is a multi-center trial evaluating the safety and efficacy of lonigutamab dosed subcutaneously in three cohorts of patients with active thyroid eye disease (TED). Cohort 1 is placebo-controlled testing lonigutamab 40mg every three weeks (Q3W) through six weeks, cohort 2 is open label testing a 50mg loading dose followed by 25mg every week (QW), and cohort 3 is testing every four weeks (Q4W) dosing.
For more information about the Phase 1/2 trial, please visit www.clinicaltrials.gov.
About Thyroid Eye Disease
Thyroid Eye Disease (TED) is a vision-threatening autoimmune disease in which there is both inflammation and expansion of the tissues behind the eye, resulting in eye bulging, known as proptosis, and the subsequent inability to close the eyelids. Double vision, or diplopia, can occur, as well as the potential for compression of the retinal nerve, which can lead to blindness. Thus, TED is a progressive, chronic inflammatory disease where longer-term treatment has the potential to improve depth and durability of response. More than 100,000 people in the United States are estimated to suffer from TED.
About Lonigutamab (anti-IGF-1R)
Lonigutamab is a humanized IgG1 monoclonal antibody targeting the IGF-1 receptor and is delivered subcutaneously. Relative to standard of care, lonigutamab binds to a distinct epitope, which results in internalization of the receptor within minutes, and in preclinical binding and functional laboratory assays, it has been shown to be 75-fold more potent. The characteristics of lonigutamab that enable subcutaneous delivery also enable the potential for longer-term dosing, which we believe can improve depth and durability of clinical response. Based on our preclinical and pharmacodynamic data from our completed single ascending dose study with lonigutamab, we can optimize the therapeutic window utilizing the SC route of administration. The characteristics of lonigutamab also allow the potential to minimize exposures relative to IV therapy. IGF-1 is neuroprotective to cochlear cells of the inner ear and serves to repair damage that can occur over time. We hypothesize that high concentrations of anti-IGF-1R due to Cmax from IV administration can penetrate the blood-labyrinth barrier and interfere with this normal function. Lonigutamab originated from Pierre Fabre Laboratories, a French pharmaceutical group.
About ACELYRIN, INC.
ACELYRIN, INC. (Nasdaq: SLRN) is a Los Angeles area-based late-stage clinical biopharma company – with additional operations in the San Francisco Bay area – focused on providing patients life-changing new treatment options by identifying, acquiring, and accelerating the development and commercialization of transformative medicines. ACELYRIN has two programs in late-stage clinical development. Izokibep is a next generation inhibitor of IL-17A in Phase 3 development for the treatment of psoriatic arthritis, hidradenitis suppurativa and uveitis. Lonigutamab is a subcutaneously delivered monoclonal antibody targeting IGF-1R being investigated for the treatment of TED.
For more information about ACELYRIN, visit us at www.acelyrin.com or follow us on LinkedIn and X.
Acelyrin gains after positive phase 1/2 data for thyroid eye disease drug
Mar. 20, 2024 10:09 AM ET
By: Arundhati Sarkar, SA News Editor1 Comment
- Acelyrin (NASDAQ:SLRN) shares rose +2.89% to $8.19 on Wednesday, after announcing positive early-stage study data from an ongoing trial of its drug lonigutamab, in treating thyroid eye disease.
- Lonigutamab is a subcutaneously delivered humanized IgG1 monoclonal antibody targeting the insulin-like growth factor-1 receptor (IGF-1R), a validated mechanism of action for the treatment for TED.
- https://seekingalpha.com/news/4081595-acelyrin-gains-after-positive-phase-12-data-for-thyroid-eye-disease-drug
- Acelyrin, Inc. (SLRN) Stock
- https://www.acelyrin.com/
- https://www.acelyrin.com/lonigutamab
TRYVIO (aprocitentan)
Awiqli® (once-weekly basal insulin icodec)
Fibroblast-based Diabetes Treatment
US FDA approves Idorsia’s once-daily TRYVIO (aprocitentan) – the first and only endothelin receptor antagonist for the treatment of high blood pressure not adequately controlled in combination with other antihypertensives
Ad hoc announcement pursuant to Art. 53 LR
- TRYVIO™ (aprocitentan) is indicated for the treatment of hypertension in combination with other antihypertensive drugs, to lower blood pressure in adult patients who are not adequately controlled on other drugs.
- TRYVIO is the first oral anti-hypertensive therapy which works via a new therapeutic pathway to be approved in almost 40 years.
- Idorsia plans to make TRYVIO available to the millions of patients in the US who are not controlled on other drugs in the second half of 2024.
- Idorsia to host an investor webcast to discuss the approval today, March 20, at 15:00hrs CET.
Allschwil, Switzerland – March 20, 2024
Idorsia Ltd (SIX: IDIA) announced today that the US Food and Drug Administration (FDA) has approved TRYVIO™ (aprocitentan) for the treatment of hypertension in combination with other antihypertensive drugs, to lower blood pressure in adult patients who are not adequately controlled on other drugs.1 Lowering blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions.1 The recommended dosage of TRYVIO is 12.5 mg orally once daily, with or without food.1
Jean-Paul Clozel, MD and Chief Executive Officer of Idorsia commented:
“Today, there are millions of Americans whose blood pressure is not well-controlled despite existing therapies. This is a major public health issue leading to a high incidence of cardio- and cerebrovascular events. In order to help address this issue, Idorsia developed aprocitentan, an endothelin receptor antagonist suited to the treatment of these patients. Idorsia conducted an ambitious clinical program in patients remaining hypertensive despite a minimum of three drugs at their optimal dose and sometimes up to four, five, or even six antihypertensives. I’m very proud of the Idorsia team and very happy that physicians will have a new treatment option to treat patients whose blood pressure is not controlled.”
TRYVIO (aprocitentan) is an endothelin receptor antagonist that inhibits the binding of endothelin (ET)-1 to ETA and ETB receptors.1,2 The effects of ET-1 bear many similarities with the pathophysiology of hypertension,3 and ET-1 is a major driver of aldosterone production.4 Until the approval of TRYVIO, no systemic antihypertensive medications targeted the ET pathway,5 as approved antihypertensive therapies focus on the regulation of salt and water (diuretics), antagonism of the renin–angiotensin–aldosterone (RAAS) system, reduction of influx of extracellular calcium into the cell (calcium channel blockers), sympatholytic activity (beta blockers, central alpha-agonist agents), or non-selective vasodilatory effects.6,7
TRYVIO was evaluated as a monotherapy in a Phase 2 study in patients with hypertension,8 and as an add-on therapy in a Phase 3 study called PRECISION in patients with confirmed resistant hypertension.9 In PRECISION, aprocitentan was well tolerated and superior to placebo in lowering blood pressure at week 4, with a sustained effect at week 40.10
Martine Clozel, MD and Chief Scientific Officer of Idorsia, commented:
“Early on, we realized that endothelin was involved in patients with hypertension, especially in those remaining uncontrolled despite other anti-hypertensive drugs. Since the endothelin pathway was not yet tackled in these patients, we selected aprocitentan, an endothelin receptor antagonist with the ideal properties for use in this condition. We were delighted when we saw the safety and efficacy data with TRYVIO, even on top of multiple antihypertensives, in patients whose hypertension is not adequately controlled. The recognition of its potential with today’s FDA approval is great news for prescribers and patients.”
Michael A. Weber, MD, Professor of Medicine, Division of Cardiovascular Medicine State University of New York, and an investigator in the PRECISION study commented:
“Today, we are not able to reduce blood pressure below recommended levels in at least 10% of the hypertensive patients we treat. As well, it is often patients at high risk of adverse cardiovascular outcomes and typically with comorbidities who pose this challenge. We have had to wait for over 30 years to see the approval of an oral anti-hypertensive agent that works on a new therapeutic pathway, so TRYVIO provides transformational progress in the field of systemic hypertension. It is taken as a single daily oral dose that works in combination with whatever other drugs are being prescribed and without drug-drug interactions in patients with the burden of uncontrolled hypertension. TRYVIO is easy for physicians to prescribe and easy for patients to use.”
Phase 3 clinical study1,9,10
The efficacy of TRYVIO (aprocitentan) was evaluated in a multipart, Phase 3 multicenter study (PRECISION, NCT03541174) in adults with systolic blood pressure (SBP) ≥140 mmHg who were prescribed at least three antihypertensive medications. The trial included a placebo run-in period, which was followed by three parts as described below. Prior to the placebo run-in period, all patients were switched to standard background antihypertensive therapy consisting of an angiotensin receptor blocker, a calcium channel blocker, and a diuretic, which was continued throughout the study. Patients with concomitant use of beta-blockers continued this treatment throughout the study.
Following the 4-week placebo run-in period, 730 patients were randomized equally to aprocitentan at either 12.5 mg, 25 mg, or placebo once daily during the initial 4-week double-blind (DB) treatment period (part 1). At the end of 4 weeks, all patients entered the single-blind treatment period (part 2) where they received 25 mg aprocitentan once daily for 32 weeks. At the end of the 32 weeks, patients were re-randomized to receive either 25 mg aprocitentan or placebo, once daily, during a 12-week DB-withdrawal period (part 3).
The primary efficacy endpoint was the change in sitting SBP (SiSBP) from baseline to Week 4 during part 1, measured at trough by unattended automated office blood pressure (uAOBP).
The key secondary endpoint was the change in SiSBP measured at trough by uAOBP from Week 36 (i.e., prior to randomized withdrawal to 25 mg aprocitentan or placebo in part 3) to Week 40.
Patients had a mean age of 62 years (range 24 to 84 years) and 60% were male. Patients were White (83%), African American (11%) or Asian (5%). Approximately 10% were Hispanic. The mean body mass index (BMI) was 34 kg/m2 (range 18 to 64 kg/m2). At baseline, 19% of patients had an eGFR 30–59 mL/min/1.73 m2 and 3% had an eGFR 15–29 mL/min/1.73 m2. At baseline, 24% of patients had a urine albumin-to-creatinine ratio (UACR) of 30–300 mg/g and 13% had a UACR >300 mg/g. Approximately 54% of patients had a medical history of diabetes mellitus, 31% ischemic heart disease, and 20% congestive heart failure. At baseline, 63% of patients reported taking four or more antihypertensive medications.
TRYVIO 12.5 mg was statistically superior to placebo in reducing SiSBP at Week 4 (part 1). The treatment effect was consistent for sitting diastolic BP (SiDBP).
The persistence of the BP-lowering effect of TRYVIO was demonstrated in part 3 of the trial, in which patients on aprocitentan were re-randomized to placebo or 25 mg aprocitentan following a period during which all patients were treated with 25 mg. In patients re-randomized to placebo, the mean SiSBP increased, whereas in patients re-randomized to 25 mg aprocitentan the mean effect on SiSBP was maintained and was statistically superior to placebo at Week 40. The treatment effect was consistent for SiDBP.
Most of the BP-lowering effect occurred within the first two weeks of treatment with TRYVIO. TRYVIO is not approved for use at a 25 mg dose. The efficacy for the 25 mg aprocitentan dose as measured in the primary end point of change in sitting SBP (SiSBP) from baseline to Week 4 in part 1, was similar to the 12.5 mg dose and thus aprocitentan 12.5 mg is the approved dose.
TRYVIO’s BP-lowering effect appeared consistent among subgroups defined by age, sex, race, BMI, baseline eGFR, baseline UACR, medical history of diabetes, and between BP measurement methodologies (uAOBP and ambulatory BP measurements).
The most frequently reported adverse reactions to TRYVIO during the 4-week double-blind placebo-controlled treatment period (part 1) of the PRECISION study were edema/fluid retention and anemia. During the initial 4-week double-blind placebo-controlled treatment period (part 1), 0.8% of patients experienced an adverse reaction of hypersensitivity (i.e., rash, erythema, allergic edema) on TRYVIO compared to no reports in patients treated with placebo. One patient experienced allergic dermatitis requiring hospitalization while receiving aprocitentan 25 mg. TRYVIO is contraindicated in patients who are hypersensitive to aprocitentan or any of its excipients. Use of TRYVIO is contraindicated in pregnancy.
Lowering BP reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes. There are no controlled trials demonstrating reduction of risk of these events with TRYVIO.
Alberto Gimona, MD and Head of Global Clinical Development of Idorsia, commented:
“When designing PRECISION, we did not shy away from including patients who are most at risk of the serious negative consequences of hypertension. In addition, while all patients needed to be on three antihypertensives to join the study, 63 percent of patients were on four or more anti-hypertensives. The study was therefore truly reflective of the real-world patient population whose blood pressure is not adequately controlled on other drugs. TRYVIO demonstrated a clear and consistent effect across all endpoints of blood pressure measurement and in key sub-populations. As a result, TRYVIO brings hope as a novel, effective and well-tolerated treatment option for patients with hypertension not adequately controlled.”
Tosh Butt, President and General Manager of Idorsia US commented:
“The approval of TRYVIO in the US marks another major milestone for Idorsia. With TRYVIO, we've got an innovative medicine with a unique mode of action in systemic hypertension. The team at Idorsia has a deep understanding and rich history in the field of endothelin receptor antagonism. We are eager to provide physicians and patients with a novel medicine working in a new pathway in uncontrolled hypertension that can provide additional blood pressure control. We recognize that the resources required to reach the entire prescribing community could be substantial, so we will carefully craft the TRYVIO launch strategy in the coming months, while preparing to make TRYVIO available during the second half of 2024.”
The team at Idorsia has been working on the research and development of endothelin receptor antagonists for more than 30 years, successfully bringing three other molecules from this class to patients in different indications. ET-1, via its receptors (ETA and ETB), mediates a variety of deleterious effects such as vasoconstriction, fibrosis, cell proliferation, and inflammation. In hypertension, ET-1 can cause endothelial dysfunction, vascular hypertrophy and remodeling, sympathetic activation, and increased aldosterone synthesis.1
Martine Clozel, MD and Chief Scientific Officer of Idorsia, concluded:
“After more than 30 years working in the field of endothelin science, our research has brought about changes in the treatment paradigm of several cardiovascular diseases. Now we are bringing significant medical progress for patients with systemic hypertension. I am convinced that with the data we have seen, the approval of TRYVIO heralds a new era of endothelin research beyond hypertension, where we intend to investigate the utility of aprocitentan for first-in-class applications in new indications.”
TRYVIO REMS
TRYVIO is available only through a restricted program under a REMS called the TRYVIO REMS because of the risk of embryo-fetal toxicity. Prescribers must be certified with the TRYVIO REMS by enrolling and completing training. Pharmacies that dispense TRYVIO must be certified with the TRYVIO REMS.
Important Safety Information
TRYVIO may cause serious side effects, including:
TRYVIO can cause major birth defects if used by pregnant patients and has a BOXED Warning for embryo-fetal toxicity.
- People who can become pregnant must not be pregnant when they start taking TRYVIO or become pregnant during treatment with TRYVIO or for 1 month after stopping treatment with TRYVIO.
- People who can become pregnant should have a negative pregnancy test before starting treatment with TRYVIO, each month during treatment with TRYVIO, and 1 month after stopping TRYVIO.
- People who can become pregnant should use acceptable birth control before starting treatment with TRYVIO, during treatment with TRYVIO, and for 1 month after stopping TRYVIO because the medicine may still be in your body.
People can only receive TRYVIO through a restricted program called the TRYVIO REMS. If you are a person who can become pregnant, your healthcare provider will talk to you about pregnancy testing recommendations and the need to use acceptable birth control, the benefits and risks of TRYVIO, and the need to report suspected pregnancy right away to your healthcare provider.
What is TRYVIO?
TRYVIO is a prescription medicine used to treat high blood pressure (hypertension) in adults who are taking other high blood pressure medicines and whose blood pressure is not well controlled.
Do not take TRYVIO if you are
- pregnant or currently trying to become pregnant.
- allergic to aprocitentan or any of the ingredients in TRYVIO.
About Idorsia US
Idorsia US, an affiliate of Idorsia, is reaching out for more – we have more ideas, we see more opportunities, and we want to help more patients. To achieve this, we will help develop Idorsia into a leading biopharmaceutical company, with a strong scientific core. With commercial operations based outside of Philadelphia, PA, one of densest communities of life sciences talent in the world, we are helping to realize the company’s ambition of bringing innovative medicines from bench to bedside. Our goal is to build a commercial footprint that will deliver Idorsia’s deep pipeline of products from its R&D engine to the US market – with the potential to change the lives of many patients.
About Idorsia
Idorsia Ltd is reaching out for more – We have more ideas, we see more opportunities and we want to help more patients. In order to achieve this, we will develop Idorsia into a leading biopharmaceutical company, with a strong scientific core.
Headquartered near Basel, Switzerland – a European biotech-hub – Idorsia is specialized in the discovery, development and commercialization of small molecules to transform the horizon of therapeutic options. Idorsia has a 20-year heritage of drug discovery, a broad portfolio of innovative drugs in the pipeline, an experienced team of professionals covering all disciplines from bench to bedside, and commercial operations in Europe and North America – the ideal constellation for bringing innovative medicines to patients.
Idorsia was listed on the SIX Swiss Exchange (ticker symbol: IDIA) in June 2017 and has over 800 highly qualified specialists dedicated to realizing our ambitious targets.
Attachment
Idorsia gets FDA approval for hypertension drug Tryvio
Mar. 20, 2024 4:07 PM ET
By: Val Brickates Kennedy, SA News Editor
Idorsia (OTC:IDRSF) has received FDA approval for its drug Tryvio to treat hypertension in patients who have not adequately responded to other high blood pressure medications.
The Swiss company said its plans to make Tryvio, also known as aprocitentan, available in the US in the second half of the year.
https://seekingalpha.com/news/4081772-idorsia-gets-fda-approval-for-hypertension-drug-tryvio
Fibroblast-based Diabetes Treatment
Fibroblast-based Diabetes Treatment
Fibroblast-based Diabetes Treatment
FibroBiologics Announces Preliminary Proof of Concept for Fibroblast-based Diabetes Treatment
March 19, 2024 9:31am EDT
HOUSTON, March 19, 2024 /PRNewswire/ -- FibroBiologics, Inc., (Nasdaq: FBLG) ("FibroBiologics"), a clinical-stage biotechnology company with 150+ patents issued and pending with a focus on the development of therapeutics and potential cures for chronic diseases using fibroblasts and fibroblast-derived materials, announced the progress of a clinical program under development using a fibroblast-based pancreatic beta cell spheroid that secretes insulin in vitro upon glucose stimulation. The development and reproducibility of this work demonstrates that an organoid composed of fibroblasts, beta cells and other components can successfully and durably secrete insulin.
"This early proof of concept is encouraging and may lead to a new and durable potential allogeneic treatment option for people with insulin-dependent diabetes," said Hamid Khoja, Ph.D., Chief Scientific Officer. "We look forward to confirming these early results and in vivo utility. We will then determine whether to designate the program as an early phase pre-clinical project for developing a minimally invasive therapeutic for type 1 diabetes."
About Diabetes
Diabetes mellitus is a chronic heterogeneous metabolic disease characterized by elevated blood glucose levels due to abnormalities in either insulin production or insulin action that impacts more than 37 million people in the United States and over 500 million people worldwide. Type 1 diabetes, an autoimmune disorder in which the immune system destroys the pancreatic beta cells that produce insulin, accounts for 10% of diabetes cases worldwide, and type 2 diabetes, in which the body does not respond to insulin, accounts for the remaining 90% of diabetes cases. With such a high and growing prevalence of the disease, over 200 million individuals are dependent on consistent and often daily insulin therapy for their health. To date, durable, long-term, and economical treatment options are not available.
About FibroBiologics
Based in Houston, FibroBiologics is a cell therapy and regenerative medicine company developing a pipeline of treatments and seeking potential cures for chronic diseases using fibroblast cells and fibroblast-derived materials. FibroBiologics holds 150+ US and internationally issued patents/patents pending across various clinical pathways, including disc degeneration, orthopedics, multiple sclerosis, wound healing, reversing organ involution, and cancer. FibroBiologics represents the next generation of medical advancement in cell therapy. For more information, visit www.FibroBiologics.com.
SOURCE FibroBiologics
Released March 19, 2024
FibroBiologics reports encouraging early data for diabetes cell therapy
Mar. 19, 2024 11:57 AM ET
FibroBiologics, Inc. (FBLG) Stock
By: Val Brickates Kennedy, SA News Editor
Shares of newly public FibroBiologics (NASDAQ:FBLG) rose 4% in morning trading Tuesday after the company reported encouraging results from an early proof-of-concept study for a potential cell therapy for diabetes.
FibroBiologics said the study demonstrated that “an organoid composed of fibroblasts, beta cells and other components can successfully and durably secrete insulin.”
FibroBiologics, Inc. (FBLG) Stock
TEVIMBRA® (tislelizumab-jsgr)
Fibroblast-based Diabetes Treatment
TEVIMBRA® (tislelizumab-jsgr)
BeiGene Receives FDA Approval for TEVIMBRA® for the Treatment of Advanced or Metastatic Esophageal Squamous Cell Carcinoma After Prior Chemotherapy
Mar 14, 2024 4:28 PM
Results from the global, Phase 3 RATIONALE 302 trial showed TEVIMBRA prolonged the survival of patients who received prior systemic treatment compared to chemotherapy
Approval represents the first indication in the U.S. for TEVIMBRA
BASEL, Switzerland & BEIJING & CAMBRIDGE, Mass.--(BUSINESS WIRE)-- BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global oncology company, today announced that the U.S. Food and Drug Administration (FDA) has approved TEVIMBRA® (tislelizumab-jsgr) as monotherapy for the treatment of adult patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) after prior systemic chemotherapy that did not include a PD-(L)1 inhibitor. TEVIMBRA will be available in the U.S. in the second half of 2024.
“Today’s FDA approval of TEVIMBRA for patients with ESCC who have previously received chemotherapy, along with its ongoing review of our BLA for first-line ESCC patients, represents a significant step in our commitment to bringing this therapy to more patients around the world,” said Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeiGene. “As BeiGene’s first drug candidate produced through our immuno-oncology program and second approved medicine in the U.S., TEVIMBRA is poised to be a critical pillar of our solid tumor development program, which spans more than 17 registration-enabling clinical trials in more than 30 countries across regions globally.”
The approval is based on the RATIONALE 302 trial, which met its primary endpoint in the intention-to-treat (ITT) population with a statistically significant and clinically meaningful survival benefit for TEVIMBRA compared with chemotherapy. In the ITT population, the median overall survival (OS) in the TEVIMBRA arm was 8.6 months (95% CI: 7.5, 10.4) compared to 6.3 months (95% CI: 5.3, 7.0) in the chemotherapy arm (p=0.0001; hazard ratio [HR]=0.70 [95% CI: 0.57, 0.85]). The safety profile of TEVIMBRA was favorable over chemotherapy.i The most common (≥20%) adverse reactions for TEVIMBRA, including laboratory abnormalities, were increased glucose, decreased hemoglobin, decreased lymphocytes, decreased sodium, decreased albumin, increased alkaline phosphatase, anemia, fatigue, increased AST, musculoskeletal pain, decreased weight, increased ALT and cough.i
“Patients diagnosed with advanced or metastasized ESCC, the most common histologic subtype of esophageal cancer, often progress following initial therapy and are in need of new options,” Syma Iqbal, M.D., Associate Professor of Clinical Medicine, Section Chief Gastrointestinal Oncology, Division of Medical Oncology and Cancer Physician in Chief, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California. “The RATIONALE 302 trial showed that patients with previously treated ESCC who received TEVIMBRA saw a clinically meaningful survival benefit, highlighting its potential as an important treatment option for these patients.”
Tislelizumab received approval by the European Commission for advanced or metastatic ESCC after prior chemotherapy in 2023 and a positive opinion by the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMA) in February 2024 as a treatment for non-small cell lung cancer across three indications.
The FDA is also reviewing Biologics License Applications (BLAs) for tislelizumab as a first-line treatment for patients with unresectable, recurrent, locally advanced, or metastatic ESCC and patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. The target action dates are July and December 2024, respectively.
BeiGene has launched more than 17 potentially registration-enabling trials with TEVIMBRA, of which 11 Phase 3 randomized trials and four Phase 2 trials have already had positive readouts. Through these trials, TEVIMBRA has demonstrated its potential to deliver clinically meaningful improvements in survival benefits and quality of life for hundreds of thousands of cancer patients across a range of tumor types – in many cases, regardless of PD-(L)1 status – both as monotherapy and in combination with other regimens. More than 900,000 patients have been prescribed TEVIMBRA globally to date.
About RATIONALE 302
RATIONALE 302 is a global, randomized, open-label, Phase 3 study (NCT03430843) designed to investigate the efficacy and safety of TEVIMBRA when compared with investigator’s choice of chemotherapy as a second-line treatment for patients with unresectable, locally advanced or metastatic ESCC. The study randomized 512 patients from 132 research sites in 11 countries in Europe, Asia and North America.
About ESCC
Globally, esophageal cancer (EC) is the sixth most common cause of cancer-related deaths, and ESCC is the most common histologic subtype, accounting for nearly 90% of ECs.ii An estimated 957,000 new EC cases are projected in 2040, an increase of nearly 60% from 2020, underscoring the need for additional effective treatments.ii EC is a rapidly fatal disease, and more than two-thirds of patients have advanced or metastatic disease at the time of diagnosis, with an expected five-year survival rate of less than 6% for those with distant metastases.iii
About TEVIMBRA® (tislelizumab-jsgr)
Tislelizumab is a uniquely designed humanized immunoglobulin G4 (IgG4) anti-programmed cell death protein 1 (PD-1) monoclonal antibody with high affinity and binding specificity against PD-1. It is designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages, helping to aid the body’s immune cells to detect and fight tumors.
U.S. Indication and Important Safety Information for TEVIMBRA (tislelizumab-jsgr)
INDICATION
TEVIMBRA (tislelizumab-jsgr), as a single agent, is indicated for the treatment of adult patients with unresectable or metastatic esophageal squamous cell carcinoma after prior systemic chemotherapy that did not include a PD-(L)1 inhibitor.
Please see full U.S. Prescribing Information including Medication Guide.
About BeiGene
BeiGene is a global oncology company that is discovering and developing innovative treatments that are more affordable and accessible to cancer patients worldwide. With a broad portfolio, we are expediting development of our diverse pipeline of novel therapeutics through our internal capabilities and collaborations. We are committed to radically improving access to medicines for far more patients who need them. Our growing global team of more than 10,000 colleagues spans five continents, with administrative offices in Basel, Beijing, and Cambridge, U.S. To learn more about BeiGene, please visit www.beigene.com and follow us on LinkedIn and X (formerly known as Twitter).
View source version on businesswire.com: https://www.businesswire.com/news/home/20240314638305/en/
Source: BeiGene, Ltd.
BeiGene gets FDA approval for esophageal cancer drug Tevimbra
Mar. 14, 2024 6:46 PM ET
By: Val Brickates Kennedy, SA News Editor1 Comment
BeiGene (NASDAQ:BGNE) has received FDA approval for its drug Tevimbra in the treatment of advanced or metastatic esophageal squamous cell carcinoma, or ESCC.
The drug, also known as tislelizumab-jsgr, was approved as a monotherapy for patients with unresectable or metastatic ESCC after prior systemic chemotherapy that didn’t include a PD-L1 inhibitor.
Imetelstat
Fibroblast-based Diabetes Treatment
TEVIMBRA® (tislelizumab-jsgr)
Geron Announces FDA Oncologic Drugs Advisory Committee Votes in Favor of the Clinical Benefit/Risk Profile of Imetelstat for the Treatment of Transfusion-Dependent Anemia in Patients with Lower-Risk MDS
March 14, 2024
- FDA Oncologic Drugs Advisory Committee voted 12 to 2 in favor of the clinical benefit/risk profile of imetelstat based on results from the IMerge Phase 3 clinical trial
- There are significant unmet needs across key TD LR-MDS patient populations, including difficult-to-treat subgroups that are underserved by currently available treatment options
- June 16, 2024 PDUFA target action date for imetelstat NDA for the treatment of TD anemia in adult patients with LR-MDS
FOSTER CITY, Calif.--(BUSINESS WIRE)-- Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company developing investigational first-in-class telomerase inhibitor, imetelstat, to treat hematologic malignancies, today announced that the U.S. Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) voted 12 to 2 in favor of the clinical benefit/risk profile of imetelstat for the treatment of transfusion-dependent (TD) anemia in adult patients with low-to-intermediate-1 risk myelodysplastic syndromes (LR-MDS) who have not responded to or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESAs).
“We are pleased with the Committee’s decision to recognize the positive clinical benefit/risk profile of imetelstat for the treatment of transfusion-dependent anemia in adult patients with lower-risk MDS. There are few treatment options and significant unmet medical need remains for these patients, particularly among those with difficult-to-treat subtypes of this blood cancer,” said Faye Feller, M.D., Geron’s Executive Vice President, Chief Medical Officer. “We believe that imetelstat has the potential to be an important new medicine for patients and look forward to continuing our collaboration with the FDA as they complete their review of our New Drug Application.”
The ODAC reviewed the results from the IMerge Phase 3 clinical trial. The primary endpoint of red blood cell transfusion independence (RBC-TI) for at least eight consecutive weeks was significantly higher with imetelstat vs. placebo (p<0.001), with median RBC-TI duration approaching one year for imetelstat ≥8-week RBC-TI responders. In addition, 28% of imetelstat-treated patients compared to 3% on placebo obtained a statistically significant improvement in the key secondary endpoint of at least 24-week RBC-TI. For those patients achieving ≥24-week RBC-TI, the median duration was 80 weeks. Clinically meaningful RBC-TI was achieved across key MDS subgroups irrespective of ring sideroblast (RS) status, baseline transfusion burden and International Prognostic Scoring (IPSS) risk category. Additionally, a sustained increase in mean hemoglobin levels in imetelstat-treated patients was observed over time compared to placebo patients. Consistent with prior imetelstat clinical experience, the most common Grade 3-4 adverse events were thrombocytopenia (62%) and neutropenia (68%) that were generally manageable and of short duration.
The FDA assigned a Prescription Drug User Fee Act (PDUFA) target action date of June 16, 2024 for Geron’s New Drug Application (NDA) for imetelstat for the treatment of TD anemia in adult patients with low- to intermediate-1 risk myelodysplastic syndromes, who have failed to respond, or have lost response to, or are ineligible for ESAs. The ODAC provides the FDA with independent opinions and recommendations from outside medical experts, patients and caregivers, though the recommendations are not binding. Geron plans to commercially launch imetelstat in the U.S. upon potential FDA approval.
About IMerge Phase 3
The Phase 3 portion of the IMerge Phase 2/3 trial is a double-blind, 2:1 randomized, placebo-controlled clinical trial to evaluate imetelstat in patients with IPSS Low or Intermediate-1 risk (lower-risk) transfusion-dependent MDS who were relapsed after, refractory to, or ineligible for, erythropoiesis stimulating agent (ESA) treatment, had not received prior treatment with either a hypomethylating agent or lenalidomide and were non-del(5q). To be eligible for IMerge Phase 3, patients were required to be transfusion-dependent, defined as requiring at least four units of packed red blood cells (RBCs), over an eight-week period during the 16 weeks prior to entry into the trial. The primary efficacy endpoint of IMerge Phase 3 is the rate of red blood cell transfusion independence (RBC-TI) lasting at least eight weeks, defined as the proportion of patients without any RBC transfusion for at least eight consecutive weeks since entry to the trial (8-week RBC-TI). Key secondary endpoints include the rate of RBC-TI lasting at least 24 weeks (24-week RBC-TI), the duration of RBC-TI and the rate of hematologic improvement erythroid (HI-E), which is defined under 2006 IWG criteria as a rise in hemoglobin of at least 1.5 g/dL above the pretreatment level for at least eight weeks or a reduction of at least four units of RBC transfusions over eight weeks compared with the prior RBC transfusion burden. A total of 178 patients were enrolled in IMerge Phase 3 across North America, Europe, the Middle East and Asia.
About Imetelstat
Imetelstat is a novel, first-in-class investigational telomerase inhibitor exclusively owned by Geron and being developed by Geron in hematologic malignancies. Data from non-clinical studies and clinical trials of imetelstat provide strong evidence that imetelstat targets telomerase to inhibit the uncontrolled proliferation of malignant stem and progenitor cells in myeloid hematologic malignancies, resulting in malignant cell apoptosis. Imetelstat has been granted Fast Track designation by the U.S. Food and Drug Administration for both the treatment of adult patients with transfusion-dependent anemia due to Low or Intermediate-1 risk MDS that is not associated with del(5q) who are refractory or resistant to an erythropoiesis stimulating agent, and for adult patients with Intermediate-2 or High-risk myelofibrosis (MF) whose disease has relapsed after or is refractory to Janus kinase (JAK) inhibitor treatment. Imetelstat is currently not approved by any regulatory authority.
About Geron
Geron is a late-stage clinical biopharmaceutical company pursuing therapies with the potential to extend and enrich the lives of patients living with hematologic malignancies. Our first-in-class investigational telomerase inhibitor, imetelstat, harnesses Nobel Prize-winning science in a treatment that may alter the underlying drivers of disease. The New Drug Application (NDA) for imetelstat for the treatment of transfusion-dependent anemia in patients with lower-risk myelodysplastic syndromes (TD LR-MDS) who have failed to respond or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESAs), based on the results from the Phase 3 IMerge clinical trial, is currently under review by the U.S. Food and Drug Administration (FDA) with a Prescription Drug User Fee Act (PDUFA) target action date of June 16, 2024. In addition, the European Medicines Agency (EMA) validated the Marketing Authorization Application (MAA) for the same proposed indication and is under review. Furthermore, Geron currently has an ongoing pivotal Phase 3 clinical trial evaluating imetelstat in relapsed/refractory myelofibrosis (R/R MF). To learn more, visit www.geron.com or follow us on LinkedIn.
Source: Geron Corporation
Geron wins FDA AdCom backing for blood cancer drug
Mar. 14, 2024 3:39 PM ET
Geron Corporation (GERN) Stock
By: Dulan Lokuwithana, SA News Editor50 Comments
A group of independent experts at the FDA voted in favor of Geron's (NASDAQ:GERN) marketing application for its blood cancer therapy imetelstat on Thursday, paving the way for the company to receive a potential U.S. regulatory nod for the drug this year.
The voting comes at a meeting of the FDA's cancer drug experts, who evaluated the telomerase inhibitor as a late-line option for transfusion-dependent anemia in patients with myelodysplastic syndromes (MDS).
On the question of whether the benefits of the drug outweighed its risks in the targeted population, the advisors voted 12 to 2 in favor of imetelstat.
Imetelstat, Geron's (GERN) lead asset, is currently under FDA review for lower-risk MDS, with a target action date of June 16.
https://seekingalpha.com/news/4079642-geron-wins-fda-adcom-backing-blood-cancer-drug
biotecHOPE™ 2024
Rezdiffra™ (resmetirom)
Rezdiffra™ (resmetirom)
Rezdiffra™ (resmetirom)
Madrigal Pharmaceuticals Announces FDA Approval of Rezdiffra™ (resmetirom) for the Treatment of Patients with Noncirrhotic Nonalcoholic Steatohepatitis (NASH) with Moderate to Advanced Liver Fibrosis
- Rezdiffra becomes the first and only medication approved by the FDA for the treatment of NASH (also known as “MASH”)
- Accelerated approval was based on Phase 3 data demonstrating that Rezdiffra improved liver fibrosis and resolved NASH in patients with noncirrhotic NASH with moderate to advanced liver fibrosis
- Rezdiffra prescribing information does not include a liver biopsy requirement for diagnosis
- Madrigal conference call scheduled for March 14, 2024, at 5:15 pm ET
CONSHOHOCKEN, Pa., March 14, 2024 (GLOBE NEWSWIRE) -- Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL), a biopharmaceutical company focused on delivering novel therapeutics for nonalcoholic steatohepatitis (NASH), today announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval for Rezdiffra (resmetirom) in conjunction with diet and exercise for the treatment of adults with noncirrhotic NASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis). Continued approval for this indication may be contingent upon verification and description of clinical benefit in ongoing confirmatory trials.
Bill Sibold, Chief Executive Officer of Madrigal, stated, “NASH with moderate to advanced liver fibrosis is a serious and progressive liver disease that, until now, has not had an FDA-approved therapy. The accelerated approval of Rezdiffra is a culmination of more than 15 years of research from our founder Dr. Becky Taub and a small R&D team that took on one of the biggest challenges in drug development. This is a historic moment for the NASH field and represents the best of what our industry is capable of. We’re excited to deliver Rezdiffra to patients in need.”
Becky Taub, M.D., the Founder, Chief Medical Officer and President of Research & Development of Madrigal, stated, “Madrigal would like to thank the many patients who made the accelerated approval of Rezdiffra possible by participating in our clinical studies. We believe Rezdiffra will change the treatment paradigm for NASH with moderate to advanced liver fibrosis, giving physicians a liver-directed therapy to help improve fibrosis and resolve NASH before their patients progress to cirrhosis.”
Wayne Eskridge, Co-Founder and Chief Executive Officer of the Fatty Liver Foundation, stated, “This is a day of celebration for patients with NASH who have been waiting many years for the first approved therapy. I believe this approval milestone will bring new energy and momentum to the NASH community, accelerating our efforts to improve disease education, build care pathways, and expand investment in NASH research.”
Rezdiffra is a once-daily, oral THR-β agonist designed to target key underlying causes of NASH. The accelerated approval of Rezdiffra was based on results from the Phase 3 MAESTRO-NASH trial, which was recently published in the New England Journal of Medicine. MAESTRO-NASH is an ongoing pivotal, multicenter, randomized, double-blind, placebo-controlled trial that enrolled 1,759 patients with biopsy-confirmed NASH. Following 52 weeks of treatment, both 100 mg and 80 mg doses of Rezdiffra demonstrated statistically significant improvement compared to placebo on two primary endpoints: NASH resolution (including a reduction in the nonalcoholic fatty liver disease [NAFLD] activity score by ≥2 points) with no worsening of fibrosis, and an improvement in fibrosis by at least one stage with no worsening of the NAFLD activity score. Fibrosis improvement and NASH resolution were consistent regardless of age, gender, type 2 diabetes status, or fibrosis stage.
The Rezdiffra prescribing information does not include a liver biopsy requirement for diagnosis. The recommended dosage of Rezdiffra is based on actual body weight. For patients weighing <100 kg (220 lbs.), the recommended dosage is 80 mg orally once daily. For patients weighing ≥100 kg (220 lbs.), the recommended dosage is 100 mg orally once daily.
Stephen Harrison, M.D., Chairman for both Pinnacle Clinical Research and Summit Clinical Research, San Antonio, Texas, Visiting Professor of Hepatology, Oxford University, and lead Principal Investigator of the MAESTRO studies, commented, “The approval of the first medication for NASH is a true game-changer for healthcare providers, the research community and, most importantly, patients living with this serious liver condition. Based on the robust efficacy and safety data generated in two large Phase 3 MAESTRO studies, I believe Rezdiffra will become the foundational therapy for patients with NASH with moderate to advanced liver fibrosis.”
Dr. Harrison continued, “Importantly, we continue to study Rezdiffra to determine if the positive results observed in the MAESTRO studies will lead to reduced risk of progression to cirrhosis, liver failure, need for liver transplant and premature mortality.”
MAESTRO-NASH remains ongoing as an outcomes study designed to generate confirmatory data that, if positive, will help verify clinical benefit and may support full approval. A second ongoing outcomes trial is evaluating progression to liver decompensation events in patients with well-compensated NASH cirrhosis treated with Rezdiffra versus placebo.
Rezdiffra should not be used in patients with decompensated cirrhosis. The most common adverse reactions reported in patients treated with Rezdiffra included diarrhea, nausea, pruritis, abdominal pain, vomiting, constipation, and dizziness. Diarrhea and nausea typically began early in treatment initiation and were mild to moderate in severity. A separate, noninvasive Phase 3 trial, MAESTRO-NAFLD-1, evaluated the safety and tolerability of Rezdiffra and contributed to the safety database supporting regulatory benefit-risk assessment.
Rezdiffra is expected to be available to patients in the U.S. in April and will be distributed through a limited specialty pharmacy network. Madrigal is committed to helping appropriate patients who may benefit from Rezdiffra access the medication through the Madrigal Patient Support program. This program is designed to help patients navigate insurance and affordability challenges and provide co-pay support for eligible patients. Madrigal has also established a patient assistance program (PAP) to help patients with no insurance access Rezdiffra.
Conference Call and Webcast
Madrigal will host a conference call and webcast today at 5:15 PM ET to discuss the accelerated approval of Rezdiffra. To access the webcast of the call with slides please visit the Investors section of Madrigal’s website or click here. An archived webcast will be available on the Madrigal website after the event.
Phase 3 MAESTRO-NASH Trial Results
MAESTRO-NASH is an ongoing Phase 3 trial that enrolled 1759 patients with biopsy-confirmed NASH. Patients were randomly assigned in a 1:1:1 ratio to receive once-daily Rezdiffra at a dose of 80 mg or 100 mg or placebo. The two primary endpoints at week 52 were NASH resolution with no worsening of fibrosis and an improvement in fibrosis by at least one stage with no worsening of the NAFLD activity score. The key secondary endpoint was the percent change from baseline in LDL cholesterol at week 24.
Rezdiffra achieved both primary endpoints and the key secondary endpoint of the MAESTRO-NASH trial. Additionally, Rezdiffra improved liver enzymes, fibrosis biomarkers and imaging tests as compared with placebo. The primary results of the trial were published in the New England Journal of Medicine in February 2024.
Patients enrolled in the MAESTRO-NASH trial continue on therapy after the initial 52-week treatment period for up to 54 months to accrue and measure hepatic clinical outcome events including progression to cirrhosis on biopsy and hepatic decompensation events, as well as all-cause mortality. The 54-month outcomes portion of the trial is designed to generate confirmatory data that, if positive, will help verify Rezdiffra’s clinical benefit and may support full approval.
About NASH
Nonalcoholic steatohepatitis (NASH) is a more advanced form of nonalcoholic fatty liver disease (NAFLD). NASH is a leading cause of liver-related mortality and an increasing burden on healthcare systems globally. Additionally, patients with NASH, especially those with more advanced metabolic risk factors (hypertension, concomitant type 2 diabetes), are at increased risk for adverse cardiovascular events and increased morbidity and mortality.
Once patients progress to NASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis), the risk of adverse liver outcomes increases dramatically. NASH is rapidly becoming the leading cause of liver transplantation in the U.S.
Madrigal estimates that approximately 1.5 million patients have been diagnosed with NASH in the U.S., of which approximately 525,000 have NASH with moderate to advanced liver fibrosis. Madrigal plans to focus on approximately 315,000 diagnosed patients with NASH with moderate to advanced liver fibrosis under the care of the liver specialist physicians during the launch of Rezdiffra.
NASH is also known as metabolic dysfunction associated steatohepatitis (MASH). In 2023, global liver disease medical societies and patient groups came together to rename the disease, with the goal of establishing an affirmative, non-stigmatizing name and diagnosis. Nonalcoholic fatty liver disease (NAFLD) was renamed metabolic dysfunction-associated steatotic liver disease (MASLD), NASH was renamed MASH, and an overarching term, steatotic liver disease (SLD), was established to capture multiple types of liver diseases associated with fat buildup in the liver. In addition to liver disease, patients with MASH have at least one related comorbid condition (e.g., obesity, hypertension, dyslipidemia, or type 2 diabetes).
About Rezdiffra
What is Rezdiffra?
Rezdiffra is a prescribed medicine used along with diet and exercise to treat adults with nonalcoholic steatohepatitis (NASH) with moderate to advanced liver scarring (fibrosis), but not with cirrhosis of the liver.
It is not known if Rezdiffra is safe and effective in children (under 18 years old).
This indication is approved based on improvement of NASH and liver scarring (fibrosis). There are ongoing studies to confirm the clinical benefit of Rezdiffra.
Before you take Rezdiffra, tell your healthcare provider about all of your medical conditions, including if you:
- have any liver problems other than NASH.
- have gallbladder problems or have been told you have gallbladder problems, including gallstones.
- are pregnant or plan to become pregnant. It is not known if Rezdiffra will harm your unborn baby.
- are breastfeeding or plan to breastfeed. It is not known if Rezdiffra passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take Rezdiffra.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
- Rezdiffra and other medicines may affect each other, causing side effects. Rezdiffra may affect the way other medicines work, and other medicines may affect how Rezdiffra works.
- Especially tell your healthcare provider if you take medicines that contain gemfibrozil to help lower your triglycerides, or cyclosporine to suppress your immune system, because Rezdiffra is not recommended in patients taking these medicines.
- Tell your healthcare provider if you are taking medicines such as clopidogrel to thin your blood or statin medicines to help lower your cholesterol.
- Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.
What are the possible side effects of Rezdiffra?
Rezdiffra may cause serious side effects, including:
- liver injury (hepatotoxicity). Stop taking Rezdiffra and call your healthcare provider right away if you develop the following signs or symptoms of hepatotoxicity: tiredness, nausea, vomiting, fever, rash, your skin or the white part of your eyes turns yellow (jaundice), pain or tenderness in the upper middle or upper right area of your stomach (abdomen).
- gallbladder problems. Gallbladder problems such as gallstones, inflammation of the gallbladder, or inflammation of the pancreas from gallstones can occur with NASH and may occur if you take Rezdiffra. Call your healthcare provider right away if you develop any signs or symptoms of these conditions including nausea, vomiting, fever, or pain in your stomach area (abdomen) that is severe and will not go away. The pain may be felt going from your abdomen to your back and the pain may happen with or without vomiting.
The most common side effects of Rezdiffra include: diarrhea, nausea, itching, stomach (abdominal) pain, vomiting, dizziness, constipation.
These are not all the possible side effects of Rezdiffra. For more information, ask your healthcare provider or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Madrigal at 1-800-905-0324.
Please see the full Prescribing Information, including Patient Information, for Rezdiffra.
About Madrigal Pharmaceuticals
Madrigal Pharmaceuticals, Inc. (Nasdaq: MDGL) is a biopharmaceutical company pursuing novel therapeutics for nonalcoholic steatohepatitis (NASH), a liver disease with high unmet medical need. Madrigal’s medication, Rezdiffra (resmetirom), is a once-daily, oral, liver-directed THR-β agonist designed to target key underlying causes of NASH. For more information, visit www.madrigalpharma.com.
Rezdiffra
Rezdiffra product image
Source: Madrigal Pharmaceuticals, Inc.
Madrigal climbs amid hopes for new NASH drug; B. Riley upgrades
Mar. 15, 2024 8:19 AM ET
Madrigal Pharmaceuticals, Inc. (MDGL) StockNVO, LLY, IONS, ARWR, NONOF, GALT, ENTA, VKTX, NGM, AKRO, ETNB, IVA, TERN, SGMT
By: Dulan Lokuwithana, SA News Editor
Shares of Madrigal Pharmaceuticals (NASDAQ:MDGL) gained in the premarket Friday as Wall Street welcomed the company's newly approved liver disease medication, Rezdiffra, indicated for nonalcoholic steatohepatitis (NASH).
The landmark decision enables Madrigal (MDGL) to launch the first U.S.-approved therapy for NASH, currently known as metabolic dysfunction-associated steatohepatitis (MASH). The company has a set list price of $47K for Rezdiffra.
Madrigal Pharmaceuticals, Inc. (MDGL) Stock
https://www.madrigalpharma.com/
BRUKINSA® (zanubrutinib)
Rezdiffra™ (resmetirom)
Rezdiffra™ (resmetirom)
First Doses of BRUKINSA® provided to Patients with Chronic Lymphocytic Leukemia in Low- and Middle-Income Countries Under Collaboration of The Max Foundation, BeiGene, and the BeiGene Foundation
Mar 13, 2024 8:00 AM
Armenia and Nepal are the first of 29 countries to receive BRUKINSA
SEATTLE & BASEL, Switzerland & BEIJING & CAMBRIDGE, Mass.--(BUSINESS WIRE)-- The Max Foundation (Max), a global nonprofit organization dedicated to accelerating health equity by delivering medication, technology, and supportive services to patients worldwide, BeiGene, a global oncology company, and the BeiGene Foundation, a nonprofit charitable foundation, today announced that the first doses of BRUKINSA® (zanubrutinib) have been administered for the treatment of adult patients with chronic lymphocytic leukemia (CLL) to patients in Armenia and Nepal, as part of a three-year collaboration to provide access to the medicine in 29 low- and middle-income countries (LMICs).
This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20240313093081/en/
“We are thrilled to share that the first group of people diagnosed with CLL in Armenia and Nepal have received treatment free of charge through our collaboration with BeiGene and the BeiGene Foundation,” said Pat Garcia-Gonzalez, CEO of Max. “BeiGene has demonstrated that it is possible for companies to provide access to innovative treatments to regions in the world where access is limited or unavailable during the same year a drug receives approval in the U.S. We look forward to working together to expand access to this much-needed treatment to more patients.”
Last year, BeiGene joined Max’s Humanitarian Partnership for Access to Cancer Treatments (Humanitarian PACT), a collaboration among professional, nonprofit, and commercial organizations that share the commitment to increase global access to treatment, care, and support for people living with cancer. As a member of the Humanitarian PACT, BeiGene provided a monetary grant through the BeiGene Foundation and is providing BRUKINSA free of charge for eligible patients in a number of low- and middle-income countries.
“BeiGene and Max share a commitment to advance global health equity and ensure that patients in underserved regions have access to the best possible cancer care. The administration of the first doses of BRUKINSA to patients with CLL in Armenia and Nepal under our collaboration with Max and the BeiGene Foundation represents a crucial step in achieving this mission,” said John V. Oyler, Co-Founder, Chairman and CEO at BeiGene. “We are honored to participate in this worthy collaboration and support Max’s efforts to deliver innovative cancer medicines to patients in need around the world.”
“For many years, the treatment of blood cancer, particularly CLL, has posed and continues to pose a significant challenge in Armenia. New medicines and treatments have simply not been accessible to those in need,” said Karen Meliksetyan, M.D., Head of Bone Marrow Transplant Department, Yeolyan Hematology and Oncology Center, Yerevan, Armenia. “The donation of BRUKINSA presents a tremendous opportunity for our patients to access treatment and will have a positive impact on many patients.”
CLL is the most common leukemia in adults, accounting for about one third of new cases of leukemia worldwidei. BeiGene and Max aim to provide access to CLL treatment to patients in need in 29 low- and middle-income countries. In each country, verified physicians within Max’s network will submit a request for treatment to Max for patients who are under their care and are candidates for BRUKINSA. Upon patient identity verification and CLL diagnosis confirmation, Max will deliver the treatment directly to the health institution providing care to the patient through well-established supply chains.
About The Max Foundation
The Max Foundation is a global health nonprofit organization dedicated to accelerating health equity. For 26 years, Max has pioneered practical, scalable, high-quality solutions to bring lifesaving treatments and patient-centered health care to more than 100,000 people living with cancer and critical illness in low- and middle-income countries. Max believes in a world where all people can access high-impact medicines, where geography is not destiny, and where everyone can strive for health with dignity and with hope. Learn more at www.themaxfoundation.org.
About BeiGene
BeiGene is a global oncology company that is discovering and developing innovative treatments that are more affordable and accessible to cancer patients worldwide. With a broad portfolio, we are expediting development of our diverse pipeline of novel therapeutics through our internal capabilities and collaborations. We are committed to radically improving access to medicines for far more patients who need them. Our growing global team of more than 10,000 colleagues spans five continents, with administrative offices in Basel, Beijing, and Cambridge, U.S. To learn more about BeiGene, please visit www.beigene.com and follow us on LinkedIn and X (formerly known as Twitter).
About the BeiGene Foundation
The BeiGene Foundation is a charitable organization established by BeiGene, Ltd. It is a separate legal entity from BeiGene, Ltd. with distinct legal restrictions. The foundation’s mission is to advance global health by improving access to high quality therapies to more people around the world focused on three strategic areas: health equity, disaster relief, and community engagement.
Please see full U.S. Prescribing Information including U.S. Patient Information.
View source version on businesswire.com: https://www.businesswire.com/news/home/20240313093081/en/
Source: BeiGene
BeiGene gains as access to leukemia drug Brukinsa expands
Mar. 13, 2024 11:57 AM ET
By: Dulan Lokuwithana, SA News Editor1 Comment
ADRs of BeiGene (NASDAQ:BGNE) traded higher on Wednesday after the company announced that patients in Nepal and Armenia were among the first to receive its FDA-approved leukemia therapy Brukinsa as part of a program to widen its access across the globe.
https://seekingalpha.com/news/4079007-beigene-stock-gains-access-brukinsa-widens
ION224
Rezdiffra™ (resmetirom)
PRALUENT® (ALIROCUMAB)
Ionis announces positive results from Phase 2 study of ION224, an investigational medicine demonstrating clinical efficacy in the treatment of NASH/MASH
March 13, 2024 at 7:00 AM EDT
- Significant improvement in steatohepatitis with >2 point improvement in NAS score without worsening fibrosis, the primary endpoint of the study
- Achieved key secondary endpoint of MASH resolution without worsening of fibrosis
- More ION224 treated patients had an improvement of >1 stage fibrosis compared to placebo
- ION224 was safe and well-tolerated in this study with once-monthly subcutaneous dosing
CARLSBAD, Calif., March 13, 2024 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) announced positive results from a Phase 2 study of ION224, an investigational DGAT2 antisense inhibitor in development for the treatment of metabolic dysfunction-associated steatohepatitis (MASH), previously referred to as nonalcoholic steatohepatitis (NASH). The study met its primary endpoint at both doses (120 mg and 90 mg), achieving liver histologic improvement, and also met the important secondary endpoint of MASH resolution.
Key highlights from the 160-patient study at 51 weeks included:
- ION224 achieved statistically significant liver histologic improvement as measured by at least a 2-point reduction in NAFLD Activity Score (NAS)* (p<0.001 (120 mg) and p=0.015 (90 mg)).
- Subgroup analysis indicated that significant improvements in the primary endpoint were observed in patients with both F2 and F3 (advanced) fibrosis.
- ION224 achieved statistically significant MASH resolution without worsening of fibrosis, as measured by biopsy (p=0.039).
- 44% of patients treated with 120 mg achieved ≥50% relative reduction in liver steatosis as measured by MRI-PDFF compared to 3% for placebo.
- 32% of patients treated with 120 mg achieved a ≥1 stage improvement in fibrosis without worsening steatohepatitis as measured by biopsy compared to 12.5% for placebo.
- ION224 was safe and well-tolerated in the study.
"This Phase 2 trial of ION224 is the first to demonstrate clinical evidence that the reduction of hepatic fat after DGAT2 inhibition correlates with improvements in MASH histological endpoints," said Rohit Loomba, MD, MHSc, professor of medicine and chief, division of gastroenterology and hepatology, University of California San Diego; founding director, MASLD Research Center, University of California San Diego. "I believe ION224 offers a unique precision medicine opportunity with an approach that is potentially complementary to others in development for MASH, and I look forward to continued evaluation of this important investigational medicine."
MASH is the more severe form of metabolic dysfunction-associated steatotic liver disease (MASLD) and can lead to liver fibrosis, cirrhosis and liver-related death. ION224 is an investigational LIgand-Conjugated Antisense (LICA) medicine designed to reduce the production of diacylglycerol acyltransferase 2 (DGAT2) to treat patients with MASH.
"Reducing the production of DGAT2 enzyme decreases the overproduction of triglycerides that contribute to excess liver fat, which can result in liver damage and inflammation. We are encouraged by these ION224 data, showing that a monthly subcutaneous medicine targeting DGAT2 has the potential to improve MASH and prevent its progression to more severe stages, including advanced liver fibrosis and cirrhosis," said Sanjay Bhanot, MD, PhD, senior vice president and chief medical officer at Ionis. "The inhibition of DGAT2 represents a novel approach for MASH, a progressive disease in need of better treatment options. We look forward to sharing the full results from this study at an upcoming medical conference and discussing next steps to advance this potentially promising therapy for patients."
In this study, ION224 was safe and well-tolerated in MASH participants. Those in the ION224 study arms did not experience any worsening of hepatic or renal function or gastrointestinal side effects, and there was a lower rate of early termination compared to placebo. Additionally, there were no on-study deaths or treatment-related serious adverse events.
The adaptive Phase 2, two-part, multi-center, randomized, double-blind, placebo-controlled study was designed to assess the efficacy, safety and pharmacokinetics of multiple doses of ION224 when administered subcutaneously once-monthly in adults with MASH. The study enrolled 160 patients to receive ION224 or placebo over a period of 49 weeks. In Part 1, 93 patients were randomized 1:1:1 to the three dose cohorts (60, 90, and 120 mg) and within each dose cohort, randomized 3:1 to receive ION224 or placebo. In Part 2, an additional 67 patients were randomized 1:1 to two selected dose cohorts (90 and 120 mg) and then in a 2:1 ratio to receive either ION224 or placebo within each cohort. The study was powered for the primary endpoint, which was the percentage of patients who achieved MASH histologic improvement, defined as achieving at least a 2-point reduction in NAS with at least 1-point improvement in hepatocellular ballooning or lobular inflammation, and without worsening of fibrosis at end of the treatment period.
About ION224
ION224 is an investigational LIgand-Conjugated Antisense (LICA) medicine designed to reduce the production of diacylglycerol acyltransferase 2 (DGAT2) to treat patients with MASH. DGAT2 is an enzyme that catalyzes the final step in triglyceride synthesis in the liver. Reducing the production of DGAT2 should therefore decrease triglyceride synthesis in the liver. Additionally, there is evidence of an increase in both fatty acid oxidation and oxidative gene expression associated with antisense inhibition of DGAT2. ION224 offers a unique approach, which is potentially complementary to other therapies currently in clinical development.
About Metabolic dysfunction-associated steatohepatitis (MASH)
MASH is the more severe form of metabolic dysfunction-associated fatty liver disease (MASLD). It is related to the epidemic of obesity, pre-diabetes and diabetes. Unlike liver disease caused by alcohol consumption, MASH is the result of an accumulation of fat in the liver, which can lead to inflammation and cirrhosis, an advanced scarring of the liver that prevents the liver from functioning normally. About 20% of MASH patients are reported to develop cirrhosis, which is associated with increased risk of liver-related and overall mortality.i MASH is the fastest growing indication for liver transplantation in the U.S. and Europe.ii
In 2023, several multinational liver societies made the recommendation to update NAFLD to metabolic dysfunction-associated steatotic liver disease (MASLD) and to update non-alcoholic steatohepatitis (NASH) to metabolic dysfunction-associated steatohepatitis (MASH). Ionis has adopted the use of MASH to describe this Phase 2 trial. ION224-CS2 is registered on clinicaltrials.gov as a study in patients with non-alcoholic steatohepatitis (NASH) and was registered before the recommended update.
About Ionis Pharmaceuticals, Inc.
For three decades, Ionis has invented medicines that bring better futures to people with serious diseases. Ionis currently has five marketed medicines and a leading pipeline in neurology, cardiology, and other areas of high patient need. As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in RNA therapies in addition to advancing new approaches in gene editing. A deep understanding of disease biology and industry-leading technology propels our work, coupled with a passion and urgency to deliver life-changing advances for patients. To learn more about Ionis, visit Ionispharma.com and follow us on X (Twitter) and LinkedIn.
Cision View original content to download multimedia:https://www.prnewswire.com/news-releases/ionis-announces-positive-results-from-phase-2-study-of-ion224-an-investigational-medicine-demonstrating-clinical-efficacy-in-the-treatment-of-nashmash-302087276.html
SOURCE Ionis Pharmaceuticals, Inc.
Ionis stock jumps as MASH drug succeeds in mid-stage trial
Mar. 13, 2024 8:00 AM ET
Ionis Pharmaceuticals, Inc. (IONS) StockMDGL, ARWR, VKTX, NGM, AKRO, ETNB, SGMT
By: Preeti Singh, SA News Editor
Ionis Pharmaceuticals (NASDAQ:IONS) shares rose in early trading on Wednesday after the company reported positive results from a mid-stage trial of its investigational drug to treat a type of fatty liver disease.
ION224 is an investigational DGAT2 antisense inhibitor in development for the treatment of metabolic dysfunction-associated steatohepatitis (MASH).
The drug met the primary study endpoint at both doses (120 mg and 90 mg) in a Phase 2 trial, demonstrating statistically significant liver histologic improvement.
ION224 also achieved the key secondary endpoint of MASH resolution without worsening of fibrosis, as measured by biopsy. Furthermore, the drug was safe and well-tolerated in study participants, with no on-study deaths or treatment-related serious adverse events.
https://seekingalpha.com/news/4078799-ionis-stock-jumps-as-mash-drug-succeeds-in-mid-stage-trial
PRALUENT® (ALIROCUMAB)
Blenrep (belantamab mafodotin) plus PomDex
PRALUENT® (ALIROCUMAB)
March 11, 2024 at 7:00 AM EDT
PRALUENT® (ALIROCUMAB) INJECTION RECEIVES FDA APPROVAL TO TREAT CHILDREN WITH GENETIC FORM OF HIGH CHOLESTEROL
Approval extends treatment of Praluent to children aged 8 and older with heterozygous familial hypercholesterolemia (HeFH)
TARRYTOWN, N.Y., March 11, 2024 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) announced the U.S. Food & Drug Administration (FDA) has extended the approval of Praluent® (alirocumab) as an adjunct to diet and other low-density lipoprotein cholesterol (LDL-C) lowering therapies to include pediatric patients aged 8 and older with heterozygous familial hypercholesterolemia (HeFH).
“Many children with heterozygous familial hypercholesterolemia (HeFH) are able to substantially improve their LDL-C (bad cholesterol) with currently available therapies. But for those children whose LDL-C remains dangerously high, this approval is an important milestone as it gives these children and their families an additional option to help reduce and manage their LDL-C levels much earlier in their lives,” said Mary P. McGowan, M.D., Chief Medical Officer of the Family Heart Foundation.
Familial hypercholesterolemia (FH) is an inherited condition caused by mutations in one of several genes that control how the body processes cholesterol, which can lead to very high levels of LDL-C (bad cholesterol). FH can come in two forms: HeFH, which develops when one mutated gene is inherited from one parent; and homozygous familial hypercholesterolemia (HoFH), which develops when a mutated gene is inherited from both parents. Praluent is approved to treat both children and adults with HeFH and adults with HoFH.
The approval is based on a Phase 3, randomized multicenter trial evaluating pediatric patients aged 8 to 17 with HeFH, who had LDL-C levels of 130mg/dL or greater and were already being treated with lipid-lowering medications. Patients were randomized to receive Praluent (N=101) or placebo (N=52) every two or four weeks in two consecutive cohorts. Patients who received Praluent every four weeks had 31% lower LDL-C than placebo at 24 weeks (97.5% Confidence Interval: -45.0% to -17.9%; p<0.0001). Improvements in additional key lipid parameters were also observed. Results from the trial were recently published in the Journal of the American Medical Association Pediatrics.
No new adverse reactions were identified in this trial, and the safety profile was consistent with the safety profile observed in adults with HeFH. Across Praluent trials in patients with primary hyperlipidemia (N=2,476), the most common adverse reactions (≥5%) more frequently observed with Praluent than placebo have been injection site reactions (7%), and influenza (6%) and diarrhea (5%).
“The approval of Praluent for the treatment of high cholesterol was a historic landmark achievement, as it was the first approved therapy targeting the genetically-validated PCSK9 target for heart disease,” said George D. Yancopoulos, M.D., Ph.D., Board co-Chair, President and Chief Scientific Officer at Regeneron, and a principal inventor of Praluent. “Praluent has made a meaningful impact in the treatment of adults with familial hypercholesterolemia, and we are proud that our innovation will now be able to help appropriate children with the heterozygous form of this disease manage their dangerously high levels of LDL-C.”
About the Praluent HeFH Pediatric Trial
The randomized multicenter Phase 3 trial consisted of a 24-week double-blind, placebo-controlled evaluating the efficacy and safety of Praluent in pediatric patients aged 8 to 17 years with HeFH (N=79). The primary endpoint was the percent change in LDL-C from baseline to week 24 in the Praluent and placebo treated patients. At baseline, patients were on a low-fat diet and being treated with background lipid-lowering therapy. In the trial, patients were randomized 2:1 to receive Praluent or placebo every 2 or 4 weeks. The Praluent dose was based on body weight.
About Praluent
Praluent inhibits the binding of PCSK9 to the LDL receptor and thereby increases the number of available LDL receptors on the surface of liver cells to clear LDL, which lowers LDL-C levels in the blood. Praluent was developed by Regeneron and Sanofi under a global collaboration agreement and invented by Regeneron using the company's proprietary VelocImmune® technology that yields optimized fully-human monoclonal antibodies.
In the U.S., Praluent is currently indicated:
- to reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease
- as an adjunct to diet, alone or in combination with other low-density lipoprotein cholesterol (LDL-C) lowering therapies in adults with primary hyperlipidemia including HeFH to reduce LDL-C
- as an adjunct to other LDL-C-lowering therapies in adults with HoFH to reduce LDL-C
- along with diet and other LDL-C lowering treatments in children aged 8 years and older with HeFH to reduce LDL-C
In addition to the U.S., Praluent is approved in 60 countries, including the European Union, Japan, Canada, Switzerland and Brazil.
About Regeneron’s VelocImmune Technology
Regeneron’s VelocImmune technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies. When Regeneron's President and Chief Scientific Officer George D. Yancopoulos was a graduate student with his mentor Frederick W. Alt in 1985, they were the first to envision making such a genetically humanized mouse, and Regeneron has spent decades inventing and developing VelocImmune and related VelociSuite® technologies. Dr. Yancopoulos and his team have used VelocImmune technology to create a substantial proportion of all original, FDA-approved fully human monoclonal antibodies currently available. This includes Evkeeza® (evinacumab-dgnb), REGEN-COV® (casirivimab and imdevimab), Dupixent® (dupilumab), Libtayo® (cemiplimab-rwlc), Praluent, Kevzara® (sarilumab), Inmazeb® (atoltivimab, maftivimab and odesivimab-ebgn) and Veopoz® (pozelimab-bbfg).
IMPORTANT SAFETY INFORMATION AND INDICATIONS
INDICATIONS
PRALUENT is an injectable prescription medicine used:
- in adults with cardiovascular disease to reduce the risk of heart attack, stroke, and certain types of chest pain conditions (unstable angina) requiring hospitalization.
- along with diet, alone or together with other cholesterol-lowering medicines in adults with high blood cholesterol levels called primary hyperlipidemia (including a type of high cholesterol called heterozygous familial hypercholesterolemia [HeFH]), to reduce low-density lipoprotein cholesterol (LDL-C) or bad cholesterol.
- along with other LDL-lowering treatments in adults with a type of high cholesterol called homozygous familial hypercholesterolemia, who need additional lowering of LDL-C.
- along with diet and other LDL-C lowering treatments in children aged 8 years and older with HeFH to reduce LDL-C.
It is not known if PRALUENT is safe and effective in children who are younger than 8 years of age or in children with other types of high cholesterol (hyperlipemias).
Please click here for full Prescribing Information.
About Regeneron
Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led for over 35 years by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous FDA-approved treatments and product candidates in development, almost all of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, hematologic conditions, infectious diseases and rare diseases.
Regeneron is accelerating and improving the traditional drug development process through our proprietary VelociSuite® technologies, such as VelocImmune, which uses unique genetically humanized mice to produce optimized fully human antibodies and bispecific antibodies, and through ambitious research initiatives such as the Regeneron Genetics Center, which is conducting one of the largest genetics sequencing efforts in the world.
For more information, please visit www.Regeneron.com or follow Regeneron on LinkedIn.
Source: Regeneron Pharmaceuticals, Inc.
Regeneron's Praluent injection gets FDA approval to treat kids with genetic form of high cholesterol
Mar. 11, 2024 7:52 AM ET
Regeneron Pharmaceuticals, Inc. (REGN) StockSNY
By: Preeti Singh, SA News Editor
Regeneron Pharmaceuticals (NASDAQ:REGN) has received approval from the U.S. Food & Drug Administration (FDA) for its Praluent (alirocumab) injection to treat children with genetic form of high cholesterol.
The drug regulator extended the approval of Praluent as an adjunct to diet and other LDL-C lowering therapies to include pediatric patients aged 8 and older with heterozygous familial hypercholesterolemia (HeFH).
The label expansion is based on a Phase 3 trial, which showed that patients who received Praluent every four weeks had 31% lower LDL-C than placebo at 24 weeks.
Praluent, a PCSK9 inhibitor, was developed by Regeneron (REGN) and Sanofi (SNY) under a global collaboration agreement. The medication is currently indicated to treat both children and adults with HeFH and adults with homozygous familial hypercholesterolemia (HoFH).
Donanemab
Blenrep (belantamab mafodotin) plus PomDex
Blenrep (belantamab mafodotin) plus PomDex
U.S. Food and Drug Administration to Convene Advisory Committee Meeting to Discuss the TRAILBLAZER-ALZ 2 Study of Donanemab
March 8, 2024
INDIANAPOLIS, March 8, 2024 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced that the U.S. Food and Drug Administration (FDA) expects to convene a meeting of the Peripheral and Central Nervous System Drugs Advisory Committee (PCNS) to discuss the Phase 3 TRAILBLAZER-ALZ 2 trial, which evaluated the efficacy and safety of donanemab in early symptomatic Alzheimer's disease.
The FDA has informed Lilly it wants to further understand topics related to evaluating the safety and efficacy of donanemab, including the safety results in donanemab-treated patients and the efficacy implications of the unique trial design of the TRAILBLAZER-ALZ 2 study, including its limited-duration dosing regimen that allowed patients to complete treatment based on an assessment of amyloid plaque and the inclusion of participants based on tau levels.
The date of the advisory committee meeting for donanemab has yet to be set by the FDA, and, as a result, the timing of expected FDA action on donanemab will be delayed beyond the first quarter of 2024. While it is unusual for an advisory committee to occur after the anticipated FDA action date, the advisory committee meeting for donanemab follows similar meetings for the two other amyloid plaque-targeting therapies the FDA has approved.
"We are confident in donanemab's potential to offer very meaningful benefits to people with early symptomatic Alzheimer's disease. It was unexpected to learn the FDA will convene an advisory committee at this stage in the review process, but we look forward to the opportunity to further present the TRAILBLAZER-ALZ 2 results and put donanemab's strong efficacy in the context of safety. We will work with the FDA and the stakeholders in the community to make that presentation and answer all questions," said Anne White, executive vice president of Eli Lilly and Company, and president of Lilly Neuroscience.
TRAILBLAZER-ALZ 2 is a Phase 3, double-blind, placebo-controlled study to evaluate the safety and efficacy of donanemab in participants ages 60-85 years with early symptomatic Alzheimer's disease (MCI or mild dementia due to Alzheimer's disease) with the presence of confirmed Alzheimer's disease neuropathology. Alzheimer's disease is a progressive and fatal disease that in its early symptomatic stages affects 6-7.5 million Americans. The trial enrolled 1,736 participants, across eight countries, selected based on cognitive assessments in conjunction with amyloid plaque imaging and tau staging by positron emission tomography (PET) imaging.
Compared to participants in similar trials of other amyloid plaque-targeting therapies, the TRAILBLAZER-ALZ 2 participants were more progressed in their disease. All groups of trial participants, regardless of tau level, benefited from treatment with donanemab, with patients in earlier stages of the disease experiencing the strongest results. Donanemab also demonstrated clinical benefits using a limited-duration treatment regimen, with nearly half of clinical trial participants completing their course of treatment in six or 12 months. The key risk associated with donanemab is amyloid related imaging abnormalities, or ARIA, which can be serious and life-threatening. Other most commonly reported risks include infusion-related reactions, headache and nausea.
The Phase 3 TRAILBLAZER-ALZ 2 study results were published in the Journal of the American Medical Association (JAMA). Lilly continues to study donanemab in multiple clinical trials.
This action does not result in a change to Lilly's 2024 financial guidance.
About Lilly
Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help more than 51 million people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news, or follow us on Facebook, Instagram and LinkedIn. P-LLY
View original content to download multimedia:https://www.prnewswire.com/news-releases/us-food-and-drug-administration-to-convene-advisory-committee-meeting-to-discuss-the-trailblazer-alz-2-study-of-donanemab-302083661.html
SOURCE Eli Lilly and Company
https://seekingalpha.com/symbol/LLY
LLY Dividend History
https://www.nasdaq.com/market-activity/stocks/lly/dividend-history
Blenrep (belantamab mafodotin) plus PomDex
Blenrep (belantamab mafodotin) plus PomDex
Blenrep (belantamab mafodotin) plus PomDex
07 March 2024
Issued: London, UK
GSK announces positive results from DREAMM-8 phase III trial for Blenrep versus standard of care combination in relapsed/refractory multiple myeloma
- Trial unblinded early at an interim analysis based on Independent Data Monitoring Committee recommendation
- Blenrep (belantamab mafodotin) plus PomDex showed statistically significant and clinically meaningful progression-free survival compared to bortezomib plus PomDex
- Consistent efficacy results observed for Blenrep combinations in two phase III head-to-head trials
GSK plc (LSE/NYSE: GSK) today announced positive headline results from an interim analysis of the DREAMM-8 phase III head-to-head trial evaluating Blenrep (belantamab mafodotin), in combination with pomalidomide plus dexamethasone (PomDex), versus a standard of care, bortezomib plus PomDex, as a second line and later treatment for relapsed or refractory multiple myeloma. The trial met its primary endpoint of progression-free survival (PFS) at a pre-specified interim analysis and was unblinded early based on the recommendation by an Independent Data Monitoring Committee (IDMC).
The belantamab mafodotin combination significantly extended the time to disease progression or death versus the standard of care combination. A positive overall survival (OS) trend favouring the Blenrep combination was also observed at the time of this analysis. The trial continues to follow up for OS. The safety and tolerability of the belantamab mafodotin regimen were broadly consistent with the known safety profile of the individual agents.
Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said: “The results seen in both DREAMM-7 and DREAMM-8 provide strong clinical evidence of the robust efficacy shown with belantamab mafodotin in use with standard of care combinations. We now look forward to discussing these data with regulators. If approved, we believe these combinations have the potential to redefine the treatment of relapsed or refractory multiple myeloma and advance the standard of care. This is exciting news for patients given the high unmet medical need for both efficacious and easily administered therapies with differing mechanisms of action.”
DREAMM-8 is the second phase III head-to-head belantamab mafodotin combination trial in second line and later treatment for multiple myeloma to report positive results. Positive findings from DREAMM-7, a phase III head-to-head trial evaluating belantamab mafodotin in combination with bortezomib and dexamethasone (BorDex) versus daratumumab plus BorDex in the same treatment setting, were presented1 at the American Society of Clinical Oncology (ASCO) Plenary Series on 6 February 2024. Detailed findings from DREAMM-8 will be presented at a future medical congress and shared with regulatory authorities.
About DREAMM-8
The DREAMM-8 phase III clinical trial is a multicentre, open-label, randomised trial evaluating the efficacy and safety of belantamab mafodotin in combination with PomDex compared to a combination of bortezomib and PomDex in patients with relapsed/refractory multiple myeloma previously treated with at least one prior line of multiple myeloma therapy, including a lenalidomide-containing regimen, and who have documented disease progression during or after their most recent therapy.
A total of 302 participants were randomised at a 1:1 ratio to receive either belantamab mafodotin plus PomDex, or bortezomib plus PomDex.
The primary endpoint is PFS. Secondary endpoints include OS, overall response rate, duration of response, minimal residual disease negativity as assessed by next-generation sequencing, safety, and patient-reported and quality of life outcomes.
About multiple myeloma
Multiple myeloma is the third most common blood cancer globally and is generally considered treatable but not curable.2,3 There are approximately 176,000 new cases of multiple myeloma diagnosed globally each year.4 Research into new therapies is needed as multiple myeloma commonly becomes refractory to available treatments.5
About Blenrep
Blenrep is an antibody-drug conjugate comprising a humanised B-cell maturation antigen monoclonal antibody conjugated to the cytotoxic agent auristatin F via a non-cleavable linker. The drug linker technology is licensed from Seagen Inc.; the monoclonal antibody is produced using POTELLIGENT Technology licensed from BioWa Inc., a member of the Kyowa Kirin Group.
Refer to the Blenrep UK Summary of Product Characteristics6 for a full list of adverse events and the complete important safety information in the United Kingdom.
GSK in oncology
Oncology is an emerging therapeutic area for GSK where we are committed to maximising patient survival with a current focus on haematologic malignancies, gynaecologic cancers, and other solid tumours through breakthroughs in immuno-oncology and tumour-cell targeting therapies.
About GSK
GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com.
GSK’s Blenrep combo therapy meets key goal in multiple myeloma trial
Mar. 07, 2024 5:23 AM ET
GSK plc SPONSORED ADR (GSK) Stock
By: Preeti Singh, SA News Editor1 Comment
GSK (NYSE:GSK) reported on Thursday positive results from an interim analysis of a trial evaluating a combination therapy for the relapsed or refractory multiple myeloma.
DREAMM-8 is the second phase III head-to-head belantamab mafodotin combination trial in second line and later treatment for multiple myeloma to report positive results.
BESPONSA® (inotuzumab ozogamicin)
Islatravir & Sunlenca (300 mg tablet and 463.5 mg/1.5 mL injection) [(lenacapavir)]
Islatravir & Sunlenca (300 mg tablet and 463.5 mg/1.5 mL injection) [(lenacapavir)]
FDA approves inotuzumab ozogamicin for pediatric patients with acute lymphoblastic leukemia
FDA approves inotuzumab ozogamicin for pediatric patients with acute lymphoblastic leukemia
On March 6, 2024, the Food and Drug Administration approved inotuzumab ozogamicin (Besponsa, Pfizer) for pediatric patients 1 year and older with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia (ALL).
Full prescribing information for Besponsa will be posted here.
Efficacy was evaluated in a multicenter, single-arm, open-label study in 53 pediatric patients 1 year and older with relapsed or refractory CD22-positive B-cell precursor ALL. Two dose levels were evaluated--an initial dose of 1.4 mg/m2/cycle in 12 patients and 1.8 mg/m2/cycle in 41 patients. Premedications included methylprednisolone 1 mg/kg (maximum of 50 mg), an antipyretic, and an antihistamine. Patients received a median of 2 cycles of therapy (range: 1 to 4 cycles).
The main efficacy outcome measures were complete remission (CR), duration of CR, and the proportion of patients with minimal residual disease (MRD) negative CR. CR was defined as < 5% blasts in the bone marrow and the absence of peripheral blood leukemia blasts, full recovery of peripheral blood counts (platelets ≥ 100 × 109 and ANC ≥1 × 109/L), and resolution of any extramedullary disease. MRD was defined by leukemic cells comprising < 1 × 10-4 (<0.01%) of bone marrow nucleated cells by flow cytometry or by PCR.
In all patients, 22/53 (42%, 95% CI: 28.1, 55.9%) achieved CR and the median duration of CR was 8.2 months (95% CI: 2.6, NE). The MRD negativity rate in patients with CR was 21/22 [95.5% (95% CI: 77.2, 99.9)] based on flow cytometry, and 19/22 [86.4% (95% CI: 65.1, 97.1] based on RQ-PCR.
The most common adverse reactions (≥20%), including laboratory abnormalities, were thrombocytopenia, pyrexia, anemia, vomiting, infection, hemorrhage, neutropenia, nausea, leukopenia, febrile neutropenia, increased transaminases, abdominal pain, and headache.
For the first cycle, the recommended inotuzumab ozogamicin dose is 1.8 mg/m2 per cycle, administered as 3 divided doses on Day 1 (0.8 mg/m2), Day 8 (0.5 mg/m2), and Day 15 (0.5 mg/m2). Cycle 1 is 3 weeks in duration but may be extended to 4 weeks if the patient achieves a complete remission or complete remission with incomplete hematologic recovery, and/or to allow recovery from toxicity. See the prescribing information for the recommended dosage after the first cycle.
This application was granted priority review and orphan drug designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.
Follow the Oncology Center of Excellence on X (formerly Twitter) @FDAOncology
Pfizer wins FDA nod for antibody drug conjugate Besponsa in children
Mar. 06, 2024 3:28 PM ET
By: Dulan Lokuwithana, SA News Editor1 Comment
The U.S. Food and Drug Administration (FDA) announced Wednesday that Pfizer (NYSE:PFE) has received U.S. regulatory approval for its antibody-drug conjugate inotuzumab ozogamicin, marketed as Besponsa for an additional indication in children with a form of leukemia.
In 2017, the agency cleared the CD22-targeting ADC for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL), the most common type of ALL.
Islatravir & Sunlenca (300 mg tablet and 463.5 mg/1.5 mL injection) [(lenacapavir)]
Islatravir & Sunlenca (300 mg tablet and 463.5 mg/1.5 mL injection) [(lenacapavir)]
Islatravir & Sunlenca (300 mg tablet and 463.5 mg/1.5 mL injection) [(lenacapavir)]
March 06, 2024
Gilead and Merck Announce Phase 2 Data Showing an Investigational Oral Once-Weekly Combination Regimen of Islatravir and Lenacapavir Maintained Viral Suppression at Week 24
– Week 24 Results Support Continued Development as a Potential Long-Acting Oral Combination Treatment Option in Virologically Suppressed People with HIV –
– Novel Investigational Combination Regimen has the Potential to be the First Oral Weekly HIV Treatment, Helping to Address Unmet Needs –
FOSTER CITY, Calif., & RAHWAY, N.J.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) and Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced results from the Phase 2 clinical study evaluating the investigational combination of islatravir, an investigational nucleoside reverse transcriptase translocation inhibitor, and lenacapavir, a first-in-class capsid inhibitor. These late-breaking data were presented during an oral session at the 31st Conference on Retroviruses and Opportunistic Infections (CROI). Prior to the late-breaker oral presentation, the key findings were featured in a CROI press conference.
At 24 weeks, the novel investigational combination maintained a high rate (94.2%) of viral suppression (HIV-1 RNA <50 copies/mL), which is a secondary endpoint of the study. Results of the primary endpoint (HIV-1 RNA ≥50 copies/mL (c/mL) showed that one participant (1.9%) treated with islatravir and lenacapavir had a viral load of >50 copies/mL at Week 24; the participant later suppressed on islatravir and lenacapavir at Week 30.
The potent antiviral activities, along with pharmacokinetic profiles of islatravir and lenacapavir, support their development as an investigational once-weekly oral combination regimen. Single-tablet daily oral therapies have helped to transform HIV care, but options that allow for less frequent dosing have the potential to address adherence, stigma and other challenges faced by some individuals taking daily oral antiretroviral therapy.
“HIV treatment is not one size fits all – developing once-weekly treatment options could help meet the needs of each individual, aiming toward maximizing long-term outcomes for people with HIV,” said Jared Baeten, Vice President, MD, PhD, HIV Clinical Development, Gilead Sciences. “These promising data presented at CROI help bring us one step closer to our goal of providing a wide range of options that may help transform the HIV treatment landscape.”
In this open-label, active-controlled study (NCT05052996), virologically suppressed adults (n=104) on Biktarvy® (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg tablets, B/F/TAF) were randomly allocated in a 1:1 ratio to receive either oral islatravir 2 mg and lenacapavir 300 mg once a week (n=52) or to continue daily oral Biktarvy (n=52). The median age of participants was 40 years. Eighteen percent of participants were assigned female at birth, 50% were non-white, and 29% were Hispanic or Latinx.
Results of the primary endpoint, measured as HIV-1 RNA ≥50 copies/mL (c/mL) at Week 24 per FDA Snapshot algorithm, showed that one participant (1.9%) treated with islatravir and lenacapavir had a viral load of more than 50 copies/mL at Week 24; the participant later suppressed on islatravir and lenacapavir at Week 30. No participants in the Biktarvy group had a viral load of more than 50 copies/mL at Week 24. Results of the secondary endpoint, as measured by the proportion of individuals with HIV-1 RNA < 50 c/mL at Week 24, showed that participants who switched to treatment with once-weekly islatravir and lenacapavir or continued Biktarvy both maintained comparable high rates of HIV suppression at Week 24 (94.2% v. 94.2%).
Grade 1 and 2 treatment-related-adverse events (TRAEs) reported in the islatravir and lenacapavir group included dry mouth and nausea (each 3.8%). No grade 1 and 2 TRAEs were reported in the Biktarvy group. No grade 3 or 4 TRAEs related to study drug in either treatment group were reported. Two participants discontinued islatravir and lenacapavir due to adverse events unrelated to the drug. In addition, no differences were seen between treatment groups for changes in CD4+ T cell counts or absolute lymphocyte counts.
“Our strategies for managing and treating HIV must evolve with the needs of the HIV community and we are excited to have these promising first data from the Phase 2 study for islatravir and lenacapavir presented at CROI,” said Dr. Elizabeth Rhee, vice president, global clinical development, Merck Research Laboratories. “Gilead and Merck remain committed to this collaboration and to the development of a potential once-weekly oral therapy for people living with HIV who may need additional options to help maintain viral suppression.”
The Phase 2 study will continue in an open-label fashion through Week 48. Longer-term data will be presented at a future scientific conference.
Islatravir, alone or in combination with lenacapavir, is investigational and not approved anywhere globally. The safety and efficacy of the combination of islatravir and lenacapavir have not been established.
Lenacapavir, marketed as Sunlenca®, is approved in Australia, Canada, the European Union, Israel, Japan, Switzerland, the United Arab Emirates, the United Kingdom and the United States for the treatment of people with multi-drug resistant HIV in combination with other antiretroviral(s).
Please see below for the U.S. Indication and Important Safety Information for Sunlenca. Please also see below for U.S. Indication and Important Safety Information, including Boxed Warning, for Biktarvy.
There is currently no cure for HIV or AIDS.
About islatravir (MK-8591)
Islatravir (MK-8591) is Merck’s investigational nucleoside reverse transcriptase translocation inhibitor under evaluation for the treatment of HIV-1 in combination with other antiretrovirals. For an overview of Merck’s HIV treatment and prevention clinical development program, please click here.
About Sunlenca ®
Sunlenca (300 mg tablet and 463.5 mg/1.5 mL injection) [(lenacapavir)] is a first-in-class, long-acting HIV capsid inhibitor indicated for the treatment of HIV infection, in combination with other antiretroviral(s), in adults with multi-drug resistant HIV who are heavily treatment-experienced. Sunlenca is the only HIV treatment option administered twice-yearly. Sunlenca tablets are approved for oral loading during initiation of Sunlenca treatment, prior to or at the time of the first long-acting lenacapavir injection depending on initiation option.
The multi-stage mechanism of action of Sunlenca’s active pharmaceutical agent, lenacapavir, is distinguishable from other currently approved classes of antiviral agents. While most antivirals act on just one stage of viral replication, Sunlenca is designed to inhibit HIV at multiple stages of its lifecycle and has no known cross resistance exhibited in vitro to other existing drug classes.
Lenacapavir is being developed as a foundation for future HIV therapies developed by Gilead. The goal is to offer both long-acting oral and injectable options with various dosing frequencies in combination with other antiretroviral agents for treatment or as a single agent for prevention. This approach aims to help address the individual needs and preferences of people with HIV and people who could benefit from pre-exposure prophylaxis (PrEP). The use of lenacapavir for HIV prevention is investigational and the safety and efficacy of lenacapavir for this use has not been established. Lenacapavir is being evaluated as a potential long-acting option in multiple ongoing and planned early and late-stage clinical studies in Gilead’s HIV prevention and treatment research program.
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.
Merck’s Commitment to HIV
For more than 35 years, Merck has been committed to scientific research and discovery in HIV. Today, we are developing a series of antiviral options designed to help people manage HIV and protect people from HIV, with the goal of reducing the growing burden of infection worldwide. We remain committed to collaborating with others in the global HIV community to address the complex challenges that impede progress toward ending the epidemic.
About Gilead Sciences in HIV
For more than 35 years, Gilead has been a leading innovator in the field of HIV, driving advances in treatment, prevention and cure research. Gilead researchers have developed 12 HIV medications, including the first single-tablet regimen to treat HIV, the first antiretroviral for pre-exposure prophylaxis (PrEP) to help reduce HIV infections, and the first long-acting injectable HIV treatment medication administered twice-yearly. Our advances in medical research have helped to transform HIV into a treatable, preventable, chronic condition for millions of people.
Gilead is committed to continued scientific innovation to provide solutions for the evolving needs of people affected by HIV around the world. Through partnerships, collaborations, and charitable giving, the company also aims to improve education, expand access and address barriers to care, with the goal of ending the HIV epidemic for everyone, everywhere. Gilead was recognized as the number one philanthropic funder of HIV-related programs in a report released by Funders Concerned About AIDS.
Learn more about Gilead’s unique collaborations worldwide and the work to help end the global HIV epidemic.
U.S. Indication for Sunlenca
Sunlenca, a human immunodeficiency virus type 1 (HIV-1) capsid inhibitor, in combination with other antiretroviral(s), is indicated for the treatment of HIV-1 infection in heavily treatment-experienced adults with multidrug resistant HIV-1 infection failing their current antiretroviral regimen due to resistance, intolerance, or safety considerations.
U.S. full Prescribing Information for Biktarvy, including BOXED WARNING, and U.S. full Prescribing Information for Sunlenca are available at www.gilead.com .
Biktarvy, Sunlenca, Gilead and the Gilead logo are registered trademarks of Gilead Sciences, Inc., or its related companies. All other marks are the property of their respective owners.
For more information about Gilead, please visit the company’s website at www.gilead.com , follow Gilead on Twitter ( @Gilead Sciences ) and LinkedIn , or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
Source: Gilead Sciences, Inc.
Gilead, Merck once weekly combo HIV therapy shows promise in phase 2
Mar. 06, 2024 12:54 PM ET
Merck & Co., Inc. (MRK) Stock, GILD Stock
By: Jonathan Block, SA News Editor
- New data from a phase 2 trial showed that a combination of Gilead Sciences' (NASDAQ:GILD) Sunlenca (lenacapavir) and Merck's (NYSE:MRK) experimental islatravir demonstrated a high rate of HIV viral suppression at 24 weeks, meeting a secondary endpoint.
- In the trial, 104 virologically suppressed adults on Biktarvy (bictegravir/emtricitabine/tenofovir) were randomized to receive either islatravir and lenacapavir once a week or continue on daily Biktarvy.
- Regarding the primary endpoint, HIV-1 RNA ≥50 copies/mL (c/mL), one participant (1.9%) treated with islatravir and lenacapavir had a viral load of more than 50 copies/mL at week 24, though by week 30 the patient suppressed. No one in the Biktarvy group had a viral load of more than 50 copies/mL at week 24.
- https://seekingalpha.com/news/4076721-gilead-merck-once-weekly-combo-hiv-therapy-shows-promise-phase-2?mailingid=34588809&messageid=2900&serial=34588809.11044&utm_campaign=rta-stock-news&utm_content=link-1&utm_medium=email&utm_source=seeking_alpha&utm_term=34588809.11044
- Merck & Co., Inc. (MRK) Stock, GILD Stock
- https://www.sunlenca.com/
Avutometinib Alone or in Combination With Defactinib
Islatravir & Sunlenca (300 mg tablet and 463.5 mg/1.5 mL injection) [(lenacapavir)]
Avutometinib Alone or in Combination With Defactinib
MARCH 5, 2024 AT 5:27 PM EST
Verastem Oncology Receives Orphan Drug Designation from FDA for Avutometinib Alone or in Combination With Defactinib in Recurrent Low-Grade Serous Ovarian Cancer
Recurrent low-grade serous ovarian cancer is a rare cancer with no FDA-approved treatments
Ongoing Phase 3 RAMP 301 trial is evaluating avutometinib and defactinib in recurrent low-grade serous ovarian cancer
On track to submit rolling NDA for Accelerated Approval in H1 2024
BOSTON--(BUSINESS WIRE)--Mar. 5, 2024-- Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients, today announced that the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation (ODD) to avutometinib, a RAF/MEK clamp, alone or in combination with defactinib, a selective FAK inhibitor, for the treatment of all patients with recurrent low-grade serous ovarian cancer (LGSOC).
“The FDA Orphan Drug Designation for avutometinib alone or in combination with defactinib in low-grade serous ovarian cancer is an important step in recognizing this rare cancer as a distinct disease that currently has no FDA-approved treatments,” said Dan Paterson, president and chief executive officer of Verastem Oncology. “We are rapidly advancing the development program for avutometinib and defactinib in low-grade serous ovarian cancer with our ongoing Phase 3 clinical trial to deliver this new combination treatment to patients as quickly as possible. We remain on track to begin submission of an NDA to the FDA for Accelerated Approval of this combination in the first half of 2024 and preparing for a potential launch in 2025.”
Approximately 70% of LGSOC is associated with RAS/MAPK Pathway alterations including KRAS, NRAS HRAS, and other non-RAS associated mutations. Unfortunately, approximately 85% of patients with LGSOC experience recurrence of the disease. LGSOC is a highly recurrent, chemotherapy-resistant cancer, associated with slow tumor growth and high mortality rate. An estimated 6,000 women in the U.S. and 80,000 worldwide are living with this disease. LGSOC affects a younger patient population with bimodal peaks at ages 20-30 and 50-60 years of age and has a median survival of approximately ten years. The majority of patients experience severe pain and complications as the disease progresses. While chemotherapy is the standard of care for this disease, there are no treatments specifically approved by the FDA to treat LGSOC.
About the Avutometinib and Defactinib Combination
Avutometinib is a RAF/MEK clamp that induces inactive complexes of MEK with ARAF, BRAF and CRAF potentially creating a more complete and durable anti-tumor response through maximal RAS/MAPK pathway inhibition. In contrast to currently available MEK-only inhibitors, avutometinib blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows avutometinib to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other MEK-only inhibitors. The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation for the combination of Verastem Oncology’s investigational RAF/MEK clamp avutometinib, with defactinib, a selective FAK inhibitor, for the treatment of all patients with recurrent low-grade serous ovarian cancer (LGSOC) regardless of KRAS status after one or more prior lines of therapy, including platinum-based chemotherapy.
Verastem Oncology is currently conducting clinical trials with its RAF/MEK clamp avutometinib in RAS/MAPK driven tumors as part of its (Raf And Mek Program). RAMP 301 (NCT06072781) is a Phase 3 confirmatory trial evaluating the combination of avutometinib and defactinib versus standard chemotherapy or hormonal therapy for the treatment of recurrent LGSOC. RAMP 201 (NCT04625270) is a Phase 2 registration-directed trial of avutometinib in combination with defactinib in patients with recurrent LGSOC and has completed enrollment in the dose optimization, expansion phase, and low-dose evaluation cohorts.
Verastem Oncology has established clinical collaborations with Amgen and Mirati to evaluate LUMAKRAS™ (sotorasib) and KRAZATI™ (adagrasib) in combination with avutometinib in KRAS G12C mutant NSCLC as part of the RAMP 203 (NCT05074810) and RAMP 204 (NCT05375994) trials, respectively. Supported by the “Therapeutic Accelerator Award” Verastem Oncology received from PanCAN, the Company is conducting RAMP 205 (NCT05669482), a Phase 1b/2 clinical trial evaluating avutometinib and defactinib with gemcitabine/nab-paclitaxel in patients with front-line metastatic pancreatic cancer.
About Verastem Oncology
Verastem Oncology (Nasdaq: VSTM) is a late-stage development biopharmaceutical company committed to the development and commercialization of new medicines to improve the lives of patients diagnosed with cancer. Our pipeline is focused on novel small molecule drugs that inhibit critical signaling pathways in cancer that promote cancer cell survival and tumor growth, including RAF/MEK inhibition and FAK inhibition. For more information, please visit www.verastem.com and follow us on LinkedIn.
View source version on businesswire.com: https://www.businesswire.com/news/home/20240305616374/en/
Source: Verastem Oncology
Verastem gets FDA orphan drug status for low-grade ovarian cancer therapy
Mar. 06, 2024 5:48 AM ET
By: Preeti Singh, SA News Editor
- Verastem Oncology (NASDAQ:VSTM) has received FDA orphan drug designation for its drug candidate avutometinib for the treatment of a rare cancer.
- The orphan drug status was assigned to avutometinib, a RAF/MEK clamp, alone or in combination with defactinib, a selective FAK inhibitor, for the treatment of recurrent low-grade serous ovarian cancer (LGSOC), which has no FDA-approved treatments yet.
- https://seekingalpha.com/news/4076424-verastem-gets-fda-orphan-drug-status-for-low-grade-ovarian-cancer-therapy
- Verastem, Inc. (VSTM) Stock
- https://www.verastem.com/
- https://www.verastem.com/research/pipeline/
Zilebesiran
Efruxifermin (EFX)
Avutometinib Alone or in Combination With Defactinib
Alnylam Reports Positive KARDIA-2 Topline Study Results Demonstrating Clinically Significant Blood Pressure Reductions When Zilebesiran is Added to Standard of Care Antihypertensives
Mar 05, 2024
– Study Met the Primary Endpoint Demonstrating Clinically Significant Systolic Blood Pressure Reductions at Month 3 When Zilebesiran Was Added to a Diuretic, Calcium-Channel Blocker or Angiotensin Receptor Blocker –
– Zilebesiran Demonstrated an Encouraging Safety and Tolerability Profile When Added to Standard of Care Antihypertensives –
– Study Results Support Potential for Biannual Dosing of Zilebesiran –
– Full Study Results to Be Presented as a Late-Breaking Clinical Trial at the 2024 American College of Cardiology Annual Scientific Session on April 7 –
– Alnylam and Roche Also Announce Initiation of the KARDIA-3 Phase 2 Study in Patients at High Cardiovascular Risk with Uncontrolled Hypertension Despite Standard of Care Antihypertensive Treatments –
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Mar. 5, 2024-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced that the KARDIA-2 Phase 2 study of zilebesiran, an investigational RNAi therapeutic targeting liver-expressed angiotensinogen (AGT) in development for the treatment of hypertension, met the primary endpoint showing that zilebesiran resulted in clinically and statistically significant additive, placebo-adjusted reductions in 24-hour mean systolic blood pressure (SBP) at Month 3 as measured by ambulatory blood pressure monitoring (ABPM) in each of three independent patient cohorts receiving the standardized background therapies of either a thiazide-like diuretic (indapamide), calcium channel blocker (amlodipine) or angiotensin receptor blocker (olmesartan). Zilebesiran demonstrated an encouraging safety and tolerability profile when added to these standard of care antihypertensives. The Company believes these findings support further development.
“We are thrilled that a single dose of zilebesiran achieved clinically significant, additional reductions in systolic blood pressure when administered to patients who are not adequately controlled with commonly prescribed antihypertensives,” said Simon Fox, Ph.D., Vice President, Zilebesiran Program Lead at Alnylam. “These KARDIA-2 results, showing durable additional levels of blood pressure reduction on top of what is achieved by standard of care first-line antihypertensives with an encouraging safety profile, reinforce our confidence in zilebesiran’s differentiated profile. We look forward to sharing the full KARDIA-2 data as a late-breaking clinical trial at the upcoming American College of Cardiology Annual Scientific Session.”
The KARDIA-2 Phase 2 study is a randomized, double-blind (DB), placebo-controlled study designed to evaluate the efficacy and safety of zilebesiran, when added to standard of care antihypertensive medications, in adults with mild-to-moderate hypertension. This global, multicenter study enrolled 672 adults with hypertension. Patients who met all inclusion criteria and none of the exclusion criteria during a screening period were first randomized into three different cohorts to receive open-label therapy with olmesartan, amlodipine or indapamide as their protocol-specified background antihypertensive medication during a run-in period of at least four weeks. Following the run-in period, eligible patients were randomized 1:1 to receive 600 mg zilebesiran or placebo in addition to their protocol-specified background antihypertensive medication for six months.
The primary endpoint is the change from baseline in mean SBP at Month 3, assessed by 24-hour ABPM. Additional endpoints include the change in 24-hour mean SBP after six months of treatment assessed by ABPM, change in office SBP at Month 3 and Month 6, and change in diastolic blood pressure (DBP) measured by ABPM and office blood pressure at Month 3 and Month 6. Safety will be assessed throughout the study.
Alnylam and Roche today also announced the initiation of the global KARDIA-3 (NCT06272487) Phase 2 study, a randomized, DB, placebo-controlled, multicenter study designed to evaluate the efficacy and safety of zilebesiran used as an add-on therapy in adult patients with high cardiovascular risk and uncontrolled hypertension despite treatment with two to four standard of care antihypertensive medications. Patients with estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73m2 will be enrolled to cohort A, and patients with eGFR 30 to <45 mL/min/1.73m2 will be enrolled to cohort B. Patients who meet all of the inclusion and none of the exclusion criteria after the screening period will be randomized to receive 300 or 600 mg zilebesiran or placebo in cohort A on day 1, or 150, 300, or 600 mg zilebesiran or placebo in cohort B on day 1, of a 6-month DB treatment period as add-on therapy to their background antihypertensive medications. After the 6-month DB treatment period, patients will enter the 6-month safety follow-up period.
The primary endpoint is the change from baseline at Month 3 in mean seated office SBP. Additional endpoints include change from baseline at Month 3 in 24-hour mean SBP assessed by ABPM, change from baseline at Month 6 in mean seated office SBP and in 24-hour mean SBP assessed by ABPM. Safety will be assessed throughout the study.
About Zilebesiran
Zilebesiran is an investigational, subcutaneously administered RNAi therapeutic targeting angiotensinogen (AGT) in development for the treatment of hypertension in high unmet need populations. AGT is the most upstream precursor in the Renin-Angiotensin-Aldosterone System (RAAS), a cascade which has a demonstrated role in blood pressure (BP) regulation and its inhibition has well-established anti-hypertensive effects. Zilebesiran inhibits the synthesis of AGT in the liver, potentially leading to durable reductions in AGT protein and ultimately, in the vasoconstrictor angiotensin (Ang) II. Zilebesiran utilizes Alnylam’s Enhanced Stabilization Chemistry Plus (ESC+) GalNAc-conjugate technology, which enables infrequent subcutaneous dosing with increased selectivity and the potential to achieve tonic blood pressure control demonstrating consistent and durable blood pressure reduction throughout a 24-hour period, sustained up to six months after a single dose of zilebesiran. The safety and efficacy of zilebesiran have not been established or evaluated by the FDA, EMA or any other health authority. Zilebesiran is being co-developed and co-commercialized by Alnylam and Roche.
About Hypertension
Uncontrolled hypertension is the chronic elevation of blood pressure (BP), defined by the 2017 ACC/AHA guidelines as ≥130 mmHg systolic blood pressure (SBP) and ≥80 mmHg diastolic blood pressure (DBP). More than one billion people worldwide live with hypertension.i Approximately one in three adults are living with hypertension worldwide, with up to 80% of individuals remaining uncontrolled despite the availability of several classes of oral anti-hypertensive treatments. Despite the availability of anti-hypertensive medications, there remains a significant unmet medical need, especially given the poor rates of adherence to existing daily oral medications, resulting in inconsistent BP control and an increased risk for stroke, heart attack and premature death.ii In particular, there are a number of high unmet need settings where novel approaches to hypertension warrant additional development focus, including patients with poor medication adherence and in patients with high cardiovascular risk.
About RNAi
RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines known as RNAi therapeutics is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA) – the genetic precursors that encode for disease-causing or disease pathway proteins – thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.
About Alnylam Pharmaceuticals
Alnylam Pharmaceuticals (Nasdaq: ALNY) has led the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare and prevalent diseases with unmet need. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach yielding transformative medicines. Since its founding in 2002, Alnylam has led the RNAi Revolution and continues to deliver on a bold vision to turn scientific possibility into reality. Alnylam’s commercial RNAi therapeutic products are ONPATTRO® (patisiran), AMVUTTRA® (vutrisiran), GIVLAARI® (givosiran), OXLUMO® (lumasiran), and Leqvio® (inclisiran), which is being developed and commercialized by Alnylam’s partner, Novartis. Alnylam has a deep pipeline of investigational medicines, including multiple product candidates that are in late-stage development. Alnylam is executing on its “Alnylam P5x25” strategy to deliver transformative medicines in both rare and common diseases benefiting patients around the world through sustainable innovation and exceptional financial performance, resulting in a leading biotech profile. Alnylam is headquartered in Cambridge, MA. For more information about our people, science and pipeline, please visit www.alnylam.com and engage with us on X (formerly Twitter) at @Alnylam, or on LinkedIn, Facebook, or Instagram.
View source version on businesswire.com: https://www.businesswire.com/news/home/20240305182792/en/
Alnylam Pharmaceuticals, Inc.
Source: Alnylam Pharmaceuticals, Inc.
Alnylam, Roche mark second Phase 2 win for blood pressure therapy
Mar. 05, 2024 9:57 AM ET
Alnylam Pharmaceuticals, Inc. (ALNY) Stock, RHHBY Stock, RHHBF Stock
By: Dulan Lokuwithana, SA News Editor1 Comment
Alnylam Pharma (NASDAQ:ALNY) traded higher on Tuesday premarket after the RNAi therapeutics company said its experimental blood pressure therapy zilebesiran, co-developed with Roche (OTCQX:RHHBY) (OTCQX:RHHBF), succeeded in its second mid-stage study.
The Phase 2 global study named KARDIA-2 met the primary endpoint for zilebesiran with standardized background therapies in adults with high cardiovascular risk and uncontrolled hypertension, according to the company.
Alnylam Pharmaceuticals, Inc. (ALNY) Stock, RHHBY Stock,
https://www.alnylam.com/sites/default/files/pdfs/ALN-AGT-Fact-Sheet.pdf
RGX-202
Efruxifermin (EFX)
Efruxifermin (EFX)
REGENXBIO ANNOUNCES NEW POSITIVE INITIAL EFFICACY DATA FROM AFFINITY DUCHENNE® TRIAL
Mar 05, 2024 at 7:05 AM EST
- New three-month assessment in first patient at dose level 2 demonstrates robust microdystrophin expression
- Patient aged 12 years at dosing had expression level at 75.7% of control
- Early evidence of strength and motor function improvement observed
- On track to initiate pivotal trial in second half of 2024
- Webcast this morning, Tuesday, March 5, 8:30 a.m. ET, with principal investigator
ROCKVILLE, Md., March 5, 2024 /PRNewswire/ -- REGENXBIO Inc. (Nasdaq: RGNX) today reported additional interim safety and efficacy data in the Phase I/II AFFINITY DUCHENNE® trial of RGX-202 in patients with Duchenne muscular dystrophy (Duchenne) ages 4 to11 years old, including RGX-202 microdystrophin expression from dose level 2 and video of trial clinic assessments demonstrating initial evidence of strength and functional improvement.
"RGX-202 at dose level 2 is demonstrating significantly increased microdystrophin expression in a 12-year-old patient," said Kenneth T. Mills, President and CEO, REGENXBIO. "We know there is an insufficient level of data available to the community for boys older than 7 years, and we are committed to being transparent with our data for a Duchenne community in need of new treatment options that can meaningfully impact disease. In addition, we are encouraged by the safety data at both dose levels and initial caregiver observations of strength and motor function improvement in boys treated with RGX-202. We look forward to following these patients to establish durability and greater separation from baseline, which we hope will further establish RGX-202 as an important option among treatments in development."
"There is a need for treatment options for boys with Duchenne that have the potential to alter the disease trajectory," said Aravindhan Veerapandiyan, M.D., Arkansas Children's Hospital. "I am very pleased with the new microdystrophin expression data from RGX-202 dose level 2. It is encouraging to see that patients are safely progressing through their trial protocol strength and motor function assessments with early observations of improvement, including in older boys."
Safety Update
As of February 28, 2024, RGX-202 has been well tolerated with no drug-related serious adverse events in five patients, aged 4.4 to 12.1 at dose level 1 (1x1014 genome copies (GC)/kg body weight) and dose level 2 (2x1014 GC/kg body weight). Time of post-administration follow up ranges from approximately seven weeks to over eleven months. All patients who reached three-month follow-up have completed the immunosuppression regimen per study protocol.
Biomarker Data and Recorded Strength and Functional Observations
In new data from the first patient, aged 12.1 years, who received RGX-202 at dose level 2, RGX-202 microdystrophin expression was measured to be 75.7% compared to control at three months. A reduction from baseline in serum creatinine kinase (CK) levels of 77% was observed at ten weeks.
All four patients, across both dose levels, who completed three-month trial assessments indicate encouraging increases in expression of RGX-202 microdystrophin and reduction from baseline in serum CK levels, supporting evidence of clinical improvement.
RGX-202 microdystrophin levels were measured using an automated and precise western blot method (Jess), and comparable results were confirmed with a proprietary liquid chromatography-mass spectrometry (LC-MS) method. Elevated CK levels are associated with muscle injury and are uniformly elevated in patients with Duchenne. Among patients aged 8 to 11 years old at screening, RGX-202 microdsytrophin expression levels (change from baseline) at three months following RGX-202 administration was higher in dose level 2. The patient data is presented below.
In addition, new recordings of the AFFINITY DUCHENNE trial clinic assessments and home videos shared with trial investigators by caregivers illustrate patients treated with RGX-202 are demonstrating initial evidence of strength and functional improvement.
"Several of the items in the clinic recordings are timed tasks and they are also measured on the NSAA. We plan to present strength and functional assessment data for both dose levels from the trial later this year, but today this is a glimpse of how these boys are gaining functional skills since dosing," said Dr. Veerapandiyan, "The montage of home videos provides some insight into a family's experience with RGX-202. Being able to do these activities, which can be quite difficult for boys with Duchenne, is informal, but a set of important observations of their experience."
Clinical Program Updates
REGENXBIO expects to make a pivotal dose determination in mid-2024. The Company also expects to share strength and functional assessment data for both dose levels and the initiation of a pivotal trial in the second half of 2024. The Company plans to use RGX-202 microdystrophin expression as a surrogate endpoint to support a Biologics License Application (BLA) filing using the accelerated approval pathway.
Conference Call Details
REGENXBIO will host a webcast Tuesday, March 5 at 8:30 a.m. ET. The live webcast can be accessed in the Investors section of REGENXBIO's website at WWW.REGENXBIO.COM.
An archived replay of the webcast will be available for approximately 30 days following the presentation.
AFFINITY DUCHENNE Trial Design
The Phase I/II AFFINITY DUCHENNE trial is a multicenter, open-label dose escalation and dose expansion clinical study to evaluate the safety, tolerability and clinical efficacy of a one-time intravenous (IV) dose of RGX-202 in patients with Duchenne. In the dose evaluation phase of the trial, four ambulatory, pediatric patients (ages 4 to 11 years old) are expected to enroll in two cohorts with doses of 1x1014 GC/kg body weight (n=2) and 2x1014 GC/kg body weight (n=2). After an independent safety data review for each cohort, a dose expansion phase of the trial may allow for additional patients to be enrolled.
The trial design was informed by the Duchenne community and engagement with key opinion leaders, including a comprehensive, short-term, prophylactic immunosuppression regimen to proactively mitigate potential complement-mediated immunologic responses, and inclusion criteria based on dystrophin gene mutation status, including DMD gene mutations in exons 18 and above. Trial endpoints include safety, immunogenicity assessments, pharmacodynamic and pharmacokinetic measures of RGX-202, including microdystrophin protein levels in muscle, and strength and functional assessments, including the North Star Ambulatory Assessment (NSAA) and timed function tests.
About RGX-202
RGX-202 has differentiated and important biology most similar to naturally occurring dystrophin that protects from the muscle degradation associated with Duchenne. RGX-202 is designed to deliver a transgene for a novel microdystrophin that includes the functional elements of the C-Terminal (CT) domain found in naturally occurring dystrophin. Presence of the CT domain has been shown in preclinical studies to recruit several key proteins to the muscle cell membrane, leading to improved muscle resistance to contraction-induced muscle damage in dystrophic mice. Additional design features, including codon optimization and reduction of CpG content, may potentially improve gene expression, increase translational efficiency and reduce immunogenicity. RGX-202 is designed to support the delivery and targeted expression of genes throughout skeletal and heart muscle using the NAV AAV8 vector, a vector used in numerous clinical trials, and a well-characterized muscle-specific promoter (Spc5-12).
https://www.regenxbio.com/therapeutic-programs/rgx-202/
About Duchenne Muscular Dystrophy
Duchenne is a severe, progressive, degenerative muscle disease, affecting 1 in 3,500 to 5,000 boys born each year worldwide. Duchenne is caused by mutations in the Duchenne gene which encodes for dystrophin, a protein involved in muscle cell structure and signaling pathways. Without dystrophin, muscles throughout the body degenerate and become weak, eventually leading to loss of movement and independence, required support for breathing, cardiomyopathy and premature death.
ABOUT REGENXBIO Inc.
REGENXBIO is a leading clinical-stage biotechnology company seeking to improve lives through the curative potential of gene therapy. Since its founding in 2009, REGENXBIO has pioneered the development of AAV Therapeutics, an innovative class of gene therapy medicines. REGENXBIO is advancing a pipeline of AAV Therapeutics for retinal and rare diseases, including ABBV-RGX-314 for the treatment of wet AMD and diabetic retinopathy, being developed in collaboration with AbbVie, RGX-202 for the treatment of Duchenne and RGX-121 for the treatment of MPS II. Thousands of patients have been treated with REGENXBIO's AAV Therapeutic platform, including Novartis' ZOLGENSMA for children with spinal muscular atrophy. Designed to be one-time treatments, AAV Therapeutics have the potential to change the way healthcare is delivered for millions of people. For more information, please visit WWW.REGENXBIO.COM.
View original content to download multimedia:HTTPS://WWW.PRNEWSWIRE.COM/NEWS-RELEASES/REGENXBIO-ANNOUNCES-NEW-POSITIVE-INITIAL-EFFICACY-DATA-FROM-AFFINITY-DUCHENNE-TRIAL-302079525.HTML
SOURCE REGENXBIO Inc.
Regenxbio stock jumps 13% on positive data for DMD drug
Mar. 05, 2024 11:03 AM ET
REGENXBIO Inc. (RGNX) StockSRPT, PTCT, CAPR, SLDB, EWTX
By: Val Brickates Kennedy, SA News Editor1 Comment
Regenxbio (NASDAQ:RGNX) stock was up 13% in morning trading Tuesday after the company reported positive data from a Phase 1/2 study of its drug RGX-202 in the treatment of Duchenne muscular dystrophy, or DMD, in children aged 4 to 11 years old.
The company said the data showed that RGX-202 at dose level 2 demonstrated significantly increased microdystrophin expression in one 12-year-old patient. Caregivers also observed improved strength and motor function in children treated with the therapy, Regenxbio said in a statement.
Efruxifermin (EFX)
Efruxifermin (EFX)
Efruxifermin (EFX)
Akero Therapeutics Reports Statistically Significant Histological Improvements at Week 96 in Phase 2b HARMONY Study
Mar 4, 2024
50mg (75%, p<0.001) and 28mg (46%, p=0.07) EFX groups demonstrated ≥1 stage improvement in fibrosis without worsening of MASH, approximately three- and two-fold the placebo rate (24%)
50mg (36%, p<0.01) and 28mg (31%, p<0.01) EFX groups demonstrated ≥2 stage improvement in fibrosis without worsening of MASH, more than 10-fold the placebo rate (3%)
EFX-treated patients experienced statistically significant improvements on nearly all histological endpoints by ITT analysis as well as the primary analysis of patients with week 96 biopsies
Investor webcast at 8:00 am ET Monday, March 4, 2024
SOUTH SAN FRANCISCO, Calif., March 04, 2024 (GLOBE NEWSWIRE) -- Akero Therapeutics, Inc. (Nasdaq: AKRO), a clinical-stage company developing transformational treatments for patients with serious metabolic disease marked by high unmet medical need, today released preliminary topline week 96 results from HARMONY, a Phase 2b study evaluating the efficacy and safety of its lead product candidate efruxifermin (EFX) in patients with pre-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH), fibrosis stage 2 or 3 (F2-F3). The study previously met its primary endpoint of ≥1 stage improvement in fibrosis with no worsening of MASH after 24 weeks of treatment for both the 50mg EFX (41%) and 28mg EFX (39%) dose groups, compared to 20% for the placebo arm. At week 96, the response rates on this endpoint increased to 75% (p<0.001) for 50mg EFX and 46% (p=0.07) for 28mg EFX, compared to 24% for placebo.
The study also met additional histology endpoints at week 96—notably 36% (p<0.01) and 31% (p<0.01) of patients treated with 50mg EFX and 28mg EFX experienced a 2-stage improvement in fibrosis without worsening of MASH—which is more than 10-fold the placebo rate of 3%. Results for all of the histological endpoints are summarized in the table below, based on either the primary analysis (patients with baseline and week 96 biopsies) or intent-to-treat (ITT) analysis (all randomized and dosed patients, with missing data imputed as non-response).
“Notwithstanding inherent limitations in making cross-trial comparisons, the statistically significant results for ≥1- and 2-stage fibrosis improvement and no worsening of MASH observed for 50mg EFX at week 96 are the largest response rates reported publicly to date for these endpoints in any MASH population,” said Stephen Harrison, M.D., medical director of Pinnacle Clinical Research and the HARMONY study’s principal investigator. “I believe the magnitude and general consistency of results observed across the Phase 2a BALANCED and Phase 2b HARMONY studies in patients with pre-cirrhotic MASH are reasons to be optimistic about results of the ongoing Phase 3 SYNCHRONY Histology study and the potential for EFX to be an important MASH medicine, if approved.”
The placebo-adjusted effect size on fibrosis improvement without worsening of MASH (EFX response rate minus placebo response rate) more than doubled between week 24 and week 96 for the 50mg EFX group, with a slight increase observed for the 28mg EFX group. Specifically, the placebo-adjusted effect sizes for fibrosis improvement without worsening of MASH grew from 21% to 52% between week 24 and week 96 for 50mg EFX and from 20% to 22% for 28mg EFX. Highly statistically significant results for 50mg EFX at week 96 are notable because (1) the study was not fully powered at week 96 and (2) the placebo rate increased rather than decreased. An increase in treatment rate for placebo means that the increases in effect size are attributable to higher EFX treatment responses rather than a decline in placebo rate.
Analysis of the evolution of responses between weeks 24 and 96 indicated not only broader fibrosis improvement without worsening of MASH but also sustained response, particularly at 50mg EFX. Among those patients with available week 96 biopsies whose fibrosis improved at week 24, 92% and 83% of the 50mg and 28mg EFX groups remained responders, respectively, compared to 40% for placebo.
Analysis of a subset of patients with baseline F3 fibrosis who had week 96 biopsies showed EFX’s potential to treat patients with more advanced fibrosis, who are generally considered to be at higher risk of progression to cirrhosis. For this advanced F3 patient population, 68% (p<0.001) and 40% (p=0.053) of the 50mg EFX and 28mg EFX groups, respectively, experienced at least a one-stage improvement in fibrosis without worsening of MASH, compared to 14% for placebo.
“We believe the statistically significant 2-stage improvement in fibrosis without worsening of MASH observed in approximately one in three EFX-treated patients sets EFX apart,” said Andrew Cheng, M.D., Ph.D., president and chief executive officer of Akero. “Today’s results show that longer exposure to EFX has the potential to yield sustained fibrosis improvement as well as widening anti-fibrotic treatment responses across the treated patient populations. We look forward to continuing our evaluation of EFX in patients with pre-cirrhotic MASH and cirrhosis due to MASH in our ongoing Phase 3 SYNCHRONY program, in which two out of three studies are actively enrolling.”
EFX was reported to be generally well-tolerated. There were no deaths. Fifteen serious adverse events were reported, which were generally balanced across dose groups. Across both EFX groups, the most frequent adverse events (AEs) were grade 1 or 2 gastrointestinal events (diarrhea, nausea, and increased appetite), which were transient in nature. A total of three patients treated with EFX were discontinued due to AEs between week 24 and week 96 (two in the 28mg group and one in the 50mg group), compared with none for placebo.
In October of 2023, Akero reported week 36 results for the SYMMETRY study, a Phase 2b trial in patients with compensated cirrhosis (F4) due to MASH, Child-Pugh class A. The SYMMETRY study was designed to include a second biopsy after 96 weeks of treatment, for which the results remain on track to be reported in the first quarter of 2025.
Conference Call / Webcast Details
Akero will host a conference call and webcast with slide presentation at 8:00 a.m. ET today. The live webcast will be available on the Events & Presentations page of Akero’s website, with the recording and presentation available immediately following the event.
About MASH
MASH (metabolic-associated steatohepatitis) is a serious form of MASLD (metabolic-associated steatotic liver disease) that is estimated to affect more than 17 million Americans. MASH is characterized by an excessive accumulation of fat in the liver that causes stress and injury to liver cells, leading to inflammation and fibrosis, which can progress to cirrhosis, liver failure, cancer and eventually death. There are no approved treatments for the condition and MASH is the fastest growing cause of liver transplants and liver cancer in the United States and Europe.
About the HARMONY Study
The Phase 2b HARMONY study is a multicenter, randomized, double-blind, placebo-controlled, dose-ranging trial in biopsy-confirmed adult MASH patients with fibrosis stage 2 or 3. The study enrolled a total of 128 patients, randomized to receive once-weekly subcutaneous dosing of 28mg or 50mg EFX, or placebo for 24-weeks, 126 of whom received at least one study dose. The primary efficacy endpoint for the study was the proportion of subjects who achieve at least one-stage fibrosis improvement without worsening of MASH at week 24. Week 96 secondary measures included ≥1 stage fibrosis improvement and no worsening of MASH, 2-stage fibrosis improvement without worsening of MASH, at least one-stage fibrosis improvement and MASH resolution, change from baseline in liver enzymes, noninvasive markers of liver fibrosis, glycemic control, lipoproteins, and body weight as well as safety and tolerability measures.
About EFX
Efruxifermin (EFX), is Akero’s lead product candidate for MASH, currently being evaluated in the ongoing Phase 2b SYMMETRY, Phase 3 SYNCHRONY Histology, and Phase 3 SYNCHRONY Real-World studies. EFX has been observed to reduce liver fat and inflammation, reverse fibrosis, increase insulin sensitivity and improve lipoproteins in multiple clinical trials. This holistic profile offers the potential to address the complex, multi-system disease state of MASH, including improvements in lipoprotein risk factors linked to cardiovascular disease – the leading cause of death in MASH patients. Engineered to mimic the biological activity profile of native FGF21, EFX is designed to offer convenient once-weekly dosing and has been generally well-tolerated in clinical trials to date.
About Akero Therapeutics
Akero Therapeutics is a clinical-stage company developing transformational treatments for patients with serious metabolic diseases marked by high unmet medical need, including metabolic dysfunction-associated steatohepatitis (MASH), a disease without any approved therapies. Akero's lead product candidate, EFX, is currently being evaluated in two ongoing Phase 3 clinical trials: the SYNCHRONY Histology study in patients with pre-cirrhotic MASH (F2-F3 fibrosis) and the SYNCHRONY Real-World study in patients with MASH or MASLD. A third clinical trial, the SYNCHRONY Outcomes study in patients with cirrhosis due to MASH, is expected to be initiated in the first half of 2024. The Phase 3 SYNCHRONY program builds on the results of two Phase 2b clinical trials, the HARMONY study in patients with pre-cirrhotic MASH and the SYMMETRY study in patients with cirrhosis due to MASH. Akero is headquartered in South San Francisco. Visit us at akerotx.com and follow us on LinkedIn and Twitter for more information.
Akero stock jumps as lead drug shows added fibrosis improvement in MASH patients
Mar. 04, 2024 7:38 AM ET
Akero Therapeutics, Inc. (AKRO) Stock
By: Preeti Singh, SA News Editor
Shares of Akero Therapeutics (NASDAQ:AKRO) jumped around 70% in early trading on Monday after a Phase 2 study of its lead drug, efruxifermin (EFX), showed statistically significant histological improvements in patients with pre-cirrhotic metabolic dysfunction-associated steatohepatitis (MASH).
biotecHOPE™ 2024
Axatilimab
TEVIMBRA® (tislelizumab)
Axatilimab
Incyte Announces U.S. Food And Drug Administration Grants Priority Review For Axatilimab For The Treatment Of Chronic Graft-Versus-Host Disease
February 27, 2024 at 4:08 PM EST
- Priority Review acceptance based on positive results of AGAVE-201 study
WILMINGTON, Del.--(BUSINESS WIRE)--Feb. 27, 2024-- Incyte (Nasdaq:INCY) today announced that the U.S. Food and Drug Administration (FDA) has accepted for Priority Review the Biologics License Application (BLA) for axatilimab, an anti-CSF-1R antibody, for the treatment of chronic graft-versus-host disease (GVHD) after failure of at least two prior lines of systemic therapy. The Prescription Drug User Fee Act (PDUFA) date for the FDA decision is August 28, 2024.
The BLA is supported by positive data from the AGAVE-201 trial (NCT04710576), recently highlighted in a Plenary Scientific Session at the American Society of Hematology Annual Meeting 2023, which showed that treatment with axatilimab resulted in clinically meaningful results and was generally well-tolerated, with a safety profile that was manageable and consistent with the mechanism of action of CSF-1R inhibition.
Axatilimab is being developed by Incyte and Syndax Pharmaceuticals (Nasdaq:SNDX) as part of an exclusive worldwide co-development and co-commercialization license agreement.
“Despite recent advancements in the treatment of patients with chronic GVHD, there remains a significant unmet need for patients who progressed on earlier lines of therapy,” said Hervé Hoppenot, Chief Executive Officer, Incyte. “Axatilimab’s novel mechanism offers a differentiated treatment approach which may help patients suffering from this devastating disease. We look forward to working closely with the FDA and our partners at Syndax on the review of our application for axatilimab for this indication.”
The FDA grants Priority Review designation to applications for medicines that, if approved, would treat a serious condition and provide significant improvements in the safety or effectiveness of the treatment.
About Chronic Graft-Versus-Host Disease
Chronic graft-versus-host disease (GVHD), an immune response of the donor-derived hematopoietic cells against recipient tissues, is a serious, potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation which can last for years. Chronic GVHD is estimated to develop in approximately 40% of transplant recipients, and affects approximately 14,000 patients in the U.S.1,2. Chronic GVHD typically manifests across multiple organ systems, with skin and mucosa being commonly involved, and is characterized by the development of fibrotic tissue3.
About Axatilimab
Axatilimab is an investigational monoclonal antibody that targets colony stimulating factor-1 receptor, or CSF-1R, a cell surface protein thought to control the survival and function of monocytes and macrophages. In pre-clinical models, inhibition of signaling through the CSF-1 receptor has been shown to reduce the number of disease-mediating macrophages along with their monocyte precursors, which has been shown to play a key role in the fibrotic disease process underlying diseases such as chronic GVHD and idiopathic pulmonary fibrosis (IPF). Phase 1/2 data of axatilimab in chronic GVHD demonstrating its broad activity and tolerability were last presented at the 63rd American Society of Hematology Annual Meeting and data were published in the Journal of Clinical Oncology. Additionally, positive topline results and additional data from the Phase 2 AGAVE-201 trial highlighted in a Plenary Scientific Session at the American Association of Hematology Annual Meeting 2023 were announced. Axatilimab was granted Orphan Drug Designation by the U.S. FDA for the treatment of patients with chronic GVHD and IPF.
In September 2021, Syndax and Incyte entered into an exclusive worldwide co-development and co-commercialization license agreement for axatilimab. Axatilimab is being developed under an exclusive worldwide license from UCB entered into between Syndax and UCB in 2016.
About AGAVE-201 (NCT04710576)
The global Phase 2 AGAVE-201 dose-ranging trial evaluated the efficacy, safety, and tolerability of axatilimab in 241 adult and pediatric patients with recurrent or refractory active chronic GVHD whose disease had progressed after two prior therapies. Patients were randomized to one of three treatment groups that investigated a distinct dose of axatilimab administered at 0.3 mg/kg every two weeks, 1.0 mg/kg every two weeks or 3.0 mg/kg every four weeks. The trial's primary endpoint is the proportion of patients in each dose group who achieved an objective response as defined by 2014 NIH Consensus Criteria for chronic GVHD by cycle 7 day 1. Secondary endpoints include duration of response, percent reduction in daily steroids dose, organ specific response rates and validated quality-of-life assessments using the Modified Lee Symptom Scale.
For more information about AGAVE-201, visit https://www.clinicaltrials.gov/study/NCT04710576.
About Incyte
Incyte is a Wilmington, Delaware-based, global biopharmaceutical company focused on finding solutions for serious unmet medical needs through the discovery, development and commercialization of proprietary therapeutics. For additional information on Incyte, please visit Incyte.com and follow @Incyte.
View source version on businesswire.com: https://www.businesswire.com/news/home/20240227083647/en/
Source: Incyte
FDA accepts Incyte application for graft-versus-host disease drug
Feb. 27, 2024 5:22 PM ET
Incyte Corporation (INCY) Stock, SNDX Stock
By: Val Brickates Kennedy, SA News Editor
The FDA has accepted Incyte’s (NASDAQ:INCY) market application for priority review of its drug candidate axatilimab for the treatment of chronic graft-versus-host disease in patients who have had at least two prior lines of systemic therapy.
Incyte Corporation (INCY) Stock, SNDX Stock
NVL-520
TEVIMBRA® (tislelizumab)
Axatilimab
Nuvalent Receives U.S. FDA Breakthrough Therapy Designation for NVL-520
CAMBRIDGE, Mass., Feb. 27, 2024 /PRNewswire/ -- Nuvalent, Inc.
(Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, today announced that the U.S. Food and Drug Administration (FDA) has granted breakthrough therapy designation (BTD) to NVL-520 for the treatment of patients with ROS1-positive metastatic non-small cell lung cancer (NSCLC) who have been previously treated with two or more ROS1 tyrosine kinase inhibitors (TKIs).
ROS1 rearrangements occur in up to approximately 3% of metastatic NSCLCs. At the time of diagnosis, up to 40% of these patients present with accompanying brain metastases, and approximately 40% of patients develop resistance mutations following current front-line treatment. There remains no clear standard of care for patients who have been previously treated with two or more ROS1 TKIs.
NVL-520 is a novel brain-penetrant ROS1-selective tyrosine kinase inhibitor (TKI) created with the aim to simultaneously overcome the clinical challenges of emergent treatment resistance, brain metastases, and off-target central nervous system (CNS) adverse events associated with inhibition of the structurally-related tropomyosin receptor kinase (TRK) family that may limit the use of currently available ROS1 TKIs.
"In line with our commitment to bringing new potential best-in-class medicines to patients with cancer as quickly as possible, we are always looking for opportunities to further accelerate our programs," said James Porter, Ph.D., Chief Executive Officer at Nuvalent. "We're very encouraged by today's announcement of FDA breakthrough therapy designation for NVL-520, as it recognizes the continued need for innovation for patients with ROS1-positive NSCLC who have exhausted available therapies. We look forward to providing an update from the ARROS-1 trial of NVL-520 at a medical meeting later this year."
BTD is designed to expedite the development and review of therapies intended to treat a serious or life-threatening condition and whose preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on one or more clinically significant endpoints over existing available therapies. Under the designation, the FDA provides intensive guidance, organizational commitment involving senior managers, and eligibility for rolling review and other actions to expedite review.
The BTD for NVL-520 is based on the preliminary safety and activity of NVL-520 in heavily pretreated patients with advanced ROS1-positive NSCLC in the Phase 1 portion of the Phase 1/2 ARROS-1 clinical trial. Enrollment in the Phase 2 portion of the trial is ongoing, and the company expects to share updated data from the trial at a medical meeting in 2024.
About NVL-520
NVL-520 is a novel brain-penetrant ROS1-selective inhibitor created with the aim to overcome limitations observed with currently available ROS1 inhibitors. NVL-520 is designed to remain active in tumors that have developed resistance to currently available ROS1 inhibitors, including tumors with treatment-emergent ROS1 mutations such as G2032R. In addition, NVL-520 is designed for central nervous system (CNS) penetrance to improve treatment options for patients with brain metastases, and to avoid inhibition of the structurally-related tropomyosin receptor kinase (TRK) family. Together, these characteristics have the potential to avoid TRK-related CNS adverse events seen with dual TRK/ROS1 inhibitors and to drive deep, durable responses for patients across all lines of therapy. NVL-520 has received orphan drug designation for ROS1-positive non-small cell lung cancer (NSCLC) and is currently being investigated in the ARROS-1 trial (NCT05118789), a first-in-human Phase 1/2 clinical trial for patients with advanced ROS1-positive NSCLC and other solid tumors.
About Nuvalent
Nuvalent, Inc. (Nasdaq: NUVL) is a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for patients with cancer, designed to overcome the limitations of existing therapies for clinically proven kinase targets. Leveraging deep expertise in chemistry and structure-based drug design, we develop innovative small molecules that have the potential to overcome resistance, minimize adverse events, address brain metastases, and drive more durable responses. Nuvalent is advancing a robust pipeline with investigational candidates for ROS1-positive, ALK-positive, and HER2-positive non-small cell lung cancer, and multiple discovery-stage research programs.
Nuvalent lung cancer candidate gets FDA breakthrough therapy status
Feb. 27, 2024 7:26 AM ET
By: Preeti Singh, SA News Editor
Nuvalent (NASDAQ:NUVL) reported Tuesday that its lung cancer drug candidate, NVL-520, has been granted breakthrough therapy designation by the U.S. Food and Drug Administration (FDA).
NVL-520 received breakthrough therapy status for the treatment of patients with ROS1-positive metastatic non-small cell lung cancer (NSCLC) who have been previously treated with two or more ROS1 tyrosine kinase inhibitors (TKIs).
The therapy has already received orphan drug designation for ROS1-positive NSCLC and is currently being investigated in the ARROS-1 trial.
TEVIMBRA® (tislelizumab)
TEVIMBRA® (tislelizumab)
TEVIMBRA® (tislelizumab)
BeiGene’s Biologics License Application for TEVIMBRA® (tislelizumab) for First-Line Gastric or Gastroesophageal Junction Cancers Accepted by FDA
Feb 27, 2024 6:00 AM
Application based on results from global Phase 3 RATIONALE-305 trial demonstrating TEVIMBRA plus chemotherapy significantly improved overall survival in advanced gastric/GEJ cancer
Prescription Drug User Fee Act target action date set for December 2024
BASEL, Switzerland & BEIJING & CAMBRIDGE, Mass.--(BUSINESS WIRE)-- BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global oncology company, today announced that the U.S. Food and Drug Administration (FDA) has accepted a Biologics License Application (BLA) for TEVIMBRA® (tislelizumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, for the treatment of patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. The FDA’s action date on the BLA is expected in December 2024.
“There is an urgent need for new treatment options for gastric cancer, which is often diagnosed at the advanced or metastatic stage,” said Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeiGene. “In clinical trials, TEVIMBRA has demonstrated its potential to improve survival for patients with gastric and gastroesophageal junction cancer. This FDA acceptance brings us one step closer to delivering on a new treatment option for patients who often face poor prognoses.”
The filing is based on results from the global RATIONALE-305 trial. The study met its primary endpoint of overall survival of 15.0 months for patients treated with TEVIMBRA in combination with investigator’s choice of chemotherapy compared to 12.9 months for patients treated with placebo plus chemotherapy (n=997; HR: 0.80 [95% CI: 0.70, 0.92]; P=0.0011), demonstrating a 20% reduction in the risk of death. Additionally, TEVIMBRA plus chemotherapy was associated with a higher objective response rate (47.3% vs. 40.5%) and median duration of response (8.6 months vs. 7.2 months) compared to placebo plus chemotherapy. Median progression-free survival for TEVIMBRA plus chemotherapy was 6.9 months vs. 6.2 months respectively; (HR: 0.78 [95% CI: 0.67, 0.90]). The safety profile for TEVIMBRA in combination with chemotherapy was manageable and in line with the known safety profile of anti-PD-1 antibodies.
Grade ≥3 treatment-related adverse events (TRAEs) occurred in 53.8% of patients in the TEVIMBRA plus chemotherapy arm and 49.8% of patients in the placebo plus chemotherapy arm. The most common TRAEs of any grade with an incidence ≥30% were nausea, decreased appetite, platelet count decreased, neutrophil count decreased, vomiting, and anaemia.
TEVIMBRA was recently approved by the European Commission for the treatment of patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) after prior chemotherapy. The FDA is also reviewing a BLA for TEVIMBRA as a first-line treatment for patients with unresectable, recurrent, locally advanced, or metastatic ESCC with a target action date in July 2024. A BLA for the treatment of patients with advanced or metastatic ESCC after prior chemotherapy is also under review by the FDA.
BeiGene has launched more than 17 potentially registration-enabling trials with TEVIMBRA, of which 11 Phase 3 randomized trials and 4 Phase 2 trials have already had positive readouts. Through these trials, TEVIMBRA has demonstrated its ability to safely deliver clinically meaningful improvements in survival benefits and quality of life for hundreds of thousands of cancer patients across a range of tumor types – in many cases, regardless of PD-(L)1 status – both as monotherapy and in combination with other regimens. More than 900,000 patients have been prescribed TEVIMBRA globally to date.
About RATIONALE-305
RATIONALE-305 (NCT03777657) is a randomized, double-blind, placebo-controlled, global Phase 3 that enrolled 997 patients with advanced unresectable or metastatic G/GEJ adenocarcinoma. The primary endpoint was OS, with prespecified hierarchy testing for the PD-L1 high population followed by the intent-to-treat (ITT) population. Results of the final analysis of the ITT population were presented as a late-breaking oral presentation during the European Society for Medical Oncology (ESMO) Congress 2023.
About Gastric and Gastroesophageal Junction (G/GEJ) Adenocarcinoma
Gastric (stomach) cancer is the fifth most common cancer worldwide and the fifth highest leading cause of cancer mortality.1 Nearly 1 million new patients were diagnosed with gastric cancer in 2022, and 660,000 deaths were reported globally. In the U.S., it is estimated there were approximately 27,000 patients diagnosed with gastric cancer and 11,000 deaths from the disease in 2024.2 The five-year survival rate for gastric cancer in the U.S. is 36%.3 Gastroesophageal junction adenocarcinoma occurs at the area where the esophagus joins the stomach, which is just beneath the diaphragm (the thin sheet of breathing muscle under the lungs).4
About TEVIMBRA® (tislelizumab)
Tislelizumab is a uniquely designed humanized immunoglobulin G4 (IgG4) anti-programmed cell death protein 1 (PD-1) monoclonal antibody with high affinity and binding specificity against PD-1. It is designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages, helping to aid the body’s immune cells to detect and fight tumors.
About BeiGene
BeiGene is a global oncology company that is discovering and developing innovative treatments that are more affordable and accessible to cancer patients worldwide. With a broad portfolio, we are expediting development of our diverse pipeline of novel therapeutics through our internal capabilities and collaborations. We are committed to radically improving access to medicines for far more patients who need them. Our growing global team of more than 10,000 colleagues spans five continents, with administrative offices in Basel, Beijing, and Cambridge, U.S. To learn more about BeiGene, please visit www.beigene.com and follow us on LinkedIn and X (formerly known as Twitter).
View source version on businesswire.com: https://www.businesswire.com/news/home/20240227824706/en/
Source: BeiGene, Ltd.
FDA accepts BeiGene license application for gastric cancer combo therapy
Feb. 27, 2024 7:14 AM ET
By: Preeti Singh, SA News Editor
BeiGene (NASDAQ:BGNE) reported on Tuesday that its biologics license application (BLA) for a combination therapy for gastric or gastroesophageal junction cancer has been accepted by the U.S. Food and Drug Administration (FDA).
Tevimbra, a humanized IgG4 anti-PD-1 monoclonal antibody, was recently approved by the European Commission for the treatment of patients with advanced or metastatic esophageal squamous cell carcinoma after prior chemotherapy (ESCC).
TEVIMBRA® (tislelizumab)
TEVIMBRA® (tislelizumab)
TEVIMBRA® (tislelizumab)
BeiGene Receives Positive CHMP Opinion for Tislelizumab as Treatment for Non-Small Cell Lung Cancer
Feb 26, 2024 5:00 AM
Recommendation based on results of three Phase 3 clinical trials demonstrating benefit of tislelizumab as a first- and second-line treatment for patients with NSCLC
BASEL, Switzerland & BEIJING & CAMBRIDGE, Mass.--(BUSINESS WIRE)-- BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global oncology company, today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a positive opinion recommending approval of tislelizumab as a treatment for non-small cell lung cancer (NSCLC) across three indications:
- In combination with carboplatin and either paclitaxel or nab-paclitaxel for the first-line treatment of adult patients with squamous NSCLC who have locally advanced NSCLC and are not candidates for surgical resection or platinum-based chemoradiation, or metastatic NSCLC.
- In combination with pemetrexed and platinum-containing chemotherapy for the first-line treatment of adult patients with non-squamous NSCLC whose tumors have PD-L1 expression on ≥50% of tumor cells with no EGFR or ALK positive mutations and who have locally advanced NSCLC and are not candidates for surgical resection or platinum-based chemoradiation, or metastatic NSCLC.
- As monotherapy for the treatment of adult patients with locally advanced or metastatic NSCLC after prior platinum-based therapy. Patients with EGFR mutant or ALK positive NSCLC should also have received targeted therapies before receiving tislelizumab.
“Through three Phase 3 clinical trials enrolling nearly 1,500 patients across the world including in the European Union, tislelizumab has been shown to be an effective therapy for patients with treatment-naïve and treatment-resistant NSCLC,” said Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeiGene. “Today's positive CHMP opinion brings us one step closer to providing an important treatment option to patients in Europe with lung cancer, which is among the most common cancers and a leading cause of cancer death in the region.”
The Marketing Authorization Application (MAA) for NSCLC is based on results from three Phase 3 studies that enrolled 1,499 patients. First-line combination therapy results from RATIONALE 307 evaluating tislelizumab in advanced squamous NSCLC and from RATIONALE 304 evaluating tislelizumab in locally advanced or metastatic non-squamous NSCLC were published in JAMA Oncology and in the Journal of Thoracic Oncology, respectively. Second-line monotherapy results from RATIONALE 303 evaluating tislelizumab in previously treated advanced NSCLC were published in the Journal of Thoracic Oncology.
Dr. Lanasa added, “As we strengthen our global portfolio in solid tumors, this positive CHMP opinion marks another significant milestone in the European Union for tislelizumab only a few months after it was approved for the treatment of advanced esophageal squamous cell carcinoma. We will continue to follow the science and data to advance tislelizumab as a monotherapy and combination treatment to address unmet needs of patients across the world.”
Tislelizumab, under the brand name TEVIMBRA®, received approval from the European Commission for advanced or metastatic ESCC after prior chemotherapy in 2023 and is currently under review with the U.S. Food and Drug Administration. Tislelizumab is also under review by the FDA as a first-line treatment for patients with unresectable, recurrent, locally advanced, or metastatic ESCC. BeiGene has launched more than 17 potentially registration-enabling trials with tislelizumab with over 13,000 patients enrolled to-date, of which 15 have already reported positive readouts. In these clinical studies, tislelizumab has consistently demonstrated its ability deliver clinically meaningful improvements in survival and quality of life with a positive benefit-risk balance for cancer patients across a range of tumor types – in many cases, regardless of PD-(L)1 status – both as monotherapy and in combination with other regimens. More than 900,000 patients have been prescribed tislelizumab to date.
About RATIONALE 307
RATIONALE 307 (NCT03594747) is an open-label, randomized Phase 3 trial that enrolled 360 patients with advanced squamous NSCLC. The study met its primary endpoint with first-line tislelizumab in combination with chemotherapy resulting in statistically significant improvement in progression free survival (PFS), as well as higher objective response rates (ORRs) and a manageable safety/tolerability profile, regardless of PD-L1 expression. The median PFS was 7.7 months for tislelizumab in combination with paclitaxel and carboplatin (hazard ratio, HR: 0.45 [95% CI: 0.326-0.619]; P< 0.001) and 9.6 months for tislelizumab in combination with nab-paclitaxel and carboplatin (HR: 0.43 [95% CI: 0.308-0.60]; P< 0.001) versus 5.5 months for paclitaxel and carboplatin alone, at a median study follow-up of 8.6 months. The most common grade ≥3 treatment emergent adverse events were decreased neutrophil levels, neutropenia and leukopenia.
About RATIONALE 304
RATIONALE 304 (NCT03663205) is an open-label, randomized Phase 3 trial that enrolled 334 patients with locally advanced or metastatic non-squamous NSCLC. The study met its primary endpoint, with first-line tislelizumab in combination with chemotherapy resulting in statistically significant improvement in PFS compared to chemotherapy (HR: 0.65 [95% CI: 0.47-0.91]; P=0.0054) along with higher response rates and longer response duration. The median PFS in the overall and in the PD-L1≥50% populations was 9.7 months for tislelizumab in combination with platinum (carboplatin or cisplatin) and pemetrexed versus 7.6 months for platinum and pemetrexed alone and 14.6 months with tislelizumab in combination with chemotherapy vs. 4.6 months with chemotherapy alone (stratified HR: 0.31 [95% CI: 0.178-0.547]) respectively, at a median study follow-up of 9.8 months. The most common grade ≥3 treatment emergent adverse events were associated with chemotherapy and included neutropenia and leukopenia.
About RATIONALE 303
RATIONALE 303 (NCT03358875) is an open-label, randomized Phase 3 trial with tislelizumab versus docetaxel that enrolled 805 patients with advanced NSCLC who progressed on prior platinum-based chemotherapy. The study met its primary endpoint, with second- or third-line tislelizumab resulting in statistically significant and clinically meaningful improvement in overall survival (OS) compared with docetaxel in the intent-to-treat population (HR: 0.66 [95% CI: 0.56-0.79]; P<0.0001), regardless of PD-L1 expression. The median OS was 16.9 months for tislelizumab versus 11.9 months for docetaxel. At the final analysis, OS in the PD-L1 positive population was also significantly improved in favor of tislelizumab (median 19.3 versus 11.5 months, respectively; HR: 0.53 [95% CI: 0.41-0.70]; P<0.0001). The most commonly reported grade ≥3 treatment emergent adverse events were pneumonia, anemia and dyspnea.
About NSCLC
Lung cancer is the second most common type of cancer and the leading cause of cancer-related death worldwide.1 Lung cancer is the third most common cancer in Europe; NSCLC represents 85–90% of all lung cancers.2 In 2020, the number of new cases of lung cancer diagnosed in Europe was estimated at 477,534.3
About Tislelizumab
Tislelizumab is a uniquely designed humanized immunoglobulin G4 (IgG4) anti-programmed cell death protein 1 (PD-1) monoclonal antibody with high affinity and binding specificity against PD-1. It is designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages, helping to aid the body’s immune cells to detect and fight tumors.
About BeiGene
BeiGene is a global oncology company that is discovering and developing innovative treatments that are more affordable and accessible to cancer patients worldwide. With a broad portfolio, we are expediting development of our diverse pipeline of novel therapeutics through our internal capabilities and collaborations. We are committed to radically improving access to medicines for far more patients who need them. Our growing global team of more than 10,000 colleagues spans five continents, with administrative offices in Basel, Beijing, and Cambridge, U.S. To learn more about BeiGene, please visit www.beigene.com and follow us on LinkedIn and X (formerly known as Twitter).
View source version on businesswire.com: https://www.businesswire.com/news/home/20240226759239/en/
Source: BeiGene, Ltd.
BeiGene gets EU backing for lung cancer therapy
Feb. 26, 2024 6:55 AM ET
By: Preeti Singh, SA News Editor
- BeiGene (NASDAQ:BGNE) announced Monday that an expert panel of the EU drug regulator, the European Medicines Agency (EMA), has adopted a positive opinion for the approval of tislelizumab as a treatment for non-small cell lung cancer (NSCLC) across three indications.
- The Committee for Medicinal Products for Human Use (CHMP) recommendation is based on results of three Phase 3 clinical trials demonstrating benefit of tislelizumab as a first- and second-line treatment for patients with NSCLC.
- https://seekingalpha.com/news/4071472-beigene-gets-eu-backing-for-lung-cancer-therapy
- BeiGene, Ltd. (BGNE) Stock
- https://www.beigene.com/our-science-and-medicines/tislelizumab/
- https://www.beigene.com/
Voydeya (danicopan)
TEVIMBRA® (tislelizumab)
Voydeya (danicopan)
Recommendation of first-in-class, oral, Factor D inhibitor based on ALPHA Phase III
trial results
Voydeya (danicopan) has been recommended for marketing authorisation in the European Union (EU) as an add-on to ravulizumab or eculizumab for the treatment of adult patients with paroxysmal nocturnal haemoglobinuria (PNH) who have residual haemolytic anaemia. Voydeya is a first-in-class, oral, Factor D inhibitor developed as an add-on to standard-of-care Ultomiris (ravulizumab) or Soliris (eculizumab) to address the needs of the approximately 10-20% of patients with PNH who experience clinically significant extravascular haemolysis (EVH) while treated with a C5 inhibitor.1,2
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinion on results from the pivotal ALPHA Phase III trial. Results from the 12-week primary evaluation period of the trial were published in The Lancet Haematology.1
PNH is a rare and severe blood disorder characterised by the destruction of red blood cells within blood vessels, known as intravascular haemolysis (IVH), and white blood cell and platelet activation that can cause thrombosis (blood clots) and result in organ damage and potentially premature death.3-5 Immediate, complete and sustained terminal complement inhibition by blocking the C5 protein helps reduce symptoms and complications, resulting in improved survival for patients with PNH.5-8 Approximately 10-20% of people living with PNH who are treated with a C5 inhibitor experience clinically significant EVH, which can result in continued symptoms of anaemia and require blood transfusions.1-3,9-11
Professor Hubert Schrezenmeier, MD, Medical Director, Institute of Transfusion Medicine at The University of Ulm, said: “C5 inhibition with Ultomiris or Soliris is the standard-of-care in PNH, proven to control IVH and reduce life-threatening thrombotic events, yet a small portion of patients may experience clinically significant EVH. In the ALPHA trial, Voydeya as an add-on to Soliris or Ultomiris increased haemoglobin levels and reduced fatigue, anaemia and transfusion dependence. If approved, Voydeya may optimise care for people impacted by this burdensome condition while allowing patients to maintain disease control with an established C5 inhibitor.”
Marc Dunoyer, Chief Executive Officer, Alexion, said: “Today’s positive CHMP recommendation recognises the promise of Voydeya as an add-on to standard-of-care to address signs and symptoms of clinically significant EVH for this small subset of patients. As we saw in the pivotal ALPHA Phase III trial, dual complement pathway inhibition at Factor D and C5 may be an optimal treatment approach for these patients.”
The ALPHA Phase III trial evaluated the efficacy and safety of Voydeya as an add-on to Ultomiris or Soliris in patients with PNH who experienced clinically significant EVH. Results showed that Voydeya met the primary endpoint of change in haemoglobin from baseline to week 12 and all key secondary endpoints, including transfusion avoidance and change in Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-Fatigue) score.1
Results from the ALPHA Phase III trial showed Voydeya was generally well tolerated, and no new safety concerns were identified. In the trial, the most common treatment-emergent adverse events were headache, nausea, arthralgia and diarrhoea.1
Voydeya has been granted Breakthrough Therapy designation by the US Food and Drug Administration and PRIority MEdicines (PRIME) status by the EMA. Voydeya has also been granted Orphan Drug Designation in the US, EU and Japan for the treatment of PNH. Voydeya was recently approved in Japan, and regulatory submissions for Voydeya are currently under review in additional countries.
Notes
PNH
PNH is a rare, chronic, progressive and potentially life-threatening blood disorder. It is characterised by red blood cell destruction within blood vessels (also known as intravascular haemolysis) and white blood cell and platelet activation, which can result in thrombosis (blood clots).3-5
PNH is caused by an acquired genetic mutation that may happen any time after birth and results in the production of abnormal blood cells that are missing important protective blood cell surface proteins. These missing proteins enable the complement system, which is part of the immune system and is essential to the body’s defence against infection, to ‘attack’ and destroy or activate these abnormal blood cells.3 Living with PNH can be debilitating, and signs and symptoms may include blood clots, abdominal pain, difficulty swallowing, erectile dysfunction, shortness of breath, excessive fatigue, anaemia and dark-coloured urine.3,9,12
Clinically Significant EVH
EVH, the removal of red blood cells outside of the blood vessels, can sometimes occur in PNH patients who are treated with C5 inhibitors.13,14 Since C5 inhibition enables PNH red blood cells to survive and circulate, EVH may occur when these now surviving PNH red blood cells are marked by proteins in the complement system for removal by the spleen and liver.3,5,7 PNH patients with EVH may continue to experience anaemia, which can have various causes, and may require blood transfusions.13-16 A small subset of people living with PNH who are treated with a C5 inhibitor experience clinically significant EVH, which can result in continued symptoms of anaemia and require blood transfusions.3,9-11
ALPHA
ALPHA is a pivotal, global Phase III trial designed as a superiority study to evaluate the efficacy and safety of Voydeya as an add-on to C5 inhibitor therapy Soliris or Ultomiris in patients with PNH who experience clinically significant EVH. In the double-blind, placebo-controlled, multiple-dose trial, patients were enrolled and randomised to receive Voydeya or placebo (2:1) in addition to their ongoing Soliris or Ultomiris therapy for 12 weeks. A prespecified interim analysis was performed once 63 randomised patients had completed 12 weeks of the primary evaluation period or discontinued treatment as of 28 June 2022. At 12 weeks, patients on placebo plus a C5 inhibitor were switched to Voydeya plus Soliris or Ultomiris, and patients on Voydeya plus Soliris or Ultomiris remained on treatment for an additional 12 weeks. Patients who completed both treatment periods (24 weeks) had the option to participate in a two-year long-term extension period and continue to receive Voydeya in addition to Soliris or Ultomiris. The open-label period of the study is ongoing.1,17
Voydeya (danicopan)
Voydeya (danicopan) is a first-in-class oral Factor D inhibitor. The medication works by selectively inhibiting Factor D, a complement system protein that plays a key role in the amplification of the complement system response. When activated in an uncontrolled manner, the complement cascade over-responds, leading the body to attack its own healthy cells. Voydeya has been granted Breakthrough Therapy designation by the US Food and Drug Administration and PRIority MEdicines (PRIME) status by the European Medicines Agency. Voydeya has also been granted Orphan Drug Designation in the US, EU and Japan for the treatment of PNH.
Voydeya is approved in Japan for certain adults with PNH in combination with C5 inhibitor therapy.
Alexion is also evaluating Voydeya as a potential monotherapy for geographic atrophy in a Phase II clinical trial.
Alexion
Alexion, AstraZeneca Rare Disease, is the group within AstraZeneca focused on rare diseases, created following the 2021 acquisition of Alexion Pharmaceuticals, Inc. As a leader in rare diseases for more than 30 years, Alexion is focused on serving patients and families affected by rare diseases and devastating conditions through the discovery, development and commercialisation of life-changing medicines. Alexion focuses its research efforts on novel molecules and targets in the complement cascade and its development efforts on haematology, nephrology, neurology, metabolic disorders, cardiology and ophthalmology. Headquartered in Boston, Massachusetts, Alexion has offices around the globe and serves patients in more than 50 countries.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca.
AstraZeneca gets EU backing for blood disorder add-on therapy
Feb. 26, 2024 5:46 AM ET
By: Preeti Singh, SA News Editor
- AstraZeneca (NASDAQ:AZN) announced Monday that an expert panel of the EU drug regulator, the European Medicines Agency (EMA), adopted a positive opinion for the marketing authorization of Voydeya (danicopan) as an add-on therapy for a rare blood disorder, paroxysmal nocturnal haemoglobinuria (PNH).
- Voydeya is an oral, Factor D inhibitor developed as an add-on to Ultomiris/Soliris to address the needs of the approximately 10-20% of patients with PNH who experience clinically significant extravascular haemolysis (EVH) while treated with a C5 inhibitor.
- https://seekingalpha.com/news/4071441-astrazeneca-gets-eu-backing-for-blood-disorder-add-on-therapy?mailingid=34471101&messageid=2900&serial=34471101.3207&utm_campaign=rta-stock-news&utm_content=link-1&utm_medium=email&utm_source=seeking_alpha&utm_term=34471101.3207
- AstraZeneca PLC (AZN) Stock
- https://www.astrazeneca.com/
LINVOSELTAMAB BLA
TEVIMBRA® (tislelizumab)
Voydeya (danicopan)
February 21, 2024 at 7:00 AM EST
LINVOSELTAMAB BLA FOR TREATMENT OF RELAPSED/REFRACTORY MULTIPLE MYELOMA ACCEPTED FOR FDA PRIORITY REVIEW
TARRYTOWN, N.Y., Feb. 21, 2024
(GLOBE NEWSWIRE) --
Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced that the U.S. Food and Drug Administration (FDA) has accepted for Priority Review the Biologics License Application (BLA) for linvoseltamab to treat adult patients with relapsed/refractory (R/R) multiple myeloma (MM) that has progressed after at least three prior therapies. The target action date for the FDA decision is August 22, 2024. Linvoseltamab is an investigational bispecific antibody designed to bridge B-cell maturation antigen on multiple myeloma cells with CD3-expressing T cells to facilitate T-cell activation and cancer-cell killing.
The BLA is supported by data from a Phase 1/2 pivotal trial (LINKER-MM1) investigating linvoseltamab in R/R MM, which were last shared in December 2023. Earlier this month, the European Medicines Agency accepted for review the Marketing Authorization Application for linvoseltamab in the same indication.
As the second most common blood cancer, it’s estimated 35,000 people will be diagnosed with MM in the U.S. every year. MM is characterized by the proliferation of cancerous plasma cells (MM cells) that crowd out healthy blood cells in the bone marrow, infiltrate other tissues and cause potentially life-threatening organ injury. MM is not curable despite treatment advances. While current treatments are able to slow the progression of the cancer, most patients will ultimately experience disease progression and require additional therapies.
The linvoseltamab clinical development program includes a Phase 3 confirmatory trial in patients with R/R MM (LINKER-MM3) that is currently enrolling. Additional trials in earlier lines of therapy and stages of disease are planned or underway, including a Phase 1/2 trial in the first-line setting, a Phase 2 trial in high-risk smoldering MM and a Phase 2 trial in monoclonal gammopathy of undetermined significance. A Phase 1 trial of linvoseltamab in combination with a Regeneron CD38xCD28 costimulatory bispecific in MM is also planned. For more information, visit the Regeneron clinical trials website, or contact via clinicaltrials@regeneron.com or 844-734-6643.
Linvoseltamab is currently under clinical development, and its safety and efficacy have not been fully evaluated by any regulatory authority.
About the Phase 1/2 Trial
The ongoing, open-label, multicenter Phase 1/2 dose-escalation and dose-expansion LINKER-MM1 trial is investigating linvoseltamab in 282 enrolled patients with R/R MM. Eligibility in the Phase 2 portion required patients to have received at least three prior lines of therapy or have triple-class refractory MM. Linvoseltamab was administered with an initial step-up dosing regimen followed by the full dose. Additionally, in the Phase 2 portion, a response-adapted regimen enabled patients treated with linvoseltamab 200 mg who achieved a very good partial response or a complete response to shift from every two-week to every four-week dosing after a minimum of 24 weeks of therapy.
The Phase 1 dose-escalation portion of the trial, which is now complete, primarily assessed safety, tolerability and dose-limiting toxicities across nine dose levels of linvoseltamab exploring different administration regimens. The Phase 2 dose expansion portion is assessing the safety and anti-tumor activity of linvoseltamab, with a primary endpoint of objective response rate. Key secondary endpoints include duration of response, progression free survival, rate of minimal residual disease negative status and overall survival.
About Regeneron in Hematology
At Regeneron, we’re applying more than three decades of biology expertise with our proprietary VelociSuite® technologies to develop medicines for patients with diverse blood cancers and rare blood disorders.
Our blood cancer research is focused on bispecific antibodies that are being investigated both as monotherapies and in various combinations and emerging therapeutic modalities. Together, they provide us with unique combinatorial flexibility to develop customized and potentially synergistic cancer treatments.
Our research and collaborations to develop potential treatments for rare blood disorders include explorations in antibody medicine, gene editing and gene-knockout technologies, and investigational RNA-approaches focused on depleting abnormal proteins or blocking disease-causing cellular signaling.
About Regeneron
Regeneron is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led for over 35 years by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous FDA-approved treatments and product candidates in development, almost all of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, hematologic conditions, infectious diseases and rare diseases.
Regeneron is accelerating and improving the traditional drug development process through our proprietary VelociSuite technologies, such as VelocImmune®, which uses unique genetically humanized mice to produce optimized fully human antibodies and bispecific antibodies, and through ambitious research initiatives such as the Regeneron Genetics Center®, which is conducting one of the largest genetics sequencing efforts in the world.
For more information about Regeneron, please visit www.Regeneron.com or follow Regeneron on LinkedIn.
Source: Regeneron Pharmaceuticals, Inc.
Regeneron multiple myeloma therapy granted FDA priority review
Feb. 21, 2024 8:14 AM ET
Regeneron Pharmaceuticals, Inc. (REGN) Stock
By: Dulan Lokuwithana, SA News Editor4 Comments
Regeneron (NASDAQ:REGN) announced Wednesday that the FDA granted priority review for its Biologics License Application (BLA) seeking U.S. market access for its multiple myeloma therapy linvoseltamab.
The regulatory body has issued August 22, 2024, as the target action date for its review.
With the BLA, the New York-based biotech seeks FDA approval for linvoseltamab as a late-line option for adults with relapsed/refractory multiple myeloma, the second most common type of blood cancer, affecting an estimated 35K Americans each year.
https://seekingalpha.com/news/4069510-regeneron-wins-fda-priority-review-multiple-myeloma-drug
AMTAGVI™ (lifileucel)
REVASCOR® (REXLEMESTROCEL-L)
REVASCOR® (REXLEMESTROCEL-L)
Iovance’s AMTAGVI™ (lifileucel) Receives U.S. FDA Accelerated Approval for Advanced Melanoma
AMTAGVI is the first FDA-approved T cell therapy for a solid tumor cancer and first treatment option for advanced melanoma after anti-PD-1 and targeted therapy
AMTAGVI deploys patient-specific immune cells that recognize and fight cancer
SAN CARLOS, Calif., Feb. 16, 2024 (GLOBE NEWSWIRE) -- Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a biotechnology company focused on innovating, developing and delivering novel polyclonal tumor infiltrating lymphocyte (TIL) cell therapies for patients with cancer, today announced that the U.S. Food and Drug Administration (FDA) has approved AMTAGVI™ (lifileucel) suspension for intravenous infusion. AMTAGVI is a tumor-derived autologous T cell immunotherapy indicated for the treatment of adult patients with unresectable or metastatic melanoma previously treated with a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without a MEK inhibitor. This indication is approved under an accelerated approval based on overall response rate (ORR) and duration of response. Iovance is also conducting TILVANCE-301, a Phase 3 trial to confirm clinical benefit.
AMTAGVI is the first and the only one-time, individualized T cell therapy to receive FDA approval for a solid tumor cancer. The proposed mechanism for AMTAGVI offers a new cell therapy approach that deploys patient-specific T cells called TIL cells. When cancer is detected, the immune system creates TIL cells to locate, attack, and destroy cancer. TIL cells recognize distinctive tumor markers on the cell surface of each person’s cancer. When cancer develops and prevails, the body’s natural TIL cells can no longer perform their intended function to fight cancer.
AMTAGVI is manufactured using a proprietary process to collect and expand a patient’s unique T cells from a portion of their tumor. AMTAGVI returns billions of the patient’s T cells back to the body to fight their cancer.* Authorized Treatment Centers (ATCs) will administer AMTAGVI to patients as part of a treatment regimen that includes lymphodepletion and a short course of high-dose PROLEUKIN® (aldesleukin).
“The accelerated approval of AMTAGVI™ is the first step in realizing Iovance’s ambition to usher in the next generation of cell therapy by bringing this breakthrough to patients with advanced solid tumors,” said Frederick Vogt, Ph.D., J.D., Interim Chief Executive Officer and President of Iovance. “Given the significant unmet needs in the advanced melanoma community, we are proud to offer a personalized, one-time therapeutic option for these patients. We are continuing our development efforts to address additional unmet medical needs in patients with solid tumor cancers, making our novel cell therapies available to more patients with melanoma and other types of cancers.”
Each year, approximately 8,000 people in the U.S. die from melanoma.1 Until now, there have been no FDA-approved treatment options for patients with advanced melanoma whose disease progressed following initial treatment with an immune checkpoint inhibitor and, if appropriate, targeted therapy.
“The approval of AMTAGVI™ offers hope to those with advanced melanoma who have progressed following initial standard of care therapies, as the current treatment options are not effective for many patients,” said Samantha R. Guild, J.D., President, AIM at Melanoma Foundation. “This one-time cell therapy represents a promising innovation for the melanoma community, and we are excited by its potential to transform care for patients who are in dire need of additional therapeutic options.”
The FDA approval is based on safety and efficacy results from the C-144-01 clinical trial. C-144-01 is a global, multicenter trial investigating AMTAGVI in patients with advanced melanoma previously treated with anti-PD-1 therapy and targeted therapy, where applicable. AMTAGVI demonstrated deep and durable responses. The primary efficacy analysis set included 73 patients from Cohort 4 who received the recommended AMTAGVI dose from an approved manufacturing facility. Among the 73 patients, 31.5% achieved an objective response by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) with a median duration of response not reached at 18.6 months follow-up2 (43.5% of responses had a duration greater than 12 months). Additionally, the supporting pooled efficacy set included a total of 153 patients from Cohort 4 and Cohort 2. Among the 153 patients, 31.4% achieved an objective response by RECIST 1.1 with a median duration of response not reached at 21.5 months follow-up2 (54.2% of responses had a duration greater than 12 months). The detailed results of clinical trial C-144-01 are published in The Journal for ImmunoTherapy of Cancer (Chesney 2022).
AMTAGVI is for autologous use only. AMTAGVI has a boxed warning for treatment-related mortality, prolonged severe cytopenia, severe infection, and cardiopulmonary and renal impairment. Warnings and precautions include treatment-related mortality, prolonged severe cytopenia, internal organ hemorrhage, severe infection, cardiac disorder, respiratory failure, acute renal failure, and hypersensitivity reactions. Please see Important Safety Information and Prescribing Information below.
“This landmark FDA approval reflects significant advancements in TIL cell therapy since we initially showed that TIL cells isolated from patients with metastatic melanoma could be expanded in the lab and returned to the patient to mediate cancer regression,” said Steven Rosenberg, M.D., Ph.D., Chief, Surgery Branch, National Cancer Institute, and a TIL and immunotherapy pioneer. “This approval is transformative for the entire research field and supports continued investigation of TIL cell therapy across additional types of solid tumors.”
“One-time treatment with AMTAGVI™ offered clinically meaningful and deep, durable responses in the Phase 2 clinical trial, and I am excited by its potential as a much-needed new treatment option for the many advanced melanoma patients who progress on the current standard of care,” said Dr. Alexander N. Shoushtari, Melanoma Oncologist & Cellular Therapist at Memorial Sloan Kettering Cancer Center. “This welcome news represents an important step forward in harnessing cell therapy to treat solid tumors,” added Dr. Jae Park, Chief of Cellular Therapy Service at Memorial Sloan Kettering Cancer Center.
AMTAGVI will be manufactured in Philadelphia at the Iovance Cell Therapy Center (iCTC), with capacity for up to several thousand patients annually, including a nearby contract manufacturer. Additional expansion at iCTC is underway, which will significantly increase this capacity over the next few years. iCTC is the first FDA-approved, centralized, and scalable manufacturing facility dedicated to producing TIL cell therapies for patients with solid tumors. AMTAGVI must be administered in an ATC, and more than 30 ATCs are prepared to collect and ship tumor tissue from patients for AMTAGVI manufacturing.
Iovance is dedicated to providing access to AMTAGVI for patients with advanced melanoma. A comprehensive support program, IovanceCares™, is now available for patients and ATCs throughout the treatment journey. IovanceCares will also offer copay support, financial assistance, and travel and lodging assistance for eligible patients during AMTAGVI therapy. For more information, physicians and patients may call 833-400-IOVA (4682) or visit www.iovancecares.com.
Iovance is investigating AMTAGVI in frontline advanced melanoma in the Phase 3 confirmatory trial, TILVANCE-301, as well as additional solid tumor types, which represent 91% of the cancers in the U.S.1 For more information, please visit: https://www.iovance.com/clinical-trials/.
1 National Cancer Institute Surveillance, Epidemiology and End Results (SEER) Program. 2023 Estimates. https://seer.cancer.gov. Accessed February 2024.
2 Kaplan-Meier estimate of median potential follow-up for duration of response.
* A single dose of AMTAGVI contains 7.5 × 109 to 72 × 109 viable cells.
Webcast and Conference Call
Iovance will host a conference call and live audio webcast today to discuss the FDA approval of AMTAGVI. Details will be shared in a subsequent announcement.
About the C-144-01 Clinical Trial
C-144-01 is a global, multicenter Phase 2 study in which patients received treatment with lifileucel. The study enrolled patients with metastatic melanoma who were previously treated with at least one systemic therapy, including a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor or BRAF inhibitor with MEK inhibitor. Efficacy was established on the basis of objective response rate (ORR), and duration of response (DOR) by Independent Review Committee (IRC) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The pivotal Cohort 4 and supportive Cohort 2 of Study C-144-01 enrolled patients that met the same primary eligibility criteria, had the same assessments, and had received the same regimen and AMTAGVI that was produced using the same manufacturing process, and product formulation. The detailed results of C-144-01 were published in the Journal for ImmunoTherapy of Cancer in 2022.
What is AMTAGVI (lifileucel)?
AMTAGVI is a prescription medicine used to treat adults with a type of skin cancer that cannot be removed surgically or has spread to other parts of the body called unresectable or metastatic melanoma.
AMTAGVI is used when your melanoma has not responded or stopped responding to a PD-1 blocking drug either by itself or in a combination, and if your cancer is BRAF mutation positive, a BRAF inhibitor drug with or without a MEK inhibitor drug that has also stopped working.
The approval of AMTAGVI is based on a study that measured response rate. Continued approval for this use may depend on the results of an ongoing study to confirm benefit.
About Iovance Biotherapeutics, Inc.
Iovance Biotherapeutics aims to be the global leader in innovating, developing and delivering tumor infiltrating lymphocyte (TIL) cell therapies for patients with cancer. We are pioneering a transformational approach to cure cancer by harnessing the human immune system’s ability to recognize and destroy diverse cancer cells in each patient. The Iovance TIL platform has demonstrated promising clinical data across multiple solid tumors. Iovance’s AMTAGVI™ is the first FDA-approved T cell therapy for a solid tumor indication. We are committed to continuous innovation in cell therapy, including gene-edited cell therapy, which may be a promising option for patients with cancer. For more information, please visit www.iovance.com.
AMTAGVI™ and its accompanying design marks, PROLEUKIN®, IOVANCE®, and IOVANCECARES™ are trademarks and registered trademarks of Iovance Biotherapeutics, Inc. or its subsidiaries. All other trademarks and registered trademarks are the property of their respective owners.
A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/b01f4de7-8dc3-47e6-bada-df2a7ec36604
AMTAGVI (lifileucel) Product Shot
AMTAGVI (lifileucel) product packaging
Source: Iovance Biotherapeutics, Inc.
Iovance gets FDA accelerated approval for advanced melanoma therapy (update)
Feb. 16, 2024 3:38 PM ET
Iovance Biotherapeutics, Inc. (IOVA) Stock
By: Val Brickates Kennedy, SA News Editor52 Comments
Iovance Biotherapeutics (NASDAQ:IOVA) has received FDA accelerated approval for its T-cell immunotherapy lifileucel, also known as Amtagvi, in the treatment of advanced melanoma.
REVASCOR® (REXLEMESTROCEL-L)
REVASCOR® (REXLEMESTROCEL-L)
REVASCOR® (REXLEMESTROCEL-L)
UNITED STATES FOOD & DRUG ADMINISTRATION (FDA) GRANTS MESOBLAST ORPHAN-DRUG DESIGNATION FOR REVASCOR® (REXLEMESTROCEL-L) IN CHILDREN WITH CONGENITAL HEART DISEASE Melbourne, Australia; February 15 and New York, USA;
February 14, 2024: Mesoblast Limited (ASX:MSB; Nasdaq:MESO), global leader in allogeneic cellular medicines for inflammatory diseases, today announced that the United States Food and Drug Administration (FDA) has granted its allogeneic cell therapy Revascor® (rexlemestrocel-L) an Orphan-Drug Designation (ODD) following submission of results from the randomized controlled trial in children with hypoplastic left heart syndrome (HLHS), a potentially life threatening congenital heart condition. This follows the Rare Pediatric Disease Designation (RPDD) granted by FDA last month. Mesoblast Chief Executive Silviu Itescu said: “We are very pleased to have now been granted both Orphan-Drug Designation and Rare Pediatric Disease Designation by FDA for REVASCOR in the treatment of children with this often-fatal congenital heart condition. The designations were granted on the back of the results from children in a randomized controlled trial indicating that REVASCOR may increase the ability to successfully accomplish life-saving surgery. We plan to meet with FDA to discuss the pathway for approval in this indication.” Results from a blinded, randomized, placebo-controlled prospective trial of REVASCOR conducted in the United States in children with HLHS were published in the December 2023 issue of the peer reviewed The Journal of Thoracic and Cardiovascular Surgery Open (JTCVS Open).1 In the HLHS trial conducted in 19 children, a single intramyocardial administration of REVASCOR at the time of staged surgery resulted in the desired outcome of significantly larger increases in left ventricular (LV) end-systolic and end-diastolic volumes over 12 months compared with controls as measured by 3D echocardiography, (p=0.009 & p=0.020 respectively). These changes are indicative of clinically important growth of the small left ventricle, facilitating the ability to have a successful surgical correction, known as full biventricular (BiV) conversion, which allows for a normal two ventricle circulation with the surgically repaired left ventricle taking over circulatory support to the body. Without full BiV conversion the right heart chamber is under excessive strain with increased risk of heart failure and death. As noted in our recent publication, “The fact that 100% of REVASCOR-treated children compared with 57% of controls had large enough LVs to accommodate the full BiV conversion suggests that REVASCOR treatment may help increase the ability to ‘better grow’ the HLHS LV after LV recruitment surgery.” About Orphan Drug Designation The FDA’s Orphan Drug Designation Program provides orphan status to drugs and biologics which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases and disorders that affect fewer than 200,000 people in the United States. Orphan designation qualifies the sponsor of the drug for various development incentives, including eligibility for seven years of market exclusivity upon regulatory approval, exemption from FDA application fees, tax credits for qualified clinical trials, and other potential assistance in the drug development process. About Rare Pediatric Disease Designation FDA awards priority review vouchers to sponsors of rare pediatric disease product applications that meet certain criteria. Under this program, a sponsor who receives an approval for a drug or biologic for a "rare pediatric disease" may qualify for a Priority Review Voucher (PRV) that can be redeemed to receive a priority review of a subsequent marketing application for a different product or may be sold or transferred to a third party. About Hypoplastic Left Heart Syndrome (HLHS) HLHS is a severe congenital heart disease in which the left side of the heart does not fully develop and effective pumping of oxygenated blood by the left ventricle to the rest of the body is reduced. Without immediate surgery after birth, the prognosis is dismal with HLHS overall being responsible for 25% to 40% of all neonatal cardiac mortality.2 In the longer term, surgery that creates a two-ventricle series circulation with the left ventricle (LV) pumping blood to the body and the right ventricle pumping blood to the lungs is the ideal anatomic repair. Unfortunately, achievement of this objective is limited by the inability in most patients for the left ventricle to grow sufficiently to support the circulation to the body. About Revascor® (rexlemestrocel-L) in Heart Disease REVASCOR is an allogeneic preparation of immunoselected and culture-expanded mesenchymal precursor cells which have been shown previously to have multiple mechanisms-of-action that may be beneficial to children with HLHS including neovascularization, anti-fibrosis, anti-apoptosis, immunomodulation, reduction in inflammation, and reversal of endothelial dysfunction. In the DREAMHF randomized sham-placebo controlled prospective trial of REVASCOR in 565 randomized adult patients with heart failure with low ejection fraction (HFrEF), a single intramyocardial administration of REVASCOR into the left ventricle resulted in significant improvement in LV ejection fraction at 12 months,3 indicative of strengthened overall LV systolic function. About Mesoblast Mesoblast (the Company) is a world leader in developing allogeneic (off-the-shelf) cellular medicines for the treatment of severe and life-threatening inflammatory conditions. The Company has leveraged its proprietary mesenchymal lineage cell therapy technology platform to establish a broad portfolio of latestage product candidates which respond to severe inflammation by releasing anti-inflammatory factors that counter and modulate multiple effector arms of the immune system, resulting in significant reduction of the damaging inflammatory process. Mesoblast has a strong and extensive global intellectual property portfolio with protection extending through to at least 2041 in all major markets. The Company’s proprietary manufacturing processes yield industrial-scale, cryopreserved, off-the-shelf, cellular medicines. These cell therapies, with defined pharmaceutical release criteria, are planned to be readily available to patients worldwide. Mesoblast is developing product candidates for distinct indications based on its remestemcel-L and rexlemestrocel-L allogeneic stromal cell technology platforms. Remestemcel-L is being developed for inflammatory diseases in children and adults including steroid refractory acute graft versus host disease, biologic-resistant inflammatory bowel disease, and acute respiratory distress syndrome. Rexlemestrocel-L is in development for advanced chronic heart failure and chronic low back pain. Two products have been commercialized in Japan and Europe by Mesoblast’s licensees, and the Company has established commercial partnerships in Europe and China for certain Phase 3 assets. Mesoblast has locations in Australia, the United States and Singapore and is listed on the Australian Securities Exchange (MSB) and on the Nasdaq (MESO). For more information, please see www.mesoblast.com, LinkedIn: Mesoblast Limited and Twitter: @Mesoblast
Mesoblast gets FDA orphan drug status for Revascor
Feb. 15, 2024 11:54 AM ET
Mesoblast Limited (MESO) Stock
By: Val Brickates Kennedy, SA News Editor
Mesoblast (NASDAQ:MESO) said the FDA has granted orphan drug designation to its cell therapy Revascor in the treatment of children with hypoplastic left heart syndrome, a congenital heart condition.
The product received rare pediatric disease designation from the FDA last month.
https://seekingalpha.com/news/4067744-mesoblast-gets-fda-orphan-drug-status-for-revascor
Mesoblast Limited (MESO) Stock
https://www.mesoblast.com/product-candidates/cardiovascular-diseases/congestive-heart-failure
Sebetralstat
REVASCOR® (REXLEMESTROCEL-L)
Sebetralstat
KalVista Pharmaceuticals Reports Phase 3 KONFIDENT Trial Meets All Endpoints for Sebetralstat as First Oral On-demand Therapy for Hereditary Angioedema
Feb 13, 2024
– Sebetralstat 300 mg achieved beginning of symptom relief in 1.6 hours –
– Safety profile comparable to placebo –
– On track for submission of new drug application to U.S. FDA in the first half of 2024 –
– Conference call to discuss trial results today at 8:30 a.m. ET –
CAMBRIDGE, Mass. & SALISBURY, England--(BUSINESS WIRE)--Feb. 13, 2024-- KalVista Pharmaceuticals, Inc. (NASDAQ: KALV), a clinical stage pharmaceutical company focused on the discovery, development, and commercialization of small molecule protease inhibitors, today announced positive results from the phase 3 KONFIDENT clinical trial demonstrating statistically and clinically significant efficacy of sebetralstat as oral on-demand therapy for hereditary angioedema (HAE). KONFIDENT was the largest and most representative trial ever conducted in HAE, and included adolescents, patients using long-term prophylaxis, and all attack severities and locations.
The clinical trial met all primary and key secondary endpoints and demonstrated a favorable safety profile. HAE attacks treated with both 300 mg and 600 mg of sebetralstat achieved the primary endpoint of beginning of symptom relief significantly faster than placebo (p<0.0001 for 300 mg, p=0.0013 for 600 mg). The median time to beginning of symptom relief was 1.61 hours with sebetralstat 300 mg (CI 1.28, 2.27), 1.79 hours with sebetralstat 600 mg (CI 1.33, 2.27) and 6.72 hours with placebo (CI 2.33, >12).
Consistent with previous studies, sebetralstat was well-tolerated, with a safety profile similar to placebo. There were no patient withdrawals due to any adverse event and no treatment-related serious adverse events (SAEs) were observed. Treatment-related adverse event rates were 2.3% for 300 mg sebetralstat, 2.2% for 600 mg sebetralstat, and 4.8% for placebo.
“We are thrilled to announce positive phase 3 results for the KONFIDENT trial, which we believe position sebetralstat to become the first oral, on-demand therapy for the treatment of HAE. These clinically meaningful results represent a potentially significant advance for people living with HAE. If approved, sebetralstat may offer a compelling treatment option for patients and their caregivers given the long-standing preference for an effective and safe oral therapy that provides rapid symptom relief for HAE attacks,” said Andrew Crockett, Chief Executive Officer of KalVista.
Mr. Crockett added, “Most importantly, we want to thank the people living with HAE, their families, and the investigator teams around the world who supported KONFIDENT and made it the largest clinical trial ever conducted in HAE. We look forward to submitting a new drug application for sebetralstat to the U.S. FDA in the first half of 2024 and in the EU and Japan later this year.”
Primary and key secondary endpoints were analyzed in a fixed, hierarchical sequence and adjusted for multiplicity. Key secondary endpoints showed:
- Attacks treated with sebetralstat 300 mg or 600 mg achieved a significantly faster time to a reduction in attack severity from baseline, compared to placebo (p=0.0036 for 300 mg and p=0.0032 for 600 mg)
- Attacks treated with sebetralstat 300 mg or 600 mg demonstrated a significantly faster time to complete attack resolution, compared to placebo (p=0.0022 for 300 mg and p<0.0001 for 600 mg)
“These highly encouraging phase 3 results show that sebetralstat provided rapid symptom relief in a broad HAE population that reflects my clinical practice,” said Danny Cohn, MD, PhD, Department of Vascular Medicine, University of Amsterdam, and principal investigator for the KONFIDENT phase 3 trial. “If approved, sebetralstat could transform the management of HAE.”
“With no new on-demand therapies for HAE approved for nearly a decade, having a safe and effective oral, on-demand treatment for HAE attacks could be immensely valuable in addressing unmet needs and reducing the treatment burden associated with current injectable treatments,” said Marc A. Riedl, MD, professor of medicine and clinical director, U.S. Hereditary Angioedema Association Center at the University of California, San Diego, and an investigator for the KONFIDENT phase 3 trial. “Against the backdrop of patient needs and opportunities, the results of this trial with sebetralstat are extremely encouraging for the HAE community.”
The Company plans to present phase 3 data for the KONFIDENT trial at the annual meeting of the American Academy of Allergy Asthma and Immunology (AAAAI) on February 25, 2024.
Webcast Details
KalVista will host a webcast today at 8:30am ET. In conjunction, the Company will post a presentation with data from the phase 3 KONFIDENT trial of sebetralstat on the investors section of the company website. Stockholders and other interested parties may participate in the call by following the instructions below. The live webcast can be accessed on the Event Calendar portion of the KalVista investor page. A replay will be available on the KalVista website shortly after completion of the event and will be archived for up to 30 days.
Webcast Link: https://edge.media-server.com/mmc/p/mzfxtn9e
Participant Call Link: https://register.vevent.com/register/BI9a15a8c461b94eca9b3f649b83cdec60
About the KONFIDENT Phase 3 Trial
The KONFIDENT phase 3 trial was a randomized, double blind, event-driven, crossover clinical trial evaluating the efficacy and safety of sebetralstat 300 mg and 600 mg versus placebo for the on-demand treatment of HAE. The trial enrolled a total of 136 adult and adolescent HAE patients from 66 clinical sites across 20 countries, making it the largest clinical trial ever conducted in HAE. In the trial, patients treated each eligible attack with up to two doses of study drug, and each patient could treat up to three attacks over the course of the study. The trial included type 1 and type 2 HAE patients who had at least two attacks in 90 days prior to enrollment.
About Sebetralstat
Discovered by KalVista, sebetralstat is an investigational novel, oral plasma kallikrein inhibitor for the on-demand treatment of hereditary angioedema (HAE). Sebetralstat received Fast Track and Orphan Drug designations from the U.S. FDA, as well as Orphan Drug Designation and an approved Pediatric Investigational Plan from the European Medicines Agency (EMA).
https://www.kalvista.com/pipeline/sebetralstat/
About Hereditary Angioedema
Hereditary angioedema (HAE) is a rare genetic disease resulting in deficiency or dysfunction in the C1 esterase inhibitor (C1INH) protein and subsequent uncontrolled activation of the kallikrein-kinin system. People living with HAE experience painful and debilitating attacks of tissue swelling in various locations of the body that can be life-threatening depending on the location affected. All currently approved on-demand treatment options require either intravenous or subcutaneous administration.
About KalVista Pharmaceuticals, Inc.
KalVista Pharmaceuticals, Inc. is a pharmaceutical company focused on the discovery, development, and commercialization of oral, small molecule protease inhibitors for diseases with significant unmet need. KalVista disclosed positive phase 3 data for the KONFIDENT trial for its oral, on-demand therapy sebetralstat in February 2024. The Company anticipates submitting a new drug application to the U.S. FDA for sebetralstat in the first half of 2024 and expects to file for approval in Europe and Japan later in 2024. In addition, KalVista’s oral Factor XIIa inhibitor program represents a new generation of therapies that may further improve the treatment for people living with HAE and other diseases.
For more information about KalVista, please visit www.kalvista.com.
View source version on businesswire.com: https://www.businesswire.com/news/home/20240213650216/en/
KalVista Pharmaceuticals, Inc.
KalVista jumps as rare disease therapy hits main goal in Phase 3 trial
Feb. 13, 2024 7:17 AM ET
KalVista Pharmaceuticals, Inc. (KALV) StockHAE
By: Dulan Lokuwithana, SA News Editor
- KalVista Pharmaceuticals (NASDAQ:KALV) added ~27% premarket Tuesday after the company said sebetralstat, an oral therapy it has developed for a rare genetic disease called hereditary angioedema (HAE), reached the main goals in a Phase 3 trial.
- The Cambridge, Massachusetts-based biotech said that the KONFIDENT clinical trial, which enrolled more than 130 adults and adolescents across 20 countries, met all primary and key secondary endpoints.
- https://seekingalpha.com/news/4065965-kalvista-stock-jumps-trial-success
- KalVista Pharmaceuticals, Inc. (KALV) Stock
- https://www.kalvista.com/
ST-920
Nipocalimab
Sebetralstat
News Release Details
Sangamo Therapeutics Announces U.S. FDA Alignment on Abbreviated Pathway to Potential Approval and EMA Prime Eligibility for ST-920 in Fabry Disease
February 12, 2024 at 8:05 AM EST
- U.S. Food and Drug Administration (FDA) advises that a single study with up to 25 patients, in combination with confirmatory evidence, may be acceptable pathway to Biologics License Application (BLA) submission for isaralgagene civaparvovec, which would significantly reduce anticipated complexity, cost and time to potential approval.
- European Medicines Agency (EMA) granted priority medicines (PRIME) eligibility to isaralgagene civaparvovec, which includes enhanced regulatory support and scientific guidance.
- Sangamo is actively seeking a collaboration partner to advance isaralgagene civaparvovec through potential registration and commercialization.
RICHMOND, Calif.--(BUSINESS WIRE)--Feb. 12, 2024-- Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicine company, today announced important U.S. and European regulatory updates for isaralgagene civaparvovec, or ST-920, its wholly owned gene therapy product candidate for the treatment of Fabry disease.
The FDA has agreed in a Type D meeting that data from a single, adequate, and well-controlled study may form the primary basis of approval of a BLA for isaralgagene civaparvovec. The proposed study would enroll up to 25 patients, both male and female, without the need for a control arm. A head-to-head comparison with Enzyme Replacement Therapy (ERT) is not part of the proposed study design deemed acceptable by the FDA. This approach enables a potentially more rapid, efficient and cost-effective pathway to BLA submission than originally anticipated.
Additionally, the EMA has granted PRIME eligibility to isaralgagene civaparvovec. PRIME is a program designed to enhance support for the development of medicines that target an unmet medical need and is intended to optimize development plans and expedite review and approval processes so that these medicines may reach patients as early as possible. Isaralgagene civaparvovec has already received Orphan Medicinal Product designation from the EMA as well as Orphan Drug, Fast Track and RMAT designations from the FDA.
“The U.S. and European regulatory support for ST-920 and the serious unmet medical need in Fabry Disease signal the important role that ST-920 could play in improving the lives of Fabry patients across the globe,” said Nathalie Dubois Stringfellow, Ph.D., Chief Development Officer of Sangamo. “We are thankful for the FDA’s support and alignment on a regulatory pathway that could potentially deliver a new treatment option for Fabry disease patients on an expedited, cost-effective timeline. Similarly, we appreciate the support from the EMA and the opportunity to advance our development plans in Europe. Fabry is a debilitating disease in need of new medicines, and we are grateful that regulatory agencies across geographies recognize this and support our proposed development plans.”
Updated Phase 1/2 STAAR study data showing sustained clinical benefit and a differentiated safety profile across 24 patients were shared at the 20th Annual WORLDSymposiumTM in San Diego, CA on Wednesday, February 7, 2024. A total of 29 patients have been treated to date in the Phase 1/2 STAAR study. All 13 patients withdrawn from ERT remain off ERT as of February 12, 2024. Screening and enrollment are complete in the study and dosing of the remaining enrolled patients is expected in the first half of 2024. Sangamo is deferring additional investments in planning for a registrational trial until a collaboration partnership is secured.
About the STAAR Study
The Phase 1/2 STAAR study is a global open-label, single-dose, dose-ranging, multicenter clinical study designed to evaluate the safety and tolerability of isaralgagene civaparvovec, or ST-920, a gene therapy product candidate in patients with Fabry disease. Isaralgagene civaparvovec requires a one-time infusion without preconditioning. The STAAR study enrolled patients who are on ERT, are ERT pseudo-naïve (defined as having been off ERT for six or more months), or who are ERT-naïve. The FDA has granted Orphan Drug, Fast Track and RMAT designations to isaralgagene civaparvovec, which has also received Orphan Medicinal Product designation and PRIME eligibility from the EMA.
About Fabry Disease
Fabry disease is a lysosomal storage disorder caused by mutations in the galactosidase alpha gene (GLA), which leads to deficient alpha-galactosidase A (α-Gal A) enzyme activity, which is necessary for metabolizing globotriaosylceramide (Gb3). The buildup of Gb3 in the cells can cause serious damage to vital organs, including the kidney, heart, nerves, eyes, gut and skin. Symptoms of Fabry disease can include decreased or absent sweat production, heat intolerance, angiokeratoma (skin blemishes), vision problems, kidney disease, heart failure, gastrointestinal disturbance, mood disorders, neuropathic pain and tingling in the extremities.
About Sangamo Therapeutics
Sangamo Therapeutics is a genomic medicine company dedicated to translating ground-breaking science into medicines that transform the lives of patients and families afflicted with serious neurological diseases who do not have adequate or any treatment options. Sangamo’s zinc finger epigenetic regulators are ideally suited to potentially address devastating neurological disorders and Sangamo’s capsid discovery platform is making progress toward potentially expanding delivery beyond currently available intrathecal delivery capsids, including in the central nervous system. Sangamo’s pipeline also includes multiple partnered programs and programs with opportunities for partnership and investment. To learn more, visit www.sangamo.com and connect with us on LinkedIn and Twitter/X.
Source: Sangamo Therapeutics, Inc.
Sangamo stock soars 37% on updates for Fabry disease therapy
Feb. 12, 2024 1:29 PM ET
Sangamo Therapeutics, Inc. (SGMO) Stock
By: Val Brickates Kennedy, SA News Editor10 Comments
Sangamo Therapeutics (NASDAQ:SGMO) stock rallied 37% Monday after the biotech company announced regulatory updates for its gene therapy candidate ST-920 in the treatment of Fabry disease and said it was actively seeking a collaboration partner for the product.
The biotech company said the FDA has advised that a study of up to 25 patients in combination with confirmatory evidence may be sufficient to support approval of ST-920, also known as isaralgagene civaparvovec.
https://seekingalpha.com/news/4065704-sangamo-stock-soars-37-on-updates-for-fabry-disease-therapy
Sangamo Therapeutics, Inc. (SGMO) Stock
https://www.sangamo.com/programs/clinical-trials/fabry-disease/
Nipocalimab
Nipocalimab
Nipocalimab
Johnson & Johnson’s nipocalimab granted U.S. FDA Breakthrough Therapy Designation for the treatment of individuals at high risk for severe hemolytic disease of the fetus and newborn (HDFN)
Breakthrough Therapy Designation for nipocalimab based on results from the Phase 2 UNITY clinical trial for HDFN
Phase 3 clinical trial enrollment underway, representing the only therapy reported to be under clinical development for this serious, life-threatening and rare condition
FEBRUARY 09, 2024
Spring House, Pa. (February 9, 2024) – Johnson & Johnson today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) for nipocalimab for the treatment of alloimmunizeda pregnant individuals at high risk of severe hemolytic disease of the fetus and newborn (HDFN). Nipocalimab is currently the only therapy reported to be in clinical development for the treatment of alloimmunized pregnant individuals at risk of severe HDFN, a serious and rare condition that occurs when the blood types of a pregnant individual and the fetus are incompatible, potentially causing life-threatening anemia in the fetus or infant.1
“Nipocalimab represents a novel approach for the treatment of patients at risk of severe HDFN who need proven, safe, non-surgical solutions to help address the serious health consequences of this condition,” said Katie Abouzahr, M.D., Vice President, Autoantibody and Maternal Fetal Immunology Disease Area Leader, Johnson & Johnson. “We are committed to addressing the substantial unmet need in this devastating disease.”
The data from the proof-of-concept Phase 2 open-label UNITY clinical trial provided support for the BTD.2 The trial met the primary endpoint, with the majority of pregnant patients who received nipocalimab achieving a live birth at or after the gestational age of 32 weeks, without the need for an intrauterine transfusion (IUT) throughout their entire pregnancy.3 Severe or serious adverse events were generally low and consistent with events associated with pregnancy, HDFN, and gestational age at birth.3
Nipocalimab was granted Fast Track designation in July 2019, orphan drug status in June 2020 by the FDA, and orphan medicinal product designation by the European Medicines Agency in October 2019 for the HDFN indication.
The FDA grants BTD to expedite the development and regulatory review of an investigational medicine that is intended to treat a serious or life-threatening condition and is based on preliminary clinical evidence that demonstrates the drug may have substantial improvement in at least one clinically significant endpoint over available therapies. The AZALEA Phase 3 pivotal trial is currently enrolling pregnant individuals who are at risk for severe HDFN who have a history of severe HDFN in a prior pregnancy(ies).2
About the UNITY trial
UNITY (NCT03842189) is a global, multicenter, non-blinded Phase 2 clinical trial designed to evaluate the safety, efficacy, pharmacokinetics and pharmacodynamics of nipocalimab for the treatment of pregnant individuals at high risk for EOS HDFN. 5The trial enrolled RhD (D) or Kell (K) alloimmunized pregnant individuals with singleton pregnancies at high risk for EOS HDFN due to an obstetric history of severe fetal anemia, fetal hydrops, or a stillbirth at ≤24 weeks gestation.3 The primary endpoint was live birth at or after gestational age of 32 weeks, without a need for an IUT throughout the entire pregnancy.3 Safety was monitored for 24 weeks post-delivery for the 13 maternal individuals enrolled, and up to 96 weeks post-birth for infants.3 Participants received once-weekly intravenous infusions.3 The trial met the primary endpoint, with 54% of pregnant patients who received nipocalimab achieving a live birth at or after the gestational age (GA) of 32 weeks, without the need for an intrauterine transfusion throughout their entire pregnancy.
About HDFN
Hemolytic disease of the fetus and newborn (HDFN) is a rare disease (and in its severe form, even rarer) that arises in pregnancies with maternal-fetal incompatibility in certain red blood cell types. Alloantibodies produced by the maternal immune system against fetal red blood cells cross the placenta during pregnancy and attack fetal red blood cells causing fetal anemia or persist after birth in the neonate to cause neonatal hyperbilirubinemia and anemia.1 The symptoms of HDFN can range from mild jaundice, to neurotoxic hyperbilirubinema in the neonate, to life-threatening fetal anemia requiring invasive intervention.6 The potential for in utero onset at increasingly earlier gestational age with increasing risk of severe outcomes may occur with each incompatible pregnancy due to pregnancy-related alloimmunization.7 Currently no non-surgical interventions are approved for pregnancies at high risk of early-onset severe (EOS) HDFN in the U.S. Pregnancies affected by severe HDFN may necessitate repeated intrauterine transfusions (IUTs).8 IUTs are invasive, technically complex surgical procedures performed by specialists at specialized medical centers, and these procedures may be associated with an increased rate of fetal mortality and premature birth.9,10 The most difficult to treat cases of HDFN are those that develop before 24 weeks gestational age, defined here as EOS, due to high rates of IUT-related complications associated with mortality.11 According to the American Journal of Obstetrics and Gynecology, in the U.S., it is estimated that up to 80 of every 100,000 pregnancies are affected by HDFN each year.12
About Nipocalimab
Nipocalimab is an investigational, high-affinity, fully human, aglycosylated, effectorless, monoclonal antibody that aims to selectively block FcRn to reduce levels of circulating immunoglobulin G (IgG) antibodies, including autoantibodies and alloantibodies that underlie multiple conditions.13 Nipocalimab is the only anti-FcRn being studied across three key segments in the autoantibody space: Rare Autoantibody diseases (e.g., generalized myasthenia gravis in adults and children, chronic inflammatory demyelinating polyneuropathy, warm autoimmune hemolytic anemia, and idiopathic inflammatory myopathies); Maternal Fetal diseases mediated by maternal alloantibodies (e.g., HDFN); and Prevalent Rheumatology (e.g., rheumatoid arthritis, Sjögren’s disease, and systemic lupus erythematosus).5,14,15,16,17,18,19,20,21 Blockade of FcRn has the potential to reduce overall autoantibody levels while preserving immune function without causing broad immunosuppression. Blockade of IgG binding to FcRn in the placenta is also believed to prevent transplacental transfer of maternal alloantibodies to the fetus.5,22
About Johnson & Johnson
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity.
Learn more at https://www.jnj.com/ or at www.janssen.com/johnson-johnson-innovative-medicine. Follow us at @JanssenUS and @JNJInnovMed.
Janssen Research & Development, LLC and Janssen Biotech, Inc. are both Johnson & Johnson companies.
© Johnson & Johnson 2024. All rights reserved.
Johnson & Johnson antibody therapy gets FDA breakthrough designation for HDFN indication
Feb. 09, 2024 8:27 AM ET
By: Preeti Singh, SA News Editor
Johnson & Johnson (NYSE:JNJ) has received breakthrough therapy designation from the U.S. Food and Drug Administration (FDA) for its investigational antibody therapy, nipocalimab, for hemolytic disease of the fetus and newborn (HDFN) indication.
Nipocalimab, a high-affinity, fully human monoclonal antibody, is currently the only therapy reported to be in clinical development for the treatment of alloimmunized pregnant individuals at risk of severe HDFN.
OK-101
Nipocalimab
Nipocalimab
OKYO Pharma Receives FDA Approval of IND for OK-101 in Neuropathic Corneal Pain
Feb 9, 2024
- OK-101 is the first IND clearance granted by FDA for a drug to begin clinical studies specifically to treat patients suffering with neuropathic corneal pain (NCP), a major unmet medical need
- The initial trial of OK-101 to treat NCP is designed as a randomized, placebo-controlled, double-masked Phase 2 clinical trial and is planned to begin in 2Q 2024
- NCP is an Orphan disease as listed in the National Organization for Rare Disorders
London and New York, NY, February 9, 2024 – OKYO Pharma Limited (NASDAQ: OKYO), a clinical-stage biopharmaceutical company developing innovative ocular therapies for the treatment of inflammatory dry eye disease (DED), a multi-billion-dollar market, and for neuropathic corneal pain (NCP), an ocular condition associated with pain but without an FDA approved therapy, announced today that the U.S. Food and Drug Administration (FDA) has cleared OK-101 as its first Investigational New Drug (IND) application for the treatment of NCP.
Notably, the initial IND submission to FDA proposed an open-label design for the clinical trial. Based on positive feedback from FDA, the Phase 2 study is now designed as a double-masked, randomized, 12-week placebo-controlled trial comparing OK-101 to placebo in NCP patients. A total of 54 patients are planned for the study, with NCP disease confirmed via confocal microscopy. The primary endpoint will be measured utilizing VAS pain relief scores. These protocol changes will enable a statistically valid demonstration of a true drug effect of OK-101 on NCP symptoms. OKYO Pharma is scheduling this trial to begin in Q2 2024.
The OK-101 trial, designed as a single-center trial, will be led by Pedram Hamrah, MD, of Tufts Medical Center, as Principal Investigator. Dr. Hamrah is Professor and Vice Chair of Research and Academic Programs, Co-Director of the Cornea Service and Director of the Center for Translational Ocular Immunology at Tufts Medical Center. An ophthalmologist and a clinician-scientist, Dr. Hamrah is a leading expert in NCP and co-inventor on the OK-101 patent. He is also a member of OKYO’s Scientific Advisory Board.
“I am very pleased that we have gained FDA IND clearance for the first drug to be tested for NCP, a debilitating disease,” said Dr. Hamrah. “Receiving the IND clearance in an important and novel indication was not a trivial hurdle to overcome. Now that the path has been opened for drugs to be tested in NCP, I am looking forward to working with the OKYO team to launch this important trial.”
“We are pleased to gain IND clearance for OK-101 to treat NCP as a second important disease target for the Company,” said Dr. Gary S. Jacob, CEO of OKYO. “OK-101 recently demonstrated favorable tolerability in a Phase 2 trial of dry eye patients along with statistically significant improvements in dry eye symptoms such as stinging/burning and blurred vision, which are also hallmarks of NCP. OK-101 was also shown in a cutting-edge mouse model of NCP to significantly reduce ocular neuropathic pain. We are looking forward to advancing OK-101 to potentially treat NCP, a chronically painful ocular disease with no FDA-approved therapy and a major unmet medical need for patients suffering from this condition.”
About NCP
Neuropathic corneal pain (NCP) is a condition that causes pain and sensitivity of the eyes, face, or head. The exact cause of NCP is unknown but thought to result from nerve damage to the cornea combined with inflammation. NCP, which can exhibit as a severe, chronic, or debilitating condition in patients suffering from a host of ophthalmic conditions, is presently treated by various topical and systemic treatments in an off-label fashion. There are no approved commercial treatments currently available for this condition.
About OK-101
OK-101 is a lipid conjugated chemerin peptide agonist of the ChemR23 G-protein coupled receptor which is typically found on immune cells of the eye responsible for the inflammatory response. OK-101 was developed using a membrane-anchored-peptide technology to produce a novel long-acting drug candidate for treating dry eye disease. OK-101 has been shown to produce anti-inflammatory and pain-reducing activities in mouse models of dry eye disease and corneal neuropathic pain (NCP), respectively, and is designed to combat washout through the inclusion of the lipid anchor built into the drug molecule to enhance the residence time of OK-101 within the ocular environment. OK-101 recently showed clear statistical significance in multiple endpoints in a recently completed Phase 2, multi-center, double-blind, placebo-controlled trial of OK-101 to treat DED.
About OKYO
OKYO Pharma Limited (NASDAQ: OKYO) is a clinical stage biopharmaceutical company developing innovative therapies for the treatment of DED and NCP, with ordinary shares listed for trading on the NASDAQ Capital Market. OKYO is focused on the discovery and development of novel molecules to treat inflammatory DED and ocular pain. In addition to the recently completed Phase 2 DED trial, OKYO also has plans underway for the opening of a Phase 2 trial for OK-101 to treat NCP in patients with this debilitating condition. For further information, please visit www.okyopharma.com.
OKYO Pharma gains on receiving FDA nod of IND for OK-101 in neuropathic corneal pain
Feb. 09, 2024 9:01 AM ET
OKYO Pharma Limited (OKYO) Stock
By: Jaskiran Singh, SA News Editor
- OKYO Pharma (NASDAQ:OKYO) Friday rose about 18% in premarket as the company announced that the U.S. Food and Drug Administration (FDA) cleared OK-101 as its first Investigational New Drug (IND) application for treating neuropathic corneal pain.
- https://seekingalpha.com/news/4065121-okyo-pharma-gains-on-receiving-fda-nod-of-ind-for-ok-101-in-neuropathic-corneal-pain
- OKYO Pharma Limited (OKYO) Stock
- https://okyopharma.com/
biotecHOPE™ 2024
Acoramidis
BLENREP (belantamab mafodotin-blmf)
Acoramidis
Positive high-level results from Japan Phase III trial of acoramidis in adults with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) showed consistency with global ATTRibute-CM Phase III trial
PUBLISHED
2 February 2024
Results from open-label trial advance ambition to transform amyloidosis care and support local regulatory submission in Japan
Positive high-level results from the Japan Phase III trial of acoramidis in adults with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) showed consistency to those in the global BridgeBio Pharma, Inc. (BridgeBio) ATTRibute-CM Phase III trial (NCT03860935), including survival, cardiac-related hospitalisations and other measures of improved functions (measured by six-minute walk test) and quality of life (measured by the Kansas City Cardiomyopathy Questionnaire Overall Summary Score) at 30 months.1 This trial in Japan was conducted to support local registration.
ATTR-CM is a rare, systemic, progressive and fatal condition that leads to heart failure and high rates of fatality within four years from diagnosis.2
Alexion, AstraZeneca Rare Disease, maintains an exclusive licence with BridgeBio’s affiliate, Eidos Therapeutics, Inc. to develop and commercialise acoramidis in Japan. The success criterion in the open-label Phase III trial in Japan was defined as greater estimated survival probability at 30 months than that observed among placebo patients in ATTRibute-CM.
Professor Yukio Ando, MD, PhD, Department of Amyloidosis Research, Nagasaki International University, Nagasaki, Japan, said: “As people living with ATTR-CM are at risk of significant morbidity and mortality, including heart failure, halting disease progression is essential to improving outcomes. These results offer further evidence that TTR stabilisation with acoramidis may improve survival and reduce disease severity for patients by preventing further breakdown of these proteins.”
Marc Dunoyer, Chief Executive Officer, Alexion, AstraZeneca Rare Disease, said: “With one of the industry’s largest amyloidosis pipelines exploring multiple therapeutic modalities, we are working to redefine treatment and care as well as offer new hope for this underserved community. These positive results support our ambition to bring acoramidis to people living with ATTR-CM in Japan as soon as possible.”
Acoramidis is an investigational, next-generation, oral, highly potent small molecule stabiliser of transthyretin, designed to achieve maximal stabilisation and preserve native TTR.3
Acoramidis was well-tolerated, with no safety signals of potential clinical concern identified. The data will be presented at a forthcoming medical meeting and submitted to Japan's health authority for regulatory review.
Notes
ATTR-CM
ATTR-CM is a progressive, rare, systemic disease caused by ageing or genetic mutations, resulting in misfolded TTR protein and accumulation as amyloid fibrils in the cardiac myocardium.4,5 In patients with ATTR, both hereditary and wild type (non-hereditary), TTR protein builds up as fibrils in tissues, such as the peripheral nerves and heart, gastrointestinal system, eyes, kidneys, central nervous system, thyroid and bone marrow.4,6 The presence of TTR fibrils interferes with the normal functions of these tissues.5 As the TTR protein fibrils accumulate, more tissue damage occurs and the disease worsens, resulting in poor quality of life and eventually death.5 Worldwide, there are an estimated 300,000 - 500,000 patients with ATTR-CM; however, many of those patients remain undiagnosed.6,7
Phase III Open-Label Trial in Japan
A Phase III, open-label, multicentre, prospective trial (NCT04622046) evaluated the safety and efficacy of acoramidis in Japanese adults with ATTR-CM. This trial enrolled 25 patients in Japan, 22 of which completed the trial at 30 months. Participants were required to have a confirmed diagnosis of ATTR-CM with either wild-type TTR or a variant TTR genotype and clinical evidence of heart failure. Other requirements included class I-III symptoms due to ATTR-CM in the New York Heart Association Functional Classification.8
Enrolled patients received acoramidis hydrochloride twice daily at a dose of 800 milligrammes for an initial treatment period of 12 months followed by an additional 18 months (for a treatment period of 30 months). The primary endpoints were change from baseline to month 12 in six-minute walk distance, as well as rate of all-cause mortality and frequency of cardiovascular-related hospitalisation over 30 months.8
Statistical analyses were conducted once all participants completed 30 months of active treatment.
Patients who completed 30 months of active treatment were eligible to continue into a long-term extension period, which is ongoing.8
Acoramidis
Acoramidis is an investigational, next-generation, orally-administered, highly potent, small molecule stabiliser of transthyretin (TTR), designed to achieve maximal stabilisation and preserve native TTR.3
Alexion maintains an exclusive licence with BridgeBio’s affiliate, Eidos Therapeutics, Inc., to develop and commercialise acoramidis in Japan.
Alexion
Alexion, AstraZeneca Rare Disease, is the group within AstraZeneca focused on rare diseases, created following the 2021 acquisition of Alexion Pharmaceuticals, Inc. As a leader in rare diseases for more than 30 years, Alexion is focused on serving patients and families affected by rare diseases and devastating conditions through the discovery, development and commercialisation of life-changing medicines. Alexion focuses its research efforts on novel molecules and targets in the complement cascade and its development efforts on haematology, nephrology, neurology, metabolic disorders, cardiology and ophthalmology. Headquartered in Boston, Massachusetts, Alexion has offices around the globe and serves patients in more than 50 countries.
AstraZeneca in Amyloidosis
Amyloidosis is a group of complex rare diseases caused by abnormal proteins that misfold and clump together to form toxic amyloids that deposit in tissues or organs, including the heart, kidneys and peripheral nerves. The build-up of these toxic amyloids can result in significant organ damage and organ failure that can severely impact quality of life and ultimately be fatal. AstraZeneca and its Rare Disease Unit, Alexion, are developing and evaluating multiple modalities with the potential to halt and reduce organ damage across various types of amyloidosis. The Company is uniquely positioned to lead therapeutic and diagnostic advances for people living with amyloidosis with the largest and fastest-growing pipeline of investigational amyloidosis therapies to address the spectrum of patient needs.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca.
Ionis-AstraZeneca amyloid cardiomyopathy candidate gets FDA fast track designation
Feb. 08, 2024 8:35 AM ET
Ionis Pharmaceuticals, Inc. (IONS) Stock, AZN Stock
By: Preeti Singh, SA News Editor
The U.S. FDA has granted fast track status to an investigation therapy by Ionis Pharmaceuticals (NASDAQ:IONS) and AstraZeneca (NASDAQ:AZN) for transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) in adults.
RGX-121
BLENREP (belantamab mafodotin-blmf)
Acoramidis
REGENXBIO Announces Pivotal Trial of RGX-121 for the Treatment of MPS II Achieves Primary Endpoint
Feb 07, 2024 at 11:40 AM EST
- Results support BLA submission in 2024 using the accelerated approval pathway
- Primary endpoint of patients achieving reduction in CSF biomarker of MPS II disease was met with statistical significance (p value of 0.00016)
- Patients treated with RGX-121 have showed continued improvement in neurodevelopmental skill acquisition up to four years and discontinued intravenous enzyme therapy
- Company plans to discuss these results as part of a full rare disease program update on its conference call today, Wednesday, February 7, 4:30 p.m. ET
ROCKVILLE, Md., Feb. 7, 2024 /PRNewswire/ -- REGENXBIO Inc. (Nasdaq: RGNX) today announced topline results from the Phase I/II/III CAMPSIITE® trial of RGX-121 for the treatment of patients up to 5 years old diagnosed with Mucopolysaccharidosis Type II (MPS II), also known as Hunter syndrome, demonstrating that the pivotal phase of the trial met its primary endpoint with statistical significance.
The results were presented at the 20th Annual WORLDSymposium™ by Paul Harmatz, M.D., UCSF Benioff Children's Hospital and trial investigator.
"The data from this pivotal trial supports that RGX-121 changes the course of disease by restoring the gene missing in boys with Hunter syndrome and has the potential to significantly improve vital brain function for patients living with this debilitating disease," said Kenneth T. Mills, President and CEO of REGENXBIO. "We are excited about these results and working quickly to complete activities to file the BLA this year. We have shared CAMPSIITE results with FDA leadership, and they have confirmed that, based on the totality of the evidence, they are open to accelerated approval if supported by review of the full data."
"There is currently no treatment to address fatal neuronopathic CNS disease in MPS II, and I am encouraged by the topline data from the pivotal trial of RGX-121," said Dr. Harmatz. "A one-time gene therapy that can help these boys develop beyond the natural history of the disease and may allow them to discontinue enzyme replacement therapy or remain ERT-naïve represents a meaningful breakthrough."
Data Summary
In the pivotal phase, MPS II patients treated with RGX-121 achieved decreased cerebrospinal fluid (CSF) levels of D2S6, a key biomarker of brain disease activity, below maximum attenuated disease levels at 16 weeks (p value of 0.00016). Patients receiving RGX-121 demonstrated an 86% median reduction in D2S6, approaching normal levels.
Pivotal results were consistent with data from the dose-finding phase of CAMPSIITE. In the dose-finding phase, the majority of patients are exceeding expectations in neurodevelopmental function compared to natural history data up to four years. New long-term follow-up of patients treated with RGX-121 in the dose-finding phase also showed there was a high rate of patients for whom trial investigators chose to discontinue standard-of-care intravenous enzyme replacement therapy (ERT) or were allowed to remain ERT-naïve. At the pivotal dose level, 80% of patients were ERT-free at last time point.
As of January 3, 2024, RGX-121 continues to be well tolerated in 25 patients dosed across all phases of the CAMPSIITE trial.
Following an RMAT meeting held with FDA at the end of 2023, REGENXBIO continues with plans to use CSF levels of D2S6 as a surrogate endpoint for accelerated approval and is completing remaining activities in order to file a BLA in the second half of 2024. Based on an expected priority review, potential approval of the planned BLA could result in receipt of a Rare Pediatric Disease Priority Review Voucher in 2025.
Data presented is available on the "Publications" section of the REGENXBIO website at WWW.REGENXBIO.COM.
Conference Call
As part of a full rare disease program update, REGENXBIO will host a conference call today, Wednesday, February 7 at 4:30 p.m. ET and will be joined by Dr. Harmatz and Raymond Wang, M.D., Children's Hospital of Orange County to discuss the CAMPSIITE trial pivotal phase topline results and the expedited plan for filing a Biologics License Application using the accelerated approval pathway in 2024.
Listeners can register for the webcast via this LINK. Analysts wishing to participate in the question and answer session should use this LINK. A copy of the slides being presented will be available via the Company's investor website. Those who plan on participating are advised to join 15 minutes prior to the start time. A replay of the webcast will also be available via the Company's investor website approximately two hours after the call's conclusion.
About the CAMPSIITE® Trial
CAMPSIITE is a Phase I/II/III multicenter, open-label trial enrolling boys with neuronopathic MPSII, aged four months up to five years of age. The primary endpoint of the trial is measurement of CSF GAGs. Heparan sulfate (HS) and D2S6, a component of HS closely correlated with severe MPS II, are GAGs that are key biomarkers of I2S enzyme activity and are being measured in the CSF at baseline and after administration of RGX-121. Accurate and sensitive measurements of CSF GAGs, such as D2S6, have the potential to be considered a surrogate endpoint that is reasonably likely to predict clinical benefit in MPS II disease under the accelerated approval pathway, as buildup of GAGs in the CSF of MPS II patients correlates with clinical manifestations including neurodevelopmental deficits.
The pivotal program is using commercial-scale cGMP material from REGENXBIO's proprietary, high-yielding suspension-based manufacturing process, named NAVXpress™. In addition to measuring GAGs in the CSF, the trial will continue to collect neurodevelopmental data and caregiver-reported outcomes.
About RGX-121
RGX-121 is an investigational, one-time gene therapy designed to deliver the iduronate-2-sulfatase gene (IDS) that encodes the iduronate-2-sulfatase enzyme (I2S) using the NAV® AAV9 vector. RGX-121 expressed protein is structurally identical to normal I2S. RGX-121 is administered directly to the central nervous system (CNS) using intracisternal or intracerebroventricular delivery. Delivery of the IDS gene within cells in the CNS could provide a permanent source of secreted I2S beyond the blood-brain barrier, allowing for long-term cross correction of cells throughout the CNS.
RGX-121 has received Orphan Drug Product, Rare Pediatric Disease, Fast Track and Regenerative Medicine Advanced Therapy designations from the U.S. Food and Drug Administration and advanced therapy medicinal products (ATMP) classification from the European Medicines Agency.
About Mucopolysaccharidosis Type II (MPS II)
MPS II, or Hunter Syndrome, is a rare, X-linked recessive disease caused by a deficiency in the lysosomal enzyme iduronate-2-sulfatase (I2S) leading to an accumulation of glycosaminoglycans (GAGs), including heparan sulfate (HS) in tissues which ultimately results in cell, tissue, and organ dysfunction, including in the central nervous system (CNS). MPS II is estimated to occur in 1 in 100,000 to 170,000 births. In severe forms of the disease, early developmental milestones may be met, but developmental delay is readily apparent by 18 to 24 months. Specific treatment to address the neurological manifestations of MPS II remains a significant unmet medical need. Key biomarkers of I2S enzymatic activity in MPS II patients include its substrate heparan sulfate (HS) D2S6, which has been shown to correlate with neurocognitive manifestations of the disorder.
About REGENXBIO Inc.
REGENXBIO is a leading clinical-stage biotechnology company seeking to improve lives through the curative potential of gene therapy. REGENXBIO's NAV Technology Platform, a proprietary adeno-associated virus (AAV) gene delivery platform, consists of exclusive rights to more than 100 novel AAV vectors, including AAV7, AAV8 and AAV9. REGENXBIO and its third-party NAV Technology Platform Licensees are applying the NAV Technology Platform in the development of a broad pipeline of candidates, including late-stage and commercial programs, in multiple therapeutic areas. REGENXBIO is committed to a "5x'25" strategy to progress five AAV Therapeutics from our internal pipeline and licensed programs into pivotal-stage or commercial products by 2025.
View original content to download multimedia:
SOURCE REGENXBIO Inc.
Regenxbio spikes after trial win for gene therapy in Hunter syndrome
Feb. 07, 2024 12:48 PM ET
By: Dulan Lokuwithana, SA News Editor3 Comments
Regenxbio (NASDAQ:RGNX) traded higher on Wednesday after the gene therapy developer said RGX-121, its one-time treatment for a rare disease called Hunter syndrome, met the primary endpoint in the pivotal phase of a small open-label trial.
https://seekingalpha.com/news/4064051-regenxbio-stock-spikes-after-trial-win-gene-therapy
BLENREP (belantamab mafodotin-blmf)
BLENREP (belantamab mafodotin-blmf)
BLENREP (belantamab mafodotin-blmf)
05 February 2024
Issued: London, UK
For media and investors only
DREAMM-7 phase III trial shows Blenrep combination nearly tripled median progression-free survival versus standard of care combination in patients with relapsed/refractory multiple myeloma
- 59% reduction in risk of disease progression or death observed in patients with Blenrep combination versus standard of care daratumumab combination
- 36.6 months of median progression-free survival observed with Blenrep combination versus 13.4 months in daratumumab combination
- Strong, clinically meaningful trend in overall survival favouring Blenrep combination was observed with 43% reduction in risk of death
GSK plc (LSE/NYSE: GSK) today announced results from an interim analysis of the DREAMM-7 phase III head-to-head trial evaluating Blenrep (belantamab mafodotin) combined with bortezomib plus dexamethasone (BorDex) versus daratumumab plus BorDex in second-line and later treatment of relapsed or refractory multiple myeloma. These data will be presented at the American Society of Clinical Oncology (ASCO) Plenary Series on 6 February 2024.
In the primary endpoint of progression-free survival (PFS), a statistically significant and clinically meaningful improvement was observed with the belantamab mafodotin combination (n=243), showing a 59% reduction in the risk of disease progression or death (hazard ratio [HR]: 0.41 [95% confidence interval (CI): 0.31-0.53], p-value<0.00001) compared to the daratumumab combination (n=251). With a median follow-up of 28.2 months, the median PFS was 36.6 months (95% CI: 28.4-not reached [NR]) with the belantamab mafodotin combination compared to 13.4 months (11.1-17.5) in the daratumumab combination. The PFS effect was observed across all prespecified subgroups, including those who were refractory to lenalidomide and those with high-risk cytogenetics. The safety and tolerability profile of the belantamab mafodotin combination was consistent with the known profile of the individual agents.
Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said: “The substantial progression-free survival benefit and strong overall survival trend compared to a daratumumab standard of care combination reinforce our belief in the potential for belantamab mafodotin used in combination to redefine the treatment of multiple myeloma at or after first relapse. We plan on sharing these results with health authorities worldwide.”
The belantamab mafodotin combination also resulted in clinically meaningful improvements in all secondary efficacy endpoints including a doubling of complete response rate (stringent complete response plus complete response), minimal residual disease (MRD) negativity rate and median duration of response (DOR). A strong and clinically meaningful overall survival (OS) trend was observed at the interim analysis, with a 43% reduction in the risk of death (HR: 0.57 [95% CI: 0.40-0.80], p-value=0.00049), which has not yet reached the interim criteria for statistical significance of OS. OS follow-up continues and further analyses are planned.
María-Victoria Mateos, MD, PhD, Head of Myeloma and Clinical Trials Unit, Haematology Department and Professor of Medicine at the University of Salamanca, Spain, and DREAMM-7 principal investigator, said: “These results from DREAMM-7 show how belantamab mafodotin in combination with BorDex represents a significant improvement over the daratumumab-based regimen in a second-line multiple myeloma treatment setting. Anti-BCMA therapies are helping to improve outcomes for patients with multiple myeloma, and having an off-the-shelf option, like belantamab mafodotin, that can be administered in a community oncology treatment centre where the majority of patients are treated has the potential to transform the way we treat myeloma at or after first relapse.”
Grade 3 or higher non-ocular adverse events of clinical interest in the belantamab mafodotin combination and daratumumab combination arms, respectively, included thrombocytopenia (55% and 35%; exposure-adjusted event rate: 40 and 29, per 100 person-years), neutropenia (12% and 6%), pneumonia (12% and 4%; exposure-adjusted event rate: 8 and 3, per 100 person-years), and anaemia (8% and 10%).
Eye-related side effects, a known risk of treatment with belantamab mafodotin, were generally reversible, manageable with dose modification, and led to low (9%) treatment discontinuations. Grade 3 or higher ocular adverse events occurred in 34% of patients receiving the belantamab mafodotin combination and primarily included blurred vision (22%), dry eye (7%), eye irritation (5%), and visual impairment (5%). Eighty-two patients (34%) with a best corrected visual acuity (BCVA) score of 20/25 or better in at least one eye at baseline had a worsening in both eyes to 20/50 or worse. Almost all these patients’ events (98%) had resolved at the time of this analysis. The median time to resolution was 22 days.
Global health status quality of life (QOL) as measured by the EORTC-QLQ-C30 indicated no difference in global QOL between different treatment arms over time.
The DREAMM (DRiving Excellence in Approaches to Multiple Myeloma) clinical development programme continues to evaluate the potential of belantamab mafodotin in early lines of treatment and in combination with novel therapies and standard of care treatments. This includes the ongoing phase III DREAMM-8 trial evaluating belantamab mafodotin in combination with pomalidomide and dexamethasone versus bortezomib in combination with pomalidomide and dexamethasone. DREAMM-8 data are expected in the second half of 2024.
About DREAMM-7
The DREAMM-7 phase III clinical trial is a multicentre, open-label, randomised trial evaluating the efficacy and safety of belantamab mafodotin in combination with bortezomib and dexamethasone (BorDex) compared to a combination of daratumumab and BorDex in patients with relapsed/refractory multiple myeloma who previously were treated with at least one prior line of multiple myeloma therapy, with documented disease progression during or after their most recent therapy.
A total of 494 participants were randomised at a 1:1 ratio to receive either belantamab mafodotin in combination with BorDex or a combination of daratumumab and BorDex. Belantamab mafodotin was scheduled to be dosed at 2.5mg/kg intravenously every three weeks.
The primary endpoint is PFS as per an independent review committee. The key secondary endpoints include OS, DOR, and MRD negativity rate as assessed by next-generation sequencing.
About multiple myeloma
Multiple myeloma is the third most common blood cancer globally and is generally considered treatable but not curable.1,2 There are approximately 176,000 new cases of multiple myeloma diagnosed globally each year.3 Research into new therapies is needed as multiple myeloma commonly becomes refractory to available treatments.4
About Blenrep
Blenrep is an antibody-drug conjugate comprising a humanised B-cell maturation antigen monoclonal antibody conjugated to the cytotoxic agent auristatin F via a non-cleavable linker. The drug linker technology is licensed from Seagen Inc.; the monoclonal antibody is produced using POTELLIGENT Technology licensed from BioWa Inc., a member of the Kyowa Kirin Group.
Refer to the Blenrep EMA Reference Information (https://www.ema.europa.eu/en/medicines/human/EPAR/blenrep) for a full list of adverse events and the complete important safety information in the EU.
GSK in oncology
Oncology is an emerging therapeutic area for GSK where we are committed to maximising patient survival with a current focus on haematologic malignancies, gynaecologic cancers and other solid tumours through breakthroughs in immuno-oncology and tumour-cell targeting therapies.
About GSK
GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com.
GSK blood cancer therapy nearly triples survival in late stage trial
Feb. 06, 2024 7:38 AM ET
By: Dulan Lokuwithana, SA News Editor
GSK (NYSE:GSK) said patients who received its antibody-drug conjugate, Blenrep, as a combination therapy lived nearly three times longer without a relapse compared to the standard of care in multiple myeloma, a common form of blood cancer.
Citing interim data from its DREAMM-7 Phase 3 trial, the British drugmaker said those who received Blenrep with a drug combination called BorDex indicated 36.6 months of median progression-free survival at a median follow-up of 28.2 months.
https://seekingalpha.com/news/4063050-gsk-blood-cancer-therapy-nearly-triples-survival
Acoramidis
R21/Matrix-M™ Malaria Vaccine
BLENREP (belantamab mafodotin-blmf)
BridgeBio Pharma Announces U.S. Food and Drug Administration (FDA) Acceptance of New Drug Application (NDA) for Acoramidis for the Treatment of Patients with Transthyretin Amyloid Cardiomyopathy (ATTR-CM)
– Accepted with Prescription Drug User Fee Act (PDUFA) action date of November 29, 2024; FDA not currently planning to hold an advisory committee meeting to discuss application
– Marketing Authorization Application accepted by the European Medicines Agency (EMA) with additional global regulatory submissions planned
– In ATTRibute-CM, acoramidis treatment demonstrated an 81% absolute survival rate and a 0.29 observed mean annual cardiovascular-related hospitalization (CVH) frequency, as well as improvements for a large proportion of patients on laboratory and functional measures
– ATTRibute-CM results also demonstrated rapid clinical benefit on the composite endpoint of all-cause mortality (ACM) and CVH in patients treated with acoramidis, with time-to-first event Kaplan-Meier curves separating at month 3 and continuing to diverge steadily through Month 30
PALO ALTO, Calif., Feb. 05, 2024 (GLOBE NEWSWIRE) — BridgeBio Pharma, Inc. (Nasdaq: BBIO) (“BridgeBio” or the “Company”), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, today announced that the U.S. Food and Drug Administration (FDA) has accepted for filing the Company’s New Drug Application (NDA) for acoramidis, an investigational drug for the treatment of ATTR-CM. The application was based on positive results from ATTRibute-CM, the Company’s Phase 3 study designed to evaluate the efficacy and safety of acoramidis, an investigational, next-generation, orally-administered, highly potent, small molecule stabilizer of transthyretin (TTR). The FDA has set an action date of November 29, 2024 under the PDUFA. The FDA also notified the Company that it is not currently planning to hold an advisory committee meeting to discuss the application.
“The FDA’s acceptance of our NDA submission for review reinforces our belief in acoramidis and its potential to make an important contribution to the care of patients with ATTR-CM,” said Jonathan Fox, MD, PhD, President and Chief Medical Officer of BridgeBio Cardiorenal. “We look forward to the upcoming review process and the potential for approval in the United States. Similarly, with the European Marketing Authorization Application accepted and with plans to extend our submissions to other countries and regions, we are committed to making acoramidis available to patients.”
In July 2023, BridgeBio announced positive results from ATTRibute-CM, reporting a highly statistically significant result, demonstrated by a Win Ratio of 1.8 (p<0.0001) on the primary endpoint (a hierarchical analysis prioritizing in order: ACM, then frequency of CVH, then change from baseline in N-terminal prohormone of brain natriuretic peptide (NT-proBNP), then change from baseline in 6-minute walk distance (6MWD)). Acoramidis was well-tolerated, with no safety signals of potential clinical concern identified. BridgeBio has also presented analyses from ATTRibute-CM at the European Society of Cardiology Congress 2023 and at the American Heart Association Scientific Sessions 2023.
“As part of our mission, we seek to improve the lives of patients with amyloidosis by providing support to them and their caregivers throughout their journey. There is a need for more treatment options that can help fill the significant unmet need that exists for patients today. We are excited by BridgeBio’s recent NDA acceptance from the FDA, which we hope moves us one step closer to having acoramidis available as a treatment for the ATTR-CM community,” said Isabelle Lousada, president and CEO of the Amyloidosis Research Consortium, a global nonprofit organization dedicated to advancements in amyloidosis.
The Company also received acceptance of its Marketing Authorization Application with the European Medicines Agency and is preparing for additional global regulatory submissions.
About BridgeBio
BridgeBio is a commercial-stage biopharmaceutical company founded to discover, create, test and deliver transformative medicines to treat patients who suffer from genetic diseases and cancers with clear genetic drivers. BridgeBio’s pipeline of development programs ranges from early science to advanced clinical trials. BridgeBio was founded in 2015 and its team of experienced drug discoverers, developers, and innovators are committed to applying advances in genetic medicine to help patients as quickly as possible. For more information visit bridgebio.com and follow us on LinkedIn and Twitter.
BridgeBio Pharma granted FDA review for amyloidosis therapy
Feb. 05, 2024 7:56 AM ET
BridgeBio Pharma, Inc. (BBIO) StockPFE
By: Dulan Lokuwithana, SA News Editor
- BridgeBio Pharma (NASDAQ:BBIO) announced Monday that the U.S. FDA accepted its New Drug Application (NDA) for its lead asset acoramidis targeted at transthyretin amyloid cardiomyopathy (ATTR-CM), a potentially fatal heart disease.
- The agency has set November 29, 2024, as the target action date for its decision and currently doesn’t intend to hold an advisory committee meeting as part of its review.
- https://seekingalpha.com/news/4062509-bridgebio-pharma-granted-fda-review-amyloidosis-drug?mailingid=34236608&messageid=2900&serial=34236608.10060&utm_campaign=rta-stock-news&utm_content=link-1&utm_medium=email&utm_source=seeking_alpha&utm_term=34236608.10060
- BridgeBio Pharma, Inc. (BBIO) Stock
- https://bridgebio.com/pipeline/#pipeline
- https://bridgebio.com/
Nipocalimab
R21/Matrix-M™ Malaria Vaccine
R21/Matrix-M™ Malaria Vaccine
Johnson & Johnson reports positive topline results for nipocalimab from a Phase 3 pivotal study in generalized myasthenia gravis (gMG) and a Phase 2 study in Sjögren’s Disease (SjD)
Nipocalimab showed clinical efficacy in gMG, a chronic debilitating autoantibody disease where significant unmet patient need exists for efficacious, safe therapies that offer sustained disease control
Nipocalimab is the first investigational anti-FcRn to show efficacy in SjD, one of the most prevalent, debilitating autoantibody diseases that has no approved advanced treatments
In the past 12 months, nipocalimab has demonstrated clinical effect in four different autoantibody-driven diseases
FEBRUARY 05, 2024
Spring House, Pa. (February 5, 2024) – Johnson & Johnson today announced topline results from the pivotal Phase 3 VIVACITY study of nipocalimab in adults living with generalized myasthenia gravis (gMG) as well as the Phase 2 DAHLIAS study of nipocalimab in adults with Sjögren’s disease (SjD). Nipocalimab has demonstrated clinical effect in four autoantibody-driven diseases within the past year, including hemolytic disease of the fetus and newborn (HDFN) and rheumatoid arthritis, in addition to gMG and SjD.
In the Phase 3 VIVACITY study in gMG, nipocalimab met the primary endpoint, achieving statistically significant reduction in MG-ADLa score from baseline over weeks 22 to 24 compared with placebo (PBO). gMG is a chronic, life-long, rare, and highly debilitating autoantibody-driven neuromuscular disease characterized by fluctuating muscle weakness.
The primary endpoint was also met in the Phase 2 DAHLIAS dose-ranging study in SjD with a statistically significant reduction in clinESSDAIb score from baseline at week 24 compared with placebo (PBO). These data represent the first positive results of an investigational anti-FcRn treatment in this chronic, debilitating autoantibody disease that is without approved advanced therapies. SjD is nine times more common in women than in men, a factor of relevance to nipocalimab and the investigative treatment’s unique status among anti-FcRns, with acceptable benefit-risk demonstrated in studies in pregnant individuals thus far.
Nipocalimab was well-tolerated by participants in both studies.
“We look forward to sharing the comprehensive results of these important studies at upcoming scientific medical meetings,” said Katie Abouzahr, M.D., Vice President, Autoantibody and Maternal Fetal Immunology Disease Area Leader, Johnson & Johnson. “Johnson & Johnson is committed to addressing the immense unmet patient need in these chronic and debilitating autoantibody-driven diseases. We are the only company developing an anti-FcRn treatment in three key segments of autoantibody disease and have achieved proof of concept in each: Rare Autoantibody with gMG, Maternal Fetal Immunology with HDFN, and Prevalent Rheumatology with today’s results in SjD building on our existing data in rheumatoid arthritis.”
As next steps, Johnson & Johnson plans to present full results from the Phase 3 VIVACITY study at an upcoming scientific medical congress and engage with global regulatory authorities about bringing nipocalimab to patients living with gMG. The results from the Phase 2 DAHLIAS study support further clinical development of nipocalimab in SjD, and the full results from the study will be presented at a scientific medical congress this year.
Nipocalimab was granted Fast Track designation in HDFN and warm autoimmune hemolytic anemia (wAIHA) in July 2019 and gMG in December 2021, and was granted orphan drug status for wAIHA in December 2019, HDFN in June 2020, gMG in February 2021, chronic inflammatory demyelinating polyneuropathy (CIDP) in October 2021 and fetal and neonatal alloimmune thrombocytopenia (FNAIT) in December 2023 by the U.S. Food and Drug Administration (FDA). The treatment was also granted orphan medicinal product designation by the European Medicines Agency in October 2019 for HDFN. Nipocalimab is under development and not currently approved.
Editor’s Notes
a. MG-ADL (Myasthenia Gravis – Activities of Daily Living) provides a rapid clinical assessment of the patient’s recall of symptoms impacting activities of daily living, with a total score range of 0 to 24; a higher score indicates greater symptom severity.
b. ClinESSDAI is an endpoint specific to SjD and is a composite scale that assesses organ disease activity across 11 organ system domains [cutaneous, pulmonary, renal, articular, muscular, peripheral nervous system (PNS), central nervous system (CNS), hematological, glandular, constitutional, lymphadenopathy and lymphoma]; a higher score indicates greater symptom severity.
About the Phase 3 VIVACITY study of nipocalimab in gMG
The Phase 3 VIVACITY study was a randomized, double-blind, placebo (PBO)-controlled study in adult patients with moderate to severe gMG with insufficient response to standard-of-care therapies.
About generalized myasthenia gravis (gMG)
Myasthenia gravis (MG) is an autoantibody disease where autoantibodies target proteins at the neuromuscular junction, disrupt neuromuscular signaling, and impair or prevent muscle contraction. The disease impacts an estimated 700,000 people worldwide, with 85% of these patients experiencing the more extensive form of the disease, gMG.1 In MG, the immune system mistakenly attacks muscle receptors by producing anti-receptor antibodies (most commonly anti-acetylcholine receptor [AChR] or anti-muscle-specific kinase [MuSK] antibodies) that can block or destroy these muscle receptors, preventing signals from transferring from nerves to muscles. Symptoms include limb weakness, drooping eyelids, double vision, and difficulties with chewing, swallowing, speech, and breathing. Although gMG may be managed with current therapies, research is needed to develop new treatments for those who may not respond well enough to or tolerate current therapies.
About the Phase 2 DAHLIAS study of nipocalimab in SjD
The Phase 2 DAHLIAS study was a randomized, double-blind, placebo (PBO)-controlled dose-ranging study in patients with SjD who had moderate to severe disease activity on standard of care.
About Sjögren’s disease (SjD)
Sjögren’s disease (SjD) is one of the most prevalent autoantibody driven diseases for which no therapies are currently approved that treat the underlying and systemic nature of the disease.2 It is a chronic autoimmune disease that is estimated to impact approximately 350,000 people in the U.S. and 560,000 across the U.S. and Europe,3 and is nine times more common in women than men,4 characterized by autoantibody production, chronic inflammation, and lymphocytic infiltration of exocrine glandular systems. Most patients are affected by mucosal dryness (eyes, mouth, vagina), joint pain, and fatigue. Extraglandular manifestations are common and may impact multiple organ systems, including joints, lungs, kidneys, and nervous system. Patients with SjD have a high risk of developing numerous associated conditions, including up to 20 times higher risk of developing B-cell lymphomas when compared to the general population. Disease burden can be as high as that of rheumatoid arthritis or systemic lupus erythematosus. It is usually associated with impaired quality of life and functional capacity.5,6
About Nipocalimab
Nipocalimab is an investigational, high-affinity, fully human, aglycosylated, effectorless, monoclonal antibody that aims to selectively block FcRn to reduce levels of circulating immunoglobulin G (IgG) antibodies, including autoantibodies and alloantibodies that underlie multiple conditions.7 Nipocalimab is the only anti-FcRn being studied across three key segments in the autoantibody space: Rare Autoantibody (e.g., generalized myasthenia gravis in adults and children, chronic inflammatory demyelinating polyneuropathy, warm autoimmune hemolytic anemia, and idiopathic inflammatory myopathies); Maternal Fetal diseases mediated by maternal alloantibodies (e.g., HDFN); and Prevalent Rheumatology (e.g., rheumatoid arthritis, SjD, and systemic lupus erythematosus)8-15 Blockade of FcRn has the potential to reduce overall autoantibody levels while preserving immune function without causing broad immunosuppression. Blockade of IgG binding to FcRn in the placenta is also believed to prevent transplacental transfer of maternal alloantibodies to the fetus.16
About Johnson & Johnson
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity.
Learn more at https://www.jnj.com/ or at www.janssen.com/johnson-johnson-innovative-medicine. Follow us at @JanssenUS and @JNJInnovMed.
Janssen Research & Development, LLC and Janssen Biotech, Inc. are both Johnson & Johnson companies.
© Johnson & Johnson 2024. All rights reserved.
Johnson & Johnson succeeds in trials for autoimmune drug
Feb. 05, 2024 10:24 AM ET
By: Dulan Lokuwithana, SA News Editor
- Johnson & Johnson (NYSE:JNJ) announced Monday that its experimental antibody therapy nipocalimab generated positive results in two clinical trials for autoimmune conditions, generalized myasthenia gravis and Sjögren's disease.
- Citing topline data, the New Brunswick, New Jersey-based pharma giant said nipocalimab reached the primary endpoint in its pivotal Phase 3 study, VIVACITY for gMG, and Phase 2 DAHLIAS study in adults with SjD.
- https://seekingalpha.com/news/4062626-johnson-johnson-wins-studies-autoimmune-drug?mailingid=34238591&messageid=2900&serial=34238591.3033&utm_campaign=rta-stock-news&utm_content=link-1&utm_medium=email&utm_source=seeking_alpha&utm_term=34238591.3033
- https://www.jnj.com/innovative-medicine
- https://www.jnj.com/
R21/Matrix-M™ Malaria Vaccine
R21/Matrix-M™ Malaria Vaccine
R21/Matrix-M™ Malaria Vaccine
R21/Matrix-M™ Malaria Vaccine Phase 3 Trial Results Published in The Lancet
February 2, 2024
Today, peer-reviewed results from a Phase 3 efficacy trial of the R21/Matrix-M™ malaria vaccine were published in The Lancet. The trial was conducted across multiple sites in four African countries with 4,800 children aged 5-36 months.
Data from this trial served as the basis for the World Health Organization’s (WHO) recent prequalification of the R21/Matrix-M vaccine, paving the way for a global rollout that is expected to commence in mid-2024 by Serum Institute of India. Availability of the R21/Matrix-M vaccine is expected to help close the gap for the vast demand for malaria vaccine doses to protect children against the disease.
The publication reported:
- Efficacy of 75% when administered prior to the high transmission season: In areas with highly seasonal malaria transmission (where malaria transmission is largely limited to four or five months per year), the R21/Matrix-M vaccine was shown to reduce symptomatic cases of malaria by 75% during the 12 months following a three-dose series.
- Efficacy of 68% when administered in an age-based schedule in regions where malaria is present perennially during the 12 months following the first three doses.
- The most common adverse events with the vaccine were fever (47%) and injection site pain (19%).
Developed by University of Oxford and Serum Institute of India, the vaccine contains Novavax’s saponin-based Matrix-M™ adjuvant. The R21/Matrix-M vaccine is one of several ongoing collaborations involving Novavax’s adjuvant technology, including additional research in malaria and other infectious diseases in both humans and animals.
According to the most current WHO data, almost 250 million cases of malaria were reported globally in 2022, causing upwards of 609,000 deaths. Most cases occurred in Africa, with children under the age of five accounting for the vast majority of deaths in the region.1
The vaccine has also been licensed by regulators in Ghana, Nigeria and Burkina Faso. More information about the R21/Matrix-M vaccine may be found here.
1 WHO World Malaria report 2023
Novavax-backed malaria vaccine shows 75% efficacy
Feb. 02, 2024 10:44 AM ET
By: Dulan Lokuwithana, SA News Editor4 Comments
- A WHO-endorsed malaria vaccine based on Novavax's (NASDAQ:NVAX) adjuvant technology led to a 75% efficacy rate in a Phase 3 trial for children in Africa, the company announced Friday, citing peer-reviewed data.
- According to data published in The Lancet, the protein-based vaccine reduced malaria symptoms by 75% over 12 months after a three-dose series in children living in areas with a high disease prevalence.
- https://seekingalpha.com/news/4062219-novavax-backed-malaria-shot-shows-75-efficacy
- Novavax, Inc. (NVAX) Stock
- https://www.novavax.com/home/usa
- https://www.novavax.com/science-technology/matrix-m-adjuvant-technology
LINVOSELTAMAB
REVASCOR® (REXLEMESTROCEL-L)
LINVOSELTAMAB
February 2, 2024 at 6:00 AM EST
LINVOSELTAMAB RECEIVES EMA FILING ACCEPTANCE FOR TREATMENT OF RELAPSED/REFRACTORY MULTIPLE MYELOMA
TARRYTOWN, N.Y., Feb. 02, 2024 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced that the European Medicines Agency (EMA) has accepted for review the Marketing Authorization Application (MAA) for linvoseltamab to treat adult patients with relapsed/refractory (R/R) multiple myeloma (MM) who have progressed after at least three prior therapies. Linvoseltamab is an investigational bispecific antibody designed to bridge B-cell maturation antigen (BCMA) on multiple myeloma cells with CD3-expressing T cells to facilitate T-cell activation and cancer-cell killing.
The MAA is supported by data from a Phase 1/2 pivotal trial (LINKER-MM1) investigating linvoseltamab in R/R MM, which were last shared in December 2023. A Biologics License Application (BLA) was also submitted to the FDA in December 2023.
As the second most common blood cancer, there are over 176,000 new cases of MM diagnosed globally every year. It is characterized by the proliferation of cancerous plasma cells (MM cells) that crowd out healthy blood cells in the bone marrow, infiltrate other tissues and cause potentially life-threatening organ injury. MM is not curable despite treatment advances. While current treatments are able to slow the progression of the cancer, most patients will ultimately experience disease progression and require additional therapies.
The linvoseltamab clinical development program includes a Phase 3 confirmatory trial (LINKER-MM3) that is currently enrolling. Additional trials in earlier lines of therapy and stages of disease are planned or underway, including a Phase 1/2 trial in the first-line setting, a Phase 2 trial in high-risk smoldering MM and a Phase 2 trial in monoclonal gammopathy of undetermined significance. A Phase 1 trial of linvoseltamab in combination with a CD38xCD28 costimulatory bispecific in MM is also planned. For more information, contact clinicaltrials@regeneron.com or 844-734-6643, or visit the Regeneron clinical trials website.
Linvoseltamab is currently under clinical development, and its safety and efficacy have not been fully evaluated by any regulatory authority.
About the Phase 1/2 Trial
The ongoing, open-label, multicenter Phase 1/2 dose-escalation and dose-expansion LINKER-MM1 trial is investigating linvoseltamab in patients with R/R MM. Among 282 patients enrolled, all received at least three prior lines of therapy or were triple refractory. Linvoseltamab was administered with an initial step-up dosing regimen followed by the full dose. Additionally, a response-adapted administration schedule enabled patients who achieved a very good partial response or a complete response to shift from every two-week to every-four-week dosing after a minimum of 24 weeks of therapy.
The Phase 1 intravenous dose-escalation portion of the trial, which is now complete, primarily assessed safety, tolerability and dose-limiting toxicities across nine dose levels of linvoseltamab exploring different administration regimens. The Phase 2 dose expansion portion is assessing the safety and anti-tumor activity of linvoseltamab, with a primary objective of objective response rate. Key secondary objectives include duration of response, progression free survival, rate of minimal residual disease negative status and overall survival.
About Regeneron in Hematology
At Regeneron, we’re applying more than three decades of biology expertise with our proprietary VelociSuite® technologies to develop medicines for patients with diverse blood cancers and rare blood disorders.
Our blood cancer research is focused on bispecific antibodies that are being investigated both as monotherapies and in various combinations and emerging therapeutic modalities. Together, they provide us with unique combinatorial flexibility to develop customized and potentially synergistic cancer treatments.
Our research and collaborations to develop potential treatments for rare blood disorders include explorations in antibody medicine, gene editing and gene-knockout technologies, and investigational RNA-approaches focused on depleting abnormal proteins or blocking disease-causing cellular signaling.
About Regeneron
Regeneron is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led for over 35 years by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous FDA-approved treatments and product candidates in development, almost all of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, hematologic conditions, infectious diseases and rare diseases.
Regeneron is accelerating and improving the traditional drug development process through our proprietary VelociSuite® technologies, such as VelocImmune®, which uses unique genetically humanized mice to produce optimized fully human antibodies and bispecific antibodies, and through ambitious research initiatives such as the Regeneron Genetics Center®, which is conducting one of the largest genetics sequencing efforts in the world.
For more information about Regeneron, please visit www.Regeneron.com or follow Regeneron on LinkedIn.
Source: Regeneron Pharmaceuticals, Inc.
Regeneron multiple myeloma therapy accepted for EU review
Feb. 02, 2024 7:17 AM ET
Regeneron Pharmaceuticals, Inc. (REGN) Stock
By: Dulan Lokuwithana, SA News Editor1 Comment
- Regeneron Pharmaceuticals (NASDAQ:REGN) announced Friday that the EU drug regulator, the European Medicines Agency (EMA), accepted its marketing authorization application for linvoseltamab, an investigational therapy targeted at a form of blood cancer called multiple myeloma.
- https://seekingalpha.com/news/4061953-regeneron-multiple-myeloma-therapy-undergoes-eu-review
- Regeneron Pharmaceuticals, Inc. (REGN) Stock
- https://www.regeneron.com/
- https://classic.clinicaltrials.gov/ct2/show/NCT05730036
Donidalorsen
REVASCOR® (REXLEMESTROCEL-L)
LINVOSELTAMAB
Ionis announces positive topline results from Phase 3 OASIS-HAE study of investigational donidalorsen in patients with hereditary angioedema
January 22, 2024 at 7:00 AM EST
- Donidalorsen met the primary endpoint with a statistically significant reduction in the rate of HAE attacks in patients treated every 4 weeks or patients treated every 8 weeks
- Donidalorsen demonstrated a favorable safety and tolerability profile
- Ionis is preparing to submit a New Drug Application with U.S. FDA
- Data to be presented at an upcoming medical congress
CARLSBAD, Calif., Jan. 22, 2024 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) today announced positive topline results for the Phase 3 OASIS-HAE study of donidalorsen in people with hereditary angioedema (HAE). The trial met its primary endpoint of reduction in rate of angioedema attacks in patients treated with donidalorsen (80mg) via subcutaneous injection dosed every 4 weeks (Q4W) (p<0.001) or every 8 weeks (Q8W) (p=0.004), compared to placebo. In addition, the trial showed donidalorsen achieved statistical significance on all secondary endpoints in the Q4W group and key secondary endpoints in the Q8W group. Donidalorsen demonstrated a favorable safety and tolerability profile in the study, and there were no serious adverse events in the patients treated with donidalorsen.
HAE is a rare and life-threatening genetic disease that causes unpredictable and frequent severe swelling of the skin, gastrointestinal (GI) tract, upper respiratory system, face and throat. Donidalorsen is an investigational RNA-targeted prophylactic medicine designed to precisely target and silence the production of prekallikrein (PKK), interrupting the pathway that leads to HAE attacks.
Based on these data, Ionis is preparing to submit a New Drug Application with the U.S. Food and Drug Administration. Otsuka, which has exclusive rights to commercialize donidalorsen in Europe, is preparing to submit a Marketing Authorization Application to the European Medicines Agency. Donidalorsen received Orphan Drug Designation in the U.S., and the Orphan Drug Designation procedure in the EU is ongoing.
"We are very pleased with the positive topline results from the Phase 3 OASIS-HAE study of donidalorsen," said Kenneth Newman, M.D., senior vice president, head of clinical development at Ionis. "Based on these results and the durable efficacy and favorable safety data seen in the ongoing Phase 2 open-label extension study, we believe donidalorsen, if approved, could be an attractive new treatment option for patients with HAE, many of whom continue to experience unpredictable, painful and severe breakthrough attacks despite currently available prophylactic treatments. We are grateful to the patients, caregivers, investigators and study teams who participated in the OASIS-HAE study."
"These data represent our third highly positive Phase 3 readout over the last 12 months, underscoring the strength of our LICA platform for RNA-targeted medicines," said Brett P. Monia, Ph.D., chief executive officer of Ionis. "Following the recent launch of WAINUA™ (eplontersen), we are now well on our way to independently launching medicines from our wholly owned pipeline with regulatory submissions this year for olezarsen in familial chylomicronemia syndrome and donidalorsen in HAE. These achievements, coupled with our robust R&D pipeline, position Ionis to continue to deliver a steady cadence of potentially transformational medicines to people with serious diseases for years to come."
Ionis plans to present the Phase 3 OASIS-HAE results at an upcoming medical congress by mid-year. Ionis also plans to share results from the Phase 3 OASIS-Plus study by mid-year, which includes both the open-label extension of the Phase 3 trial and a separate cohort of patients who have transitioned to donidalorsen from another prophylactic HAE medication (switch cohort).
About the OASIS-HAE Study
The global, multicenter, randomized, double-blind, placebo-controlled Phase 3 OASIS-HAE study (NCT05139810) enrolled 91 participants, age 12 and above, with Type 1 and Type 2 hereditary angioedema (HAE). Participants were randomized in a 2:1 ratio to receive donidalorsen 80 mg or placebo via subcutaneous injection once every four weeks for 24 weeks or donidalorsen 80 mg or placebo via subcutaneous injection once every eight weeks for 24 weeks. Within each cohort, participants were randomized in a 3:1 ratio to receive donidalorsen or matching-placebo. The primary endpoint was the time-normalized number of investigator-confirmed HAE attacks from week one to week 25 compared to placebo. More than 90% of patients completed the OASIS-HAE study. Following completion of the treatment period, over 90% of randomized patients entered the Phase 3 OASIS-Plus open-label extension study.
About the OASIS-Plus Study
The Phase 3 OASIS-Plus open-label extension (OLE) study is a 53-week global, multicenter study of subcutaneous injections of donidalorsen administered every four weeks (80mg) and every eight weeks (80mg) in patients completing the OASIS-HAE trial. These are patients aged 12 and above, with Type 1 and Type 2 hereditary angioedema (HAE). The study is designed to evaluate the safety and efficacy of extended dosing of donidalorsen following completion of the Phase 3 OASIS-HAE study. The OASIS-Plus switch cohort is evaluating the safety and efficacy of long-term dosing of donidalorsen every four weeks in patients who were previously treated with another prophylactic HAE medication. Additional information about OASIS-Plus (NCT04307381) may be found at ClinicalTrials.gov.
About Hereditary Angioedema (HAE)
HAE is a rare and life-threatening genetic disease characterized by unpredictable and frequently severe swelling of the skin, gastrointestinal (GI) tract, upper respiratory system, face, and throat, which can be life-threatening1,2,3,4,5. HAE is estimated to affect more than 20,000 people in the U.S. and Europe6. In the U.S., doctors frequently use prophylactic treatment approaches to prevent and reduce the severity of HAE attacks in patients.
About Donidalorsen
Donidalorsen is an RNA investigational LIgand-Conjugated Antisense (LICA) medicine designed to precisely target and silence the production of prekallikrein (PKK), interrupting the pathway that leads to HAE attacks. PKK plays an important role in activating inflammatory mediators associated with acute attacks of hereditary angioedema (HAE). By silencing the production of PKK, donidalorsen could be an effective prophylactic approach to treating HAE.
About Ionis Pharmaceuticals, Inc.
For more than 30 years, Ionis has been a leader in RNA-targeted therapy, pioneering new markets and changing standards of care. Ionis currently has five marketed medicines and a promising late-stage pipeline highlighted by cardiovascular and neurological franchises. Our scientific innovation began and continues with the knowledge that sick people depend on us, which fuels our vision to become the leader in genetic medicine, utilizing a multi-platform approach to discover, develop and deliver life-transforming therapies.
To learn more about Ionis visit www.ionispharma.com and follow us on X (Twitter) @ionispharma and LinkedIn.
About Hereditary Angioedema
Hereditary angioedema (HAE) is a rare genetic disease that is characterized by severe and potentially fatal swelling of the arms, legs, face and throat. PKK plays an important role in the activation of inflammatory mediators associated with acute attacks of HAE. By inhibiting the production of PKK, donidalorsen could be an effective prophylactic approach to preventing HAE attacks. It is estimated that there are more than 20,000 patients with HAE in the U.S. and Europe.
Ionis angioedema drug shows positive results in Phase 3 trial
Jan. 22, 2024 8:00 AM ET
Ionis Pharmaceuticals, Inc. (IONS) Stock
By: Preeti Singh, SA News Editor1 Comment
Ionis Pharmaceuticals (NASDAQ:IONS) on Monday announced positive topline Phase 3 trial results for its donidalorsen drug candidate for hereditary angioedema (HAE).
The Phase 3 OASIS-HAE study found donidalorsen met the primary endpoint of statistically significant reduction in HAE attacks in patients.
Ionis Pharmaceuticals, Inc. (IONS) Stock
REVASCOR® (REXLEMESTROCEL-L)
REVASCOR® (REXLEMESTROCEL-L)
REVASCOR® (REXLEMESTROCEL-L)
UNITED STATES FOOD & DRUG ADMINISTRATION (FDA) GRANTS MESOBLAST RARE PEDIATRIC DISEASE DESIGNATION FOR REVASCOR® (REXLEMESTROCEL-L) IN CHILDREN WITH CONGENITAL HEART DISEASE REVASCOR Increases Size of Left Heart Chamber and Improves Surgical Outcomes in Children with Hypoplastic Left Heart Syndrome: Results Published in Journal of Thoracic and Cardiovascular Surgery Open Melbourne, Australia; January 19 and New York, USA; January 18, 2024: Mesoblast Limited (ASX:MSB; Nasdaq:MESO), global leader in allogeneic cellular medicines for inflammatory diseases, today announced that the United States Food and Drug Administration (FDA) has granted its allogeneic cell therapy Revascor® (rexlemestrocel-L) a Rare Pediatric Disease (RPD) Designation following submission of results from the randomized controlled trial in children with hypoplastic left heart syndrome (HLHS), a potentially life threatening congenital heart condition. RPD Designation is granted by the FDA for certain serious or life-threatening diseases which primarily affect children. On FDA approval of a Biologics Licensing Application (BLA) for REVASCOR for the treatment of HLHS, Mesoblast may be eligible to receive a Priority Review Voucher (PRV) that can be redeemed for any subsequent marketing application or may be sold or transferred to a third party. Results from a blinded, randomized, placebo-controlled prospective trial of REVASCOR conducted in the United States in children with HLHS were published in the December 2023 issue of the peer reviewed The Journal of Thoracic and Cardiovascular Surgery Open (JTCVS Open).1 In the HLHS trial conducted in 19 children, a single intramyocardial administration of REVASCOR at the time of staged surgery resulted in the desired outcome of significantly larger increases in left ventricular (LV) end-systolic and end-diastolic volumes over 12 months compared with controls as measured by 3D echocardiography, (p=0.009 & p=0.020 respectively). These changes are indicative of clinically important growth of the small left ventricle, facilitating the ability to have a successful surgical correction, known as full biventricular (BiV) conversion, which allows for a normal two ventricle circulation with the surgically repaired left ventricle taking over circulatory support to the body. Without full BiV conversion the right heart chamber is under excessive strain with increased risk of heart failure and death. As noted in our recent publication, “The fact that 100% of REVASCOR-treated children compared with 57% of controls had large enough LVs to accommodate the full BiV conversion suggests that REVASCOR treatment may help increase the ability to ‘better grow’ the HLHS LV after LV recruitment surgery.” Mesoblast Chief Executive Silviu Itescu said: “Given the impressive enlargement of the left chamber we have seen in these children treated with REVASCOR in the randomized controlled trial and the increased ability to successfully accomplish life-saving surgery, we plan to meet with FDA to discuss the potential for this trial to support accelerated approval in this indication.” About Hypoplastic Left Heart Syndrome (HLHS) HLHS is a severe congenital heart disease in which the left side of the heart does not fully develop and effective pumping of oxygenated blood by the left ventricle to the rest of the body is reduced. Without immediate surgery after birth, the prognosis is dismal with HLHS overall being responsible for 25% to 40% of all neonatal cardiac mortality.2 In the longer term, surgery that creates a two-ventricle series circulation with the left ventricle (LV) pumping blood to the body and the right ventricle pumping blood to the lungs is the ideal anatomic repair. Unfortunately, achievement of this objective is limited by the inability in most patients for the left ventricle to grow sufficiently to support the circulation to the body. About Revascor® (rexlemestrocel-L) in Heart Disease REVASCOR is an allogeneic preparation of immunoselected and culture-expanded mesenchymal precursor cells which have been shown previously to have multiple mechanisms-of-action that may be beneficial to children with HLHS including neovascularization, anti-fibrosis, anti-apoptosis, immunomodulation, reduction in inflammation, and reversal of endothelial dysfunction. In the DREAMHF randomized sham-placebo controlled prospective trial of REVASCOR in 565 randomized adult patients with heart failure with low ejection fraction (HFrEF), a single intramyocardial administration of REVASCOR into the left ventricle resulted in significant improvement in LV ejection fraction at 12 months,3 indicative of strengthened overall LV systolic function. About Mesoblast Mesoblast (the Company) is a world leader in developing allogeneic (off-the-shelf) cellular medicines for the treatment of severe and life-threatening inflammatory conditions. The Company has leveraged its proprietary mesenchymal lineage cell therapy technology platform to establish a broad portfolio of latestage product candidates which respond to severe inflammation by releasing anti-inflammatory factors that counter and modulate multiple effector arms of the immune system, resulting in significant reduction of the damaging inflammatory process. Mesoblast has a strong and extensive global intellectual property portfolio with protection extending through to at least 2041 in all major markets. The Company’s proprietary manufacturing processes yield industrial-scale, cryopreserved, off-the-shelf, cellular medicines. These cell therapies, with defined pharmaceutical release criteria, are planned to be readily available to patients worldwide. Mesoblast is developing product candidates for distinct indications based on its remestemcel-L and rexlemestrocel-L allogeneic stromal cell technology platforms. Remestemcel-L is being developed for inflammatory diseases in children and adults including steroid refractory acute graft versus host disease, biologic-resistant inflammatory bowel disease, and acute respiratory distress syndrome. Rexlemestrocel-L is in development for advanced chronic heart failure and chronic low back pain. Two products have been commercialized in Japan and Europe by Mesoblast’s licensees, and the Company has established commercial partnerships in Europe and China for certain Phase 3 assets. Mesoblast has locations in Australia, the United States and Singapore and is listed on the Australian Securities Exchange (MSB) and on the Nasdaq (MESO). For more information, please see www.mesoblast.com, LinkedIn: Mesoblast Limited and Twitter: @Mesoblast
Mesoblast rises after cell therapy gets FDA rare pediatric disease designation
Jan. 19, 2024 6:07 AM ET
Mesoblast Limited (MESO) Stock
By: Preeti Singh, SA News Editor
Mesoblast (NASDAQ:MESO) shares jumped ~12% premarket on Friday after the biotech firm received a rare pediatric disease designation for its allogeneic cell therapy Revascor (rexlemestrocel-L) from the U.S. Food and Drug Administration.
The designation was based on results from a randomized controlled trial in children with hypoplastic left heart syndrome, a potentially life threatening congenital heart condition.
In the trial conducted in 19 children, a single intramyocardial administration of Revascor at the time of staged surgery resulted in the desired outcome of significantly larger increases in left ventricular end-systolic and end-diastolic volumes over 12 months compared with controls as measured by 3D echocardiography, (p=0.009 & p=0.020 respectively).
Mesoblast Limited (MESO) Stock
https://mesoblast.com/product-candidates/cardiovascular-diseases/congestive-heart-failure
Casdozokitug
Casdozokitug
REVASCOR® (REXLEMESTROCEL-L)
Coherus Presents Positive Phase 2 Clinical Data on Casdozokitug, a First-in-Class IL-27-Targeted Antibody, at the 2024 ASCO GI Cancers Symposium
Jan 18, 2024
– Data demonstrate early activity with casdozokitug/atezolizumab/bevacizumab; 38% objective response rate including three complete responses –
– Data support casdozo as a promising novel immuno-oncology agent with clinical activity in liver cancer that may be associated with IL-27 pathway biomarkers –
– Data support continued evaluation of casdozo with VEGF and PD-(L)1 blockade in HCC, including further clinical development to evaluate casdozokitug/toripalimab/bevacizumab –
REDWOOD CITY, Calif., Jan. 18, 2024 (GLOBE NEWSWIRE) -- Coherus BioSciences, Inc. (Coherus, Nasdaq: CHRS), today announced data from the lead-in portion of the Phase 2 clinical trial evaluating casdozokitug (casdozo), a selective and potent IL-27-targeting antibody, in combination with atezolizumab (atezo) and bevacizumab (bev) in treatment naïve patients with unresectable locally advanced or metastatic hepatocellular carcinoma (uHCC). These data are being presented at the 2024 ASCO Gastrointestinal Cancers Symposium taking place January 18-20, 2024 at Moscone West in San Francisco, California. Interleukin (IL)-27 is an immunoregulatory cytokine involved in suppressing anti-tumor immune responses and an important new target for cancer treatment. Casdozo is a first-in-class antibody, and the only clinical stage immunomodulatory cytokine antagonist targeting IL-27.
“Doublet immunotherapy combinations for the treatment of liver cancer have improved outcomes for patients for whom surgery is not an option or whose cancer has spread. However, not all patients respond to current therapy and novel treatment options that can further improve survival without added toxicity are needed,” said Daneng Li, M.D., Associate Professor in the Department of Medical Oncology & Therapeutics Research and Co-Director, Liver Cancer Collaborative Program, City of Hope Comprehensive Cancer Center. “The addition of casdozo to standard of care is encouraging and supports further evaluation of cazdozo, and its novel anti-IL-27 mechanism, as part of triplet therapy in HCC. Additionally, each person with advanced HCC is unique with respect to their tumor, co-morbidities and other factors – the biomarker data showing an association of IL-27 biology and response to casdozo is particularly interesting and the potential to identify biomarkers of response would be an important benefit to patients with liver cancer.”
“These impressive early clinical and immune activation data for casdozo in HCC demonstrating an ORR of 38%, including 3 complete responses, and a favorable safety profile add to the growing body of data supporting IL-27 as a promising novel target in combination therapy for advanced solid tumors,” said Rosh Dias, M.D., Coherus’ Chief Medical Officer. “We now have data across several tumor types for casdozo demonstrating clinical activity. Our comprehensive clinical development program of ongoing and planned clinical trials including casdozokitug in combination with our anti-PD-1 antibody backbone of toripalimab-tpzi, will further advance our internal next-generation immuno-oncology combinations focused on overcoming immune suppression in the tumor microenvironment with the goal of extending survival and improving outcomes for patients.”
Lead-in portion of Phase 2 clinical trial design
The open-label lead-in portion of the Phase 2 clinical trial evaluated casdozo in combination with atezo and bev in 30 patients with treatment-naïve uHCC. Patients received casdozo 10 mg/kg IV q3w, in combination with atezo (1200 mg) and bev (15 mg/kg). The primary endpoint of the lead-in portion of the study was safety and tolerability. Key secondary endpoints included progression-free survival (PFS) and overall response rate (ORR) based on investigator review per RECIST v1.1 (primary) and mRECIST (secondary), as well as disease control rate (DCR). Further [Phase 2] clinical development of cazdozo in HCC is planned to evaluate casdozo/toripalimab (anti-PD-1 antibody)/bev.
Lead-in portion of Phase 2 clinical trial data
As of the data cutoff date (November 9, 2023):
Triplet blockade of the IL-27, PD-(L)1 and VEGF pathways with casdozo/atezo/bev has an acceptable safety profile to date with promising antitumor activity in IO naïve HCC.
- Triplet combination treatment was well tolerated with side effect profile consistent with known adverse event (AE) profiles of atezo/bev.
- Encouraging early activity with casdozo/atezo/bev:
- RECIST v1.1: ORR of 38% (n=29) with 11 durable objective responses including 3 complete responses and 8 partial responses (1 unconfirmed); median progression-free survival of 8.1 months and disease control rate of 58.6%.
- mRECIST: ORR of 43% (n=28) with 12 durable objective responses including 3 complete responses and 9 partial responses (1 unconfirmed); median progression-free survival not reached and disease control rate of 60.7%.
- Further analyses of samples from patients who responded to treatment (small n) indicate preliminary association between response and biomarkers of IL-27.
These results support continued evaluation of casdozo with VEGF and PD-(L)1 blockade in HCC. Coherus plans to evaluate the combination of casdozo/toripalimab-tpzi(Coherus’ anti-PD-1 antibody)/bev in future clinical trials.
Poster presentation details:
Title: Results from a phase 2 study of triplet blockade of the IL-27, PD-(L)1, and VegF pathways with casdozokitug (casdozo, CHS-388) in combination with atezolizumab (atezo) and bevacizumab (bev) in patients with unresectable, locally advanced or metastatic hepatocellular carcinoma (uHCC)
Poster Board number: B15
Abstract number: 470
Date and Time: Friday, January 19, 2024, 12:30 – 2:00 pm PT
Presenter: Daneng Li, MD
Location: Level 1, West Hall, Moscone West
About Casdozokitug
Casdozokitug is a first-in-class human anti-IL-27 antibody designed to inhibit the activity of this immunosuppressive cytokine. Particular tumor types have been identified where IL-27 appears to play an important role in the immunosuppressive tumor microenvironment and may contribute to resistance to treatment with checkpoint inhibitors. Blocking IL-27 with casdozokitug in clinical trials has led to monotherapy tumor growth inhibition and partial responses in patients with non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) (NCT04374877). An ongoing trial is studying combinations with PD-(L)1 pathway blockade in NSCLC and a planned clnical trial will study the triplet combination of IL-27, PD-(L)1 and VEGF pathway blockade in hepatocellular carcinoma (HCC). Casdozokitug has been granted Orphan Drug designation and Fast Track designation for the treatment of refractory hepatocellular carcinoma from the FDA. It is the first IL-27 antibody to enter the clinic.
About Coherus BioSciences
Coherus is a commercial-stage biopharmaceutical company focused on the research, development and commercialization of innovative immunotherapies to treat cancer. Coherus is developing an innovative immuno-oncology pipeline that will be synergistic with its proven commercial capabilities in oncology.
Coherus’ immuno-oncology pipeline includes multiple antibody immunotherapy candidates focused on enhancing the innate and adaptive immune responses to enable a robust immunologic response and enhance outcomes for patients with cancer. Casdozokitug is a novel anti-IL-27 antibody currently being evaluated in two on-going clinical studies: a Phase 1/2 study in advanced solid tumors and a Phase 2 study in hepatocellular carcinoma. CHS-114 is a highly selective, competitively positioned, ADCC-enhanced anti-CCR8 antibody currently in a Phase 1/2 study as a monotherapy in patients with advanced solid tumors. CHS-1000 is a preclinical candidate targeting immune-suppressive mechanisms via the novel pathway ILT4 with an IND filing planned in the first half of 2024.
Coherus markets LOQTORZI™ (toripalimab-tpzi), a novel next generation PD-1 inhibitor, UDENYCA® (pegfilgrastim-cbqv), a biosimilar of Neulasta®, CIMERLI® (ranibizumab-eqrn), a biosimilar of Lucentis®, and YUSIMRY™ (adalimumab-aqvh), a biosimilar of Humira®.
Source: Coherus BioSciences, Inc.
Coherus spikes after mid-stage data for liver cancer therapy
Jan. 19, 2024 7:29 AM ET
Coherus BioSciences, Inc. (CHRS) Stock RHHBY, RHHBF
By: Dulan Lokuwithana, SA News Editor
Coherus BioSciences (NASDAQ:CHRS) added ~8% premarket Friday after announcing data from a Phase 2 trial for its IL-27-targeting antibody casdozokitug (casdozo) as part of a combination therapy for liver cancer.
According to a data cut on Nov. 9 based on RECIST v1.1, the primary review criteria, the casdozo combo led to a 38% objective response rate. That included three complete and eight partial responses (one unconfirmed) among 29 patients with hepatocellular carcinoma.
https://seekingalpha.com/news/4056329-coherus-stock-spikes-data-liver-cancer-therapy
Coherus BioSciences, Inc. (CHRS) Stock
PRGN-2012
Casdozokitug
Acoramidis
Precigen Receives Orphan Drug Designation for PRGN-2012 for the Treatment of Recurrent Respiratory Papillomatosis from the European Commission
JAN 16, 2024
– Designation is an important step toward bringing this potentially life-changing therapy to European patients –
– EU Orphan Drug Designation is the first regulatory designation for a gorilla adenovector based immunotherapy outside of the United States for the Company –
GERMANTOWN, Md., Jan. 16, 2024 /PRNewswire/ -- Precigen, Inc. (Nasdaq: PGEN), a biopharmaceutical company specializing in the development of innovative gene and cell therapies to improve the lives of patients, today announced that the European Commission (EC) has granted Orphan Drug Designation for the Company's first-in-class investigational medicine PRGN-2012 for the treatment of recurrent respiratory papillomatosis (RRP). RRP is a rare, difficult-to-treat and sometimes fatal neoplastic disease of the upper and lower respiratory tracts caused by human papillomavirus type 6 (HPV 6) or HPV type 11 (HPV 11). PRGN-2012 received Orphan Drug Designation from the United States Food and Drug Administration (FDA) and Precigen was the first company to receive Breakthrough Therapy Designation and an accelerated approval pathway from the FDA for an RRP treatment.
PRGN-2012 is an innovative therapeutic vaccine with optimized antigen design that uses gorilla adenovector technology, part of Precigen's proprietary AdenoVerse™ platform, to elicit immune responses directed against cells infected with HPV 6 or HPV 11. Gorilla adenovectors have numerous advantages, including the ability for repeat administration, the inability to replicate in vivo, and the ability to deliver a large genetic payload.
Orphan Drug Designation in the European Union (EU) is granted by the EC based on a positive opinion issued by the European Medicines Agency (EMA) Committee for Orphan Medicinal Products. Medicines intended for the treatment, diagnosis or prevention of seriously debilitating or life-threatening conditions that affect fewer than five in 10,000 people in the European Union (EU) are eligible for the designation. The Orphan Drug Designation allows companies certain regulatory, financial and commercial incentives to develop medicines for rare diseases where there are no satisfactory treatment options.
"Outside of the US, our commissioned research suggests that there are more than 125,000 patients diagnosed and living with RRP, a rare and debilitating disease which currently has no approved therapeutic treatment option and is treated through repeated surgical intervention," said Helen Sabzevari, PhD, President and CEO of Precigen. "The ongoing Phase 1/2 study for PRGN-2012 in the United States has shown the immense potential for this therapy. Results from the Phase 1 study showed significant clinical benefit with 50% of patients remaining surgery-free after more than two years following treatment. Additionally, PRGN-2012's favorable safety profile and ease of administration are potentially paradigm shifting for both patients and their treating physicians. This designation is an important next step as we work to expand this novel therapeutic to the EU in hopes of benefiting the unmet needs of RRP patients."
PRGN-2012 is currently under investigation in a Phase 1/2 pivotal single-arm study in adult patients with RRP in the United States (clinical trial identifier: NCT04724980). A Phase 2 data presentation is anticipated in the second quarter of 2024 and a planned Biologics License Application (BLA) submission under an accelerated approval pathway with the FDA is anticipated in the second half of 2024. Commercial readiness preparations are underway for a potential launch in the United States in 2025.
About RRP
RRP is a rare, difficult-to-treat and sometimes fatal neoplastic disease of the upper and lower respiratory tracts that is caused by infection with HPV 6 or HPV 11.1-4 RRP is classified based on age of onset as juvenile or adult. Currently, there is no cure for RRP and the current standard-of-care is repeated endoscopic debulking with ablation or excision of papillomatous lesions.3,4 Recurrence of papilloma after surgical removal is very common and repeated procedures are required to debulk and monitor the disease, which exposes patients to anesthetic and surgical risks, and emotional distress. RRP morbidity and mortality results from the effects of papilloma mass on the vocal cords, trachea, and lungs, which may cause voice changes, stridor, airway occlusion, loss of lung volume, and/or post-obstructive pneumonia.5 Although rare, one to three percent of RRP cases can transform into invasive squamous cell carcinoma.6,7
Precigen: Advancing Medicine with Precision™
Precigen (Nasdaq: PGEN) is a dedicated discovery and clinical stage biopharmaceutical company advancing the next generation of gene and cell therapies using precision technology to target the most urgent and intractable diseases in our core therapeutic areas of immuno-oncology, autoimmune disorders, and infectious diseases. Our technologies enable us to find innovative solutions for affordable biotherapeutics in a controlled manner. Precigen operates as an innovation engine progressing a preclinical and clinical pipeline of well-differentiated therapies toward clinical proof-of-concept and commercialization. For more information about Precigen, visit www.precigen.com or follow us on X @Precigen, LinkedIn or YouTube.
Trademarks
Precigen, AdenoVerse and Advancing Medicine with Precision are trademarks of Precigen and/or its affiliates. Other names may be trademarks of their respective owners.
View original content to download multimedia:https://www.prnewswire.com/news-releases/precigen-receives-orphan-drug-designation-for-prgn-2012-for-the-treatment-of-recurrent-respiratory-papillomatosis-from-the-european-commission-302035305.html
SOURCE Precigen, Inc.
Precigen gets EU orphan drug status for respiratory tract drug
Jan. 16, 2024 9:33 AM ET
By: Val Brickates Kennedy, SA News Editor
EU regulators have granted orphan drug designation to Precigen’s (NASDAQ:PGEN) drug candidate PRGN-2012 for the treatment of recurrent respiratory papillomatosis, a rare respiratory tract disease caused by HPV 6 or HPV 11.
https://seekingalpha.com/news/4055173-precigen-gets-eu-orphan-drug-status-for-respiratory-tract-drug
Acoramidis
Casdozokitug
Acoramidis
BridgeBio Pharma Announces Publication of Positive Results from Phase 3 ATTRibute-CM Study of Acoramidis for Patients with Transthyretin Amyloid Cardiomyopathy (ATTR-CM) in the New England Journal of Medicine
– ATTRibute-CM demonstrated a significant treatment effect of acoramidis on the primary endpoint (a hierarchical analysis inclusive of all-cause mortality (ACM) and frequency of cardiovascular-related hospitalization (CVH)), with a Win Ratio of 1.8 (p<0.0001)
– Acoramidis demonstrated an observed 30-month survival rate of 80.7% in the treatment arm of ATTRibute-CM; recent data from the U.S. Social Security Administration estimated 30-month survival at 85% in an age-matched cohort of the general population; similarly, the annualized CVH rate of 0.29 in the treatment arm can be viewed in the context of the annual overall hospitalization rate of 0.26 in the U.S. Medicare population
– Acoramidis is the only intervention to demonstrate cardiovascular outcomes benefit in a prospective clinical trial in the contemporary ATTR-CM population to the Company’s knowledge
– Acoramidis was well-tolerated, with no safety signals of potential clinical concern identified
– BridgeBio has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) and intends to submit marketing authorization applications to additional regulatory bodies in 2024
PALO ALTO, Calif., Jan. 10, 2024 (GLOBE NEWSWIRE) —
BridgeBio Pharma, Inc. (Nasdaq: BBIO) (“BridgeBio” or the “Company”), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, announced that positive results from its Phase 3 ATTRibute-CM study of acoramidis for patients with ATTR-CM were published in the New England Journal of Medicine (NEJM). ATTRibute-CM was designed to study the efficacy and safety of acoramidis, an investigational, next-generation, orally-administered, small molecule stabilizer of transthyretin (TTR).
“The consistent benefits of acoramidis treatment demonstrated by the ATTRibute-CM results, especially in the context of contemporary ATTR-CM care, are striking and encourage its potential use,” said Professor Julian Gillmore, M.D., Ph.D., head of University College London’s Centre for Amyloidosis and research lead at the UK National Amyloidosis Centre. “Given the efficacy and safety of acoramidis demonstrated in this trial, I am hopeful that it will soon be available to the benefit of the growing global population of patients diagnosed with ATTR-CM.”
The ATTRibute-CM study demonstrated a significant treatment effect of acoramidis in the primary analysis that compared, in a hierarchical manner, all-cause mortality (ACM), cardiovascular-related hospitalization (CVH), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and 6-minute walk distance (6MWD). Findings presented in the NEJM support acoramidis as an effective and safe treatment option for patients with ATTR-CM and reinforce the hypothesis that greater stabilization of TTR may be associated with improved clinical outcomes. Additional findings in the publication include:
- The majority of comparisons in the primary hierarchical analysis (58% in the associated Win Ratio) were determined by the first two components of ACM and CVH; statistical significance was also achieved on a F-S test with those two cardiovascular outcomes parameters alone
- Statistically significant treatment benefit was observed for change from baseline in 6MWD, Kansas City Cardiomyopathy Questionnaire (KCCQ), and serum TTR
- The observed 30-month survival rate of 74.3% in the placebo arm of ATTRibute-CM is greater than the observed 30-month survival rate of 70.5% in the combined tafamidis treatment arms of ATTR-ACT, the only previously reported cardiovascular outcomes study in ATTR-CM
- As a contemporary benchmark for placing the survival rate of 80.7% in the treatment arm of ATTRibute-CM into context, recent data from the U.S. Social Security Administration estimated 30-month survival at 85% in an age-matched cohort of the general population
- Similarly, the annualized CVH rate in the treatment arm of ATTRibute-CM of 0.29 can be viewed in the context of data on the annual overall hospitalization rate of 0.26 in the U.S. Medicare population.
- Serum TTR was promptly and consistently elevated throughout the study in patients receiving acoramidis as a result of near-complete stabilization of the protein
- Acoramidis was well-tolerated, with no safety signals of potential clinical concern identified
“These results add to the totality of the available data supporting the concept that the greater the degree of stabilization of tetrameric TTR, the greater the observed clinical benefit,” said Jonathan Fox, M.D., Ph.D., president and chief medical officer of BridgeBio Cardiorenal. “With the submission of our NDA to register acoramidis with the FDA, and with additional regional and national regulatory submissions planned, we look forward to making acoramidis available to patients who might benefit from its demonstrated efficacy and safety.”
In July, BridgeBio announced positive topline results from ATTRibute-CM. BridgeBio has also presented additional detailed results from ATTRibute-CM at the European Society of Cardiology Congress 2023 in August and at the American Heart Association Scientific Sessions 2023 in November.
The Company submitted a New Drug Application to the U.S. FDA in 2023 and intends to submit additional marketing authorization applications to regulatory bodies in 2024.
About BridgeBio
BridgeBio is a commercial-stage biopharmaceutical company founded to discover, create, test and deliver transformative medicines to treat patients who suffer from genetic diseases and cancers with clear genetic drivers. BridgeBio’s pipeline of development programs ranges from early science to advanced clinical trials. BridgeBio was founded in 2015 and its team of experienced drug discoverers, developers, and innovators are committed to applying advances in genetic medicine to help patients as quickly as possible. For more information visit bridgebio.com and follow us on LinkedIn and Twitter.
BridgeBio Phase 3 data for ATTR-CM drug published in NEJM
Jan. 11, 2024 11:08 AM ET
BridgeBio Pharma, Inc. (BBIO) StockPFE
By: Val Brickates Kennedy, SA News Editor
BridgeBio Pharma (NASDAQ:BBIO) said positive results from its Phase 3 ATTRibute-CM study for its drug acoramidis in the treatment of transthyretin amyloid cardiomyopathy, or ATTR-CM, have been published in the New England Journal of Medicine.
The biotech company released topline results from the study in July and presented additional data at the European Society of Cardiology Congress in August and the American Heart Association Scientific Sessions in November, according to a statement.
BridgeBio submitted a market application to the FDA for acoramidis in December. It intends to submit applications for market approval from additional regulatory bodies this year.
https://seekingalpha.com/news/4054421-bridgebio-phase-3-data-for-attr-cm-drug-published-in-nejm
biotecHOPE™ 2023
SLS009
ZELSUVMI™ (berdazimer topical gel, 10.3%)
ZELSUVMI™ (berdazimer topical gel, 10.3%)
SELLAS Life Sciences Receives FDA Fast Track Designation for SLS009 for Treatment of Relapsed/Refractory Acute Myeloid Leukemia and Provides Updated Data for Phase 2a Study of SLS009 in Relapsed/Refractory Acute Myeloid Leukemia Patients
Download this Press Release PDF Format (opens in new window) (PDF)
- Phase 2a Enrollment Completed in 45 mg Safety Cohort: Median Overall Survival (OS) Not Reached; 89% of Patients Alive with Significant Antileukemic Effect Observed in 87.5% of Evaluable Patients -
- First Enrolled Patient in Phase 2a Study Achieved Complete Remission and Continues on Study With Full Recovery and in Seventh Month of Survival; Second Enrolled Patient Continues on Study in Sixth Month of Survival; Median OS in Relapsed/Refractory (r/r) Acute Myeloid Leukemia (AML) Patients Treated with Standard of Care is Approximately 2.5 Months -
- Fast Track Designation Accelerates SLS009's Path for U.S. Regulatory Submission for Treatment of r/r AML -
NEW YORK, Jan. 09, 2024 (GLOBE NEWSWIRE) -- SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) (“SELLAS’’ or the “Company”), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation to SLS009 (formerly GFH009), its novel and highly selective CDK9 inhibitor, for the treatment of relapsed/refractory (r/r) acute myeloid leukemia (AML). The Fast Track Designation is intended to facilitate the development and review of drugs to treat serious conditions and fill an unmet medical need.
“Receiving Fast Track Designation for SLS009 for r/r AML, following the recent Orphan Drug Designation for the same indication, underscores the potential for SLS009 and highlights the critical unmet need for patients with AML who face a poor prognosis due to the progressive nature of the disease,” said Angelos Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. “The initial positive topline Phase 2a data at the 45 mg (safety) dose level demonstrate that SLS009 in combination with venetoclax and azacitidine (aza/ven) exhibits anti-leukemic effects with a favorable safety profile in AML patients resistant to venetoclax combination therapies. Importantly, as of the last follow-up, eight of the nine patients enrolled in the 45 mg cohort were alive. The first patient enrolled in the study achieved a complete response (CR) and continues on study in the seventh month with full peripheral blood recovery. The second enrolled patient is in the sixth month of treatment, further underscoring the potential benefit of adding CDK9 inhibition to the aza/ven regimen. We have now also enrolled several patients in the ongoing 60 mg dose cohort. Our team is committed to advancing the development of SLS009 with the goal of providing effective solutions to patients in need of viable treatment options.”
Dr. Stergiou continued, “SLS009 continues to emerge as a promising treatment for hematologic malignancies, and we are pleased by the FDA’s recognition of its potential by the grant of Fast Track and Orphan Drug Designations for AML. These designations position us to accelerate SLS009 clinical development with the goal of delivering this potentially groundbreaking treatment to AML patients in need.”
A total of nine patients have been enrolled at the 45 mg safety dose level. Eight patients (89%) remain alive (one patient succumbed to sepsis having previously contracted COVID 19) and six continue treatment. The first enrolled patient achieved a complete response and continues on the study in the seventh month with full blood recovery and the second enrolled patient is in the sixth month of treatment. The follow-up duration for the patients who are alive ranges from two to seven months and median OS has not been reached. Significant anti-leukemic effects (≥50% decrease in bone marrow blasts) were observed during treatment in seven out of eight (87.5%) assessable patients with no significant safety issues to date. No dose limiting toxicities were observed in any of the patients. In the Phase 1 study of SLS009 as monotherapy, a durable CR with no minimal residual disease (MRD) was observed in one patient with AML who had failed prior aza/ven therapy. The patient continues to be alive 16 months following commencement of treatment per last follow-up. Patients with AML that fail venetoclax-based therapies have limited treatment options and a poor prognosis with a median OS of approximately 2.5 months.
The Phase 2a clinical trial of SLS009 is an open label, single arm, multi-center study that is designed to evaluate safety, tolerability, and efficacy at two dose levels, 45 mg and 60 mg, in combination with aza/ven. In the 60 mg dose cohort, patients are being randomized to one of two groups, 60 mg flat (fixed) dose once per week and 30 mg fixed dose two times per week. Each group will enroll 5 – 10 patients. In addition to safety and tolerability of SLS009 in combination with aza/ven, the primary endpoints are composite complete response rate (CRc) and duration of response (DOR). Additional endpoints include event free survival (EFS), OS, and pharmacokinetic (PK) and pharmacodynamic (PD) assessments. Venetoclax combinations with hypomethylating agents are a commonly used regimen in this target population but despite high efficacy (up to ~67% complete response rate), approximately one-third to one-half of patients do not respond to venetoclax based regimens, and among those who respond almost all eventually relapse.
The Company expects to report additional data from the fully enrolled 45 mg (safety dose level) cohort and initial data from the 60 mg (recommended Phase 2 dose level) cohort in the first quarter of 2024 and expects the 60 mg cohort to be analyzed in the second quarter of 2024.
About SELLAS Life Sciences Group, Inc.
SELLAS is a late-stage clinical biopharmaceutical company focused on the development of novel therapeutics for a broad range of cancer indications. SELLAS’ lead product candidate, galinpepimut-S (GPS), is licensed from Memorial Sloan Kettering Cancer Center and targets the WT1 protein, which is present in an array of tumor types. GPS has potential as a monotherapy and combination with other therapies to address a broad spectrum of hematologic malignancies and solid tumor indications. The Company is also developing SLS009 (formerly GFH009), a small molecule, highly selective CDK9 inhibitor, which is licensed from GenFleet Therapeutics (Shanghai), Inc., for all therapeutic and diagnostic uses in the world outside of Greater China. For more information on SELLAS, please visit www.sellaslifesciences.com.
Source: SELLAS Life Sciences Group, Inc.
Sellas Life Sciences gains on securing orphan drug status for r/r PTCL treatment
Jan. 11, 2024 7:24 AM ET
SELLAS Life Sciences Group, Inc. (SLS) Stock
By: Preeti Singh, SA News Editor
Sellas Life Sciences (NASDAQ:SLS) shares jumped as much as 13% premarket on Thursday after the biopharmaceutical company and partner GenFleet Therapeutics disclosed yet another regulatory milestone for their CDK9 inhibitor, SLS009 (GFH009).
The therapy has gained FDA orphan drug designation for the treatment of adult patients with relapsed or refractory (r/r) peripheral T-cell lymphomas (PTCL), after having secured fast track status for r/r PTCL treatment, fast track designation r/r acute myeloid leukemia (AML) treatment and orphan drug status for AML.
SELLAS Life Sciences Group, Inc. (SLS) Stock
https://www.sellaslifesciences.com/Home/default.aspx
https://www.sellaslifesciences.com/pipeline/sellas-pipeline/default.aspx
ZELSUVMI™ (berdazimer topical gel, 10.3%)
ZELSUVMI™ (berdazimer topical gel, 10.3%)
ZELSUVMI™ (berdazimer topical gel, 10.3%)
U.S. Food and Drug Administration Approves ZELSUVMI™ as a First-in-Class Medication for the Treatment of Molluscum Contagiosum
01/05/2024
ZELSUVMI™ is expected to be commercially available during the second half of 2024
SAN DIEGO--(BUSINESS WIRE)--
Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) today announced that the U.S. Food and Drug Administration (FDA) has approved ZELSUVMI™ (berdazimer topical gel, 10.3%) for the treatment of molluscum contagiosum (molluscum) in adults and pediatric patients one year of age and older.i The FDA approved ZELSUVMI as the first novel drug for the treatment of molluscum infections.
ZELSUVMI is the first and only topical prescription medication that can be applied by patients, parents, or caregivers at home, outside of a physician's office, or other medical setting to treat this highly contagious viral skin infection.
“The approval of ZELSUVMI is a breakthrough, marking the first time that clinicians can treat molluscum with an efficacious topical prescription medication that is applied by the patient, or a family member,” said Mark D. Kaufmann, MD, FAAD, a Clinical Professor of Dermatology in the Department of Dermatology at the Icahn School of Medicine at Mount Sinai in New York City and Past President of the American Academy of Dermatology. “I look forward to having this novel medication to treat my molluscum patients.”
Molluscum is a highly contagious viral skin infection characterized by skin-colored to red lesions with a central, umbilicated viral core.ii Approximately 6 million Americans, primarily children, are infected each year.iii,iv However, up to 73% of children go untreated.v Treating the lesions is critical to preventing the viral infection from spreading to other people or to other areas of the body. vi
“It is nice to see that molluscum contagiosum is finally getting the attention it deserves. For those of us in the primary care field, it is wonderful to have an effective option that can be used at home rather than taking a wait and watch approach,” said Stephen W. Stripling, MD, Pediatrician, Study Investigator and Molluscum Researcher.
ZELSUVMI is a nitric oxide releasing agent. Nitric oxide has been shown to have antiviral properties.vii The mechanism of action of ZELSUVMI for the treatment of molluscum contagiosum is unknown. Nevertheless, ZELSUVMI's efficacy was demonstrated in 2 Phase 3 trials - B-SIMPLE 4 and B-SIMPLE 2. These trials showed ZELSUVMI's ability to reduce lesion counts and was well tolerated when used once a day.viii The B-SIMPLE Phase 3 program enrolled 1,598 patients.ix The most commonly reported adverse reactions (≥1%) in clinical trials were application site reactions. See additional Important Safety Information for ZELSUVMI below.
“We are proud of the team’s accomplishment, having completed the world’s largest clinical program in molluscum to bring this first-in-class topical medication to FDA approval,” said Todd Davis, CEO of Ligand. “Pediatricians, dermatologists, and caregivers have long-sought a convenient approach to treat this highly contagious skin infection. With ZELSUVMI, patients now have an at-home treatment option available.”
ZELSUVMI is expected to be available in the United States in the second half of 2024. Complete prescribing information is available at www.zelsuvmi.com.
About ZELSUVMI™ (berdazimer topical gel, 10.3%)
ZELSUVMI (berdazimer topical gel, 10.3%) is a nitric oxide (NO) releasing agent indicated for the topical treatment of molluscum contagiosum in adults and pediatric patients one year of age and older. Complete prescribing information is available at www.zelsuvmi.com.
Contraindications: None.
Warnings: Application site reactions, including, allergic contact dermatitis occurred. Discontinue ZELSUVMI and initiate appropriate therapy.
Adverse Reactions: The most commonly reported adverse reactions (≥1%) are application site reactions including pain such as burning or stinging sensations (18.7%), erythema (11.7%), pruritus (5.7%), exfoliation (5.0%), dermatitis (4.9%), swelling (3.5%), erosion (1.6%), discoloration (1.5%), vesicles (1.5%), irritation (1.2%), and infection (1.1%).
About Ligand Pharmaceuticals
Ligand is a biopharmaceutical company enabling scientific advancement through supporting the clinical development of high-value medicines. Ligand does this by providing financing, licensing our technologies or both. Our business model seeks to generate value for stockholders by creating a diversified portfolio of biotech and pharmaceutical product revenue streams that are supported by an efficient and low corporate cost structure. Our goal is to offer investors an opportunity to participate in the promise of the biotech industry in a profitable and diversified manner. Our business model is based on funding programs in mid- to late-stage drug development in return for economic rights and licensing our technology to help partners discover and develop medicines. We partner with other pharmaceutical companies to attempt to leverage what they do best (late-stage development, regulatory management and commercialization) in order to generate our revenue. Our Captisol® platform technology is a chemically modified cyclodextrin with a structure designed to optimize the solubility and stability of drugs. We have established multiple alliances, licenses and other business relationships with the world’s leading pharmaceutical companies including Amgen, Merck, Pfizer, Jazz, Takeda, Gilead Sciences and Baxter International. For more information, please visit www.ligand.com. Follow Ligand on X; (f/k/a Twitter) @Ligand_LGND.
We use our investor relations website and X as a means of disclosing material non-public information and for complying with our disclosure obligations under Regulation FD. Investors should monitor our website and our X account, in addition to following our press releases, SEC filings, public conference calls and webcasts.
Source: Ligand Pharmaceuticals Incorporated
FDA approves Ligand's Zelsuvmi for treatment of molluscum
Jan. 05, 2024 5:02 PM ET
Ligand Pharmaceuticals Incorporated (LGND) Stock
By: Val Brickates Kennedy, SA News Editor1 Comment
Ligand Pharmaceuticals (NASDAQ:LGND) said that the FDA has approved its topical gel product Zelsuvmi for the treatment of molluscum contagiosum, a highly contagious viral skin infection.
Ligand Pharmaceuticals Incorporated (LGND) Stock
https://www.ligand.com/royalty-portfolio/#key-pipeline-products
NEXOBRID® (anacaulase-bcdb)
ZELSUVMI™ (berdazimer topical gel, 10.3%)
NEXOBRID® (anacaulase-bcdb)
MediWound Secures Additional U.S. Department of Defense Funding to Advance NexoBrid® Development for the U.S. Army
December 28, 2023
Awarded additional $6.7 million to advance NexoBrid as a non-surgical field care solution; R&D project budget increased to $14.4 million
YAVNE, Israel, Dec. 28, 2023 (GLOBE NEWSWIRE) -- MediWound Ltd. (Nasdaq: MDWD), a fully-integrated biopharmaceutical company focused on next-generation enzymatic therapeutics for tissue repair, today announced that the U.S. Department of Defense (DoD), through the Medical Technology Enterprise Consortium (MTEC), has awarded MediWound an additional $6.7 million in non-dilutive funding to develop NexoBrid® as a non-surgical solution for field-care burn treatment for the U.S. Army (the "MTEC Research Project Award"). The $14.4 million project budget will advance the development and production of a new, temperature-stable formulation of NexoBrid, positioning it as the first-line non-surgical solution for treating severe burn injuries in pre-hospital settings. Vericel Corporation holds an exclusive license encompassing the commercial and development rights to NexoBrid in North America as set forth in the license agreement between the Company and Vericel.
"We are delighted to further solidify our partnership with the U.S. Department of Defense. The additional funding will enhance our CMC activities, expedite preclinical development, and facilitate the establishment of a GMP compliant aseptic production line for the temperature-stable formulation of NexoBrid," announced Ofer Gonen, Chief Executive Officer of MediWound. "This new award underscores our shared commitment to ensuring NexoBrid's availability for military use and its potential to significantly change the early treatment approach for severe burns."
The MTEC Research Project Award was granted by the DoD’s U.S. Army Medical Research and Development Command (USAMRDC) and funded by the Defense Health Agency through MTEC, a biomedical technology consortium working to advance innovative medical solutions to keep military personnel healthy and fully operational. In alignment with this mission, it's vital to have field solutions for severe burn treatments that are both easy-to-use and effective. Such solutions should be applicable immediately post-injury and demand minimal preparation and training.
About U.S. Army Medical Research and Development Command (USAMRDC)
The U.S. Army Medical Research and Development Command is the Army’s medical materiel developer, with responsibility for medical research, development, and acquisition. USAMRDC produces medical solutions for the battlefield with a focus on various areas of biomedical research, including military infectious diseases, combat casualty care, military operational medicine, medical chemical, and biological defense https://mrdc.health.mil/.
Please note, the views expressed in this press release are those of MediWound and may not reflect the official policy or position of the Department of the Army, Department of Defense, or the U.S. Government.
About Medical Technology Enterprise Consortium (MTEC)
The Medical Technology Enterprise Consortium is a biomedical technology consortium collaborating with multiple government agencies under a 10-year renewable Other Transaction Agreement with the U.S. Army Medical Research and Development Command. The consortium focuses on the development of medical solutions that protect, treat, and optimize the health and performance of U.S. military personnel. To find out more about MTEC, visit mtec-sc.org.
About MediWound
MediWound Ltd. (Nasdaq: MDWD) is the global leader in next-generation enzymatic therapeutics focused on non-surgical tissue repair. Specializing in the development, production and commercialization of solutions that seek to replace existing standards of care, the Company is committed to providing rapid and effective biologics that improve patient experiences and outcomes, while reducing costs and unnecessary surgeries.
MediWound’s first drug, NexoBrid®, is an FDA-approved orphan biologic for eschar removal in severe burns that can replace surgical interventions and minimize associated costs and complications. Utilizing the same core biotherapeutic enzymatic platform technology, MediWound has developed a strong R&D pipeline including the Company’s lead drug under development, EscharEx®. EscharEx is a Phase III-ready biologic for debridement of chronic wounds with significant advantages over the $300 million monopoly legacy drug and an opportunity to expand the market. MediWound’s pipeline also includes MW005, a topical therapeutic for the treatment of basal cell carcinoma that has demonstrated positive results in a recently completed Phase I/II study.
For more information visit www.mediwound.com and follow the Company on LinkedIn.
MediWound wins DoD funding to develop NexoBrid for U.S. Army
Dec. 28, 2023 7:20 AM ET
MediWound Ltd. (MDWD) Stock, VCEL Stock
By: Dulan Lokuwithana, SA News Editor
- MediWound (NASDAQ:MDWD) announced Thursday that the U.S. Department of Defense ((DoD)) awarded the company $6.7M in additional funding to develop its wound care product NexoBrid as a burn treatment for the U.S. Army.
- Specifically, the non-dilutive funding channeled through the DoD's Medical Technology Enterprise Consortium will be used to develop NexoBrid as a non-surgical solution for field-care burn treatment, the Israel-based pharma said.
- As part of a licensing agreement with MediWound (MDWD), the U.S. biotech Vericel Corporation (NASDAQ:VCEL) owns the rights to sell and develop NexoBrid in North American markets.
- https://seekingalpha.com/news/4050897-mediwound-dod-funding-develop-nexobrid-us-army
- MediWound Ltd. (MDWD) Stock, VCEL Stock
- https://www.mediwound.com/
- https://www.vcel.com/
- https://www.nexobrid-us.com/
Aficamten
WAINUA™ (eplontersen)
NEXOBRID® (anacaulase-bcdb)
Cytokinetics Announces Positive Results From SEQUOIA-HCM, the Pivotal Phase 3 Clinical Trial of Aficamten in Patients With Obstructive Hypertrophic Cardiomyopathy
December 27, 2023 at 7:30 AM EST
Statistically Significant and Clinically Meaningful Increase
in Primary Efficacy Endpoint at 24 Weeks of Treatment;
Improvement Consistent Across All Prespecified Subgroups
Statistically Significant and Clinically Meaningful Improvements in All Secondary Endpoints
No Instances of Treatment Interruptions Due to Low LVEF
Company to Host Conference Call and Webcast Today at 8:30 a.m. Eastern Time
SOUTH SAN FRANCISCO, Calif., Dec. 27, 2023 (GLOBE NEWSWIRE) -- Cytokinetics, Incorporated (Nasdaq: CYTK) today announced positive topline results from SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM), the pivotal Phase 3 clinical trial of aficamten in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM).
The results of SEQUOIA-HCM show that treatment with aficamten significantly improved exercise capacity compared to placebo, increasing peak oxygen uptake (pVO2) measured by cardiopulmonary exercise testing (CPET) by a least square mean difference (95% CI) of 1.74 (1.04 - 2.44) mL/kg/min (p=0.000002). The treatment effect with aficamten was consistent across all prespecified subgroups reflective of patient baseline characteristics and treatment strategies, including patients receiving or not receiving background beta-blocker therapy.
Statistically significant (p<0.0001) and clinically meaningful improvements were also observed in all 10 prespecified secondary endpoints, including Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) at weeks 12 and 24, the proportion of patients with ≥1 class improvement in New York Heart Association (NYHA) functional class at weeks 12 and 24, change in provoked left ventricular outflow tract gradient (LVOT-G) and proportion <30 mmHg at weeks 12 and 24, as well as exercise workload and guideline-eligibility for septal reduction therapy.
Aficamten was well-tolerated in SEQUOIA-HCM with an adverse event profile comparable to placebo. Treatment emergent serious adverse events occurred in 8 (5.6%) and 13 (9.3%) patients on aficamten and placebo, respectively. Core echocardiographic left ventricular ejection fraction (LVEF) was observed to be <50% in 5 patients (3.5%) on aficamten compared to 1 patient (0.7%) on placebo. There were no instances of worsening heart failure or treatment interruptions due to low LVEF.
The full results from SEQUOIA-HCM will be presented at an upcoming medical conference.
“The results from SEQUOIA-HCM meet our high expectations for both efficacy and safety, demonstrating that aficamten added to standard of care therapy had a positive impact on exercise capacity as well as rapid and sustained effects on symptoms and functional class in patients with obstructive HCM while maintaining the safety and tolerability that we have previously observed,” said Fady I. Malik, M.D., Ph.D., Cytokinetics’ Executive Vice President of Research & Development. “We believe these results are consistent with those observed in REDWOOD-HCM, the Phase 2 clinical trial of aficamten, and FOREST-HCM, the ongoing open label extension clinical trial, and may reflect a profile enabling of aficamten to become the cardiac myosin inhibitor of choice among physicians and patients. We thank the patients, investigators and site personnel who participated in SEQUOIA-HCM and continue to support our ongoing clinical research and look forward to sharing the full results from this trial at a medical meeting in 2024.”
“Cardiac myosin inhibition represents an exciting new therapy option for patients with symptomatic obstructive HCM and I am pleased to see these impressive results from SEQUOIA-HCM,” said Martin Maron, M.D., Director, Hypertrophic Cardiomyopathy Center, Lahey Hospital and Medical Center, Burlington, MA; Tufts University School of Medicine, and National Principal Investigator of SEQUOIA-HCM. “A therapy like aficamten that improves exercise capacity in a clinically meaningful manner, absent low LVEF events that interrupt treatment, should be a welcome addition for HCM patients as well as the clinicians who treat them.”
Conference Call and Webcast Information
Cytokinetics will host a conference call today at 8:30 AM Eastern Time that will be simultaneously webcast and can be accessed from the Investors & Media section of Cytokinetics’ website at www.cytokinetics.com. The live audio of the conference call can also be accessed by telephone by registering in advance at the following link: Topline Results from SEQUOIA-HCM. Upon registration, participants will receive a dial-in number and a unique passcode to access the call.
About Aficamten and the Broad Phase 3 Clinical Trials Program
Aficamten is an investigational selective, small molecule cardiac myosin inhibitor discovered following an extensive chemical optimization program that was conducted with careful attention to therapeutic index and pharmacokinetic properties and as may translate into next-in-class potential in clinical development. Aficamten was designed to reduce the number of active actin-myosin cross bridges during each cardiac cycle and consequently suppress the myocardial hypercontractility that is associated with hypertrophic cardiomyopathy (HCM). In preclinical models, aficamten reduced myocardial contractility by binding directly to cardiac myosin at a distinct and selective allosteric binding site, thereby preventing myosin from entering a force producing state.
The development program for aficamten is assessing its potential as a treatment that improves exercise capacity and relieves symptoms in patients with HCM as well as its potential long-term effects on cardiac structure and function. Aficamten was evaluated in SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM), a pivotal Phase 3 clinical trial in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). Aficamten is currently the subject of two ongoing Phase 3 clinical trials: MAPLE-HCM (Metoprolol vs Aficamten in Patients with LVOT Obstruction on Exercise Capacity in HCM), evaluating aficamten as monotherapy compared to metoprolol as monotherapy in patients with obstructive HCM, and ACACIA-HCM (Assessment Comparing Aficamten to Placebo on Cardiac Endpoints In Adults with Non-Obstructive HCM), evaluating aficamten in patients with symptomatic non-obstructive HCM. Aficamten received Breakthrough Therapy Designation for the treatment of symptomatic obstructive HCM from the U.S. Food & Drug Administration (FDA) as well as the National Medical Products Administration (NMPA) in China.
About Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is a disease in which the heart muscle (myocardium) becomes abnormally thick (hypertrophied). The thickening of cardiac muscle leads to the inside of the left ventricle becoming smaller and stiffer, and thus the ventricle becomes less able to relax and fill with blood. This ultimately limits the heart’s pumping function, resulting in reduced exercise capacity and symptoms including chest pain, dizziness, shortness of breath, or fainting during physical activity. HCM is the most common monogenic inherited cardiovascular disorder, with approximately 280,000 patients diagnosed in the U.S., however, there are an estimated 400,000-800,000 additional patients who remain undiagnosed.1,2,3 Two-thirds of patients with HCM have obstructive HCM (oHCM), where the thickening of the cardiac muscle leads to left ventricular outflow tract (LVOT) obstruction, while one-third have non-obstructive HCM (nHCM), where blood flow isn’t impacted, but the heart muscle is still thickened. People with HCM are at high risk of also developing cardiovascular complications including atrial fibrillation, stroke and mitral valve disease.4 People with HCM are at risk for potentially fatal ventricular arrhythmias and it is one of the leading causes of sudden cardiac death in younger people or athletes.5 A subset of patients with HCM are at high risk of progressive disease leading to dilated cardiomyopathy and heart failure necessitating cardiac transplantation.
About Cytokinetics
Cytokinetics is a late-stage, specialty cardiovascular biopharmaceutical company focused on discovering, developing and commercializing first-in-class muscle activators and next-in-class muscle inhibitors as potential treatments for debilitating diseases in which cardiac muscle performance is compromised. As a leader in muscle biology and the mechanics of muscle performance, the company is developing small molecule drug candidates specifically engineered to impact myocardial muscle function and contractility. Aficamten is a next-in-class cardiac myosin inhibitor being evaluated in a broad development program inclusive of SEQUOIA-HCM, the pivotal Phase 3 clinical trial in obstructive hypertrophic cardiomyopathy, and the ongoing Phase 3 clinical trials MAPLE-HCM, evaluating aficamten as monotherapy compared to metoprolol as monotherapy in patients with obstructive HCM and ACACIA-HCM, evaluating aficamten in patients with non-obstructive HCM. Cytokinetics is also developing omecamtiv mecarbil, a cardiac muscle activator, in patients with heart failure. Additionally, Cytokinetics is developing CK-136, a cardiac troponin activator for the potential treatment HFrEF and other types of heart failure, such as right ventricular failure, resulting from impaired cardiac contractility, and CK-586, a cardiac myosin inhibitor with a mechanism of action distinct from aficamten for the potential treatment of HFpEF. In 2023, Cytokinetics is celebrating its 25-year history of pioneering innovation in muscle biology and related pharmacology focused to diseases of muscle dysfunction and conditions of muscle weakness.
For additional information about Cytokinetics, visit www.cytokinetics.com and follow us on X, LinkedIn, Facebook and YouTube.
CYTOKINETICS® and the CYTOKINETICS and C-shaped logo are registered trademarks of Cytokinetics in the U.S. and certain other countries.
Source: Cytokinetics, Incorporated
Cytokinetics gains on positive Phase 3 data for heart disease therapy
Dec. 27, 2023 8:08 AM ET
Cytokinetics, Incorporated (CYTK) Stock
By: Dulan Lokuwithana, SA News Editor
Cytokinetics (NASDAQ:CYTK) shares rose ~43% in the premarket Wednesday after the biotech posted encouraging data from a pivotal Phase 3 trial for its cardiac myosin inhibitor, aficamten, in patients with a form of cardiomyopathy.
According to topline data from the trial SEQUOIA-HCM, after 24 weeks of therapy, patients on aficamten indicated a statistically significant and clinically meaningful increase in the primary efficacy endpoint compared to placebo.
https://seekingalpha.com/news/4050439-cytokinetics-stock-gains-data-heart-disease-therapy
WAINUA™ (eplontersen)
WAINUA™ (eplontersen)
WAINUA™ (eplontersen)
Wainua (eplontersen) granted first-ever regulatory approval in the US for the treatment of adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis
PUBLISHED21 December 2023
US FDA approval based on NEURO-TTRansform Phase III results showing Wainua demonstrated consistent and sustained benefit improving neuropathy impairment and quality of life
Additional regulatory reviews underway in rest of world
AstraZeneca and Ionis’ Wainua (eplontersen) has been approved in the US for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults, commonly referred to as hATTR-PN or ATTRv-PN.1 Wainua is the only approved medicine for the treatment of ATTRv-PN that can be self-administered via an auto-injector.2-4
The approval by the US Food and Drug Administration (FDA) was based on the positive 35-week interim analysis from the NEURO-TTRansform Phase III trial, which showed patients treated with Wainua demonstrated consistent and sustained benefit on the co-primary endpoints of serum transthyretin (TTR) concentration and neuropathy impairment measured by modified Neuropathy Impairment Score +7 (mNIS+7), and key secondary endpoint of quality of life (QoL) on the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN).2,5 Positive results from the NEURO-TTRansform Phase III trial were published in The Journal of the American Medical Association (JAMA) further demonstrating the benefit of Wainua across the spectrum of ATTRv-PN at 35, 66 and 85 weeks.2
Michael J. Polydefkis, M.D., Professor of Neurology at Johns Hopkins University School of Medicine and an investigator in the NEURO-TTRansform study, said: “Many people living with hereditary transthyretin-mediated amyloid polyneuropathy are unable to fully enjoy their lives because of the relentless, progressive and debilitating effects of the disease. Approval of Wainua represents a meaningful advancement in treatment, one that gives those who are living with transthyretin-mediated amyloid polyneuropathy help managing the disease.”
ATTRv-PN is a debilitating disease that leads to peripheral nerve damage with motor disability within five years of diagnosis and, without treatment, is generally fatal within a decade.6 Wainua is a ligand-conjugated antisense oligonucleotide (LICA) medicine designed to reduce the production of TTR protein at its source to treat both hereditary and non-hereditary forms of transthyretin-mediated amyloidosis (ATTR).3,7,8
Ruud Dobber, Executive Vice-President, BioPharmaceuticals Business Unit, AstraZeneca, said: “There is an urgent medical need for new therapies for people living with hereditary transthyretin-mediated amyloid polyneuropathy. The US approval of Wainua offers a new treatment option that provides consistent and sustained reduction in serum TTR concentration compared to baseline while halting disease progression and improving quality of life for people living with this debilitating condition.”
Isabelle Lousada, President and CEO, Amyloidosis Research Consortium, said: “People with hereditary transthyretin-mediated amyloid polyneuropathy, and other forms of amyloidosis, are often misdiagnosed since symptoms can mirror other conditions. The path to getting an accurate diagnosis can often be a long, arduous journey and it is critical that a timely and accurate diagnosis is made not only for the individual experiencing symptoms but for their families and loved ones. It is exciting to see new innovations coming through and increased efforts to raise awareness in an area that has often been overlooked or neglected.”
As part of a global development and commercialisation agreement, AstraZeneca and Ionis will commercialise Wainua for the treatment of ATTRv-PN in the US and are seeking regulatory approval in Europe and other parts of the world.8 This agreement was recently expanded to include exclusive rights for AstraZeneca to commercialise Wainua in Latin America in addition to all other countries outside the US.9 Wainua was granted Orphan Drug Designation in the US and in the EU for the treatment of ATTR.9,10 Wainua will be available in the US in January 2024.
Brett P. Monia, Ph.D., chief executive officer at Ionis, said: “The FDA approval of Wainua marks an important milestone for people living with hereditary transthyretin-mediated amyloid polyneuropathy, who will now have an effective, well-tolerated treatment that can be self-administered via auto-injector to combat this devastating disease. It is also a pivotal moment for Ionis as Wainua will be the first in a steady cadence of potential commercial launches for the company. We are proud to have discovered and, together with AstraZeneca, developed Wainua, and are grateful to the patients, caregivers and investigators who participated in our clinical studies, as well as for the dedication of our scientists and researchers.”
Eplontersen is currently being evaluated in the CARDIO-TTRansform Phase III trial for treatment of transthyretin-mediated amyloid cardiomyopathy (ATTR-CM), a systemic, progressive and fatal condition that typically leads to progressive heart failure and often death within three-to-five years from disease onset.11-13
Notes
TTR Amyloidosis
ATTR cardiomyopathy and polyneuropathy are progressive systemic diseases caused by aging or genetic mutations (variants), resulting in misfolded TTR protein and accumulation as amyloid fibrils in the cardiac myocardium and peripheral nerves, respectively.11,12 In patients with ATTR, both hereditary and wild type (non-hereditary), TTR protein builds up as fibrils in tissues, such as the peripheral nerves and heart, gastrointestinal system, eyes, kidneys, central nervous system, thyroid and bone marrow.3,11 The presence of TTR fibrils interferes with the normal functions of these tissues.12 As the TTR protein fibrils accumulate, more tissue damage occurs and the disease worsens, resulting in poor QoL and eventually death.12 Worldwide, there are an estimated 300,000 – 500,000 patients with ATTR-CM and about 40,000 patients with ATTRv-PN.3,12
NEURO-TTRansform
NEURO-TTRansform is a global, open-label, randomised trial evaluating the efficacy and safety of eplontersen in patients with ATTRv-PN.2,5 The trial enrolled adult patients with ATTRv-PN Stage 1 or Stage 2 compared to the external placebo group from the TEGSEDI® (inotersen) NEURO-TTR registrational trial that Ionis completed in 2017.2,5 The comparison of efficacy and safety for Wainua versus external placebo was based on data up to week 66, and all patients were followed on treatment until week 85, when they had the option to transition into an open-label extension study, which is still ongoing.2,5
Wainua
Wainua (eplontersen) is a ligand-conjugated antisense oligonucleotide (LICA medicine designed to reduce the production of transthyretin, or TTR protein.2,7 Wainua has been approved in the US for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults (also referred to as ATTRv-PN).1
AstraZeneca in CVRM
Cardiovascular, Renal and Metabolism (CVRM), part of BioPharmaceuticals, forms one of AstraZeneca’s main disease areas and is a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys, liver and pancreas, AstraZeneca is investing in a portfolio of medicines for organ protection by slowing or stopping disease progression, and ultimately paving the way towards regenerative therapies. The Company’s ambition is to improve and save the lives of millions of people, by better understanding the interconnections between CVRM diseases and targeting the mechanisms that drive them, so we can detect, diagnose and treat people earlier and more effectively.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca
FDA approves AstraZeneca, Ionis drug for ATTRv-PN
Dec. 22, 2023 11:43 AM ET
Ionis Pharmaceuticals, Inc. (IONS) Stock, AZN StockPFE
By: Val Brickates Kennedy, SA News Editor
The FDA has approved AstraZeneca (NASDAQ:AZN) and Ionis Pharmaceuticals’ (NASDAQ:IONS) drug Wainua for the treatment of polyneuropathy of hereditary transthyretin-mediated amyloidosis, also known as hATTR-PN or ATTRv-PN.
AstraZeneca said the product is the only approved treatment for the condition in the US that can be self-administered via an autoinjector. The product will be launched in the US in 2024.
https://seekingalpha.com/news/4050017-fda-approves-astrazeneca-ionis-drug-for-attrv-pn
Ionis Pharmaceuticals, Inc. (IONS) Stock, AZN Stock
https://www.ionispharma.com/ionis-technology/antisense-pipeline/
Lomecel-B™
WAINUA™ (eplontersen)
WAINUA™ (eplontersen)
Longeveron Announces Additional Positive Clinical Data and Imaging Biomarker Results from the CLEAR MIND Phase 2a Trial of Lomecel-B™ in the Treatment of Mild Alzheimer’s Disease
December 20, 2023
- New clinical data showed that Lomecel-B™ improved cognitive function in multiple measures in a dose-response fashion
- Caregiver ratings documented improved quality of life in Lomecel-B™ treated patients
- MRI Biomarker study data showed that Lomecel-B™ countered loss of brain volume in multiple areas associated with Alzheimer’s disease, reduced brain neuroinflammation and improved cerebral blood flow
- Overall results confirmed the drug product’s therapeutic potential in the treatment of mild Alzheimer’s disease and support further development
MIAMI, Dec. 20, 2023 (GLOBE NEWSWIRE) -- Longeveron Inc. (NASDAQ: LGVN) (“Longeveron” or “Company”), a clinical stage biotechnology company developing cellular therapies for life-threatening and chronic aging-related conditions such as hypoplastic left heart syndrome (HLHS), Alzheimer’s disease and Aging-related Frailty, today announces additional new clinical and biomarker results from its Phase 2a CLEAR MIND trial of its investigational product Lomecel-B™ for the treatment of mild Alzheimer’s disease.
The expanded data set reinforced the earlier top-line findings showing that the primary safety endpoint was met and provided further support for Lomecel-B’s positive benefit/risk profile. Additional analysis of cognitive function and daily living data consistently showed favorable results with Lomecel-B™ over placebo in a dose-response fashion, with administration of Lomecel-B™ associated with slowing and in some cases improving certain measurements of cognitive function (MoCA, MMSE). New analyses of imaging data measured using MRI showed that administration of Lomecel-B™ was associated with reduced neuroinflammation assessed by Diffusion Tensor Imaging (DTI), and also appeared to counter loss in brain volume in areas associated with Alzheimer’s disease (TBV, hippocampus, ventricles, thalamus).
Wa’el Hashad, CEO of Longeveron, commented: “These new data support our initial results for CLEAR MIND that we announced in October and provide further validation of both the safety and therapeutic potential of Lomecel-B™ in the treatment of mild Alzheimer’s disease. We believe these new data may provide evidence for Lomecel-B’s mechanism of action and add to the robust foundation we are building for its further investigation in Alzheimer’s disease as well as other indications. We anticipate presenting the CLEAR MIND results in a major medical meeting in 2024.”
Summary of new findings:
The latest data further supports the prior findings regarding Lomecel-B’s potential prevention of cognitive decline and improvement in quality of life. In addition to these clinical findings, brain imaging showed improvement in brain architecture measured by volumetric MRI and DTI, respectively.
- Lomecel-B™ (25M x 1 dose, p=0.009) and the pooled treatment group (25M x 1 dose, 25M x 4 doses, 100M x 4 doses, p=0.015) demonstrated statistically significant improvements in the Montreal Cognitive Assessment (MOCA), relative to placebo
- Lomecel-B™ demonstrated a dose-response improvement in Mini-Mental State Examination (MMSE) relative to baseline (mean + SD increase: 3.0+3.6 at highest dose, 39 weeks, p=0.028)
Lomecel-B™ (100M x 4 doses) demonstrated a higher level of improvement in quality of life observed by caregiver and measured by Alzheimer’s Disease Related Quality of Life scale (ADRQOL).
Neuronal loss in Alzheimer’s disease leads to a common feature of disease such as progressive atrophy resulting in reduction in brain volume and cortical thickness that can be measured with volumetric MRI. Brain tissue loss begins with reduction in temporal lobes structures such as hippocampus followed by atrophy in other parts of the brain (parietal, frontal).
- Lomecel-B™ (100M x 4 doses) reduced the whole brain volume loss by 49% (p=0.034)
Lomecel-B™ (25M x 1 dose, p=0.015) and the pooled treatment group (25M x 1 dose, 25M x 4 doses, 100M x 4 doses, p=0.038) demonstrated statistically significant reductions in left hippocampal volume loss at Week 39 relative to placebo (Degree of reduction was 84% for 25M x 1 dose). - Brain volume preservation in the Lomecel-B™ (100M x 4 dose) dose group was accompanied by 20% and 33% reduction in left and right ventricular enlargement at Week 39 compared to placebo, respectively.
- The level of neuroinflammation measured by DTI was lower in all Lomecel-B™ doses at Week 39 compared to placebo.
Taken together, the Company believes the results of the CLEAR MIND study build a strong foundation for further development in mild Alzheimer's disease patients.
CLEAR MIND Results:
Overall, Lomecel-B™ appeared to demonstrate a positive benefit/risk profile. The primary endpoint of safety was met based on statistical and medical assessment.
The study safety data were consistent with an established safety profile with no incidence of hypersensitivity, infusion-related reactions, no cases of Alzheimer Related Imagine Abnormalities of Edema (ARIA-E) or microhemorrhages and superficial siderosis (ARIA-H) on Magnetic Resonance Imaging (MRI), and no notable changes in laboratory evaluations and electrocardiogram (EKG).
The secondary endpoint of change from baseline to Week 39 in CADS, demonstrated positive results, at the prespecified statistical level of p<0.1, 2-tailed:
- Statistically significant improvement at Week 39 in CADS was observed for the Lomecel-B™ 25 x 106 cells (25M) x 1 dose (p=0.091) versus placebo and for the pooled Lomecel-B™ Groups (25M x 1 dose, 25M x 4 doses, 100 x 106 cells (100M) x 4 doses) (p=0.099).
In terms of the specific components of the CADS score, evaluated at p<0.05, 2-tailed:
- Lomecel-B™ (25M x 1 dose) demonstrated statistically significant slowing of disease progression in left hippocampal volume (p=0.015) relative to placebo
- ADCS-ADL and left hippocampal volume at Week 39 were statistically significant for the pooled Lomecel-B™ treatment groups (25M x 1 dose, 25M x 4 doses, 100M x 4 doses) relative to placebo (p=0.047) and (p=0.038), respectively
- Other doses demonstrated numerical slowing and prevention of disease worsening relative to placebo in CADS, ADAS-cog-13, CDR-SB, ADCS-ADL and left hippocampal volume at Week 39
About The CLEAR MIND Study
The trial was designed to study Lomecel-B™ Effects on mild Alzheimer’s disease: A Randomized, Double-Blinded, Placebo-Controlled Phase 2 Trial (NCT05233774), named the CLEAR MIND trial. The trial included a total of 50 patients who were 60-85 years old and had a diagnosis of mild Alzheimer’s disease in accordance with National Institutes of Health – Alzheimer’s Association (NIA-AA) criteria, Mini-Mental State Examination (MMSE) score of 18-24, and a brain MRI and positron emission tomography (PET) scan consistent with Alzheimer’s disease. The trial was designed to test three different dosing regimens of Lomecel-B™ vs. placebo, and patients were randomized in a 1:1:1:1 ratio. The following doses were studied: Lomecel-B™ at a dose of 25 x 106 cells (25M) on Day 0, followed by placebo infusions at Week 4, Week 8 and Week 12; Lomecel-B™ at a dose of 25M administered on Day 0, Week 4, Week 8, and Week 12 for a total of 4 doses; and at a dose of 100 x 106 cells (100M) administered on Day 0, Week 4, Week 8, and Week 12, for a total of 4 doses.
The trial randomized 50 patients (49 were treated) and was conducted at 10 centers in the U.S. The primary endpoint of the trial is safety as measured by the occurrence of serious adverse events (SAEs) within the first 30 days after each administration of Lomecel-B™.
In consideration of the study sample size (N=49 patients), the study employed a novel global statistical test approach known as a Composite Alzheimer’s Disease Score (CADS, which is accepted and increasingly used by the scientific community for AD clinical trials). The CADS served as the secondary outcome measure of the trial and combined information across cognitive, functional capacity and brain MRI domains.
The Secondary Endpoint definition is the change from baseline to Week 39 in the CADS. This score comprised of ADAS-cog-13, ADCS-ADL, CDR-SB, and left hippocampal volume (normalized for intercranial volume).
For efficacy analysis, testing of the secondary endpoint proceeded using a pre-specified, two-sided alpha of 0.1. If statistical significance was achieved at this level for any dose comparison, the study was considered positive and supportive of further study of Lomecel-B™ in a larger, higher-powered study. The individual components of the CADS were evaluated at two-sided alpha of 0.05.
Exploratory endpoints included cognitive evaluation (MMSE, MOCA), quality of life (ADRQOL), brain volumetry (vMRI), other imaging modalities, and biomarkers relevant to inflammation and vascular function.
Assessment Scales
ADAS-cog-13 — Alzheimer’s Disease Assessment Scale-Cognitive 13
CDR-SB ― Clinical Dementia Rating Scale Sum of Boxes
ADCS-ADL — Alzheimer’s Disease Cooperative Study Activity of Daily Living
ADRQOL — Alzheimer’s Disease Related Quality of Life
DTI — Diffusion Tensor Imaging
MMSE — Mini-Mental State Examination
MOCA — Montreal Cognitive Assessment
About Lomecel-B™
Lomecel-B™ is a living cell product made from specialized cells isolated from the bone marrow of young healthy adult donors. These specialized cells, known as medicinal signaling cells (MSCs), are essential to our endogenous biological repair mechanism. MSCs have been shown to perform a number of complex functions in the body, including the formation of new tissue. They also have been shown to respond to sites of injury or disease and secrete bioactive factors that are immunomodulatory and regenerative. We believe that Lomecel-B™ may have multiple potential mechanisms of action that may lead to anti-inflammatory, pro-vascular regenerative responses, and therefore may have broad application for a range of rare and aging related diseases.
About Longeveron Inc.
Longeveron is a clinical stage biotechnology company developing regenerative medicines to address unmet medical needs. The Company’s lead investigational product is Lomecel-B™, an allogeneic medicinal signaling cell (MSC) therapy product isolated from the bone marrow of young, healthy adult donors. Lomecel-B™ has multiple potential mechanisms of action encompassing pro-vascular, pro-regenerative, anti-inflammatory, and tissue repair and healing effects with broad potential applications across a spectrum of disease areas. Longeveron is currently advancing Lomecel-B™ through clinical trials in three indications: hypoplastic left heart syndrome (HLHS), Alzheimer’s disease, and Aging-related Frailty. Additional information about the Company is available at www.longeveron.com.
Source: Longeveron
Longeveron reports positive results from Alzheimer's treatment trial
Dec. 20, 2023 12:21 PM ET
By: Arundhati Sarkar, SA News Editor1 Comment
- Longeveron (NASDAQ:LGVN) Wednesday reported additional new clinical and biomarker results from its Phase 2a CLEAR MIND trial of its investigational product Lomecel-B for the treatment of mild Alzheimer’s disease.
- Longeveron (LGVN) said the MRI Biomarker study data showed that Lomecel-B countered loss of brain volume in multiple areas associated with Alzheimer’s disease, reduced brain neuroinflammation and improved cerebral blood flow.
- https://seekingalpha.com/news/4048596-longeveron-reports-positive-results-from-alzheimers-treatment-trial
- Longeveron Inc. (LGVN) Stock
- https://longeveron.com/lomecel-b/
- https://longeveron.com/
ANAVEX®2-73 (BLARCAMESINE)
ANAVEX®2-73 (BLARCAMESINE)
ANAVEX®2-73 (BLARCAMESINE)
Anavex Announces First Entire Clinical Gene Pathway Data of ANAVEX®2-73 from AVATAR Study in Patients with Rett Syndrome
Significant activation of key developmental and metabolic gene pathways and potential compensatory mechanism with ANAVEX®2-73 in Rett syndrome patients
NEW YORK – December 20, 2023
Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq: AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders including Alzheimer’s disease, Parkinson’s disease, Rett syndrome and other central nervous system (CNS) diseases, today announced the first entire clinical gene pathway data from the ANAVEX®2-73-RS-002 AVATAR Rett syndrome trial.
A whole genome and exome analysis comparing drug and placebo in patients with Rett syndrome was performed. We believe the results confirm that Rett syndrome is indeed a neurodevelopmental disorder with a key metabolic component, which can be addressed with therapeutic intervention and is likely relevant for other neurodevelopmental disease indications.
AVATAR study was a randomized, placebo-controlled clinical trial in 33 patients with Rett syndrome which included prespecified biomarkers of response as well as Whole Exome Sequencing (WES) DNA data and full RNA exome expression (RNA-seq) data collection. The study included analysis of gene expression changes in each treatment group as well as analysis of the impact of single nucleotide polymorphisms/variants (SNPs/SNVs) on treatment response.
ANAVEX®2-73 transcriptomics analysis (RNAseq) identified gene networks that are differentially expressed in Rett syndrome patients treated with ANAVEX®2-73 compared to placebo. Patient samples that were analyzed contained on average over 20 million unique reads in both placebo and ANAVEX®2-73 treated patients. Biological relevance of this pool of genes was assessed through pathway analysis and confirmed the impact of ANAVEX®2-73 treatment on pathways involved in neurodevelopmental diseases.
The results highlight many significant differences between active treatment group and placebo, such as the differential expression of several genes in response to ANAVEX®2-73 treatment as shown in the following heatmap figure:
The scope of these detected gene expression changes identified through ANAVEX®2-73 effect may represent additional potential biomarkers of disease pathology and response.
Christopher U Missling, PhD, President and Chief Executive Officer of Anavex, stated, "We believe, this represents an extensive transcriptomics analysis (RNAseq) of a therapeutic agent in patients with Rett syndrome and it is very exciting to witness ANAVEX®2-73’s demonstration of its platform Precision Medicine potential for Rett syndrome with ability to compensate for expression levels of dysregulated developmental and metabolic genes, apparent within the Rett syndrome pathology. We are steadily making progress to learn more about this debilitating disorder and further analysis will be dedicated to evaluating the significance of each identified gene and gene variant and should deepen the understanding of the underlying signaling pathways involved in response to ANAVEX®2-73 treatment in patients with Rett syndrome.”
About Anavex Life Sciences Corp.
Anavex Life Sciences Corp. (Nasdaq: AVXL) is a publicly traded biopharmaceutical company dedicated to the development of novel therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders, including Alzheimer's disease, Parkinson's disease, Rett syndrome, and other central nervous system (CNS) diseases, pain, and various types of cancer. Anavex's lead drug candidate, ANAVEX®2-73 (blarcamesine), has successfully completed a Phase 2a and a Phase 2b/3 clinical trial for Alzheimer's disease, a Phase 2 proof-of-concept study in Parkinson's disease dementia, and both a Phase 2 and a Phase 3 study in adult patients with Rett syndrome. ANAVEX®2-73 is an orally available drug candidate that restores cellular homeostasis by targeting sigma-1 and muscarinic receptors. Preclinical studies demonstrated its potential to halt and/or reverse the course of Alzheimer's disease. ANAVEX®2-73 also exhibited anticonvulsant, anti-amnesic, neuroprotective, and anti-depressant properties in animal models, indicating its potential to treat additional CNS disorders, including epilepsy. The Michael J. Fox Foundation for Parkinson's Research previously awarded Anavex a research grant, which fully funded a preclinical study to develop ANAVEX®2-73 for the treatment of Parkinson's disease. ANAVEX®3-71, which targets sigma-1 and M1 muscarinic receptors, is a promising clinical stage drug candidate demonstrating disease-modifying activity against the major hallmarks of Alzheimer's disease in transgenic (3xTg-AD) mice, including cognitive deficits, amyloid, and tau pathologies. In preclinical trials, ANAVEX®3-71 has shown beneficial effects on mitochondrial dysfunction and neuroinflammation. Further information is available at www.anavex.com. You can also connect with the Company on Twitter, Facebook, Instagram, and LinkedIn.
Anavex gets EMA green light to submit blarcamesine application for Alzheimer's
Dec. 19, 2023 5:03 PM ET
Anavex Life Sciences Corp. (AVXL) Stock
By: Jonathan Block, SA News Editor9 Comments
- A department within the European Medicines Agency granted Anavex Life Sciences (NASDAQ:AVXL) the go-ahead to submit a Marketing Authorization Application for its Alzheimer's candidate blarcamesine.
- The Committee for Medicinal Products for Human Use said the blarcamesine application is eligible for submission under a procedure for single application. This means that if approved, the drug could be marketed in all EU member states.
- https://seekingalpha.com/news/4048247-anavex-gets-ema-green-light-submit-blarcamesine-application-alzheimers
- Anavex Life Sciences Corp. (AVXL) Stock
- https://www.anavex.com/
ACI-35.030 (JNJ-64042056)
ANAVEX®2-73 (BLARCAMESINE)
ANAVEX®2-73 (BLARCAMESINE)
AC Immune’s Targeted Anti-PTau Active Immunotherapy For Alzheimer’s Disease Advances Into Phase 2b Trial
Dec 15, 2023
AC Immune’s Targeted Anti-pTau Active Immunotherapy for Alzheimer’s Disease Advances into Phase 2b Trial
- Potentially registration-enabling Phase 2b study (ReTain) will evaluate the effect of ACI-35.030 on cognition and Tau pathology in approximately 500 participants with preclinical Alzheimer’s disease (AD)
- Anti-pTau active immunotherapy being designed to potentially prevent or reduce cognitive decline could address need of over 315 million people globally1 with preclinical AD
- AC Immune to receive approximately CHF 40 million in total milestone payments under terms of the licensing agreement, following trial initiation and enrollment milestone
Lausanne, Switzerland, December 15, 2023 – AC Immune SA (NASDAQ: ACIU), a clinical-stage biopharmaceutical company pioneering precision medicine for neurodegenerative diseases, today announced that its development partner has programmed the launch of a Phase 2b clinical study to evaluate ACI-35.030 (JNJ-64042056) in patients with preclinical Alzheimer’s disease (AD), those individuals not yet showing symptoms. ACI-35.030 is an investigational targeted active immunotherapy, selective for pathological phosphorylated Tau (pTau). Studies have shown that pTau correlates with AD progression and the trial aims to show that ACI-35.030 can prevent or slow down the progression of tau pathology and onset of clinical symptoms.
Under the terms of the licensing agreement with Janssen Pharmaceuticals, Inc. (Janssen), a Johnson & Johnson company, AC Immune will now receive a milestone payment of CHF 15 million and will receive another milestone payment of CHF 25 million related to achieving a non-disclosed enrollment target. The partnership with Janssen aims to develop and commercialize therapeutic anti-Tau active immunotherapies for the treatment of AD and potentially other Tauopathies.
Dr. Andrea Pfeifer, CEO of AC Immune SA, commented: “In the recently completed Phase 1b/2a trial, data showed that ACI-35.030 was able to activate patients’ immune systems with a robust polyclonal antibody response against phosphorylated Tau and its neurotoxic aggregated form, which is believed to contribute to the pathology and progression of Alzheimer’s disease. Our partner’s decision to move forward with this robust clinical trial shows that treatment with this active immunotherapy so early in the disease process that individuals are not yet showing symptoms, holds tremendous promise to slow or possibly even prevent progression to symptomatic AD.”
The Phase 2b ReTain trial is a potentially registration-enabling trial and is a randomized, multicenter, double-blind, placebo-controlled clinical study in participants with preclinical AD to assess the clinical effect of active immunization with ACI-35.030. It is designed to test the hypothesis that ACI-35.030 has a disease-modifying effect that can delay or prevent the onset of cognitive impairment or other clinical symptoms in individuals with preclinical AD through inhibition of seeding and spreading of pathological Tau.
- Approximately 500 participants with preclinical AD (cognitively normal, amyloid positive, Tau positive) will be randomized in a 1:1 ratio to a single dose level of ACI-35.030 or placebo and administered as intramuscular injections for a maximum of 4 years.
- The primary endpoint will measure cognitive decline as assessed by the Preclinical AD Cognitive Composite 5 (PACC-5) score, which combines tests that evaluate episodic memory, timed executive function, and global cognition. It is sensitive enough to detect early changes in cognitive function, even before the first clinical signs of mild cognitive impairment (MCI) are apparent2.
- The key secondary efficacy endpoint will assess the effect of ACI-35.030 on the propagation and/or accumulation of Tau pathology compared with placebo, as measured by Tau PET imaging in the Tau Naïve Composite region of interest. PET imaging for pathological Tau will be performed at baseline and annually for 4 years. This endpoint may be sufficient for a Biologics License Application (BLA) filing seeking accelerated approval from the U.S. Food & Drug Administration (FDA), with the primary endpoint serving as the basis for a traditional approval.
- Gustavsson et al. Alzheimer’s and Dement. 2023 19:658-670. https://doi.org/10.1002/alz.12694
- Donohue MC, Sperling RA, Salmon DP, Rentz DM, Raman R, Thomas RG, Weiner M, Aisen PS, Australian Imaging, Biomarkers, and Lifestyle Flagship Study of Ageing, Alzheimer’s Disease Neuroimaging Initiative, and Alzheimer’s Disease Cooperative Study (2014) The preclinical Alzheimer cognitive composite: measuring amyloid-related decline. JAMA Neurol 71(8):961–970. https://doi.org/10.1001/jamaneurol.2014.803
- Gustavsson et al. Alzheimer’s and Dement. 2023 19:658-670. https://doi.org/10.1002/alz.12694
About ACI-35.030 (JNJ-64042056)
ACI-35.030 (JNJ-64042056) is an investigational active immunotherapy designed using AC Immune’s SupraAntigen® platform. Its liposomal formulation incorporates a conformationally-constrained, membrane bound target peptide antigen, phosphorylated Tau (pTau), in addition to adjuvants and non-Tau T-helper peptides. Immunization with ACI-35.030 has been shown in a recent Phase 1b/2a clinical trial to rapidly elicit antibodies after the first injection against extracellular pathological pTau in 100% of elderly patients with Alzheimer’s disease. Importantly, the antibody response was sustained, boostable, and focused on pathological pTau, including enriched paired helical filaments (ePHF). Aggregation of pTau leads to the formation of neurotoxic ePHF and Tau tangles. Antibodies against non-phosphorylated Tau diminished over time. To date, no safety or tolerability issues have been observed following ACI-35.030 immunization.
About the SupraAntigen® platform
AC Immune’s clinically validated SupraAntigen® platform uses proprietary liposomes to rapidly generate novel product candidates for active immunotherapy as well as best-in-class monoclonal antibodies for passive immunization against key neurodegenerative disease targets. Antibodies generated by the platform are highly specific for the pathological conformations of misfolded proteins and have shown strong safety. The SupraAntigen® platform has successfully generated two active immunotherapies and two antibody candidates that have been validated in clinical studies and has led to multiple global partnerships with world-leading pharmaceutical companies. In addition to targeting Amyloid-beta and Tau, AC Immune has generated conformation-specific antibodies against emerging neurodegenerative disease targets including alpha-synuclein, TDP-43, and the NLRP3 inflammasome pathway.
About AC Immune SA
AC Immune SA is a clinical-stage biopharmaceutical company that aims to become a global leader in precision medicine for neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and NeuroOrphan indications driven by misfolded proteins. The Company’s two clinically validated technology platforms, SupraAntigen® and Morphomer®, fuel its broad and diversified pipeline of first- and best-in-class assets, which currently features ten therapeutic and three diagnostic candidates, five of which are currently in Phase 2 clinical trials and one of which is in Phase 3. AC Immune has a strong track record of securing strategic partnerships with leading global pharmaceutical companies including Genentech, a member of the Roche Group, Eli Lilly and Company, and others, resulting in substantial non-dilutive funding to advance its proprietary programs and >$3 billion in potential milestone payments.
SupraAntigen® is a registered trademark of AC Immune SA in the following territories: AU, EU, CH, GB, JP, RU, SG and USA. Morphomer® is a registered trademark of AC Immune SA in CN, CH, GB, JP, KR, NO and RU.
The information on our website and any other websites referenced herein is expressly not incorporated by reference into, and does not constitute a part of, this press release.
Source: AC Immune SA
AC Immune Alzheimer's drug advanced into Phase 2b testing
Dec. 15, 2023 1:48 PM ET
By: Val Brickates Kennedy, SA News Editor
AC Immune (NASDAQ:ACIU) said that development partner Johnson & Johnson (JNJ) has advanced its drug candidate ACI-35.030 into Phase 2b testing for Alzheimer’s disease.
The study will evaluate the drug in approximately 500 people with preclinical Alzheimer’s, meaning those who have tested positive for amyloid and Tau protein accumulations but are cognitively normal.
https://seekingalpha.com/news/4046963-ac-immune-alzheimers-drug-advanced-into-phase-2b-testing
SKYCLARYS® (omaveloxolone)
ANAVEX®2-73 (BLARCAMESINE)
PulseSelect™ Pulsed Field Ablation System
CHMP Issues Positive Opinion for Biogen’s SKYCLARYS® (omaveloxolone), the First Therapy to Treat Friedreich’s Ataxia, a Rare Neurodegenerative Disease
DECEMBER 15, 2023 • NEWS RELEASE
- Friedreich’s ataxia is a genetic, debilitating and life-shortening neuromuscular disease1
- Milestone highlights Biogen’s growing portfolio in rare diseases and focus on addressing unmet needs of patients living with neuromuscular diseases
CAMBRIDGE, Mass., Dec. 15, 2023 (GLOBE NEWSWIRE) -- Biogen Inc. (Nasdaq: BIIB) announced the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended marketing authorization for SKYCLARYS® (omaveloxolone) for the treatment of Friedreich’s ataxia (FA) in people aged 16 years and older. If approved by the European Commission (EC), SKYCLARYS will be the first treatment authorized within the European Union for this rare, genetic, progressive neuromuscular disease.1 If approved, omaveloxolone will be marketed as SKYCLARYS.
“The CHMP’s recommendation for SKYCLARYS is a significant milestone toward our goal of bringing a treatment that slows the progression of FA to the patient community in the region,” said Priya Singhal, M.D., M.P.H., Head of Development at Biogen. “Upon approval of SKYCLARYS, we look forward to leveraging Biogen’s rare disease expertise and capabilities to bring this groundbreaking treatment to patients in the European Union living with this debilitating disease.”
The CHMP’s positive opinion for SKYCLARYS is based on efficacy and safety data from the placebo-controlled MOXIe Part 2 trial. At the end of the 48-week MOXIe Part 2 study, patients who received SKYCLARYS had less physical impairment compared to patients who received placebo, as measured by the modified Friedreich Ataxia Rating Scale (mFARS). Improvements across subscales of mFARS, including upright stability, lower limb coordination, ability to swallow and upper limb coordination, were also observed in patients treated with SKYCLARYS compared to placebo. Additional data was provided from a post hoc, propensity-matched analysis in which patients treated with SKYCLARYS in MOXIe (Parts 1 and 2) had lower mFARS score at 3 years, as compared to a matched natural history group. The most common side effects are increased liver enzymes, decreased weight and appetite, nausea, vomiting, diarrhea, headache, fatigue, oropharyngeal and back pain, muscle spasms, and influenza.
The CHMP’s recommendation for SKYCLARYS will now be reviewed by the EC for marketing authorization in the European Union with a final decision expected in the first quarter of 2024. The U.S. Food and Drug Administration (FDA) approved omaveloxolone, marketed as SKYCLARYS®, in February 2023 for the treatment of Friedreich’s ataxia in adults and adolescents aged 16 years and older.
About SKYCLARYS® (omaveloxolone)
SKYCLARYS® (omaveloxolone) is an oral, once-daily medication indicated for the treatment of Friedreich’s ataxia (FA) in adults and adolescents aged 16 years and older in the U.S. SKYCLARYS has received Orphan Drug, Fast Track, and Rare Pediatric Disease Designations from the U.S. Food and Drug Administration. The European Commission has granted Orphan Drug designation in Europe to omaveloxolone for the treatment of FA.
About Friedreich's Ataxia
Friedreich’s ataxia (FA) is a rare, genetic, life-shortening, debilitating, and degenerative neuromuscular disorder. It is the most common inherited ataxia.2,3 Early symptoms of FA, such as progressive loss of coordination, muscle weakness and fatigue, typically appear in childhood and can overlap with other diseases.4 Most people living with FA will need to use a wheelchair within 10-20 years of their first symptoms.2 The reported average age of death for FA patients is just 37 years old, although with appropriate and targeted care, individuals may live many years after confinement to a wheelchair.5-7
About Biogen
Founded in 1978, Biogen is a leading global biotechnology company that has pioneered multiple breakthrough innovations including a broad portfolio of medicines to treat multiple sclerosis, the first approved treatment for spinal muscular atrophy, two co-developed treatments to address a defining pathology of Alzheimer’s disease, the first treatment to target a genetic form of ALS, the first oral treatment approved for postpartum depression, and the first approved treatment for Friedreich’s ataxia. Biogen is advancing a pipeline of potential novel therapies across neurology, neuropsychiatry, specialized immunology and rare diseases and remains acutely focused on its purpose of serving humanity through science while advancing a healthier, more sustainable and equitable world.
We routinely post information that may be important to investors on our website at www.biogen.com. Follow us on social media - Facebook, LinkedIn, X, YouTube.
EU regulators issue positive opinion for Biogen Friedreich's Ataxia drug
Dec. 15, 2023 12:26 PM ET
By: Val Brickates Kennedy, SA News Editor
Biogen (NASDAQ:BIIB) said that EU regulators have issued a positive opinion for approval of its drug omaveloxolone, also known as Skyclarys, for the treatment of Friedreich’s Ataxia, a rare neuromuscular disease.
If approved, Skyclarys would be the first authorized treatment for the disease in the EU, Biogen said.
The company expects the European Commission to decide on whether to approve the product in Q1 2024. The drug was approved by the FDA in February.
PulseSelect™ Pulsed Field Ablation System
mRNA-4157 (V940) in Combination with KEYTRUDA® (pembrolizumab)
PulseSelect™ Pulsed Field Ablation System
DEC 13, 2023
Medtronic creates history with FDA approval of its novel PulseSelect™ Pulsed Field Ablation System to treat atrial fibrillation
Safe, efficient, and effective treatment for both paroxysmal and persistent atrial fibrillation
DUBLIN, Dec. 13, 2023 /PRNewswire(opens new window)/ -- Medtronic plc (NYSE: MDT), a global leader in healthcare technology, today announced that the United States Food and Drug Administration (FDA) has approved the PulseSelect Pulsed Field Ablation (PFA) System for the treatment of both paroxysmal and persistent atrial fibrillation (AF). This is the first PFA technology to receive FDA approval and follows the recent European CE (Conformité Européenne) Mark of the PulseSelect PFA system in November.
- View File Download FileMedtronic PulseSelect
- View File Download FileMedtronic PulseSelect PFA System
"Launching the first FDA-approved PFA technology is not just a milestone; the PulseSelect PFA system is setting a new standard in safety for AF ablation with excellent efficacy and efficiency1. It's a major step towards fulfilling our vision of providing disruptive electrophysiology solutions for patients," said Rebecca Seidel, SVP and President of the Cardiac Ablation Solutions business, which is part of the Cardiovascular Portfolio. "The PulseSelect PFA system, together with the CE Marked Affera™ mapping and ablation system and our strong Cryo platform, enables us to provide a broad portfolio of solutions to clinicians and their patients, all developed with years of research and supported by compelling scientific evidence."
The PulseSelect PFA system was engineered with differentiated safety features and provides rapid, effective pulmonary vein isolation (PVI) through consistent and predictable energy delivery and catheter maneuverability. The system is designed to enable a seamless transition to PFA in a clinician's preferred workflow2. The PulseSelect PFA system's safety, efficacy, and efficiency is supported by the PULSED AF study, which showed a 0.7% safety event rate and clinical success rates of 80% in both paroxysmal and persistent AF patients1.
"The PulseSelect PFA system ushers the EP community to a new era of safe, effective, and efficient AF ablation that overcomes many challenges in our current practice," said Dr. Amin Al-Ahmad, clinical cardiac electrophysiologist at St. David's Medical Center in Austin, TX and one of 67 global operators in the PULSED AF trial. "In my clinical experience with the catheter, it was designed for AF ablation procedures. The learning curve in using the catheter and system is short, and the catheter enables the operator to deliver fast and controlled pulsed field energy for AF ablation."
The PulseSelect PFA system also includes the following:
- Designed as a plug-and-play system, PulseSelect can be used with any mapping system or with just fluoroscopy2.
- Built-in safety features such as a phrenic nerve test pulse, a non-therapeutic low voltage pulse that provides a preemptive assessment of catheter proximity to the phrenic nerve prior to delivering a therapeutic application.
- Fixed spacing for the nine-electrode catheter, which produces a predictable and consistent electric field for contiguous ablation2. In addition to ablation, the nine electrodes can also be used for pacing and sensing.
- The small, 9Fr bidirectional catheter enhances maneuverability and access to various anatomical structures and is compatible with a 10Fr sheath, including the custom bidirectional FlexCath Contour™ sheath.
"We are thrilled to see the continuous innovation of our legacy Cryoablation portfolio alongside the approval of the PulseSelect PFA system in the U.S.," said Khaldoun Tarakji, MD MPH, Chief Medical Officer of the Cardiac Ablation Solutions business at Medtronic. "Every patient deserves the best care. What motivates all of us at Medtronic is the privilege of serving patients by empowering electrophysiologists globally with the safest and most effective ablation technologies that seamlessly integrate with their workflows and enable them to tailor therapy based on their patients' needs."
The PulseSelect PFA system is also the first FDA Breakthrough-designated PFA technology to be approved. The designation is intended to help patients gain more timely access to medical devices that have the potential to make a significant impact in the diagnosis or treatment of life-threatening conditions.
Commercialization of the PulseSelect PFA system will start in early 2024.
About Atrial Fibrillation and Pulsed Field Ablation
AF is one of the most common and undertreated heart rhythm disorders, affecting more than 60 million people worldwide3. AF is a progressive disease, meaning it can become worse over time and can increase the risk of serious complications including heart failure, stroke and increased risk of death.4-7 Current ablation technologies rely on thermal effects to target cardiac tissue and risk damage to additional collateral structures in the heart. PFA is a breakthrough ablation technology that uses pulsed electric fields to efficiently isolate the pulmonary veins for the treatment of AF. Because the mechanism of cell death is non-thermal, the risk of collateral structure damage is potentially lower.
About Medtronic
Bold thinking. Bolder actions. We are Medtronic. Medtronic plc, headquartered in Dublin, Ireland, is the leading global healthcare technology company that boldly attacks the most challenging health problems facing humanity by searching out and finding solutions. Our Mission — to alleviate pain, restore health, and extend life — unites a global team of 95,000+ passionate people across 150 countries. Our technologies and therapies treat 70 health conditions and include cardiac devices, surgical robotics, insulin pumps, surgical tools, patient monitoring systems, and more. Powered by our diverse knowledge, insatiable curiosity, and desire to help all those who need it, we deliver innovative technologies that transform the lives of two people every second, every hour, every day. Expect more from us as we empower insight-driven care, experiences that put people first, and better outcomes for our world. In everything we do, we are engineering the extraordinary. For more information on Medtronic (NYSE:MDT), visit www.Medtronic.com(opens new window), and follow @Medtronic on LinkedIn.
SOURCE Medtronic plc
Medtronic heart device for atrial fibrillation cleared in U.S.
Dec. 14, 2023 6:53 AM ET
By: Dulan Lokuwithana, SA News Editor1 Comment
The U.S. Food and Drug Administration (FDA) has greenlighted Medtronic’s (NYSE:MDT) PulseSelect Pulsed Field Ablation (PFA) System targeted at a heart rhythm disorder called atrial fibrillation (AF).
https://www.medtronic.com/us-en/index.html
https://www.medtronic.com/us-en/c/cardiac-rhythm/pulsed-field-ablation.html
mRNA-4157 (V940) in Combination with KEYTRUDA® (pembrolizumab)
mRNA-4157 (V940) in Combination with KEYTRUDA® (pembrolizumab)
mRNA-4157 (V940) in Combination with KEYTRUDA® (pembrolizumab)
Moderna and Merck Announce mRNA-4157 (V940) in Combination with KEYTRUDA® (pembrolizumab) Demonstrated Continued Improvement in Recurrence-Free Survival and Distant Metastasis-Free Survival in Patients with High-Risk Stage III/IV Melanoma Following Complete Resection Versus KEYTRUDA At Three Years
December 14, 2023 6:30 am ET
At a median planned follow-up of approximately three years, mRNA-4157 (V940) in combination with KEYTRUDA reduced the risk of recurrence or death by 49% (HR=0.510 [95% CI, 0.288-0.906]; one-sided nominal p=0.0095) and the risk of distant metastasis or death by 62% (HR=0.384 [95% CI, 0.172-0.858]; one-sided nominal p= 0.0077) compared to KEYTRUDA alone in stage III/IV melanoma patients with high risk of recurrence following complete resection
Data builds on the primary analysis reported at AACR and ASCO in 2023, which showed that mRNA-4157 (V940) in combination with KEYTRUDA reduced the risk of recurrence or death by 44% and reduced the risk of distant metastasis or death by 65% at a median planned follow-up of approximately two years
Companies have initiated Phase 3 studies in the adjuvant setting in patients with high-risk melanoma and non-small cell lung cancer and plan to rapidly expand to additional tumor types
CAMBRIDGE, MA and RAHWAY, NJ / ACCESSWIRE / December 14, 2023/ Moderna, Inc. (NASDAQ:MRNA) and Merck (NYSE:MRK), known as MSD outside of the United States and Canada, today announced follow-up data from the Phase 2b randomized KEYNOTE-942/mRNA-4157-P201 study, a clinical trial evaluating mRNA-4157 (V940), an investigational individualized neoantigen therapy (INT), in combination with KEYTRUDA, Merck’s anti-PD-1 therapy, in patients with resected high-risk melanoma (stage III/IV) following complete resection. In this planned analysis occurring with a median follow-up of approximately three years, adjuvant treatment with mRNA-4157 (V940) in combination with KEYTRUDA continued to demonstrate a clinically meaningful improvement in recurrence-free survival (RFS), reducing the risk of recurrence or death by 49% (HR=0.510 [95% CI, 0.288-0.906]; one-sided nominal p=0.0095) compared with KEYTRUDA alone. mRNA-4157 (V940) in combination with KEYTRUDA also continued to demonstrate a meaningful improvement in distant metastasis-free survival (DMFS), compared with KEYTRUDA alone, reducing the risk of developing distant metastasis or death by 62% (HR=0.384 [95% CI, 0.172-0.858]; one-sided nominal p= 0.0077).
“As we continue to follow participants in the KEYNOTE-942/mRNA-4157-P201 study, we are excited to see such a robust clinical benefit with mRNA-4157 (V940) as adjuvant treatment in combination with KEYTRUDA in people with resected high-risk melanoma,” said Kyle Holen, M.D., Moderna’s Senior Vice President and Head of Development, Therapeutics and Oncology. “These data add another positive analysis to the multiple endpoints and subgroups previously assessed in this study. Importantly for this technology, the KEYNOTE-942/mRNA-4157-P201 study was the first demonstration of efficacy for an investigational mRNA cancer treatment in a randomized clinical trial and the first combination therapy to show a significant benefit over KEYTRUDA alone in adjuvant melanoma. We look forward to sharing these data with people impacted by this disease and the broader scientific community.”
“We are committed to driving research forward for innovative modalities in earlier stages of cancer, where we can make the most meaningful impact for patients, by combining Merck’s expertise in immuno-oncology with Moderna’s innovative mRNA technology,” said Dr. Marjorie Green, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories. “We are pleased to see the results from these planned analyses on recurrence-free survival for V940 (mRNA-4157), and look forward to working with Moderna in expanding our clinical development program for the individualized neoantigen therapy.”
Adverse events observed with mRNA-4157 (V940) in KEYNOTE-942 remain consistent with those previously reported. At a median planned follow-up of approximately three years, the number of patients reporting treatment-related Grade ≥ 3 adverse events were similar between the arms (25% for mRNA-4157 (V940) in combination with KEYTRUDA vs 20% for KEYTRUDA alone). The most common adverse events of any grade attributed to mRNA-4157 (V940) were fatigue (60.6%), injection site pain (56.7%), and chills (49%).
Based on data from the Phase 2b KEYNOTE-942/mRNA-4157-P201 study, the U.S. Food and Drug Administration and European Medicines Agency granted Breakthrough Therapy Designation and the Priority Medicines (PRIME) scheme, respectively, for mRNA-4157 (V940) in combination with KEYTRUDA for the adjuvant treatment of patients with high-risk melanoma. The companies previously presented data on the study’s primary analysis with a median planned follow-up of approximately two years. The study’s primary endpoint, RFS, was presented in April 2023 at the American Association for Cancer Research (AACR) Annual Meeting, and the study’s secondary endpoint, DMFS, data was presented in June 2023 at the American Society of Clinical Oncology (ASCO) Annual Meeting. Data from the primary analysis has been submitted for publication in a peer-reviewed journal.
In July, Moderna and Merck announced the initiation of a pivotal Phase 3 randomized INTerpath-001 (V940-001) clinical trial evaluating mRNA-4157 (V940) in combination with KEYTRUDA, as an adjuvant treatment in patients with resected high-risk (Stage IIB-IV) melanoma. Global recruitment in INTerpath-001 has begun NCT05933577). The companies have also initiated a Phase 3 trial in non-small cell lung cancer that is actively enrolling globally (INTerpath-002,NCT06077760) and plan to expand the development program to additional tumor types.
About mRNA-4157 (V940)
mRNA-4157 (V940) is a novel investigational messenger RNA (mRNA)-based individualized neoantigen therapy (INT) consisting of a synthetic mRNA coding for up to 34 neoantigens that is designed and produced based on the unique mutational signature of the DNA sequence of the patient’s tumor. Upon administration into the body, the algorithmically derived and RNA-encoded neoantigen sequences are endogenously translated and undergo natural cellular antigen processing and presentation, a key step in adaptive immunity.
Individualized neoantigen therapies are designed to train and activate an antitumor immune response by generating specific T-cell responses based on the unique mutational signature of a patient’s tumor. KEYTRUDA is an immunotherapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. As previouslyannounced from the Phase 2b KEYNOTE-942/mRNA-4157-P201 trial evaluating patients with high-risk stage III/IV melanoma, combining mRNA-4157 (V940) with KEYTRUDA may provide a meaningful benefit over KEYTRUDA alone.
About KEYNOTE-942/mRNA-4157-P201 (NCT03897881)
KEYNOTE-942 is an ongoing randomized, open-label Phase 2b trial that enrolled 157 patients with high-risk stage III/IV melanoma. Following complete surgical resection, patients were assigned 2:1 (stratified by stage) to receive mRNA-4157 (V940) (1 mg every three weeks for nine doses) and KEYTRUDA (200 mg every three weeks up to 18 cycles [for approximately one year]) versus KEYTRUDA alone for approximately one year until disease recurrence or unacceptable toxicity. The primary endpoint is RFS, defined as the time from first dose of KEYTRUDA until the date of first recurrence (local, regional, or distant metastasis), a new primary melanoma, or death from any cause in the intention-to-treat population. Secondary endpoints include distant metastasis-free survival and safety, and exploratory endpoints include distribution of TMB expression in baseline tumor samples across study arms and their association with the primary RFS endpoint.
Key eligibility criteria for the trial included: patients with resectable cutaneous melanoma metastatic to a lymph node and at high risk of recurrence, patients with complete resection within 13 weeks prior to the first dose of KEYTRUDA, patients were disease free at study entry (after surgery) with no loco-regional relapse or distant metastasis and no clinical evidence of brain metastases, patients had a formalin fixed paraffin embedded (FFPE) tumor sample available suitable for sequencing, Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 and patients with normal organ and marrow function reported at screening.
About melanoma
Melanoma, the most serious form of skin cancer, is characterized by the uncontrolled growth of pigment-producing cells. The rates of melanoma have been rising over the past few decades, with nearly 325,000 new cases diagnosed worldwide in 2020. In the U.S., skin cancer is one of the most common types of cancer diagnosed, and melanoma accounts for a large majority of skin cancer deaths. It is estimated there will be nearly 100,000 new cases of melanoma diagnosed and almost 8,000 deaths resulting from the disease in the U.S. in 2023.
About KEYTRUDA® (pembrolizumab) injection, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.
KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.
Additional Selected KEYTRUDA Indications in the U.S.
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.
KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.
Non-Small Cell Lung Cancer
KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:
- stage III where patients are not candidates for surgical resection or definitive chemoradiation, or
- metastatic.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.
KEYTRUDA is indicated for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC.
Head and Neck Squamous Cell Cancer
KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.
Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).
KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.
Primary Mediastinal Large B-Cell Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy.
KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.
Microsatellite Instability-High or Mismatch Repair Deficient Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic MSI-H or dMMR solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.
Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC) as determined by an FDA-approved test.
Gastric Cancer
KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumor express PD-L1 (CPS ≥1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval of this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
KEYTRUDA, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Esophageal Cancer
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:
- in combination with platinum- and fluoropyrimidine-based chemotherapy, or
- as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
Cervical Cancer
KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
Hepatocellular Carcinoma
KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Biliary Tract Cancer
KEYTRUDA, in combination with gemcitabine and cisplatin, is indicated for the treatment of patients with locally advanced unresectable or metastatic biliary tract cancer (BTC).
Merkel Cell Carcinoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC).
Renal Cell Carcinoma
KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.
Endometrial Carcinoma
KEYTRUDA, as a single agent, is indicated for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Tumor Mutational Burden-High Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.
Cutaneous Squamous Cell Carcinoma
KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.
Triple-Negative Breast Cancer
KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
Merck’s focus on cancer
Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.
About Merck’s research in melanoma
Merck is committed to delivering meaningful advances for patients with melanoma and to continuing research in skin cancers through a broad clinical development program across investigational and approved medicines. KEYTRUDA has been established as an important treatment option for the adjuvant treatment of patients with resected Stage IIB, IIC, or III melanoma based on results of KEYNOTE-054 and KEYNOTE-716. KEYTRUDA is also approved worldwide for the treatment of patients with unresectable or metastatic melanoma.
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on
X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.
About Moderna
Moderna is a leader in the creation of the field of mRNA medicine. Through the advancement of mRNA technology, Moderna is reimagining how medicines are made and transforming how we treat and prevent disease for everyone. By working at the intersection of science, technology and health for more than a decade, the company has developed medicines at unprecedented speed and efficiency, including one of the earliest and most effective COVID-19 vaccines.
Moderna’s mRNA platform has enabled the development of therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases and autoimmune diseases. With a unique culture and a global team driven by the Moderna values and mindsets to responsibly change the future of human health, Moderna strives to deliver the greatest possible impact to people through mRNA medicines. For more information about Moderna, please visit modernatx.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.
Moderna’s focus on cancer
At Moderna, we are delivering on the promise of mRNA science to create a new generation of transformative medicines for patients. We are relentlessly working to grow our cancer therapeutic modality by discovering mRNA medicines that harness the body’s immune system to identify and kill cancer cells in the same way the immune system identifies and targets infections. One example of a promising oncology candidate is the creation of individualized, mRNA-based cancer therapies. We also continue to strengthen our portfolio through strategic collaborations that increase our potential to improve treatment options for patients with cancer.
Please see Prescribing Information for KEYTRUDA (pembrolizumab) at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf .
Moderna, Merck post three-year data for mRNA-based skin cancer therapy
Dec. 14, 2023 7:26 AM ET
Moderna, Inc. (MRNA) Stock, MRK Stock
By: Dulan Lokuwithana, SA News Editor1 Comment
Moderna (NASDAQ:MRNA) and Merck (NYSE:MRK) said on Thursday that an mRNA-based skin cancer regimen tested against the pharma giant’s blockbuster immunotherapy Keytruda cut the risk of disease recurrence or death by 49% at a follow-up of approximately three years.
https://seekingalpha.com/news/4046284-moderna-merck-update-data-mrna-based-skin-cancer-drug
Tarlatamab
mRNA-4157 (V940) in Combination with KEYTRUDA® (pembrolizumab)
mRNA-4157 (V940) in Combination with KEYTRUDA® (pembrolizumab)
FDA GRANTS PRIORITY REVIEW TO AMGEN'S TARLATAMAB APPLICATION FOR ADVANCED SMALL CELL LUNG CANCER
Currently There are no Approved Therapeutic Options for Third-Line Treatment of Advanced SCLC1
If Approved, Tarlatamab Would be the First BiTE® Therapy for a Major Solid Tumor
FDA Target Action Date is June 12, 2024
THOUSAND OAKS, Calif., Dec. 13, 2023 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced that the U.S. Food and Drug Administration (FDA) has accepted and granted Priority Review for the Company's Biologics License Application (BLA) for tarlatamab.
Tarlatamab is a potential first-in-class, investigational delta-like ligand 3 (DLL3) targeting Bispecific T-cell Engager (BiTE®) therapy for the treatment of adult patients with advanced small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy.
"The FDA's Priority Review designation for this application underscores the urgency to provide new treatment options for patients with advanced SCLC who have progressed following treatment with platinum-based chemotherapy," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "While first-line treatments often show strong responses, patients can experience aggressive recurrences and long-term survival remains a challenge.2,3 Unfortunately, for patients who relapse, there are limited treatment options, emphasizing the importance of bringing new therapies to this patient population with advanced disease."
The FDA grants Priority Review to applications for medicines that offer, if approved, significant improvements over available options or may provide a treatment option where no adequate therapy currently exists. Based on the Priority Review designation, the Prescription Drug User Fee Action (PDUFA) date for tarlatamab is June 12, 2024.
The BLA is based on the Phase 2 results from the DeLLphi-301 clinical trial that studied patients with advanced SCLC with disease progression on or after platinum-based chemotherapy. Results from the study were recently featured as part of a late-breaking presentation during the 2023 European Society for Medical Oncology (ESMO) Congress and simultaneously published in the New England Journal of Medicine.4,5 The data presented demonstrated antitumor activity with a durable response and encouraging survival outcomes in previously treated SCLC. The safety profile was consistent with the Phase 1 trial.6
Tarlatamab is being investigated in multiple studies including DeLLphi-302, a Phase 1b study evaluating tarlatamab in combination with an anti-PD-1 therapy in second-line or later SCLC; DeLLphi-303, a Phase 1b study investigating tarlatamab in combination with standard of care therapies in first-line SCLC; DeLLphi-304, a randomized Phase 3 trial comparing tarlatamab monotherapy with standard of care chemotherapy in second-line treatment of SCLC that is enrolling patients; DeLLphi-306, a recently-initiated, randomized Phase 3 trial of tarlatamab following chemoradiotherapy in earlier settings of SCLC; and DeLLpro-300, a Phase 1b study of tarlatamab in de novo or treatment-emergent neuroendocrine prostate cancer.7 Amgen also plans to initiate an additional Phase 3 study of tarlatamab in first-line treatment of SCLC.
In October, tarlatamab was granted Breakthrough Therapy Designation by the FDA. The application is being reviewed by the FDA under the Project Orbis framework and Real Time Oncology Review (RTOR). Project Orbis is an initiative from the FDA Oncology Center of Excellence that provides a framework for concurrent submission of oncology products among certain countries.
About Small Cell Lung Cancer (SCLC)
SCLC is one of the most aggressive and devastating solid tumors with a median survival of approximately 12 months following initial therapy and a 7% five-year relative survival rate when all stages are combined.8-10 Of the more than 2.2 million patients diagnosed with lung cancer worldwide each year, SCLC comprises 15% of cases.11,1 Despite initial high response rates to platinum-based first-line chemotherapy, patients quickly relapse and require subsequent treatment options.1
About Tarlatamab
Tarlatamab is an investigational, targeted therapy engineered by Amgen researchers that brings a patient's own T cells in close proximity to SCLC cells by binding both CD3 on T cells and DLL3 on SCLC cells. This results in the formation of a cytolytic synapse with lysis of the cancer cell.12,13 DLL3 represents an exciting therapeutic target for patients with SCLC, as approximately 85% to 96% of patients have expression of DLL3 on the cell surface of SCLC cells, with minimal expression in normal cells.6,14-16
About Tarlatamab Clinical Trials
Amgen's robust tarlatamab development program includes the DeLLphi clinical trials, which evaluate tarlatamab as a monotherapy and as part of combination regimens in earlier stages of SCLC, and DeLLpro clinical trials, which evaluate tarlatamab in neuroendocrine prostate cancer.
In the Phase 1 DeLLphi-300 study, tarlatamab showed responses in 23.4% of patients with encouraging durability in heavily pre-treated patients with SCLC. In the Phase 2 DeLLphi-301 study, tarlatamab administered as 10 mg dose every two weeks demonstrated an objective response rate of 40% in patients with advanced SCLC who had failed two or more prior lines of treatment. In both DeLLphi-300 and DeLLphi-301, the most frequent treatment-related adverse events were cytokine release syndrome (CRS; 52-55%), pyrexia (31-37%), and dysgeusia (22-26%), which were primarily grade 1-2. Treatment discontinuation for adverse events occurred in 3-4% of patients in the two trials.5,6
For more information, please visit www.tarlatamabclinicaltrials.com.
About BiTE® Technology
Bispecific T-cell Engager (BiTE®) technology is a targeted immuno-oncology platform that is designed to engage patient's own T cells to any tumor-specific antigen, activating the cytotoxic potential of T cells to eliminate detectable cancer. The BiTE® immuno-oncology platform has the potential to treat different tumor types through tumor-specific antigens. The BiTE® platform has a goal of leading to off-the-shelf solutions, which have the potential to make innovative T cell treatment available to all providers when their patients need it. Amgen is advancing multiple BiTE® molecules across a broad range of hematologic malignancies and solid tumors, further investigating BiTE® technology with the goal of enhancing patient experience and therapeutic potential. To learn more about BiTE® technology, visit https://www.amgenoncology.com/bite-platform.html.
About Amgen
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.
Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average and is also part of the Nasdaq-100 index. In 2023, Amgen was named one of "America's Greatest Workplaces" by Newsweek, one of "America's Climate Leaders" by USA Today and one of the "World's Best Companies" by TIME.
For more information, visit Amgen.com and follow us on X (formerly known as Twitter), LinkedIn, Instagram, TikTok, YouTube and Threads.
View original content to download multimedia:https://www.prnewswire.com/news-releases/fda-grants-priority-review-to-amgens-tarlatamab-application-for-advanced-small-cell-lung-cancer-302014639.html
SOURCE Amgen
Amgen gets FDA priority review for small cell lung cancer drug
Dec. 13, 2023 4:41 PM ET
By: Val Brickates Kennedy, SA News Editor
Amgen (NASDAQ:AMGN) said the FDA has accepted and granted priority review for the market application of its drug tarlatamab as a treatment for advanced small cell lung cancer.
https://seekingalpha.com/news/4046189-amgen-gets-fda-priority-review-for-small-cell-lung-cancer-drug
biotecHOPE™ 2023
Avutometinib and Defactinib Combination
Avutometinib and Defactinib Combination
Avutometinib and Defactinib Combination
DECEMBER 13, 2023 AT 7:00 AM EST
Verastem Oncology Announces Initiation of a Confirmatory Phase 3 Trial of Avutometinib and Defactinib in Recurrent Low-Grade Serous Ovarian Cancer
RAMP 301 Is Evaluating the Combination of Avutometinib and Defactinib vs Investigator’s Choice of Therapy
Reported Data from Part A of RAMP 201 Trial Show an Objective Response Rate of 45%, and Manageable Safety and Tolerability Profile with the Combination
Company Intends to Submit an Accelerated Approval New Drug Application to the U.S. Food and Drug Administration for the Combination Based on Breakthrough Therapy Designation and Mature Data from RAMP 201 and FRAME Trials
BOSTON--(BUSINESS WIRE)--Dec. 13, 2023-- Verastem Oncology (Nasdaq: VSTM) (the “Company”), a biopharmaceutical company committed to advancing new medicines for patients with cancer, announced today that it has initiated its international confirmatory Phase 3 RAMP 301 trial (GOG-3097; ENGOT-ov81/NCRI), evaluating the combination of avutometinib and defactinib versus standard chemotherapy or hormonal therapy for the treatment of recurrent low-grade serous ovarian cancer (LGSOC).
“Patients and treating physicians have advocated for more research and development in support of LGSOC. At Verastem Oncology, we are moving with urgency to offer a Phase 3 study specifically directed at this disease in an effort to address this need,” said Dan Paterson, President and Chief Executive Officer, Verastem Oncology. “Based on our Breakthrough Therapy Designation, the initiation and expected progress of this trial, along with the FRAME study data and mature RAMP 201 data, we plan to file for Accelerated Approval in the first half of next year, moving us a significant step closer to addressing the treatment needs of patients living with LGSOC.”
RAMP 301 is the confirmatory study required by the U.S. Food and Drug Administration (FDA) for the combination of avutometinib and defactinib to potentially receive full approval for the treatment of recurrent LGSOC. The Company intends to submit an Accelerated Approval New Drug Application (NDA) for the combination of avutometinib and defactinib based on mature data from the Company’s Phase 2 registration-directed RAMP 201 trial, together with the results of the investigator-initiated FRAME trial. The company recently reported results of Part A of the RAMP 201 trial, including confirmed objective response rates (ORR) by blinded independent central review of 45% with a response rate and safety profile consistent with previous studies.
“LGSOC has a unique molecular, histologic, and clinical profile that differs dramatically from the most common type of ovarian cancer. Response rates to standard of care treatments are disappointing, and there are still no FDA approved treatments specifically for LGSOC,” said Rachel Grisham, M.D., Section Head, Ovarian Cancer and Director, Gynecologic Medical Oncology at Memorial Sloan Kettering Cancer Center in Westchester, NY and RAMP 301 global lead investigator. “The combination of avutometinib and defactinib continues to show promise in recurrent LGSOC, and I am looking forward to leading this confirmatory trial with the goal of establishing a new standard of care for people with this rare form of ovarian cancer.”
According to Professor Susana Banerjee, MBBS, MA, PhD, FRCP, Consultant Medical Oncologist and Research Lead for the Gynaecology Unit at The Royal Marsden NHS Foundation Trust, Team Leader in Women's Cancers at The Institute of Cancer Research, London, and lead European investigator of the RAMP 301 trial, “Based on my experience treating women with LGSOC, it’s clear that we need better therapeutic options. I am pleased this Phase 3 trial, following the initial positive results from the Phase 2 RAMP 201 trial, is enrolling patients to potentially address the significant limitations we have seen with other available therapies.”
RAMP 301 (GOG-3097; ENGOT-ov81/NCRI) is an international collaboration between The GOG Foundation, Inc. (GOG) and the European Network of Gynaecological Oncological Trial groups (ENGOT) sponsored by Verastem Oncology. The trial is expected to enroll 270 patients who will be randomized to either the combination of avutometinib and defactinib or investigator’s choice chemotherapy (pegylated liposomal doxorubicin, paclitaxel, topotecan) or hormone therapy (letrozole, anastrozole). The primary endpoint is progression free survival (PFS) by Blinded Independent Central Review. Secondary endpoints include ORR, duration of response, disease control rate, safety and tolerability, patient reported outcomes, and overall survival. RAMP 301 is a global trial with enrollment open in the U.S. and planned enrollment in Canada, the United Kingdom, Europe, Australia, and Korea.
Dr. Grisham and Dr. Banerjee are paid consultants for Verastem Oncology.
About the Avutometinib and Defactinib Combination
Avutometinib is a RAF/MEK clamp that induces inactive complexes of MEK with ARAF, BRAF and CRAF potentially creating a more complete and durable anti-tumor response through maximal RAS pathway inhibition. In contrast to currently available MEK inhibitors, avutometinib blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows avutometinib to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other inhibitors. The U.S. Food and Drug Administration granted Breakthrough Therapy designation for the combination of Verastem Oncology’s investigational RAF/MEK clamp avutometinib, with defactinib, its FAK inhibitor, for the treatment of all patients with recurrent LGSOC regardless of KRAS status after one or more prior lines of therapy, including platinum-based chemotherapy.
Verastem Oncology is currently conducting clinical trials with its RAF/MEK clamp avutometinib in RAS pathway-driven tumors as part of its (Raf And Mek Program). RAMP 301 is a Phase 3 confirmatory trial evaluating the combination of avutometinib and defactinib versus standard chemotherapy or hormonal therapy for the treatment of recurrent LGSOC. RAMP 201 is a Phase 2 registration-directed trial of avutometinib in combination with defactinib in patients with recurrent LGSOC and has completed enrollment in the dose optimization and expansion phases and is enrolling for low-dose evaluation. Verastem Oncology has established clinical collaborations with Amgen and Mirati to evaluate LUMAKRAS™ (sotorasib) and KRAZATI™ (adagrasib) in combination with avutometinib in KRAS G12C mutant NSCLC as part of the RAMP 203 and RAMP 204 trials, respectively. Supported by the “Therapeutic Accelerator Award” Verastem Oncology received from PanCAN, the Company is conducting RAMP 205, a Phase 1b/2 clinical trial evaluating avutometinib and defactinib with gemcitabine/nab-paclitaxel in patients with front-line metastatic pancreatic cancer.
About Low-Grade Serous Ovarian Cancer (LGSOC)
LGSOC is a highly recurrent, chemotherapy-resistant cancer, associated with slow tumor growth and high mortality rate. Approximately 6,000 women in the U.S. and 80,000 worldwide are living with this disease. Mutations in the KRAS gene are present in 35-57% cases of LGSOC. LGSOC is most often diagnosed in women between the ages of 45-55 years and has a median survival of approximately ten years. The majority of patients experience severe pain and complications as the disease progresses. Chemotherapy is the standard of care for this disease, with limited treatment options currently available.
About Verastem Oncology
Verastem Oncology (Nasdaq: VSTM) is a development-stage biopharmaceutical company committed to the development and commercialization of new medicines to improve the lives of patients diagnosed with cancer. Our pipeline is focused on novel small molecule drugs that inhibit critical signaling pathways in cancer that promote cancer cell survival and tumor growth, including RAF/MEK inhibition and focal adhesion kinase (FAK) inhibition. For more information, please visit www.verastem.com.
About The GOG Foundation, Inc. (www.gog.org)
The GOG Foundation, Inc. is a not-for-profit organization with the purpose of promoting excellence in the quality and integrity of clinical and translational scientific research in the field of gynecologic malignancies. The GOG Foundation is committed to maintaining the highest standards in clinical trials development, execution, analysis, and distribution of results. The GOG Foundation is the only clinical trialist group in the United States that focuses its research on patients with pelvic malignancies, such as cancer of the ovary (including surface peritoneal malignancies), uterus (including endometrium, soft tissue sarcoma, and gestational trophoblastic neoplasia), cervix, and vulva. The GOG Foundation is multi-disciplinary in its approach to clinical trials, and includes gynecologic oncologists, medical oncologists, pathologists, radiation oncologists, oncology nurses, biostatisticians (including those with expertise in bioinformatics), basic scientists, quality of life experts, data managers, and administrative personnel.
About the GOG Partners Program
Supported by industry, GOG Partners program is structured to work directly with pharmaceutical organizations and operate clinical trials outside the National Cancer Institute (NCI) framework. The GOG Partners program promotes the mission of the GOG Foundation dedicated to transforming the standard of care in Gynecologic Oncology. By providing an alternative venue for patient accrual and site infrastructure support, GOG Partners has helped provide additional trials and opportunities for patients outside the national gynecologic clinical trials network.
About ENGOT (www.engot.esgo.org)
The European Network for Gynaecological Oncological Trial (ENGOT) groups is a research network of the European Society of Gynaecological Oncology and was founded in Berlin in October 2007. Currently, ENGOT consists of 21 trial groups from 31 European countries that perform cooperative clinical trials. ENGOT’s ultimate goal is to bring the best treatment to gynecological cancer patients through the best science and enabling every patient in every European country to access a clinical trial.
View source version on businesswire.com: https://www.businesswire.com/news/home/20231213489476/en/
Source: Verastem Oncology
Verastem starts Phase 3 study for ovarian cancer drug combination
Dec. 13, 2023 12:22 PM ET
By: Val Brickates Kennedy, SA News Editor
Verastem Oncology (NASDAQ:VSTM) said it has initiated a confirmatory Phase 3 study of its drug candidates avutometinib and defactinib in the treatment of recurrent low-grade serous ovarian cancer.
VX-548
Avutometinib and Defactinib Combination
Avutometinib and Defactinib Combination
Dec 13, 2023
Vertex Announces Positive Results From Phase 2 Study of VX-548 for the Treatment of Painful Diabetic Peripheral Neuropathy
– Treatment with the NaV1.8 inhibitor VX-548 led to statistically significant and clinically meaningful reduction in the primary endpoint of change from baseline in the Numeric Pain Rating Scale (NPRS) –
– VX-548 was generally well tolerated –
– Vertex plans to advance VX-548 into pivotal development in diabetic peripheral neuropathic pain following discussions with regulators –
– VX-548 Phase 2 study in patients with painful lumbosacral radiculopathy, another type of peripheral neuropathic pain, has initiated –
– Vertex to host investor call December 13 at 8:00 a.m. ET –
BOSTON--(BUSINESS WIRE)--Dec. 13, 2023-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced positive results from its Phase 2 dose-ranging study of the selective NaV1.8 inhibitor VX-548 in people with painful diabetic peripheral neuropathy (DPN). Treatment with all doses of VX-548 resulted in a statistically significant and clinically meaningful reduction in the primary endpoint of change from baseline in the weekly average of daily pain intensity on a Numeric Pain Rating Scale (NPRS) at Week 12. The study also included an active reference arm of pregabalin to support the evaluation of the VX-548 treatment effect.
VX-548 was generally well tolerated at all doses tested in the study. Most adverse events (AEs) were mild to moderate and there were no serious adverse events (SAEs) related to VX-548.
“We are very pleased with these results which add to the body of safety and efficacy data for VX-548 and provide further validation of the analgesic effects of NaV1.8 inhibitors,” said Carmen Bozic, M.D., Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex. “Given the favorable benefit/risk profile of VX-548 seen in this study, we are working with urgency to advance this investigational non-opioid pain medicine into Phase 3 in painful diabetic neuropathy with the goal of changing the standard of care for neuropathic pain, where treatment options are limited. In addition, our Phase 3 studies of VX-548 in acute pain are on track to read out in the first quarter of 2024.”
“I am excited by the results from the VX-548 Phase 2 DPN study, which demonstrate a promising safety and efficacy profile and represent a significant milestone in pain management,” said Roy Freeman, M.D., Professor of Neurology, Director of the Center for Autonomic and Peripheral Nerve Disorders, Beth Israel Deaconess Medical Center and a member of Vertex’s Pain Steering Committee. “Based on these Phase 2 results, VX-548 could offer the potential for a new class of medicine for the millions of patients suffering from neuropathic pain who are desperate for new options.”
Efficacy Results
The study’s primary endpoint was change from baseline in the weekly average of daily pain intensity at Week 12 in patients with painful DPN dosed with VX-548 using the standard pain assessment Numeric Pain Rating Scale, or NPRS. This 11-point scale ranges from 0 (no pain) to 10 (worst pain imaginable). Patients were randomized to four treatment arms: VX-548 once daily at 69 mg (high dose), 46 mg (mid dose), or 23 mg (low dose), or the reference arm of pregabalin 100 mg three times per day (TID) for 12 weeks.
All VX-548 treatment groups showed statistically significant and clinically meaningful reductions from baseline in pain with mean change in NPRS at Week 12 of -2.26, -2.11 and -2.18 at the high, mid and low doses, respectively. The pregabalin reference arm mean change from baseline in NPRS at Week 12 was -2.09 and is provided for context. All VX-548 dose groups had sustained mean reductions in pain from baseline starting at Week 1, with pain continuing to decrease until Week 5, which was then maintained throughout the treatment period.
Secondary and other endpoints were supportive of the study’s primary endpoint. Importantly, in the responder analysis, more than 30% of patients treated with VX-548 achieved ≥50% reduction in all dose groups, and more than 20% of patients in the mid- and high-dose groups achieved ≥70% reduction in weekly average of NPRS at Week 12 compared to baseline. In the pregabalin reference arm, 22% of patients achieved ≥50% reduction and 10% achieved ≥70% reduction in weekly average of NPRS at Week 12 compared to baseline.
Safety Results
VX-548 was generally well tolerated at all doses studied for up to 12 weeks of treatment. The majority of the AEs were mild or moderate in severity. There were no SAEs related to VX-548 or pregabalin in the study. There was one death in the mid-dose VX-548 group due to atherosclerotic cardiovascular disease, which was not related to study drug.
The most common AEs (incidence >5% in either VX-548 combined or pregabalin group, respectively) were creatinine clearance decrease (5.1%, 1.9%), dizziness (0.7%, 9.3%), peripheral edema (0.7%, 5.6%) and weight increased (0%, 7.4%). Related AEs were 14.5% in patients treated with VX-548 and 27.8% in patients treated with pregabalin.
Next Steps for the Pain Portfolio
Vertex plans to advance VX-548 into pivotal development following discussions with regulators.
Vertex has also initiated a second Phase 2 study of VX-548 in peripheral neuropathic pain. This trial will evaluate VX-548 in patients with painful lumbosacral radiculopathy, or LSR, which is pain caused by impairment or injury to nerve roots in the area of the lumbar spine.
Additionally, the three Phase 3 studies of VX-548 in acute pain are on track to read out in the first quarter of 2024.
In line with its portfolio strategy, Vertex continues to advance preclinical and clinical development of additional NaV1.8 and NaV1.7 inhibitors, for use alone or in combination, in acute and neuropathic pain.
Conference Call and Webcast
The company will host a conference call and webcast at 8:00 a.m. ET on December 13. To access the call, please dial (833) 630-2124 (U.S.) or +1 (412) 317-0651 (International) and reference the “Vertex Pharmaceuticals Conference Call.”
The conference call will be webcast live and a link to the webcast can be accessed through Vertex's website at www.vrtx.com in the "Investors" section. To ensure a timely connection, it is recommended that participants register at least 15 minutes prior to the scheduled webcast. An archived webcast will be available on the company's website.
About the VX-548 Phase 2 Study in Diabetic Peripheral Neuropathy
The Phase 2 study was a randomized, double-blind, active-controlled, dose-ranging study evaluating the efficacy and safety of VX-548 in people aged 18 to 80 years with painful diabetic peripheral neuropathy. A total of 192 patients with bilateral pain in the lower extremities due to diabetic peripheral neuropathy for at least one year were enrolled in this study. Patients were randomized to four treatment arms: VX-548 once daily of 69 mg (high dose), 46 mg (mid dose) or 23 mg (low dose), or the reference arm of pregabalin 100 mg three times per day. The primary endpoint of the study was the change from baseline in the weekly average of daily pain intensity on a Numeric Pain Rating Scale (NPRS) at Week 12.
About Peripheral Neuropathic Pain
Peripheral neuropathic pain, or PNP, is a significant area of unmet need for patients suffering from pain. PNP is a collection of chronic conditions including painful diabetic peripheral neuropathy (DPN), painful lumbosacral radiculopathy (LSR), painful small fiber neuropathy and trigeminal neuralgia. Painful DPN and LSR are two of the largest segments within the estimated 10 million patients who are prescribed a medicine for peripheral neuropathic pain every year in the U.S.
About VX-548
VX-548 is an investigational oral, selective NaV1.8 inhibitor that is highly selective for NaV1.8 relative to other NaV channels. NaV1.8 is a voltage-gated sodium channel that plays a critical role in pain signaling in the peripheral nervous system. NaV1.8 is a genetically validated target for the treatment of pain, and Vertex has previously demonstrated positive proof-of-concept results and a well-tolerated profile with VX-548 in two Phase 2 studies of acute pain following abdominoplasty and bunionectomy surgeries. Vertex’s approach is to selectively inhibit NaV1.8 using small molecules with the objective of creating a new class of medicines that have the potential to provide superior relief of pain without the limitations of opioids, including their addictive potential. VX-548 is one of the most recent molecules to enter clinical development from Vertex’s portfolio of NaV1.8 inhibitors.
About Vertex
Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has approved medicines that treat the underlying causes of multiple chronic, life-shortening genetic diseases — cystic fibrosis, sickle cell disease and transfusion-dependent beta thalassemia — and continues to advance clinical and research programs in these diseases. Vertex also has a robust clinical pipeline of investigational therapies across a range of modalities in other serious diseases where it has deep insight into causal human biology, including APOL1-mediated kidney disease, acute and neuropathic pain, type 1 diabetes and alpha-1 antitrypsin deficiency.
Vertex was founded in 1989 and has its global headquarters in Boston, with international headquarters in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia and Latin America. Vertex is consistently recognized as one of the industry's top places to work, including 14 consecutive years on Science magazine's Top Employers list and one of Fortune’s 100 Best Companies to Work For. For company updates and to learn more about Vertex's history of innovation, visit www.vrtx.com or follow us on LinkedIn, Facebook, Instagram, YouTube and Twitter/X.
View source version on businesswire.com: https://www.businesswire.com/news/home/20231213773646/en/
Source: Vertex Pharmaceuticals Incorporated
Vertex gains as diabetic pain therapy succeeds in mid-stage trial
Dec. 13, 2023 7:44 AM ET
Vertex Pharmaceuticals Incorporated (VRTX) Stock
By: Dulan Lokuwithana, SA News Editor2 Comments
Vertex Pharmaceuticals (NASDAQ:VRTX) added ~7% pre-market Wednesday after announcing that its non-opioid pain therapy VX-548 reached the primary endpoint in a Phase 2 trial for patients with painful diabetic peripheral neuropathy (DPN).
As for Numeric Pain Rating Scale (NPRS), the trial’s primary goal, the company said that VX-548, led to a statistically significant and clinically meaningful decline in the weekly average of daily pain intensity from baseline to Week 12.
The trial for 192 patients aged 18 to 80 years with painful DPN was comprised of four treatment arms: VX-548 once daily of 69 mg (high dose), 46 mg (mid dose), or 23 mg (low dose). There was an additional reference arm for FDA-approved pain therapy pregabalin.
https://seekingalpha.com/news/4045885-vertex-stock-gains-pain-drug-succeeds-mid-stage-trial
CAN-2409
Avutometinib and Defactinib Combination
Pelabresib
Candel Therapeutics Receives FDA Fast Track Designation for CAN-2409 in Pancreatic Cancer
Dec 12, 2023
NEEDHAM, Mass., Dec. 12, 2023 (GLOBE NEWSWIRE) -- Candel Therapeutics, Inc. (Candel or the Company) (Nasdaq: CADL), a clinical stage biopharmaceutical company focused on developing multimodal biological immunotherapies to help patients fight cancer, today announced that the U.S. Food and Drug Administration (FDA) granted Fast Track Designation for its lead investigational adenovirus asset CAN-2409 plus prodrug (valacyclovir) for the treatment of patients with pancreatic ductal adenocarcinoma (PDAC) to improve overall survival.
“We are pleased with the FDA's decision to grant Fast Track Designation for CAN-2409 in pancreatic cancer,” said Paul Peter Tak, MD, PhD, FMedSci, President and CEO of Candel. “This milestone follows our first interim data report from the randomized phase 2 clinical trial in patients with borderline resectable PDAC that showed prolonged and sustained survival after experimental treatment with CAN-2409, especially when compared to real-world data on patients receiving radiotherapy treatment. Candel remains on track to release updated overall survival data from the interim analysis of this clinical trial in the second quarter of 2024. We are grateful to the patients, caregivers, investigators and clinical sites that have taken part in this clinical trial.”
In November 2023, the Company presented encouraging overall survival and immunological biomarker data based on an interim analysis of the randomized, phase 2 clinical trial of CAN-2409 plus prodrug together with standard of care (SoC) neoadjuvant chemoradiation followed by resection for borderline resectable non-metastatic PDAC at the Society for Immunotherapy of Cancer (SITC) Annual Meeting. An estimated survival rate of 71.4% at both 24 and 36 months in patients who received 2 or 3 injections of the CAN-2409 plus prodrug regimen, together with SoC chemoradiation prior to surgery was observed, versus only 16.7% estimated survival at both 24 and 36 months in patients treated with SoC chemoradiation prior to surgery alone. In parallel, the immunological changes observed in the resected pancreatic tissue after CAN-2409 administration suggested that this investigational treatment can activate an effective immunologic antitumoral response in this otherwise “cold” tumor.
About Candel Therapeutics
Candel is a clinical stage biopharmaceutical company focused on developing off-the-shelf multimodal biological immunotherapies that elicit an individualized, systemic anti-tumor immune response to help patients fight cancer. Candel has established two clinical stage multimodal biological immunotherapy platforms based on novel, genetically modified adenovirus and herpes simplex virus (HSV) gene constructs, respectively. CAN-3110 is the lead product candidate from the HSV platform and is currently in an ongoing investigator-sponsored phase 1 clinical trial in recurrent high-grade glioma (HGG). In addition, Candel’s enLIGHTEN™ Discovery Platform is a systematic, iterative HSV-based discovery platform leveraging human biology and advanced analytics to create new viral immunotherapies for solid tumors. CAN-2409 is the lead product candidate from the adenovirus platform and is currently in ongoing clinical trials in non-small cell lung cancer (NSCLC) (phase 2), borderline resectable pancreatic cancer (phase 2), and localized, non-metastatic prostate cancer (phase 2 and phase 3).
For more information about Candel, visit: www.candeltx.com
About the Phase 2 Clinical Trial of CAN-2409 in Non-Metastatic Pancreatic Cancer
This randomized, open-label phase 2 clinical trial is designed to evaluate the safety, preliminary efficacy, and biologic activity of a 2-3 injection regimen of CAN-2409 plus prodrug (valacyclovir or acyclovir) in patients with borderline resectable PDAC who are being treated with neoadjuvant chemoradiation prior to resection. After a protocol amendment in 2022, when enrollment of patients with locally advanced PDAC was discontinued, the clinical trial was designed to exclusively focused on borderline resectable disease. The clinical trial remains active but is not currently enrolling new patients. In a previously completed phase 1b clinical trial, a highly significant increase in the number of CD8+ tumor infiltration lymphocytes was demonstrated at the site of the tumor after CAN-2409 treatment.
About CAN-2409
CAN-2409, Candel’s most advanced multimodal biological immunotherapy candidate, is an investigational off-the-shelf replication-defective adenovirus designed to deliver the herpes simplex virus thymidine kinase (HSV-tk) gene to a patient’s specific tumor and induce an individualized, systemic immune response against the disease. HSV-tk is an enzyme that locally converts orally administered valacyclovir into a toxic metabolite that kills nearby cancer cells. Together, this regimen is designed to induce an individualized and specific CD8+ T cell mediated response against the injected tumor and uninjected distant metastases for broad anti-tumor activity, based on in situ vaccination against a variety of tumor antigens. Because of its versatility, CAN-2409 has the potential to treat a broad range of solid tumors. Encouraging monotherapy activity as well as combination activity with standard of care radiotherapy, surgery, chemotherapy, and immune checkpoint inhibitors have previously been shown in several preclinical and clinical settings. Furthermore, to date, more than 950 patients have been dosed with CAN-2409 with a favorable tolerability profile to date, supporting the potential for combination with other therapeutic strategies without inordinate concern of overlapping adverse events. Currently, Candel is evaluating the effects of treatment with CAN-2409 in NSCLC, borderline resectable PDAC, and localized, non-metastatic prostate cancer in ongoing clinical trials. CAN-2409 has been granted Fast Track Designation by the FDA for treatment of PDAC or stage III/IV NSCLC in patients who are resistant to first line PD-(L)1 inhibitor therapy and who do not have activating molecular driver mutations or have progressed on directed molecular therapy. The Company’s pivotal phase 3 clinical trial in prostate cancer is being conducted under a Special Protocol Assessment by FDA.
About Pancreatic Ductal Adenocarcinoma (PDAC)
Pancreatic cancer is a highly lethal malignancy, and is the fourth leading cause of cancer-related death in the United States among both men and women. Based on the National Cancer Institute, Surveillance, Epidemiology and End Results (SEER) database, pancreatic cancer is expected to account for 3.3% of all new cancer cases, with an estimated 64,050 new cases and estimated 50,550 deaths in 2023.Effective therapeutics for pancreatic cancer, including PDAC, which accounts for 90% of all pancreatic carcinomas, are urgently needed.
Surgical resection offers the only chance of cure, thus a major therapeutic goal for subjects with non-metastatic disease is to achieve complete tumor resection. Surgical treatment (pancreaticoduodenectomy, also known as the Whipple procedure) or total or distal pancreatectomy (depending on tumor location) is generally the recommended treatment for patients diagnosed with resectable cancer; the addition of adjuvant chemotherapy has been shown to only slightly improve survival rates (20 to 23 months). To this end, there has been increasing use of neoadjuvant chemotherapy and chemoradiation regimens for subjects with borderline resectable pancreatic ductal adenocarcinoma. Neoadjuvant regimens are intended to debulk the tumor, thereby increasing the proportion of patients who may become eligible for surgical resection and achieve complete resection (i.e., resection with negative margins, designated ‘R0 resection’). Unfortunately, even when an R0 resection is initially achieved, cures remain elusive as most patients experience disease recurrence due to residual micrometastatic disease. In a recent meta-analysis of 20 studies representing 283 patients with borderline resectable PDAC, neoadjuvant FOLFIRINOX with or without radiotherapy, median OS was only 22.2 months (95% CI, 18.8 to 25.6 months).
Immunotherapy with PD-1 antibodies with or without CTLA-4 antibodies has been uniformly unsuccessful in patients with PDAC due to the dense stroma that surrounds PDAC tissue and the absence of tumor infiltrating lymphocytes.
About Fast Track Designation
Fast Track Designation is a program designed to facilitate the development and expedite the review of medicines with the potential to treat serious conditions and fulfill an unmet medical need. An investigational medicine that receives Fast Track Designation may be eligible for more frequent interactions with the FDA to discuss the candidate’s development plan and, if relevant criteria are met, may be eligible for accelerated approval and priority review.
Candel shares surge as pancreatic cancer candidate gets FDA fast track status
Dec. 12, 2023 9:28 AM ET
Candel Therapeutics, Inc. (CADL) Stock
By: Preeti Singh, SA News Editor
- Candel Therapeutics (NASDAQ:CADL) surged nearly +60% in the premarket session on Tuesday after its pancreatic cancer candidate was granted fast track designation by the U.S. FDA.
- CAN-2409 is the lead product candidate from Candel's adenovirus platform and is in ongoing clinical trials to treat non-small cell lung cancer, borderline resectable pancreatic cancer and localized, non-metastatic prostate cancer.
- The FDA granted fast track designation for the review of CAN-2409 plus prodrug (valacyclovir) for the treatment of patients with pancreatic ductal adenocarcinoma (PDAC).
- https://seekingalpha.com/news/4045496-candel-shares-surge-as-pancreatic-cancer-candidate-gets-fda-fast-track-status
- Candel Therapeutics, Inc. (CADL) Stock
- https://www.candeltx.com/
- https://www.candeltx.com/pipeline/
- https://clinicaltrials.gov/study/NCT04495153
Pelabresib
V940 (mRNA-4157) in Combination with KEYTRUDA® (pembrolizumab)
Pelabresib
MorphoSys’ Pelabresib Improves All Four Hallmarks of Myelofibrosis in Phase 3 MANIFEST-2 Study
EQS-News: MorphoSys AG / Key word(s): Conference
MorphoSys’ Pelabresib Improves All Four Hallmarks of Myelofibrosis in Phase 3 MANIFEST-2 Study
11.12.2023 / 01:31 CET/CEST
The issuer is solely responsible for the content of this announcement.
Media Release
Planegg/Munich, Germany,
December 10, 2023
MorphoSys’ Pelabresib Improves All Four Hallmarks of Myelofibrosis in Phase 3 MANIFEST-2 Study
Pelabresib and ruxolitinib combination significantly reduced spleen size, with an SVR35 response rate nearly double that of placebo plus ruxolitinib
Showed a strong positive trend in reducing symptom burden and a twofold increase in patients achieving both SVR35 and TSS50 versus placebo plus ruxolitinib
Improved measures of anemia, including higher hemoglobin response rates, fewer patients requiring transfusions and fewer anemia adverse events versus placebo plus ruxolitinib
Improved bone marrow fibrosis by at least one grade in more patients versus placebo plus ruxolitinib
Demonstrated safety results consistent with prior clinical trials, with fewer grade ≥3 adverse events compared with placebo plus ruxolitinib
MorphoSys will host an investor event to review findings on Monday, December 11
MorphoSys AG (FSE: MOR; NASDAQ: MOR) today announced comprehensive results from the Phase 3 MANIFEST-2 study investigating pelabresib, an investigational BET inhibitor, in combination with the JAK inhibitor ruxolitinib in JAK inhibitor-naïve patients with myelofibrosis. These findings were presented in an oral presentation at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, California.
Myelofibrosis is characterized by four hallmarks: an enlarged spleen, anemia, bone marrow fibrosis and disease-associated symptoms. In MANIFEST-2, all hallmarks were improved with the pelabresib and ruxolitinib combination versus placebo plus ruxolitinib, which is the standard of care in myelofibrosis. Ruxolitinib dosing was similar in both arms of the study and was determined based on its approved myelofibrosis indication.
“The MANIFEST-2 results demonstrated clear benefits across the four hallmarks of myelofibrosis, including a significant reduction in spleen size – a key finding given the known association between spleen volume reduction and patient survival,” said Raajit K. Rampal, M.D., Ph.D., Director, Center for Hematologic Malignancies, and Director, Myeloproliferative Neoplasms Program, Memorial Sloan Kettering Cancer Center. “The comprehensive results presented at ASH also show that the pelabresib combination improves anemia, disease-associated symptoms and bone marrow fibrosis, and that it is well-tolerated. These findings point to pelabresib and ruxolitinib as a potential paradigm-shifting first-line treatment of this debilitating disease.”
MANIFEST-2 Comprehensive Findings
MANIFEST-2 is a global, multicenter, double-blind, Phase 3 study of 430 JAK inhibitor-naïve adults with myelofibrosis, randomized 1:1 to receive the pelabresib and ruxolitinib combination or placebo plus ruxolitinib. MANIFEST-2 is one of the largest studies in this disease to date.
Strong Reductions in Spleen Size and Symptoms
In the MANIFEST-2 study, pelabresib and ruxolitinib demonstrated a near doubling in the proportion of patients achieving a ≥35% reduction in spleen volume (SVR35) at 24 weeks, the primary endpoint, versus placebo plus ruxolitinib (p<0.001).
For the first key secondary endpoint assessing symptom reduction, absolute change in total symptom score (TSS) at 24 weeks, there was a strong numerical improvement for patients receiving pelabresib and ruxolitinib versus placebo plus ruxolitinib. The response rate for the second key secondary endpoint, proportion of patients achieving ≥50% reduction in symptom score (TSS50) at 24 weeks, was also numerically greater for patients receiving pelabresib and ruxolitinib. Significant improvements in both key secondary endpoints were observed with the pelabresib combination for patients classified as intermediate-risk (Dynamic International Prognostic Scoring System [DIPSS] Int-1 and Int-2), who account for over 90% of the MANIFEST-2 population.
The proportion of patients achieving both SVR35 and TSS50 at 24 weeks was doubled with pelabresib and ruxolitinib versus placebo plus ruxolitinib (40.2% vs. 18.5%, respectively).
Improvement in Anemia
Patients receiving pelabresib in combination with ruxolitinib reported fewer anemia adverse events (43.9%, grade ≥3: 23.1%) compared with placebo plus ruxolitinib (55.6%, grade ≥3: 36.4%). Additionally, by week 24, fewer patients in the pelabresib and ruxolitinib arm required red blood cell transfusions compared with the placebo arm (30.8% vs. 41.2%, respectively).
A greater proportion of patients achieved a hemoglobin response — defined as a ≥1.5 g/dL mean increase in hemoglobin levels over baseline in the absence of transfusions during the previous 12 weeks — with pelabresib and ruxolitinib versus placebo plus ruxolitinib (9.3% vs. 5.6%, respectively). Average hemoglobin levels were greater in patients receiving pelabresib and ruxolitinib than in those receiving placebo plus ruxolitinib, starting at week 9 and continuing to week 24. Anemia benefits were observed across all studied patient risk groups.
“Anemia can reduce patients’ quality of life by causing severe fatigue and necessitating blood transfusions,” said Professor Claire Harrison, Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom. “In MANIFEST-2, patients receiving the combination therapy showed clear benefits on anemia, including greater hemoglobin levels, fewer red blood cell transfusions and fewer anemia and fatigue adverse events. Given its strong efficacy, safety profile and signs of disease modification, the pelabresib and ruxolitinib combination has the potential to become the new standard of care in the first-line treatment of myelofibrosis.”
Improvement in Bone Marrow Fibrosis
Bone marrow fibrosis, or the replacement of bone marrow with fibrous scar tissue, is a central pathological feature of myelofibrosis. In MANIFEST-2, fibrosis was improved by at least one grade in a greater proportion of patients receiving pelabresib and ruxolitinib (38.5% vs. 24.2% with placebo plus ruxolitinib) and worsened by at least one grade in a smaller proportion of patients receiving pelabresib and ruxolitinib (16.3% vs. 28.3% with placebo plus ruxolitinib) at 24 weeks. Bone marrow fibrosis is graded on a scale from 0 (normal) to 3 (most severe) based on fiber density; studies suggest a correlation between the grade of bone marrow fibrosis and patient prognosis.
Biomarker Analysis Suggests Disease Modification
In a biomarker analysis, average plasma levels of inflammatory cytokines (IL-8, IL-6, TNF-α and NF-κB-regulated cytokines) were reduced in patients receiving pelabresib and ruxolitinib compared with placebo plus ruxolitinib at 24 weeks. Increased cytokine levels are associated with all four disease hallmarks; increased IL-8 levels are also associated with worse survival outcomes. These biomolecular improvements suggest early evidence of a disease-modifying effect.
Well-Tolerated Safety Profile
Overall, grade ≥3 treatment-emergent adverse events (TEAEs) were reported less frequently with pelabresib and ruxolitinib than with placebo plus ruxolitinib (49.1% vs. 57.5%, respectively).
In the pelabresib and ruxolitinib arm, the most common (≥10%) hematologic TEAEs were anemia (43.9%; grade ≥3: 23.1%), thrombocytopenia (32.1%; grade ≥3: 9.0%) and platelet count decrease (20.8%; grade ≥3: 4.2%). In the placebo plus ruxolitinib arm, the most common hematologic TEAEs were anemia (55.6%; grade ≥3: 36.4%), thrombocytopenia (23.4%; grade ≥3: 5.6%) and platelet count decrease (15.9%; grade ≥3: 0.9%).
The most common (≥10%) nonhematologic TEAEs in the pelabresib and ruxolitinib arm were diarrhea (23.1%; grade ≥3: 0.5%), dysgeusia (18.4%; grade ≥3: 0.5%), constipation (18.4%; grade ≥3: 0%), nausea (14.2%; grade ≥3: 0.5%), cough (12.7% grade ≥3: 0), asthenia (11.8% grade ≥3: 0.5%), fatigue (11.8%; grade ≥3: 0.5%), dizziness (11.3%; grade ≥3: 0%), headache (11.3% grade ≥3: 0.5%) and COVID-19 (11.3%; grade ≥3: 0%). The most common nonhematologic TEAEs in the placebo plus ruxolitinib arm were constipation (24.3%; grade ≥3: 0%), diarrhea (18.7%; grade ≥3: 1.4%), fatigue (16.8%; grade ≥3: 0.9%), COVID-19 (15.9%; grade ≥3: 1.9%), nausea (15.0%; grade ≥3: 0%), asthenia (13.6%; grade ≥3: 0%), dyspnea (13.1%; grade ≥3: 0.9%), cough (11.2%; grade ≥3: 0%) and headache (10.7%; grade ≥3: 0%). Discontinuation rates due to adverse events were 10.7% with pelabresib and ruxolitinib and 6.5% with placebo plus ruxolitinib.
The safety profile of the pelabresib and ruxolitinib combination therapy was consistent with previous clinical studies. No new safety signals were observed.
“The four hallmarks of myelofibrosis – enlarged spleen, anemia, bone marrow fibrosis and disease-associated symptoms – have a strong impact on a patient’s life. In MANIFEST-2, the combination of JAK and BET inhibition addressed all four of these hallmarks with the potential to modify the course of the disease,” said Tim Demuth, M.D., Ph.D., MorphoSys Chief Research and Development Officer. “We are confident that the comprehensive data package will provide impactful insights into the promising and well-tolerated combination of pelabresib and ruxolitinib. Our goal now is to bring this first-line therapy to patients with intermediate- and high-risk myelofibrosis as quickly as possible. We look forward to meeting with regulatory agencies regarding these data and are diligently preparing regulatory filings with the intention of submitting applications to the U.S. Food and Drug Administration and the European Medicines Agency in the middle of 2024.”
Investor Event at ASH 2023
MorphoSys will host an in-person investor event to review these detailed findings and address questions with the company’s management team and medical experts, including Professor Claire Harrison, Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom, and Ruben Mesa, M.D., FACP, President and Executive Director, Atrium Health Levine Cancer Center and Atrium Health Wake Forest Baptist Comprehensive Cancer Center.
The event, taking place on Monday, December 11 at the Hilton San Diego Bayfront Hotel, will start with a networking breakfast at 6:30 a.m. PST and continue with a formal presentation at 7:00 a.m. PST (4:00 p.m. CET / 3:00 p.m. GMT / 10:00 a.m. EST). A webcast will also be available for those not attending ASH 2023 in person.
Webcast participants may pre-register and will receive dial-in details to access the call easily and quickly: https://services.choruscall.it/DiamondPassRegistration/register?confirmationNumber=5982651&linkSecurityString=c1a71840b. Please dial in 10 minutes before the beginning of the conference.
The live webcast (audio and presentation) can be directly accessed via https://media.choruscall.eu/mediaframe/webcast.html?webcastid=q3lG25n3 or via the Investors section under "Events & Conferences" on the MorphoSys website, www.morphosys.com; after the call, a slide-synchronized audio replay of the conference call will be available at the same location.
About MorphoSys
At MorphoSys, we are driven by our mission: More life for people with cancer. As a global commercial-stage biopharmaceutical company, we develop and deliver innovative medicines, aspiring to redefine how cancer is treated. MorphoSys is headquartered in Planegg, Germany, and has its U.S. operations anchored in Boston, Massachusetts. To learn more, visit us at www.morphosys.com and follow us on Twitter at X and LinkedIn.
About Pelabresib
Pelabresib (CPI-0610) is an investigational selective small molecule designed to promote anti-tumor activity by inhibiting the function of bromodomain and extra-terminal domain (BET) proteins to decrease the expression of abnormally expressed genes in cancer. Pelabresib is being investigated as a treatment for myelofibrosis and has not yet been approved by any regulatory authorities.
The development of pelabresib was funded in part by The Leukemia and Lymphoma Society®.
About MANIFEST-2
MANIFEST-2 (NCT04603495) is a global, double-blind, Phase 3 clinical trial that randomized 430 JAK inhibitor-naïve adult patients with myelofibrosis 1:1 to receive pelabresib in combination with ruxolitinib or placebo plus ruxolitinib. The primary endpoint of the study is a 35% or greater reduction in spleen volume (SVR35) from baseline at 24 weeks. The key secondary endpoints of the study are the absolute change in total symptom score (TSS) from baseline at 24 weeks and the proportion of patients achieving a 50% or greater improvement in total symptom score (TSS50) from baseline at 24 weeks. TSS is measured using the myelofibrosis self-assessment form (MFSAF) v4.0, which asks patients to report the severity of seven common symptoms, rating each of them on a scale from 0 (absent) to 10 (worst imaginable).
The new key secondary endpoint, absolute change in TSS, was added to directly measure change in the average TSS from baseline to week 24 of treatment and is listed as the first key secondary endpoint in the MANIFEST-2 hierarchical testing scheme. The decision to update the MANIFEST-2 clinical trial protocol was made following a Type C meeting with the U.S. Food and Drug Administration (FDA) in September 2023. The final clinical protocol amendment is subject to approvals by health authorities outside of the U.S.
Additional secondary endpoints include progression-free survival, overall survival, duration of the splenic and total symptom score response, hemoglobin response rate and improvement in bone marrow fibrosis, among others.
Constellation Pharmaceuticals, Inc., a MorphoSys company, is the MANIFEST-2 trial sponsor.
About Myelofibrosis
Myelofibrosis is a blood cancer – belonging to a group of diseases called myeloproliferative neoplasms – caused by genetic abnormalities in bone marrow stem cells and characterized by four hallmarks: enlarged spleen, anemia, impaired bone marrow microenvironment causing fibrosis, and debilitating disease-associated symptoms, including severe fatigue, night sweats, itching, increased bleeding and significant pain caused by their enlarged spleen. For many living with myelofibrosis, the combination of symptoms often severely impacts their quality of life. At diagnosis, several factors, such as age, genetics and bloodwork, help determine a patient’s long-term prognosis. About 90% of newly diagnosed patients have intermediate- to high-risk disease, which has a worse prognosis and a higher likelihood of disease-associated symptoms. While JAK inhibitors, the current standard of care, address some aspects of the disease, no agent provides broad disease control. There is an urgent need for novel, well-tolerated therapeutic options capable of changing the natural course of myelofibrosis to provide patients with deep and durable responses across its four hallmarks.
MorphoSys climbs after late-stage data for blood cancer therapy
Dec. 11, 2023 1:57 PM ET
MorphoSys AG (MOR) StockNVS, NVSEF
By: Dulan Lokuwithana, SA News Editor
MorphoSys (NASDAQ:MOR) added ~22% on Monday after the German biotech disclosed complete results from its Phase 3 MANIFEST-2 study for pelabresib, a treatment targeted at a rare form of blood cancer called myelofibrosis (MF).
Citing a presentation at the ongoing Annual Meeting of the American Society of Hematology (“ASH”), MorphoSys (MOR) said pelabresib, in combination with ruxolitinib, a JAK inhibitor marketed by Novartis (NVS) (OTCPK:NVSEF), as Jakavi improved all four hallmarks of MF.
Epcoritamab (DuoBody® CD3xCD20)
V940 (mRNA-4157) in Combination with KEYTRUDA® (pembrolizumab)
V940 (mRNA-4157) in Combination with KEYTRUDA® (pembrolizumab)
December 09, 2023
New Data for Bispecific Antibody Epcoritamab (DuoBody® CD3xCD20) Shows Strong, Durable Treatment Response for Patients with Difficult-To-Treat Relapsed/Refractory (R/R) Follicular Lymphoma (FL)
- Data from Phase 1/2 EPCORE™ NHL-1 study show patients treated with epcoritamab experienced 82% overall response rates (ORR) including 63% complete response (CR) rates as presented at the 65th American Society of Hematology (ASH) congress
- Follicular lymphoma is the second most common form of non-Hodgkin's lymphoma
NORTH CHICAGO, Ill., Dec. 9, 2023 /PRNewswire/ -- AbbVie (NYSE: ABBV) and Genmab A/S (Nasdaq: GMAB) announced today that adult patients with relapsed/refractory (R/R) follicular lymphoma (FL) previously treated with two or more prior therapies experienced strong and durable responses with high overall response (ORR) and complete response (CR) rates when treated with epcoritamab (DuoBody® CD3xCD20), an investigational, subcutaneously administered T-cell engaging bispecific antibody. More than half of patients who responded to treatment in the study remained responsive to treatment at the time of data analysis (i.e., median duration of response was not reached). Data from the dose-expansion cohort of the Phase 1/2 EPCORE™ NHL-1 clinical trial are being shared during a poster presentation on Saturday, December 9 at 5:30 PM PT at the ASH congress in San Diego, California. Updated data from this study include an optimized, step-up dosing schedule showing reduced incidence and severity of cytokine release syndrome (CRS), a notable side effect from immune-engaging cancer treatments.
"Despite treatment advances for patients with follicular lymphoma whose disease has unfortunately progressed, treating relapsed or refractory follicular lymphoma remains highly challenging, particularly as a third-line treatment," said Catherine Thieblemont, M.D., Ph.D., head of the hemato-oncology department, Paris University, Hôpital Saint-Louis Assistance-Publique-Hopitaux de Paris (APHP) in Paris. "The patients in this trial represent a historically difficult-to-treat patient population. The data presented today are especially notable because they demonstrated high overall and complete response rates for this investigational therapy and a preview for its potential as a treatment option."
"Further developing epcoritamab as a core therapy to help treat more patients with B-cell malignancies, including follicular lymphoma, is an important goal we share with our partner Genmab," said Mariana Cota Stirner, M.D., Ph.D., vice president, therapeutic area head for hematology, AbbVie. "These data at this year's ASH further build our confidence in epcoritamab's treatment potential as well as development for earlier patient treatment."
Results from this cohort of 128 adult patients show the following:
- At a median follow-up of 17.4 months, ORR, the study's primary endpoint, was 82%, with a CR rate of 63%; the median time to response and CR were 1.4 months and 1.5 months, respectively.
- Among prespecified high-risk subgroups such as patients refractory to prior treatments (double refractory (70%), or refractory to last prior treatment (69%), among others), ORR and CR rates were generally consistent with the overall study population.
- Median duration of response and duration of CR were not yet reached.
- An estimated 85% and 74% of patients who experienced a CR remained responsive to treatment at 12 and 18 months, respectively.
- Additional study data can be found here: (abstract #1655).
No new safety signals were detected. The most common treatment-emergent AE (TEAE) was CRS with 67% occurrence (40% Grade 1, 25% Grade 2, 2% Grade 3). Following an optimized step-up dose regimen in a separate cohort to reduce the risk and severity of CRS, 24 out of 50 patients (48%) experienced grade 1-2 CRS (40% Grade 1, 8% Grade 2, 0% Grade 3). As well, no cases of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) were reported. This data may support investigating optimized step-up dose in an outpatient setting. Additional common TEAEs (>20%) were injection-site reaction (57%), COVID-19 (40%), fatigue (30%), neutropenia (29%), diarrhea (27%) and pyrexia (25%). TEAEs leading to treatment discontinuation occurred in 19% of patients, and death related to TEAEs occurred in 13 patients (10%).
AbbVie and Genmab recently announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) to epcoritamab for the treatment of adult patients with R/R FL after two or more therapies. Additionally, the European Medicines Agency (EMA) has validated a Type II application for epcoritamab in the same indication. If approved, R/R FL would become the second conditionally approved indication for epcoritamab in the European Union. More information is available here.
About the Phase 1/2 EPCORE™ NHL-1 Trial
EPCORE™ NHL-1 is an open-label, multi-center safety and preliminary efficacy trial of epcoritamab that consists of three parts: a Phase 1 first-in-human, dose escalation part; a Phase 2a expansion part; and a Phase 2a dose optimization part. The trial was designed to evaluate subcutaneous epcoritamab in adult patients with relapsed, progressive or refractory CD20+ mature B-cell non-Hodgkin's lymphoma (NHL), including follicular lymphoma (FL). In the Phase 2a expansion part, additional patients are being enrolled to further explore the safety and efficacy of epcoritamab in three cohorts of patients with different types of relapsed or refractory (R/R) B-cell NHLs who have limited therapeutic options. The dose optimization part evaluates the potential for alternative step-up dosing regimens to help further minimize Grade 2 cytokine release syndrome (CRS) and mitigate Grade ≥3 CRS. The application for BTD included additional data from this cohort of patients. The primary endpoint of the expansion part was overall response rate as assessed by an independent review committee. Secondary efficacy endpoints included duration of response, complete response rate, duration of complete response, progression-free survival, and time to response as determined by the Lugano criteria. Overall survival, time to next therapy, and rate of minimal residual disease negativity were also evaluated as secondary efficacy endpoints.
About Follicular Lymphoma (FL)
FL is typically an indolent (or slow growing) form of non-Hodgkin's lymphoma (NHL) that arises from B-lymphocytes.1 FL is the second most common form of NHL, accounting for 20-30% of all NHL cases, and represents 10-20% of all lymphomas in the western world.1,2,3 Although FL is typically considered an indolent (or slow-growing) lymphoma, it remains incurable with conventional therapy4,5 and patients who achieve remission often experience relapse.6
About Epcoritamab
Epcoritamab is an investigational IgG1-bispecific antibody created using Genmab's proprietary DuoBody® technology and administered subcutaneously. Genmab's DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response toward target cell types. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B cells and induces T-cell-mediated killing of CD20+ cells.7
Epcoritamab (approved under the brand name EPKINLY® in the United States and TEPKINLY® in the European Union) has received regulatory approval in adults with certain types of large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL), globally. EPKINLY is approved under the FDA's Accelerated Approval program based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Use of epcoritamab in FL is not approved in the U.S. or in the EU. AbbVie will continue to pursue regulatory submissions for epcoritamab across international markets.
Genmab and AbbVie continue to evaluate the use of epcoritamab as a monotherapy, and in combination, across lines of therapy in a range of hematologic malignancies. This includes three ongoing Phase 3, open-label, randomized trials including a trial evaluating epcoritamab as a monotherapy in patients with R/R DLBCL (NCT: 04628494) compared to investigator's choice chemotherapy, a Phase 3 trial evaluating epcoritamab in combination with R-CHOP in adult patients with newly diagnosed DLBCL (NCT: 05578976), and a Phase 3 clinical trial evaluating epcoritamab in combination with rituximab and lenalidomide (R2) in patients with R/R FL (NCT: 05409066). Epcoritamab is not approved to treat patients with newly diagnosed DLBCL or with FL. The safety and efficacy of epcoritamab has not been established for these investigational uses. Please visit clinicaltrials.gov for more information.
EPKINLY® (epcoritamab-bysp) U.S. USE and IMPORTANT SAFETY INFORMATION
USE
EPKINLY is a prescription medicine used to treat adults with certain types of diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma that has come back (relapsed) or that did not respond to previous treatment (refractory), and who have received 2 or more treatments for their cancer.
EPKINLY is approved based on patient response data. A study is ongoing to confirm the clinical benefit of EPKINLY. It is not known if EPKINLY is safe and effective in children.
Please see the Full Prescribing Information and Medication Guide, including Important Warnings.
About AbbVie in Oncology
At AbbVie, we are committed to transforming standards of care for multiple blood cancers while advancing a dynamic pipeline of investigational therapies across a range of cancer types. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potential breakthrough medicines. We are evaluating more than 20 investigational medicines in over 300 clinical trials across some of the world's most widespread and debilitating cancers. As we work to have a remarkable impact on people's lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit http://www.abbvie.com/oncology.
About AbbVie
AbbVie's mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas – immunology, oncology, neuroscience, and eye care – and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on LinkedIn, Facebook, Instagram, X (formerly Twitter), and YouTube.
AbbVie-Genmab lymphoma drug shows strong response rate in ongoing trial
Dec. 11, 2023 6:20 AM ET
AbbVie Inc. (ABBV) Stock, GMAB Stock
By: Preeti Singh, SA News Editor3 Comments
AbbVie (NYSE:ABBV) and Genmab (GMAB) on Saturday presented latest trial data for their lymphoma drug candidate epcoritamab in patients with difficult-to-treat relapsed/refractory (R/R) follicular lymphoma (FL).
V940 (mRNA-4157) in Combination with KEYTRUDA® (pembrolizumab)
V940 (mRNA-4157) in Combination with KEYTRUDA® (pembrolizumab)
V940 (mRNA-4157) in Combination with KEYTRUDA® (pembrolizumab)
Merck and Moderna Initiate INTerpath-002, a Phase 3 Study Evaluating V940 (mRNA-4157) in Combination with KEYTRUDA® (pembrolizumab) for Adjuvant Treatment of Patients with Certain Types of Resected Non-Small Cell Lung Cancer
December 11, 2023 6:45 am ET
The initiation of the second clinical trial in the INTerpath program represents rapid expansion in research for additional tumor types for individualized neoantigen therapy, V940 (mRNA-4157)
RAHWAY, N.J. & CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, and Moderna, Inc. (Nasdaq: MRNA), today announced the initiation of INTerpath-002, a pivotal Phase 3 randomized clinical trial evaluating V940 (mRNA-4157), an investigational individualized neoantigen therapy (INT), in combination with KEYTRUDA, Merck’s anti-PD-1 therapy, as adjuvant treatment in patients with completely resected (R0) Stage II, IIIA or IIIB (with nodal involvement [N2]) non-small cell lung cancer (NSCLC). Global recruitment of the INTerpath-002 has begun, and the first patients enrolled in Australia.
“As lung cancer is the leading cause of cancer death worldwide, there is a need for continued scientific advancements to help fight this disease at earlier stages when patients have the best chance for better outcomes,” said Dr. Marjorie Green, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories. “By combining KEYTRUDA with V940 (mRNA-4157), a promising new modality, we are researching innovative new approaches for earlier stage non-small cell lung cancer.”
“Addressing lung cancer reflects the constant struggle between medical innovation and biological complexity. Each patient's cancer presents a labyrinth of genetic mutations, driving a novel approach of individualized medicines manufactured based on the distinct molecular tumor profile for each patient,” said Kyle Holen, M.D., Moderna's Senior Vice President and Head of Development, Therapeutics and Oncology. “We believe an individualized neoantigen therapy can be this catalyst for innovation and drive us forward towards the next frontier of cancer care. I’m incredibly thankful for the patients, investigators, and clinical trial sites for helping us in this mission.”
As previously announced, in addition to INTerpath-002, the combination of V940 (mRNA-4157) plus KEYTRUDA is being investigated in INTerpath-001, formerly referred to as V940-001 (NCT05933577), a global, randomized, double-blind, placebo- and active-comparator-controlled Phase 3 trial evaluating approximately 1,089 patients with resected high-risk (Stage IIB-IV) melanoma. INTerpath-001 is actively screening in 14 countries (Australia, Belgium, Canada, Chile, France, Germany, Greece, Israel, Italy, Poland, Portugal, Spain, Turkey and the United Kingdom), representing 38 sites. The companies plan to continue expansion of the comprehensive clinical development program for V940 (mRNA-4157) to additional tumor types.
About V940 (mRNA-4157)
V940 (mRNA-4157) is a novel investigational messenger RNA (mRNA)-based individualized neoantigen therapy (INT) consisting of a synthetic mRNA coding for up to 34 neoantigens that is designed and produced based on the unique mutational signature of the DNA sequence of the patient’s tumor. Upon administration into the body, the algorithmically derived and RNA-encoded neoantigen sequences are endogenously translated and undergo natural cellular antigen processing and presentation, a key step in adaptive immunity.
Individualized neoantigen therapies are designed to train and activate an antitumor immune response by generating specific T-cell responses based on the unique mutational signature of a patient’s tumor. KEYTRUDA is an immunotherapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. As previously announced from the Phase 2b KEYNOTE-942/mRNA-4157-P201 trial evaluating patients with high-risk stage III/IV melanoma, combining V940 (mRNA-4157) with KEYTRUDA may provide a meaningful benefit over KEYTRUDA alone.
About INTerpath-002 (NCT06077760)
INTerpath-002 is a global, randomized, double-blind, placebo- and active-comparator-controlled Phase 3 trial evaluating approximately 868 patients with completely resected Stage II, IIIA or IIIB [N2] NSCLC. Following complete surgical resection and adjuvant chemotherapy, participants 18 years and older will be randomized 1:1 to receive V940 (mRNA-4157) (1 mg every three weeks for up to nine doses) and KEYTRUDA (400 mg every six weeks for up to nine cycles) versus KEYTRUDA alone for approximately one year or until disease recurrence or any of the other criteria for discontinuation of study intervention are met. The primary endpoint is disease-free survival (DFS), defined as the time from randomization to any recurrence or occurrence of new primary NSCLC as assessed by the investigator, or death due to any cause. The secondary endpoints are overall survival (OS), distant metastasis-free survival (DMFS), lung cancer specific survival (LCSS), safety, and quality of life.
Key eligibility criteria for the trial include: completion of surgical resection of histologically confirmed Stage II, IIIA or IIIB (N2) squamous or nonsquamous NSCLC, confirmation that epidermal growth factor receptor (EGFR)-directed therapy is not indicated as primary therapy, no evidence of disease at the time of providing documented consent for the main study, prior treatment with at least one dose of adjuvant therapy with standard-of-care platinum-based doublet chemotherapy up to four cycles, and no more than 24 weeks between surgical resection with curative intent and the first dose of KEYTRUDA.
For further information, please see: https://clinicaltrials.gov/study/NCT06077760?term=NCT06077760&rank=1.
About lung cancer
Lung cancer is the leading cause of cancer death worldwide. In 2020 alone, there were more than 2.2 million new cases and 1.8 million deaths from lung cancer globally. Non-small cell lung cancer is the most common type of lung cancer in the U.S., accounting for about 81% of all cases. In the U.S., the overall five-year survival rate for patients diagnosed with lung cancer is 26.2%, which is a 22% improvement over the last five years. Improved survival rates are due, in part, to earlier detection and screening, reduction in smoking, advances in diagnostic and surgical procedures, as well as the introduction of new therapies. Early detection and screening remain an important unmet need, as 44% of lung cancer cases are not found until they are advanced. Only 4.5% of people in the U.S. who are eligible were screened for lung cancer in 2022.
About KEYTRUDA® (pembrolizumab) injection, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.
Non-Small Cell Lung Cancer
KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:
- stage III where patients are not candidates for surgical resection or definitive chemoradiation, or
- metastatic.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.
KEYTRUDA is indicated for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC.
See additional selected indications for KEYTRUDA in the U.S. after the Selected Important Safety Information
Additional Selected KEYTRUDA Indications in the U.S.
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.
KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.
Non-Small Cell Lung Cancer
KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:
- stage III where patients are not candidates for surgical resection or definitive chemoradiation, or
- metastatic.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.
KEYTRUDA is indicated for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC.
Head and Neck Squamous Cell Cancer
KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.
Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).
KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.
Primary Mediastinal Large B-Cell Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy.
KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.
Microsatellite Instability-High or Mismatch Repair Deficient Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic MSI-H or dMMR solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.
Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC) as determined by an FDA-approved test.
Gastric Cancer
KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumor express PD-L1 (CPS ≥1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval of this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
KEYTRUDA, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Esophageal Cancer
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:
- in combination with platinum- and fluoropyrimidine-based chemotherapy, or
- as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
Cervical Cancer
KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
Hepatocellular Carcinoma
KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Biliary Tract Cancer
KEYTRUDA, in combination with gemcitabine and cisplatin, is indicated for the treatment of patients with locally advanced unresectable or metastatic biliary tract cancer (BTC).
Merkel Cell Carcinoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC).
Renal Cell Carcinoma
KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.
Endometrial Carcinoma
KEYTRUDA, as a single agent, is indicated for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Tumor Mutational Burden-High Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.
Cutaneous Squamous Cell Carcinoma
KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.
Triple-Negative Breast Cancer
KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
Merck’s focus on cancer
Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.
About Merck’s research in lung cancer
Merck is advancing research aimed at transforming the way lung cancer is treated, with a goal of improving outcomes for patients affected by this deadly disease. Through nearly 200 clinical trials evaluating more than 36,000 patients around the world, Merck is at the forefront of lung cancer research. In NSCLC, KEYTRUDA has six approved U.S. indications (see indications below) and is approved for advanced disease in more than 95 countries. Among Merck’s research efforts are trials focused on evaluating KEYTRUDA in earlier stages of lung cancer as well as identifying new combinations and coformulations with KEYTRUDA.
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.
About Moderna
Moderna is a leader in the creation of the field of mRNA medicine. Through the advancement of mRNA technology, Moderna is reimagining how medicines are made and transforming how we treat and prevent disease for everyone. By working at the intersection of science, technology and health for more than a decade, the company has developed medicines at unprecedented speed and efficiency, including one of the earliest and most effective COVID-19 vaccines.
Moderna’s mRNA platform has enabled the development of therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases and autoimmune diseases. With a unique culture and a global team driven by the Moderna values and mindsets to responsibly change the future of human health, Moderna strives to deliver the greatest possible impact to people through mRNA medicines. For more information about Moderna, please visit modernatx.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.
Moderna’s focus on cancer
At Moderna, we are delivering on the promise of mRNA science to create a new generation of transformative medicines for patients. We are relentlessly working to grow our cancer therapeutic modality by discovering mRNA medicines that harness the body’s immune system to identify and kill cancer cells in the same way the immune system identifies and targets infections. One example of a promising oncology candidate is the creation of individualized, mRNA-based cancer therapies. We also continue to strengthen our portfolio through strategic collaborations that increase our potential to improve treatment options for patients with cancer.
Please see Prescribing Information for KEYTRUDA (pembrolizumab) at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf .
Source: Merck & Co., Inc.
Merck, Moderna begin new Phase 3 trial for mRNA-based cancer therapy
Dec. 11, 2023 7:17 AM ET
Moderna, Inc. (MRNA) Stock, MRK Stock
By: Dulan Lokuwithana, SA News Editor
- Merck (NYSE:MRK) and Moderna (NASDAQ:MRNA) have expanded their Phase 3 program for their messenger-RNA-based cancer therapy, V940 (mRNA-4157), for a new indication in lung cancer, the companies announced Monday.
- The companies said that global enrollments will begin for INTerpath-002, a pivotal Phase 3 trial designed to evaluate V940 with Merck’s (MRK) immunotherapy Keytruda for certain patients with non-small cell lung cancer (NSCLC) in an adjuvant setting (after surgical resection).
- https://seekingalpha.com/news/4045014-merck-moderna-begin-new-phase-3-trial-mrna-cancer-drug
- Moderna, Inc. (MRNA) Stock, MRK Stock
- https://www.merck.com/
- https://www.modernatx.com/
Odronextamab
LYFGENIA™ (lovotibeglogene autotemcel, also known as lovo-cel)
Odronextamab
December 10, 2023 at 7:30 PM EST
LATEST ODRONEXTAMAB DATA IN RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA SHOWED COMPELLING RESPONSES AND OVERALL MAINTENANCE OF PATIENT-REPORTED OUTCOMES
Updated results presented at ASH demonstrated an 80% objective response rate and a 73% complete response (CR), with a 23-month median duration of response and 24-month median duration of CR
Oral presentation showcased overall maintenance of patient-reported outcomes from baseline to 50 weeks during investigational odronextamab treatment, complementing the overall efficacy and safety profile in this heavily pretreated and highly refractory patient population
TARRYTOWN, N.Y., Dec. 10, 2023 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced positive data for odronextamab in patients with relapsed/refractory (R/R) follicular lymphoma (FL) from a pivotal Phase 2 trial (ELM-2). These data – which include updated efficacy, safety and patient-reported outcomes (PROs) – were presented at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition from December 9 to 12 in San Diego, CA. Odronextamab is an investigational CD20xCD3 bispecific antibody designed to bridge CD20 on cancer cells with CD3-expressing T cells to facilitate local T-cell activation and cancer-cell killing.
“The odronextamab data presented at ASH in patients with relapsed/refractory follicular lymphoma showcase a strong profile across measures of efficacy, safety and health-related quality of life,” said Benoît Tessoulin, M.D., Ph.D., Nantes University Hospital, Nantes; CRCI2NA, Nantes University, Nantes, France, and a trial investigator. “As clinicians, our focus must remain patients’ wellbeing, along with favorable outcomes. For odronextamab, it is particularly encouraging to see the unprecedented clinical results complemented by patient-reported outcomes that show quality of life and functional measures are maintained overall. These presentations underscore the potential role of odronextamab as a future medicine that treats relapsed/refractory follicular lymphoma and may allow patients to maintain health-related quality of life during the course of their therapy.”
As shared at ASH, longer-term data from the Phase 2 odronextamab trial continued to confirm high rates of durable responses in patients with R/R FL. At a prespecified interim analysis that occurred when the first 80 patients had ≥12 months of follow-up, results among 128 patients that were assessed by independent central review (ICR) demonstrated:
- 80% objective response rate (ORR), with 73% achieving a complete response (CR).
- Median duration of response (DoR) was 23 months (95% confidence interval [CI]: 17 months to not estimable [NE]) and median duration of CR was 24 months (95% CI: 18 months to NE) with a 18-month median duration of follow-up for efficacy evaluable patients (95% CI: 15 to 28 months).
- Median progression-free survival (PFS) in complete responders was 28 months (95% CI: 20 months to NE) and 21 months for all patients (95% CI: 17 to 28 months).
- Median overall survival (OS) was not reached (95% CI: 32 months to NE).
- The most common adverse events (AE) occurring in ≥30% of patients were cytokine release syndrome (CRS; 56%), neutropenia (48%), pyrexia (36%), anemia (34%), COVID-19 (31%) and infusion-related reactions (31%).
- In 60 patients that received the recommended step-up regimen, 57% experienced CRS. All cases were resolved with supportive measures, with a median duration of 2 days (range: 1 to 10 days). Among these patients, 45% (n=27) had Grade 1 CRS, 10% (n=6) had Grade 2 CRS, and 2% (n=1) had Grade 3 CRS.
- There was one Grade 2 immune effector cell-associated neurotoxicity syndrome event reported, which was not associated with CRS.
As presented during an oral session at ASH, patients with R/R FL treated with odronextamab in the ELM-2 trial completed three validated questionnaires aimed at measuring health-related quality of life (HRQoL), functioning and symptoms. Pre-specified analyses were conducted across six scales. Overall, patients reported generally good HRQoL, functioning and low symptom burden at baseline as assessed across several scales. Key findings through Week 50 showed:
- Overall maintenance of moderate to high levels of functioning and HRQoL without detriments to patient-reported symptoms based on an analysis of changes in PRO scores from baseline over time, as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) scores.
- Median time to definitive deterioration in physical function and lymphoma-specific symptoms was not reached (per EORTC QLQ-30 and Functional Assessment of Cancer Therapy Lymphoma subscale, respectively). In an individual patient-level analysis, more patients reported maintenance or clinically meaningful improvement in physical functioning and lymphoma-specific symptoms than deterioration at each assessment.
Odronextamab is currently under regulatory review for the treatment of R/R FL and diffuse large B-cell lymphoma (DLBCL) by the U.S. Food and Drug Administration, with a target action date of March 31, 2024, as well as by the European Medicines Agency (EMA). In the U.S., odronextamab has been granted Fast Track Designation by the FDA. In the European Union, odronextamab has been granted Orphan Drug Designation by the EMA.
The potential use of odronextamab in R/R FL and R/R DLBCL is currently under clinical development, and the safety and efficacy have not been fully evaluated by any regulatory authority.
Investor Webcast Information
Regeneron will host a conference call and simultaneous webcast to share updates on the company’s hematology portfolio on Thursday, December 14 at 8:30 AM ET. A link to the webcast may be accessed from the ‘Investors and Media’ page of Regeneron's website at http://investor.regeneron.com/events.cfm. To participate via telephone, please register in advance at this link. Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call. A replay of the conference call and webcast will be archived on the company's website for at least 30 days.
About the Odronextamab Clinical Program
ELM-1 is an ongoing, open-label, multicenter Phase 1 trial to investigate the safety and tolerability of odronextamab in patients with CD20-positive B-cell malignancies previously treated with CD20-directed antibody therapy. The trial includes an expansion cohort evaluating DLBCL patients who had progressed on CAR-T therapy.
ELM-2 is an ongoing, open-label, multicenter pivotal Phase 2 trial investigating odronextamab in 375 patients across five independent disease-specific cohorts, including DLBCL, FL, mantle cell lymphoma, marginal zone lymphoma and other subtypes of B-cell non-Hodgkin lymphoma (B-NHL). The primary endpoint of ELM-2 is ORR according to the Lugano Classification, and secondary endpoints include CR, PFS, OS, DoR, disease control rate, safety and quality of life.
Regeneron has initiated a broad Phase 3 development program to investigate odronextamab in earlier lines of therapy and other B-NHLs, representing one of the largest clinical programs in lymphoma.
About Follicular Lymphoma (FL)
One of the most common subtypes of B-NHL, FL is a slow-growing (indolent) form of B-NHL, with most cases diagnosed in advanced stages. Although median survival ranges from 8 to 15 years in advanced FL, current therapeutic options are not curative, and most patients relapse within five years, regardless of the regimen. In the U.S., it is estimated that approximately 13,100 people will be diagnosed with FL in 2023. In some cases, FL can transform into DLBCL, at which point it is often treated in the same way as DLBCL.
About Regeneron in Hematology
At Regeneron, we’re applying more than three decades of biology expertise with our proprietary VelociSuite® technologies to develop medicines for patients with diverse blood cancers and rare blood disorders.
Our blood cancer research is focused on bispecific antibodies that are being investigated both as monotherapies and in combination with each other and emerging therapeutic modalities. Together, they provide us with unique combinatorial flexibility to develop customized and potentially synergistic cancer treatments.
Our research and collaborations to develop potential treatments for rare blood disorders include explorations in antibody medicine, gene editing and gene-knockout technologies, and investigational RNA approaches focused on depleting abnormal proteins or blocking disease-causing cellular signaling.
If you are interested in learning more about our clinical trials, please contact us (clinicaltrials@regeneron.com or 844-734-6643) or visit our clinical trials website.
About Regeneron
Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led for 35 years by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous FDA-approved treatments and product candidates in development, almost all of which were homegrown in our laboratories. Regeneron’s medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, hematologic conditions, infectious diseases and rare diseases.
Regeneron is accelerating and improving the traditional drug development process through its proprietary VelociSuite technologies, such as VelocImmune®, which uses unique genetically humanized mice to produce optimized fully human antibodies and bispecific antibodies, and through ambitious research initiatives such as the Regeneron Genetics Center®, which is conducting one of the largest genetics sequencing efforts in the world.
For additional information about Regeneron, please visit www.regeneron.com or follow Regeneron on LinkedIn.
Source: Regeneron Pharmaceuticals, Inc.
Regeneron lymphoma therapy shows high response rate in ongoing trial
Dec. 11, 2023 6:01 AM ET
Regeneron Pharmaceuticals, Inc. (REGN) Stock
By: Preeti Singh, SA News Editor2 Comments
Regeneron Pharmaceuticals (NASDAQ:REGN) on Sunday presented updated trial data for its bispecific lymphoma antibody, odronextamab, in patients with relapsed/refractory (R/R) follicular lymphoma (FL).
Odronextamab is currently under regulatory review for the treatment of R/R FL and diffuse large B-cell lymphoma by the U.S. Food and Drug Administration, with a target action date of March 31, 2024, as well as by the European Medicines Agency.
Regeneron Pharmaceuticals, Inc. (REGN) Stock
https://www.regeneron.com/pipeline-medicines/investigational-pipeline
Zanidatamab
LYFGENIA™ (lovotibeglogene autotemcel, also known as lovo-cel)
Odronextamab
Jazz Pharmaceuticals Presents Updated Phase 2a Data at SABCS 2023 Showcasing Potential of Zanidatamab in HER2+/HR+ Metastatic Breast Cancer
December 08, 2023
First presentation of progression-free survival (PFS) primary endpoint data show zanidatamab plus palbociclib and fulvestrant demonstrated a PFS of 67% at 6 months and a median PFS of 12 months in patients with heavily pre-treated HER2+/HR+ metastatic breast cancer (mBC)
Efficacy and safety results support further investigation of this targeted combination therapy as a potential chemotherapy-free option for patients with HER2+/HR+ mBC
DUBLIN, Dec. 8, 2023 /PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today presented updated data from the Phase 2a trial of investigational zanidatamab, a HER2-targeted bispecific antibody, in combination with palbociclib, a CDK4/6 inhibitor, and fulvestrant, a selective estrogen receptor antagonist, in patients with HER2-positive (HER2+)/HR-positive (HR+) metastatic breast cancer (mBC) as part of a late-breaking oral presentation at the 2023 San Antonio Breast Cancer Symposium (SABCS).
Data from 51 patients with heavily pretreated HER2+/HR+ mBC (median of 4 prior regimens in the metastatic setting) who were treated with zanidatamab plus palbociclib and fulvestrant demonstrated a progression-free survival at six months (PFS6) of 67% (n=34) [95% confidence interval: 52, 79]. Secondary endpoint findings included a median progression-free survival (mPFS) of 12 months [95% CI: 8, 15] and a confirmed objective response rate (cORR) of 35% [95% CI: 21, 50] with a median duration of response (DOR) of 15 months. The combination regimen was well tolerated with a manageable safety profile.
"Metastatic breast cancer is a particularly aggressive and devastating disease, and patients whose cancer has progressed despite numerous therapeutic interventions are in dire need of additional treatment options – particularly chemotherapy-free options," 1,2 said Santiago Escrivá-de-Romani, MD, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, and primary trial investigator. "Targeting both the HER2 and hormone receptor pathways can be a promising approach for applicable patients, and the durable responses seen in this study signal the potential for this combination to fill a persistent and much needed treatment gap among these patients."3
"The late-breaking data presented at SABCS for zanidatamab in combination with palbociclib and fulvestrant in HER2+/HR+ metastatic breast cancer as a chemotherapy-free treatment option in heavily pretreated patients provide yet another example of the promise this HER2-targeted bispecific antibody holds in the treatment of HER2-expressing cancers where significant unmet needs exist," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development of Jazz Pharmaceuticals. "We are encouraged by the meaningful clinical benefit seen in this trial, and we look forward to continuing to advance our broader clinical development program for zanidatamab in breast cancer and other HER2-expressing solid tumors, with the goal of addressing some of the greatest unmet needs in cancer with HER2 expression."
Trial Results
Results of the Phase 2a trial (NCT04224272) presented at SABCS indicate that zanidatamab in combination with palbociclib and fulvestrant, demonstrated meaningful PFS outcomes with a well tolerated safety profile in patients with heavily pretreated HER2+/HR+ mBC.
The single-arm trial evaluated zanidatamab plus palbociclib and fulvestrant in 51 patients with HER2+/HR+ unresectable, locally advanced or metastatic breast cancer who had received prior treatment with at least trastuzumab, pertuzumab, and T-DM1, and no prior treatment with a CDK4/6 inhibitor. Patients treated with the combination regimen received a median of four prior systemic regimens in the metastatic setting (range, 1-12).
Recommended doses of the zanidatamab plus palbociclib and fulvestrant combination therapy were determined in Part 1 of the study. The primary endpoint of Part 2 was PFS6. Other endpoints included mPFS, cORR per RECIST v1.1, DCR and DOR.
At the time of data cutoff (August 3, 2023), treatment with zanidatamab in combination with palbociclib and fulvestrant resulted in a PFS6 of 67% (n=34) and mPFS of 12 months [95% CI: 8, 15]. Median duration of follow-up was 16 months (range, 2-32). Patients treated with the combination regimen achieved a cORR of 35% and DCR of 91%.
Zanidatamab plus palbociclib and fulvestrant was well tolerated with a manageable safety profile. One serious treatment-related AE (transaminases increased) was reported (which resolved). No treatment-related deaths were reported. The most common treatment-related AEs (>20% of patients) were diarrhea, neutrophil count decrease/neutropenia, nausea, stomatitis, anemia, vomiting and asthenia. One patient discontinued the combination treatment due to an AE; three patients discontinued palbociclib due to an AE.
The abstract is available to conference registrants on the SABCS conference website here. (Abstract Number LBO1-04).
Additional data being presented at SABCS for zanidatamab include a spotlight poster presentation highlighting positive results of an investigator-sponsored Phase 1 trial evaluating neoadjuvant single-agent zanidatamab in patients with stage 1 node-negative HER2+ breast cancer (Abstract Number PS09-03).
About Zanidatamab
Zanidatamab is an investigational bispecific antibody that can simultaneously bind two non-overlapping epitopes of HER2, known as biparatopic binding. This unique design and increased binding results in multiple mechanisms of action, including dual HER2 signal blockade, removal of HER2 protein from the cell surface, and immune-mediated cytotoxicity leading to encouraging antitumor activity in patients. Zanidatamab is being developed in multiple clinical trials as a targeted treatment option for patients with solid tumors that express HER2. Zanidatamab is being developed by Jazz and BeiGene, Ltd. (BeiGene) under license agreements from Zymeworks, which first developed the molecule.
The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for zanidatamab development in patients with previously treated HER2 gene-amplified biliary tract cancers (BTC), and two Fast Track designations for zanidatamab: one as a single agent for refractory BTC and one in combination with standard of care chemotherapy for first-line gastroesophageal adenocarcinoma (GEA). Additionally, zanidatamab has received Orphan Drug designations from FDA for the treatment of BTC and GEA, as well as Orphan Drug designation from the European Medicines Agency for the treatment of BTC and gastric cancer. Zanidatamab was also granted Breakthrough Therapy designation from the Center for Drug Evaluation (CDE) in China.
In this Phase 2a trial, zanidatamab is being explored in combination with palbociclib under a clinical trial and supply agreement with Pfizer Inc.
About Jazz Pharmaceuticals
Jazz Pharmaceuticals plc (Nasdaq: JAZZ) is a global biopharmaceutical company whose purpose is to innovate to transform the lives of patients and their families. We are dedicated to developing life-changing medicines for people with serious diseases—often with limited or no therapeutic options. We have a diverse portfolio of marketed medicines and novel product candidates, from early- to late-stage development, in neuroscience and oncology. Within these therapeutic areas, we are identifying new options for patients by actively exploring small molecules and biologics, and through innovative delivery technologies and cannabinoid science. Jazz is headquartered in Dublin, Ireland and has employees around the globe, serving patients in nearly 75 countries. Please visit www.jazzpharmaceuticals.com for more information.
Jazz presents encouraging Phase 2 data for breast cancer treatment
Dec. 08, 2023 3:14 PM ET
Jazz Pharmaceuticals plc (JAZZ) Stock
By: Val Brickates Kennedy, SA News Editor
Jazz Pharmaceuticals (NASDAQ:JAZZ) presented updated positive data from a Phase 2a study for its breast cancer treatment candidate zanidatamab.
The study, which consisted of 51 people, demonstrated progression-free survival of 67% at six month, with median progression-free survival of 12 months and a confirmed objective response rate of 35%. Zanidatamab was tested in combination with palbociclib and fulvestrant in the treatment of heavily pretreated patients with HER2+/HR+ metastatic breast cancer.
Jazz Pharmaceuticals plc (JAZZ) Stock
LYFGENIA™ (lovotibeglogene autotemcel, also known as lovo-cel)
LYFGENIA™ (lovotibeglogene autotemcel, also known as lovo-cel)
LYFGENIA™ (lovotibeglogene autotemcel, also known as lovo-cel)
press release
bluebird bio Details Plans for the Commercial Launch of LYFGENIA™ Gene Therapy for Patients Ages 12 and Older with Sickle Cell Disease and a History of Vaso-Occlusive Events
Outcomes-based contract offerings available to both commercial payers and Medicaid
LYFGENIA will be available through bluebird’s established national network of Qualified Treatment Centers beginning in Q1 2024
“my bluebird support” patient services program will provide personalized support for patients and their families throughout their treatment journey
Price of LYFGENIA reflects its value as a potentially curative gene therapy for sickle cell disease through durable production of anti-sickling adult hemoglobin (HbAT87Q) and resolution of vaso-occlusive events
SOMERVILLE, Mass.--(BUSINESS WIRE)--Dec. 8, 2023-- bluebird bio, Inc. (NASDAQ: BLUE) (“bluebird bio” or the “bluebird”) today announced the details of its U.S. commercial infrastructure to support timely, equitable access to LYFGENIA™ (lovotibeglogene autotemcel, also known as lovo-cel), an FDA-approved gene therapy for the treatment of patients 12 years of age and older with sickle cell disease and a history of vaso-occlusive events (VOEs). The LYFGENIA launch builds on bluebird’s demonstrated success delivering ex vivo gene therapies to patients in the United States and includes outcomes-based contract offerings for payers, as well as a personalized patient support program.
“Our approach is built on the principle that timely, equitable access to gene therapy is imperative for people living with sickle cell disease,” said Tom Klima, chief commercial & operating officer, bluebird bio. “As an established commercial gene therapy leader, we believe bluebird is well positioned to partner with providers and payers to deliver LYFGENIA to a community that is long overdue for meaningful treatment advances. The location of our Qualified Treatment Centers and our patient services offering are designed to minimize burdens for patients and their families and caregivers, while our outcomes-based contract offerings have been created specifically to address challenges payers face as they adapt to provide access to one-time, transformative therapies.”
Data from clinical studies support LYFGENIA as a potentially curative gene therapy for sickle cell disease through durable production of anti-sickling adult hemoglobin (HbAT87Q) and resolution of vaso-occlusive events. bluebird has set the wholesale acquisition cost of LYFGENIA in the U.S. at $3.1M in recognition of the value the therapy may deliver through robust and sustained clinical benefits and the estimated lifetime impact that reducing or eliminating VOEs may have on patients’ healthcare utilization, future earnings, and life opportunities.
The burden of sickle cell disease is immense and can impact every aspect of life for patients and their loved ones. Beyond the debilitating and unpredictable vaso-occlusive events that are most associated with the disease, patients are at risk for irreversible damage to vital organs, diminished quality of life, and early death. Fifty to 60% of adults living with sickle cell disease have end organ damage, and one in four people living with sickle cell disease have a stroke by age 45. Despite a median age of death of 45 years, it is estimated that U.S. patients with frequent VOEs average $4.0 -$6.0 million in direct lifetime medical costs, not including patient-incurred out-of-pocket costs or the impact on caregivers. Patients also forgo approximately $1.3 million in lifetime earnings compared to their peers based on how their disease can limit academic and professional opportunities.
Payers Are Anticipated to Enable Timely Access and Reimbursement
To support timely and equitable access, bluebird has designed outcomes-based contract options unique to LYFGENIA that offer payers meaningful risk sharing tied to VOE-related hospitalizations—a claims-based metric that is directly correlated with clinical benefit and aligned with study endpoints in the LYFGENIA clinical development program—with patients followed for three years. A second contracting option is available specifically for state Medicaid agencies, based on direct input from these payers that predictability and operational ease are essential for states that are grappling with resource constraints. Both options tie the cost of LYFGENIA to its performance and manage payer risk as clinical experience is translated into the commercial setting.
“The FDA approval of a sickle cell disease gene therapy may be a game changer,” said Dr. Shantel Herbert-Magee, Chief Medical Director, Louisiana Medicaid. “Knowing that serious consequences of sickle cell disease can now potentially be averted, there is an expectation for Medicaid programs to provide access to cutting-edge therapies that seemingly have been impenetrable for the disadvantaged and underinsured. Given the vulnerabilities of the Medicaid population, we must not only consider the near-term drug cost but the potential for lower long-term health expenditures. Hence, policymakers are exploring collective approaches to making access less challenging from a fiscal and operational stance, including working with manufacturers on innovative contracts and examining the geographic and provider barriers to the administration of gene therapy. Indisputably, Medicaid is critical to the strategy.”
bluebird is in advanced discussions with the nation’s largest commercial payers and more than 15 Medicaid agencies representing 80% of individuals with sickle cell disease in the U.S.
Qualified Treatment Centers Are Ready for Patients
LYFGENIA will be available through bluebird’s established national network of Qualified Treatment Centers (QTCs), leading healthcare institutions with experience in delivering gene and cell therapies in the commercial setting, beginning in early 2024. One hundred percent of those centers have initiated the activation process for LYFGENIA.
Centers will be onboarded to deliver LYFGENIA on a rolling basis. Today, 27 QTCs are ready to receive patient referrals and we anticipate the full network will be fully activated by the end of Q1 2024. Details are available at mybluebirdsupport.com/qualified-treatment-center-locator.
my bluebird support Available to Assist Patients and Families Throughout the LYFGENIA Treatment Journey
bluebird’s patient support program, my bluebird support, will offer personalized support for each patient/family who enrolls in the program related to all stages of the gene therapy journey—from education and decision-making resources to benefits verification and logistical and financial support for eligible patients.
bluebird’s Patient Navigators are experienced professionals with success supporting patients with both commercial and public insurance and are in place now to assist in accessing bluebird’s FDA-approved therapies. Patients can call 833-888-NEST (833-888-6378) or visit mybluebirdsupport.com for more information.
LYFGENIA Clinical Data
The FDA approval of LYFGENIA builds on decades of research into lentiviral vector gene addition therapy and the largest clinical development program of any gene therapy for sickle cell disease.
The label is based on data from patients from the Phase 1/2 HGB-206 study. Safety data supporting the application includes data from 54 patients who initiated stem cell collection. Efficacy for LYFGENIA was supported by data from 36 patients in the Phase 1/2 HGB-206 Group C study following enhancements to the treatment and manufacturing processes made through the course of the clinical development program. 32 patients were evaluable for the endpoints of complete resolution of VOEs and severe VOEs in the 6-18 months post-infusion including 8 adolescent patients. In this cohort:
- Severe vaso-occlusive events were resolved in 30/32 patients (94%)
- 28/32 patients (88.2%) experienced no vaso-occlusive events at all
In the studies, VOEs are defined as episodes of acute pain with no medically determined cause other than a vaso-occlusion, lasting more than two hours and severe enough to require care at a medical facility. This includes acute chest syndrome requiring oxygen treatment and/or blood transfusion, acute hepatic sequestration, acute priapism lasting 2 hours and requiring care at a medical facility and acute splenic sequestration. sVOEs require a 24-hour hospital stay or emergency room visit, or at least two visits to a hospital or emergency room over a 72-hour period, with both visits requiring intravenous treatment; all VOEs of priapism are also considered sVOEs.
The most common adverse reactions ≥ Grade 3 (incidence ≥ 20%) were stomatitis, thrombocytopenia, neutropenia, febrile neutropenia, anemia, and leukopenia. As previously reported, three patients died during LYFGENIA clinical trials; one from sudden cardiac death due to underlying disease and two from acute myeloid leukemia who were treated with an earlier version of LYFGENIA using a different manufacturing process and transplant procedure. Please see LYFGENIA Important Safety Information below, including a Boxed Warning for Hematologic Malignancy.
Patients treated with LYFGENIA in bluebird bio-sponsored clinical studies will be monitored for a total of 15 years through a long-term safety and efficacy follow-up study (LTF-307).
About LYFGENIA™
LYFGENIA is a one-time ex-vivo lentiviral vector gene therapy approved for the treatment of patients 12 years of age or older with sickle cell disease and a history of vaso-occlusive events (VOEs). LYFGENIA works by adding a functional β-globin gene to patients’ own hematopoietic (blood) stem cells (HSCs). Durable production of adult hemoglobin with anti-sickling properties (HbAT87Q) is possible following successful engraftment. HbAT87Q has a similar oxygen-binding affinity to wild-type HbA, limits sickling of red blood cells and has the potential to reduce and VOEs.
The Phase 1/2 HGB-206 study of LYFGENIA is ongoing with enrollment and treatment complete; and the Phase 3 HGB-210 study evaluating LYFGENIA is ongoing. bluebird bio is also conducting a long-term safety and efficacy follow-up study (LTF-307) for patients with sickle cell disease who have been treated with LYFGENIA in bluebird bio-sponsored clinical studies.
Indication
LYFGENIA is indicated for the treatment of patients 12 years of age or older with sickle cell disease and a history of vaso-occlusive events (VOEs).
Limitations of Use
Following treatment with LYFGENIA, patients with α-thalassemia trait (α3.7/ α3.7) may experience anemia with erythroid dysplasia that may require chronic red blood cell transfusions. LYFGENIA has not been studied in patients with more than two α-globin gene deletions.
Please see full Prescribing Information for LYFGENIA including Boxed WARNING and Medication Guide.
About bluebird bio, Inc.
bluebird bio is pursuing curative gene therapies to give patients and their families more bluebird days.
Founded in 2010, bluebird has been setting the standard for gene therapy for more than a decade—first as a scientific pioneer and now as a commercial leader. bluebird has an unrivaled track record in bringing the promise of gene therapy out of clinical studies and into the real-world setting, having secured FDA approvals for three therapies in under two years. Today, we are proving and scaling the commercial model for gene therapy and delivering innovative solutions for access to patients, providers, and payers.
With a dedicated focus on severe genetic diseases, bluebird has the largest and deepest ex-vivo gene therapy data set in the field, with industry-leading programs for sickle cell disease, β-thalassemia and cerebral adrenoleukodystrophy. We custom design each of our therapies to address the underlying cause of disease and have developed in-depth and effective analytical methods to understand the safety of our lentiviral vector technologies and drive the field of gene therapy forward.
bluebird continues to forge new paths as a standalone commercial gene therapy company, combining our real-world experience with a deep commitment to patient communities and a people-centric culture that attracts and grows a diverse flock of dedicated birds.
For more information, visit bluebirdbio.com or follow us on social media at @bluebirdbio, LinkedIn, Instagram and YouTube.
LYFGENIA and bluebird bio are trademarks of bluebird bio, Inc.
View source version on businesswire.com: https://www.businesswire.com/news/home/20231208301760/en/
Source: bluebird bio, Inc.
bluebird bio gains FDA approval of gene therapy lovo-cel for sickle cell disease
Dec. 08, 2023 11:39 AM ET
bluebird bio, Inc. (BLUE) StockVRTX, CRSP
By: Jonathan Block, SA News Editor4 Comments
- The U.S. FDA Friday approved bluebird bio's (NASDAQ:BLUE) Lyfgenia (lovo-cel), a gene therapy for sickle cell disease.
- The treatment uses a lentiviral vector -- a type of gene delivery vehicle -- for genetic modification. It is for patients with SCD with a history of vaso-occlusive events.
- https://seekingalpha.com/news/4044803-bluebird-bio-gains-fda-approval-gene-therapy-lovo-cell-sickle-cell-disease
- bluebird bio, Inc. (BLUE) Stock
- https://www.bluebirdbio.com/
SGT-003
LINVOSELTAMAB (BCMAXCD3)
LYFGENIA™ (lovotibeglogene autotemcel, also known as lovo-cel)
Solid Biosciences Receives FDA Fast Track Designation for Duchenne Muscular Dystrophy Gene Therapy SGT-003
December 7, 2023
– Next-generation gene transfer therapy to treat Duchenne receives FDA Fast Track Designation –
CHARLESTOWN, Mass., Dec. 07, 2023 (GLOBE NEWSWIRE) -- Solid Biosciences Inc. (Nasdaq: SLDB), a life sciences company developing precision genetic medicines for neuromuscular and cardiac diseases, today announced that it has received Fast Track Designation from the U.S. Food and Drug Administration (FDA) for SGT-003, the company’s next-generation Duchenne muscular dystrophy (Duchenne) gene therapy candidate.
“Receipt of FDA Fast Track Designation underscores the importance of rapidly developing SGT-003 to potentially aid the unmet needs of the Duchenne community,” said Bo Cumbo, President and CEO at Solid Biosciences. “Having received IND clearance for SGT-003 last month, we are pleased to be expediting the development of a potentially life-changing therapy and look forward to continuing to work closely with the FDA.”
IND clearance by the FDA for SGT-003 was received in November 2023. The planned Phase 1/2 trial, SGT-003-101, is a first-in-human, open-label, multicenter trial to determine the safety and tolerability of SGT-003 in pediatric patients with DMD at a dose of 1E14vg/kg. SGT-003 will be administered as a one-time intravenous infusion to patients in two cohorts with a minimum of three patients each, with the potential for cohort expansion. Cohort 1 will study patients aged 4 to < 6 years of age with DMD. Long-term safety and efficacy will be evaluated for a total of 5 years following treatment.
“We appreciate the FDA’s partnership and their recognition of the continuing unmet need in the DMD community,” said Jessie Hanrahan, Ph.D., Chief Regulatory Officer at Solid Biosciences. “We look forward to frequent engagements with the Agency to discuss development of SGT-003 and ensure that our clinical development program will appropriately collect the data needed to support review of SGT-003 for future marketing authorization.”
About SGT-003
SGT-003 uses a proprietary, rationally designed capsid (AAV-SLB101) to deliver a DNA sequence encoding a shortened form of the dystrophin protein (microdystrophin), containing the R16-R17 nNOS binding domain. Preclinical data suggests this may be important for both muscular function and durability of benefit in patients.
About Fast Track Designation
The Fast Track program facilitates the expedited development and review of new drugs that are intended to treat serious or life-threatening conditions and demonstrate the potential to address unmet medical needs.
About DMD
Duchenne is a genetic muscle-wasting disease predominantly affecting boys, with symptoms usually appearing between three and five years of age. Duchenne is a progressive, irreversible, and ultimately fatal disease that affects approximately one in every 3,500 to 5,000 live male births and has an estimated prevalence of 5,000 to 15,000 cases in the United States alone.
About Solid Biosciences
Solid Biosciences is a life sciences company focused on advancing a portfolio of gene therapy candidates and neuromuscular and cardiac programs, including SGT-003, for the treatment of Duchenne muscular dystrophy (Duchenne), SGT-501 for the treatment of catecholaminergic polymorphic ventricular tachycardia (CPVT), AVB-401 for the treatment of BAG3-mediated dilated cardiomyopathy, AVB-202-TT for the treatment of Friedreich’s ataxia, and additional assets for the treatment of fatal cardiac diseases. Solid is advancing its diverse pipeline across rare neuromuscular and cardiac diseases, bringing together experts in science, technology, disease management, and care. Patient-focused and founded by those directly impacted, Solid’s mandate is to improve the daily lives of patients living with these devastating diseases. For more information, please visit www.solidbio.com.
Source: Solid Biosciences Inc.
Solid Biosciences receives FDA Fast Track designation for Duchenne gene therapy candidate
Dec. 07, 2023 8:56 AM ET
Solid Biosciences Inc. (SLDB) Stock
By: Jaskiran Singh, SA News Editor
- Solid Biosciences (NASDAQ:SLDB) rose about 6% in premarket trading as the company announced the receipt of Fast Track designation for the U.S. FDA for SGT-003, its Duchenne muscular dystrophy gene therapy candidate.
- The Fast Track program facilitates the expedited development and review of new drugs that are intended to treat serious or life-threatening conditions and demonstrate the potential to address unmet medical needs.
- https://seekingalpha.com/news/4044334-solid-biosciences-receives-fda-fast-track-designation-for-duchenne-gene-therapy-candidate
- Solid Biosciences Inc. (SLDB) Stock
- https://www.solidbio.com/our-science/pipeline-programs/pipeline
- https://www.solidbio.com/
LINVOSELTAMAB (BCMAXCD3)
LINVOSELTAMAB (BCMAXCD3)
LINVOSELTAMAB (BCMAXCD3)
December 7, 2023 at 7:00 AM EST
UPDATED LINVOSELTAMAB PIVOTAL DATA DEMONSTRATED STRONG RATES AND DEPTH OF RESPONSE IN PATIENTS WITH HEAVILY PRE-TREATED MULTIPLE MYELOMA
71% objective response rate, with 46% achieving a complete response or better after 11 months of median follow-up
Data to be submitted to regulatory authorities, with Biologics License Application on track to be submitted to the FDA this year
Regeneron to host virtual investor event to discuss results alongside updates across its hematology portfolio on Thursday, December 14 at 8:30 a.m. ET
TARRYTOWN, N.Y., Dec. 07, 2023 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced that the primary endpoint analysis from the pivotal trial (LINKER-MM1) investigating linvoseltamab demonstrated high rates of deep and durable responses in patients with relapsed/refractory (R/R) multiple myeloma (MM). These Phase 1/2 results are planned to be submitted to regulatory authorities, including to the U.S. Food and Drug Administration (FDA) this year. Linvoseltamab is an investigational BCMAxCD3 bispecific antibody designed to bridge B-cell maturation antigen (BCMA) on multiple myeloma cells with CD3-expressing T cells to facilitate T-cell activation and cancer-cell killing.
“Multiple myeloma remains an incurable disease, in which patients endure cycles of relapse and remission, resulting in a critical need for innovative medicines,” said L. Andres Sirulnik, M.D., Ph.D., Senior Vice President, Translational and Clinical Sciences, Hematology at Regeneron. “With longer follow-up data on linvoseltamab, we’re seeing deep and durable responses with a complete response rate nearing 50% in a difficult-to-treat patient population who had received a median of 5 prior lines of therapy. Furthermore, in our trial, the regimen had a short monitoring time and a convenient, response-adapted administration schedule that enabled deep responders to go from every two-week to every four-week dosing. This regimen saved time for clinicians and patients, underscoring the potential for linvoseltamab as a patient-centric option in relapsed/refractory multiple myeloma.”
At a median duration of follow-up of 11 months, an objective response rate of 71% as assessed by an independent review committee, with 46% achieving a complete response or better, was observed in patients treated with linvoseltamab 200 mg in the Phase 1/2 trial (n=117). After a minimum of 24 weeks of therapy, patients who achieved a very good partial response (VGPR) or better shifted from every two-week to every four-week dosing. These results build on an earlier data cut, with 8 months of median follow-up, that will be presented at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition from December 9 to 12 in San Diego, CA.
Among this group of patients, 27% of patients were over 75 years old, 16% had extramedullary plasmacytomas, 23% had bone marrow plasma cells ≥50%, and 39% had high-risk cytogenetics – representing a patient population with a high disease burden and typically poor prognosis. Additionally, 17% were Black or African American, mirroring rates that are representative of MM in the U.S.
Based on the latest data cut, all patients treated with 200 mg experienced an adverse event (AE), including 85% who experienced Grade ≥3 adverse events (AE). The most commonly occurring AE was cytokine release syndrome (CRS; 46%). Of the CRS cases, the majority (35%) were Grade 1, 10% were Grade 2 and there was one case (1%) of Grade 3 CRS. Adjudicated immune effector cell-associated neurotoxicity syndrome (ICANS) events occurred in 9 patients (8% all Grades); Grade 3 ICANS occurred in 3 patients, and no cases of ≥Grade 4 cases. All grade infections were observed in 73% of patients; 34% were Grade 3 or 4. Deaths due to treatment-emergent AEs on-treatment or within 30 days post last dose occurred in 14 patients (12%), of which 11 (9%) were due to infections.
The development program investigating linvoseltamab, including in earlier stages of the disease is underway. In the U.S., linvoseltamab has been granted Fast Track Designation for multiple myeloma by the FDA. Linvoseltamab is currently under clinical development, and its safety and efficacy have not been fully evaluated by any regulatory authority.
Investor Webcast Information
Regeneron will host a conference call and simultaneous webcast to share updates on the company’s hematology portfolio on Thursday, December 14 at 8:30 AM ET. A link to the webcast may be accessed from the ‘Investors and Media’ page of Regeneron's website at http://investor.regeneron.com/events.cfm. To participate via telephone, please register in advance at this link. Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call. A replay of the conference call and webcast will be archived on the company's website for at least 30 days.
About the Phase 1/2 Trial
The ongoing, open-label, multicenter Phase 1/2 dose-escalation and dose-expansion trial is investigating linvoseltamab in patients with R/R MM. Among the 282 patients enrolled, all have received at least three prior lines of therapy or are triple refractory. Patients were administered linvoseltamab utilizing a step-up dosing regimen that was designed to help mitigate CRS.
The Phase 1 intravenous dose-escalation portion of the trial, which is now complete, primarily assessed safety, tolerability and dose-limiting toxicities across nine dose levels of linvoseltamab exploring different administration regimens. The Phase 2 dose expansion portion of the trial (LINKER-MM1) is further assessing the safety and anti-tumor activity of linvoseltamab, with a primary objective of ORR. Key secondary objectives include duration of response, PFS, rate of minimal residual disease negative status and overall survival.
About Multiple Myeloma
Multiple myeloma is the second most common blood cancer. Globally, there are over 176,000 new cases diagnosed annually and an estimated 35,000 people were diagnosed in the U.S. It is characterized by the proliferation of cancerous plasma cells (multiple myeloma cells) that crowd out healthy blood cells in the bone marrow, infiltrate other tissues and cause potentially life-threatening organ injury. Multiple myeloma is not curable despite treatment advances, and while current treatments are able to slow the progression of the cancer, most patients will ultimately experience cancer progression and require additional therapies.
About Regeneron in Hematology
At Regeneron, we’re applying more than three decades of biology expertise with our proprietary VelociSuite® technologies to develop medicines for patients with diverse blood cancers and rare blood disorders.
Our blood cancer research is focused on bispecific antibodies that are being investigated both as monotherapies and in combination with each other and emerging therapeutic modalities. Together, they provide us with unique combinatorial flexibility to develop customized and potentially synergistic cancer treatments.
Our research and collaborations to develop potential treatments for rare blood disorders include explorations in antibody medicine, gene editing and gene-knockout technologies, and investigational RNA-approaches focused on depleting abnormal proteins or blocking disease-causing cellular signaling.
If you are interested in learning more about our clinical trials, please contact us (clinicaltrials@regeneron.com or 844-734-6643) or visit our clinical trials website.
About Regeneron
Regeneron is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led for 35 years by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous FDA-approved treatments and product candidates in development, almost all of which were homegrown in our laboratories. Regeneron’s medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, hematologic conditions, infectious diseases and rare diseases.
Regeneron is accelerating and improving the traditional drug development process through its proprietary VelociSuite technologies, such as VelocImmune®, which uses unique genetically humanized mice to produce optimized fully human antibodies and bispecific antibodies, and through ambitious research initiatives such as the Regeneron Genetics Center®, which is conducting one of the largest genetics sequencing efforts in the world.
For additional information about Regeneron, please visit www.regeneron.com or follow Regeneron on LinkedIn.
Source: Regeneron Pharmaceuticals, Inc.
Regeneron lifts complete remission in trial for multiple myeloma candidate
Dec. 07, 2023 8:02 AM ET
Regeneron Pharmaceuticals, Inc. (REGN) Stock
By: Dulan Lokuwithana, SA News Editor
- Regeneron Pharmaceuticals (NASDAQ:REGN) updated trial results for its bispecific antibody linvoseltamab on Thursday, indicating that the investigational therapy improved complete remission in a pivotal Phase 1/2 trial for multiple myeloma.
- Citing data from 117 patients, the company said that those who received linvoseltamab at 200 mg with a median follow-up of 11 months demonstrated a 71% objective response rate (ORR), with 46% indicating a complete response or better.
- A previous readout for the same dose level showed a 71% ORR, with 30% achieving CR or better at 5.6 months of median follow-up.
- https://seekingalpha.com/news/4044293-regeneron-updates-data-multiple-myeloma-candidate
- Regeneron Pharmaceuticals, Inc. (REGN) Stock
- https://www.regeneron.com/
- https://www.regeneron.com/pipeline-medicines/investigational-pipeline
Elafibranor
LINVOSELTAMAB (BCMAXCD3)
LINVOSELTAMAB (BCMAXCD3)
Ipsen confirms U.S. FDA grants priority review for New Drug Application for elafibranor for the treatment of rare cholestatic liver disease, PBC
Rare Diseases - 07 December 2023
- New Drug Application granted priority review with PDUFA date set for June 10, 2024
- European Medicines Agency (EMA) has also validated the Marketing Authorization Application (MAA) for elafibranor
- Investigational elafibranor is the first novel second-line treatment for primary biliary cholangitis (PBC) to be filed in E.U. and U.S. in nearly a decade
PARIS, FRANCE, 07 December 2023 – Ipsen (Euronext: IPN; ADR: IPSEY) and GENFIT (Nasdaq and Euronext: GNFT) today announced that the U.S. Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for investigational elafibranor. An oral, once-daily dual peroxisome activated receptor alpha/delta (PPAR α,δ) agonist, investigational elafibranor could potentially be the first novel second-line treatment for the rare, cholestatic liver disease, PBC, in nearly a decade. The target FDA PDUFA date under priority review is June 10, 2024.
The European Medicines Agency (EMA) has also validated Ipsen’s Marketing Authorization Application (MAA) for elafibranor and the review of the submission to the EMA’s Committee for Medicinal Products for Human Use (CHMP) began on 26 October 2023. Furthermore, a third simultaneous regulatory filing of elafibranor has been validated for review by the UK Medicines and Healthcare products Regulatory Agency (MHRA).
“We are delighted to have achieved simultaneous filings for elafibranor, which is in line with our ambition to be able to bring a new and much needed medicine to as many people living with PBC as rapidly as possible,” said Christelle Huguet, EVP and Head of Research & Development, Ipsen. “This is a condition where many patients are living with worsening disease and debilitating symptoms despite being on treatment. Elafibranor, if approved, has the potential to change the management of this challenging condition for people living with PBC, offering a new second line treatment choice, where the number of effective options are currently limited.”
PBC is a rare, progressive, autoimmune cholestatic liver disease1 in which bile ducts in the liver are gradually destroyed.2 The damage to bile ducts can inhibit the liver’s ability to rid the body of toxins, and can lead to scarring of liver tissue, known as cirrhosis.1,2,3 Common symptoms of PBC include fatigue and pruritus (itch), which can be severely debilitating.4 Untreated, PBC can lead to liver failure, or in some cases death.1 It primarily affects women, with nine women diagnosed for every man.3 A significant proportion of people living with PBC do not benefit from existing therapies.5,6,7
“These simultaneous regulatory submission acceptances are another important step in the elafibranor journey. We are pleased to be partnering with Ipsen, who we know has a good understanding of the rare-disease regulatory process,” said Pascal Prigent, Chief Executive Officer of GENFIT. “We know they share the same goal as GENFIT, to bring a new, much needed treatment option to people living with PBC as fast as possible; we look forward to elafibranor’s progress through the regulatory review processes.”
ENDS
Elafibranor
Elafibranor is an oral, once-daily, dual peroxisome activated receptor (PPAR) alpha/delta (α,δ) agonist, currently under investigation as a treatment for patients with PBC, a rare cholestatic liver disease. Elafibranor, through activation of PPAR α,δ targets multiple cell types and biological processes involved in the pathophysiology of PBC, including cholestasis (impairment of bile flow in the liver), bile toxicity, inflammation and fibrosis and bile acid output. In 2019, elafibranor was granted a Breakthrough Therapy Designation by the U.S Food and Drug Administration in adults with PBC who have an inadequate response to ursodeoxycholic acid (UDCA) the existing first-line therapy for PBC. Elafibranor has not received approval by regulatory authorities anywhere in the world.
ELATIVE
ELATIVE is a multi-center, randomized, double-blind, placebo-controlled Phase III clinical trial, with an open-label long-term extension (NCT04526665). ELATIVE evaluated the efficacy and safety of elafibranor 80mg once daily versus placebo for the treatment of patients with PBC with an inadequate response or intolerance to UDCA. The trial enrolled 161 patients who were randomized 2:1 to receive either elafibranor 80mg once daily or placebo. Patients with an inadequate response to UDCA would continue to receive UDCA in combination with elafibranor or placebo, while patients unable to tolerate UDCA would receive only elafibranor or placebo. Data confirmed the potential for elafibranor to be an effective new treatment option for PBC, with 13 times more patients achieving a biochemical response, suggesting an improvement in disease progression, when treated with elafibranor compared with patients on placebo: 47% placebo-adjusted difference, elafibranor 80mg (51%) compared with placebo (4%) (P<0.001).8
Reductions in levels of alkaline phosphatase (ALP) were rapid, seen as early as Week 4 in the elafibranor group, and were sustained through Week 52, with a decrease in ALP of 41% on elafibranor compared with placebo.8 ALP and bilirubin are important predictors of PBC disease progression. ELATIVE also investigated the effect of treatment with elafibranor on pruritus (severe itch), a significant symptom burden amongst people living with PBC. Findings from the secondary endpoint using the PBC Worst Itch NRS score, showed a reduction in pruritis for elafibranor, which was not statistically significant. Data reported from two separate patient-reported outcome measures demonstrated reductions in moderate to severe pruritus, which favored elafibranor versus placebo.8 Elafibranor was well-tolerated in the trial and has a well-documented safety profile. Adverse events occurring in >10% of patients and more frequently on elafibranor versus placebo included abdominal pain, diarrhea, nausea, and vomiting.8
Ipsen
We are a global biopharmaceutical company with a focus on bringing transformative medicines to patients in three therapeutic areas: Oncology, Rare Disease and Neuroscience.
Our pipeline is fueled by external innovation and supported by nearly 100 years of development experience and global hubs in the U.S., France and the U.K. Our teams in more than 40 countries and our partnerships around the world enable us to bring medicines to patients in more than 100 countries.
Ipsen is listed in Paris (Euronext: IPN) and in the U.S. through a Sponsored Level I American Depositary Receipt program (ADR: IPSEY). For more information, visit ipsen.com.
GENFIT
GENFIT is a late-stage biopharmaceutical company dedicated to improving the lives of patients with rare and life-threatening liver diseases characterized by high unmet medical needs. GENFIT is a pioneer in liver disease research and development with a rich history and strong scientific heritage spanning more than two decades. Today, GENFIT has a growing and diversified pipeline with programs at various development stages. The Company’s area of focus is Acute on Chronic Liver Failure (ACLF). Its ACLF franchise consists of five assets in development: VS-01, NTZ, SRT-015, CLM-022 and VS-02-HE. These are all based on differentiated mechanisms of action leveraging complementary pathways. Other assets target other life-threatening disease indications such as cholangiocarcinoma (CCA) and Urea Cycle Disorders (UCD)/Organic Acidemias (OA). GENFIT’s track record in bringing early-stage assets with high potential to late development and pre-commercialization stages is highlighted in the successful 52-week Phase 3 ELATIVE® trial evaluating elafibranor in PBC. Beyond therapeutics, GENFIT’s pipeline also includes a diagnostic franchise focused on MASH (previously known as NASH) and ammonia. GENFIT has facilities in Lille and Paris (France), Zurich (Switzerland) and Cambridge, MA (USA). GENFIT is a publicly traded company listed on the Nasdaq Global Select Market and on compartment B of Euronext’s regulated market in Paris (Nasdaq and Euronext: GNFT). In 2021, IPSEN became one of GENFIT’s largest shareholders and holds 8% of the company’s share capital. For more information, visit www.genfit.com
FDA grants priority review of Genfit-Ipsen liver disease drug
Dec. 07, 2023 6:07 AM ET
Genfit S.A. (GNFT) Stock, IPSEY Stock
By: Preeti Singh, SA News Editor1 Comment
- Genfit (NASDAQ:GNFT) and partner Ipsen (OTCPK:IPSEY) announced on Thursday that their investigational drug elafibranor has been granted priority review by the U.S. Food and Drug Administration.
- In 2019, elafibranor received breakthrough therapy designation from the FDA for the treatment of adults with a rare liver disease, primary biliary cholangitis (PBC), who have shown an inadequate response to ursodeoxycholic acid (UDCA).
- https://seekingalpha.com/news/4044226-fda-grants-priority-review-of-genfit-ipsen-liver-disease-drug
- Genfit S.A. (GNFT) Stock, IPSEY Stock
- https://www.genfit.fr/
- https://www.ipsen.com/
biotecHOPE™ 2023
Fabhalta® (iptacopan)
ELAHERE® (mirvetuximab soravtansine-gynx)
Fabhalta® (iptacopan)
Novartis receives FDA approval for Fabhalta® (iptacopan), offering superior hemoglobin improvement in the absence of transfusions as the first oral monotherapy for adults with PNH
Dec 06, 2023
Ad hoc announcement pursuant to Art. 53 LR
- Approval based on APPLY-PNH trial in adults with PNH and anemia despite prior anti-C5 treatment, and supported by the APPOINT-PNH study in complement inhibitor-naïve patients1-5
- In APPLY-PNH, patients who switched to Fabhalta experienced superior increases of hemoglobin levels ≥ 2 g/dL (82.3% vs. 0%) and hemoglobin level ≥ 12 g/dL (67.7% vs. 0%), both in the absence of red blood cell transfusions, vs. patients who continued on anti-C5 treatment1,2
- Fabhalta, now available for both previously treated and treatment-naïve patients, is the only FDA-approved Factor B inhibitor of the immune system’s complement pathway, which drives complement-mediated hemolysis in PNH1,6
- Significant unmet need remains in PNH, a chronic and rare blood disorder; despite anti-C5 therapy, a large proportion of patients can remain anemic and dependent on blood transfusions7,8
- Late-stage Fabhalta development program ongoing in multiple complement-mediated conditions
Basel, December 6, 2023 —
Novartis today announced that the U.S. Food and Drug Administration (FDA) approved Fabhalta® (iptacopan) as the first oral monotherapy for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH)1. Fabhalta is a Factor B inhibitor that acts proximally in the alternative complement pathway of the immune system, providing comprehensive control of red blood cell (RBC) destruction within and outside the blood vessels (intra- and extravascular hemolysis [IVH and EVH]). In clinical trials, treatment with Fabhalta increased hemoglobin levels (≥ 2 g/dL from baseline in the absence of RBC transfusions) in the majority of patients and in APPLY-PNH nearly all patients treated with Fabhalta did not receive blood transfusions1-5.
“An efficacious oral treatment with a demonstrated safety profile could be practice-changing for physicians and help relieve burdens experienced by people with PNH,” said Vinod Pullarkat, MD, MRCP, Clinical Professor, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope. “In clinical studies, iptacopan was superior to anti-C5s in hemoglobin improvement in the absence of RBC transfusion and transfusion avoidance rate, and also effective in complement inhibitor-naïve individuals, by providing clinically meaningful hemoglobin-level increases without the need for blood transfusions.”
The FDA approval is based on the Phase III APPLY-PNH trial in patients with residual anemia (hemoglobin < 10 g/dL) despite prior anti-C5 treatment who switched to Fabhalta, which demonstrated superiority in hemoglobin improvement in the absence of RBC transfusions and in transfusion avoidance rate over patients who stayed on anti-C5 treatments1,2. Approval was also supported by the Phase III APPOINT-PNH study in complement inhibitor-naïve patients1,3. The 24-week core treatment periods in APPLY-PNH and APPOINT-PNH trials respectively showed1-3:
- Patients with sustained increase of hemoglobin levels ≥ 2 g/dLa from baseline in the absence of transfusions: 82.3% of anti-C5-experienced Fabhalta patients responded vs. 0% for anti-C5 (difference of 81.5%b, P<0.0001); 77.5% of complement inhibitor-naïve patients using Fabhalta achieved this outcome (sensitivity analysis showed 87.5%c)1-3.
- Patients with sustained hemoglobin level ≥ 12 g/dLa in the absence of transfusions: 67.7% of anti-C5-experienced Fabhalta patients responded vs. 0% for anti-C5 (difference of 66.6%b, P<0.0001)1,2.
- Patients avoiding transfusiond,e: Transfusion avoidance rate 95.2% for anti-C5-experienced Fabhalta patients vs. 45.7% for anti-C5 (difference of 49.5%b, P<0.0001)1,2.
In the APPLY-PNH trial, the most commonly reported (≥10%) adverse reactions (ARs) with Fabhalta vs. anti-C5s were: headachef (19% vs. 3%), nasopharyngitisg (16% vs. 17%), diarrhea (15% vs. 6%), abdominal painf (15% vs. 3%), bacterial infectionh (11% vs. 11%), nausea (10% vs. 3%), and viral infectioni (10% vs. 31%)1,2. In the APPOINT-PNH trial, the most commonly reported ARs (≥10%) were headachef (28%), viral infectioni (18%), nasopharyngitisg (15%), and rashj (10%)1,3. In APPLY-PNH, serious ARs were reported in two (3%) patients with PNH receiving Fabhalta, which included pyelonephritis, urinary tract infection and COVID-191,2. In APPOINT-PNH, serious ARs were reported in two (5%) patients with PNH receiving Fabhalta, which included COVID-19 and bacterial pneumonia1,3.
Fabhalta may cause serious infections caused by encapsulated bacteria and is available only through a Risk Evaluation and Mitigation Strategy (REMS) that requires vaccinations for encapsulated bacteria1.
People with PNH have an acquired mutation making red blood cells susceptible to premature destruction by the complement system6,8. PNH is characterized by hemolysis, bone marrow failure, and thrombosis in varying combinations and levels of severity6-8. Existing C5 inhibitor treatments, administered as infusions, may leave PNH symptoms uncontrolled7,8. Up to 88% of patients on anti-C5 treatment may have persistent anemia with over one-third of those patients requiring blood transfusions at least once per year7,8.
“The U.S. approval of Fabhalta is an extraordinary moment for people living with PNH, their loved ones and the healthcare providers who care for them,” said Victor Bultó, President US, Novartis. “This new, effective oral medicine may mean that patients can reset their expectations of living with PNH, a chronic and life-altering blood disease. As Novartis continues to focus on conditions with unmet patient need, we are exploring the potential of Fabhalta in other complement-mediated diseases – with an ultimate goal to drive meaningful change for patients.”
Discovered and developed by Novartis, Fabhalta is expected to be available in the United States in December. Additional regulatory filings and reviews for Fabhalta in PNH are currently underway around the world.
aAssessed between Day 126 and Day 168. bAdjusted difference in proportion. cSensitivity analysis incorporates data from local labs when central labs were not available. dAssessed between Day 14 and Day 168. eTransfusion avoidance is defined as absence of administration of packed-red blood cell transfusions between Day 14 and Day 168. fIncludes similar terms. gNasopharyngitis contains: rhinitis allergic, upper respiratory tract infection, pharyngitis, rhinitis. hBacterial infection contains: pyelonephritis, urinary tract infection, bronchitis bacterial, bronchitis haemophilus, cholecystitis, folliculitis, cellulitis, arthritis bacterial, sepsis, klebsiella infection, staphylococcal infection, Pseudomonas infection, hordeolum, pneumonia bacterial. iViral infection contains: COVID-19, herpes zoster, oral herpes, nasal herpes, influenza A virus test positive, influenza. jRash: dermatitis allergic, acne, erythema multiforme, rash maculo-papular, rash erythematous.
About APPLY-PNH
APPLY-PNH (NCT04558918) was a Phase III, randomized, multinational, multicenter, active-comparator controlled, open-label trial to evaluate the efficacy and safety of twice-daily, oral Fabhalta monotherapy (200 mg) for the treatment of PNH by assessing if switching to Fabhalta was superior to continuing on anti-C5 therapies (US-approved and non-US-approved eculizumab and ravulizumab) in adult patients presenting with residual anemia (Hb <10 g/dL) despite a stable regimen of anti-C5 treatment in the last six months prior to randomization2,9. The trial enrolled 97 patients who were randomized in an 8:5 ratio to either twice-daily, oral Fabhalta monotherapy, or intravenous anti-C5 therapies (continuing with the same regimen as they were on prior to randomization)2,9.
About APPOINT-PNH
APPOINT-PNH (NCT04820530) was a Phase III, multinational, multicenter, open-label, uncontrolled single-arm study to evaluate the efficacy and safety of twice-daily, oral Fabhalta monotherapy (200 mg) in adult PNH patients who are naïve to complement inhibitor therapy, including anti-C5 therapies (eculizumab or ravulizumab)3,10. The trial enrolled 40 patients who received twice-daily, oral Fabhalta monotherapy3,10.
About paroxysmal nocturnal hemoglobinuria (PNH)
PNH is a rare, chronic and serious complement-mediated blood disorder6. People with PNH have an acquired mutation in some of their hematopoietic stem cells (which are located in the bone marrow and can grow and develop into RBCs, white blood cells and platelets) that causes them to produce RBCs that are susceptible to premature destruction by the complement system6,8. This leads to intravascular hemolysis (destruction of RBCs within blood vessels) and extravascular hemolysis (destruction of RBCs mostly in the spleen and liver), which cause anemia (low levels of circulating RBCs), thrombosis (formation of blood clots) and other debilitating symptoms6,8.
It is estimated that approximately 10-20 people per million worldwide live with PNH6. Although PNH can develop at any age, it is often diagnosed in people between 30-40 years old11,12.
PNH has a significant unmet need not fully addressed by anti-C5 therapies (eculizumab or ravulizumab): despite treatment with anti-C5s, a large proportion of people with PNH may remain anemic, and dependent on blood transfusions6-8,13,14.
About Fabhalta® (iptacopan)
Fabhalta (iptacopan) is an oral, Factor B inhibitor of the alternative complement pathway15-17. Fabhalta is indicated for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH).
Discovered at Novartis, Fabhalta is currently in development for a range of complement-mediated diseases including immunoglobulin A nephropathy (IgA nephropathy), C3 glomerulopathy (C3G), immune complex membranoproliferative glomerulonephritis (IC-MPGN) and atypical hemolytic uremic syndrome (aHUS).
Based on disease prevalence, unmet needs and data from Phase II studies, Fabhalta has received FDA Breakthrough Therapy Designation in PNH, FDA Breakthrough Therapy Designation in C3G, orphan drug designations from the FDA and EMA in PNH and C3G, EMA PRIME designation for C3G, and EMA orphan drug designation in IgAN18-21.
About Novartis
Novartis is an innovative medicines company. Every day, we work to reimagine medicine to improve and extend people’s lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach more than 250 million people worldwide.
Reimagine medicine with us: Visit us at https://www.novartis.com and connect with us on LinkedIn, Facebook, X/Twitter and Instagram.
Novartis wins FDA nod for rare blood disorder drug
Dec. 06, 2023 5:57 AM ET
By: Preeti Singh, SA News Editor
Novartis (NYSE:NVS) has been awarded U.S. FDA approval for its drug Fabhalta (iptacopan) as the first oral monotherapy for adults with paroxysmal nocturnal hemoglobinuria (PNH).
Fabhalta is now the only FDA-approved Factor B inhibitor of the immune system's complement pathway, providing comprehensive control of red blood cell destruction within and outside the blood vessels.
PNH is a chronic and rare blood disorder that makes red blood cells susceptible to premature destruction by the complement system. It is characterized by hemolysis, bone marrow failure, and thrombosis in varying combinations and levels of severity.
https://seekingalpha.com/news/4043727-novartis-wins-fda-nod-for-rare-blood-disorder-drug
https://www.novartis.com/research-development/novartis-pipeline
Crinecerfont
ELAHERE® (mirvetuximab soravtansine-gynx)
Fabhalta® (iptacopan)
Neurocrine Biosciences Receives Breakthrough Therapy Designation from U.S. Food and Drug Administration for Crinecerfont in Congenital Adrenal Hyperplasia
12/05/23
- Company Today Also Provided Updates on R&D Portfolio and Strategy at Investor Event
- Crinecerfont New Drug Application Submission Planned in 2024
- NBI-'770, an Oral NMDA NR2B Negative Allosteric Modulator, Entering Phase 2 for the Treatment of Major Depressive Disorder
- Advancing Largest Portfolio of Muscarinic Compounds in Clinical Development
- Top-Line Phase 2 Data Readouts for Five Programs Anticipated in 2024 Including NBI-'568, an M4 Agonist, for the Treatment of Schizophrenia
SAN DIEGO, Dec. 5, 2023 /PRNewswire/ -- Neurocrine Biosciences, Inc. (Nasdaq: NBIX) today announced it received Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA) for crinecerfont in congenital adrenal hyperplasia. The Company also provided updates on its R&D portfolio and strategy at its Analyst Day, held in New York.
"We are very pleased that the FDA granted Breakthrough Therapy designation for crinecerfont, thus recognizing both the seriousness of congenital adrenal hyperplasia and the significant unmet need currently faced by patients and families living with this condition," said Eiry W. Roberts, Chief Medical Officer, Neurocrine Biosciences. "The outstanding safety and efficacy results from the Phase 3 CAHtalyst™ studies in pediatric and adult patients suggest that crinecerfont has the potential to represent a substantial improvement over current standard of care in CAH by controlling androgen levels and allowing for reduced steroid doses. We remain on track to submit the new drug application in 2024."
2023 Analyst Day R&D Portfolio and Strategy Updates
At today's Analyst Day, Neurocrine Biosciences provided an update on its R&D portfolio and strategy, including the Company's focus on building breadth and depth across therapeutic areas and modalities with key focus areas in VMAT2 inhibition, CRF antagonism, muscarinic agonism to antagonism, and gene therapy.
With a diversified early-stage portfolio spanning a range of modalities including small molecules and biologics, and a growing pre-clinical and development candidate portfolio, Neurocrine is uniquely positioned to advance a steady flow of innovative clinical candidates to patients across its neuroscience-focused therapeutic areas of interest.
The Company remains on-track to advance two gene therapies into the clinic in 2025, and anticipates at least 20 development candidates by 2027. Other key portfolio and pipeline updates include:
Valbenazine
- Ongoing Phase 3 study of valbenazine in adjunctive treatment of schizophrenia (ATS) will inform potential advancement of NBI-'890, a next-generation, long-acting VMAT2 inhibitor, which we anticipate will enter the clinic in 2024
- No additional Phase 3 studies of valbenazine in ATS planned
NBI-'770 (Oral, NMDA NR2B Negative Allosteric Modulator)
- Represents a potential first-in-class opportunity on a clinically validated target
- Program entering Phase 2 for treatment of major depressive disorder
Muscarinic Compounds
- Validated and differentiated mechanisms of action
- Five programs represent largest number of muscarinic assets in human studies, including lead molecule, NBI-'568, in Phase 2 study for the treatment of schizophrenia
- 2024 portfolio will include four Phase 1 programs:
- NBI-'570 (dual M1/M4 agonist)
- NBI-'567 (M1-preferring agonist)
- NBI-'569 (M4-preferring agonist)
- NBI-'986 (M4 antagonist, internally discovered at Neurocrine Biosciences)
Phase 2 Top-Line Clinical Data Expected in 2024
- NBI-'568 (M4 agonist) for the treatment of schizophrenia
- Luvadaxistat (DAAO inhibitor) for cognitive impairment associated with schizophrenia
- NBI-'845 (AMPA potentiator) for inadequate response to treatment in major depressive disorder
- Efmody (long-acting glucocorticoid) for adrenal insufficiency
- Efmody for congenital adrenal hyperplasia
About Breakthrough Therapy Designation
Breakthrough Therapy designation is a process developed by the FDA to expedite development and review of drugs that are intended to treat a serious condition and where clinical evidence indicates that the potential drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s). To learn more about Breakthrough Therapy designation, click here.
About Classic Congenital Adrenal Hyperplasia
Congenital adrenal hyperplasia (CAH) refers to a group of genetic conditions that result in an enzyme deficiency that alters the production of adrenal hormones which are essential for life. Approximately 95% of CAH cases are caused by a mutation that leads to deficiency of the enzyme 21-hydroxylase (21-OHD). In classic CAH, severe deficiency of this enzyme leads to an inability of the adrenal glands to produce cortisol and, in approximately 75% of cases, aldosterone. If left untreated, classic CAH can result in salt wasting, dehydration, and even death.
There are currently no non-glucocorticoid treatments approved by the U.S. Food and Drug Administration (FDA) for classic CAH. Glucocorticoids (GCs), the current standard of care, are used not only to correct the endogenous cortisol deficiency but typically used at greater than physiologic (supraphysiologic) doses to try to suppress the high levels of corticotropin-releasing factor (CRF) and adrenocorticotropic hormone (ACTH) that result in androgen excess. However, glucocorticoid treatment at supraphysiologic doses has been associated with serious and significant complications of steroid excess, including metabolic issues such as weight gain and diabetes, cardiovascular disease, and osteoporosis. Additionally, long-term treatment with supraphysiologic GC doses may have psychological and cognitive impact such as changes in mood and memory. Androgen excess has been associated with abnormal bone growth and development in pediatric patients, female health problems such as acne, excess hair growth and menstrual irregularities, testicular rest tumors in males, and fertility issues in both sexes. To learn more about CAH, click here.
About Corticotropin Releasing Factor (CRF)
Corticotropin releasing factor (CRF) regulates the secretion of adrenocorticotropic hormone (ACTH) by the pituitary gland. The neuropeptide was discovered, isolated and identified by the late Wylie W. Vale, PhD., a founder of Neurocrine Biosciences who led the Clayton Foundation Laboratories for Peptide Biology and was the Helen McLoraine Chair in Molecular Neurobiology at the Salk Institute. Dr. Vale mapped the key role CRF played in the regulation of the stress response. In the 95% of classic CAH cases caused by a mutation in the 21-hydroxylase enzyme, the severe enzyme deficiency results in little or no production of the stress hormone cortisol, which can lead to adrenal crisis. The lack of cortisol production also causes a break in the feedback loop that would normally regulate the body's secretion of CRF, and as a result ACTH, which maintains adrenal androgen production within normal ranges.
About Crinecerfont
Crinecerfont is an investigational, oral, selective corticotropin-releasing factor type 1 receptor (CRF1) antagonist being developed to reduce and control excess adrenal androgens through a steroid-independent mechanism for the treatment of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD). The compound was identified by Dimitri Grigoriadis, Ph.D., Chief Research Officer at Neurocrine Biosciences who conducted post-graduate research with Dr. Wylie Vale at the Salk Institute. Antagonism of CRF1 receptors in the pituitary has been shown to decrease adrenocorticotropic hormone (ACTH) levels, which in turn decreases the production of adrenal androgens and potentially the symptoms associated with classic CAH. Our data demonstrates that lowering androgen levels enables lower, more physiologic dosing of glucocorticoids and thus could potentially reduce the complications associated with exposure to greater than normal glucocorticoid doses in patients with classic CAH.
Prior to receiving Breakthrough Therapy designation from the FDA, crinecerfont also received Fast Track and Rare Pediatric Disease designations in congenital adrenal hyperplasia. To learn more about crinecerfont, click here.
About the CAHtalyst Phase 3 Studies
The CAHtalyst Phase 3 Pediatric and Adult global registrational studies were designed to evaluate the safety, efficacy, and tolerability of crinecerfont in children and adolescents (2–17 years of age) and adults (18 years of age and older) with classic congenital adrenal hyperplasia (CAH) due to 21-OHD, respectively.
The CAHtalyst Phase 3 Pediatric and Adult clinical studies met their primary and secondary endpoints. The CAHtalyst Pediatric study demonstrated a statistically significant decrease in serum androstenedione from baseline with crinecerfont at Week 4 over baseline, while both studies showed crinecerfont treatment led to statistically significant reductions in daily glucocorticoid from baseline while maintaining androgen control at Week 28 and Week 24, respectively.
Crinecerfont was generally well tolerated in the CAHtalyst Phase 3 studies. The most common adverse events in the CAHtalyst Pediatric study were headache, fever, vomiting, upper respiratory tract infection, and nasopharyngitis, while the most common adverse events in the CAHtalyst Adult study were fatigue, headache, and coronavirus infection. Few serious adverse events were seen in either study, with none assessed as related to crinecerfont. Both studies achieved a >95% completion rate.
Details about the Phase 3 data from the CAHtalyst Pediatric Study were reported in October 2023 and can be found here. For more information about the CAHtalyst Pediatric Phase 3 study, please visit ClinicalTrialsPediatric.gov.
Details about the Phase 3 data from the CAHtalyst Adult Study were reported in September 2023 and can be found here. For more information about the CAHtalyst Phase 3 study in adults, please visit ClinicalTrialsAdult.gov.
About Neurocrine Biosciences, Inc.
Neurocrine Biosciences is a leading neuroscience-focused, biopharmaceutical company with a simple purpose: to relieve suffering for people with great needs, but few options. We are dedicated to discovering and developing life-changing treatments for patients with under-addressed neurological, neuroendocrine and neuropsychiatric disorders. The company's diverse portfolio includes FDA-approved treatments for tardive dyskinesia, chorea associated with Huntington's disease, Parkinson's disease, endometriosis* and uterine fibroids*, as well as a robust pipeline including multiple compounds in mid- to late-phase clinical development across our core therapeutic areas. For three decades, we have applied our unique insight into neuroscience and the interconnections between brain and body systems to treat complex conditions. We relentlessly pursue medicines to ease the burden of debilitating diseases and disorders, because you deserve brave science. For more information, visit neurocrine.com, and follow the company on LinkedIn, Twitter, and Facebook.
(*in collaboration with AbbVie)
NEUROCRINE BIOSCIENCES and NEUROCRINE are registered trademark of Neurocrine Biosciences, Inc. CAHtalyst and the Neurocrine logo are trademarks of Neurocrine Biosciences, Inc.
View original content to download multimedia:https://www.prnewswire.com/news-releases/neurocrine-biosciences-receives-breakthrough-therapy-designation-from-us-food-and-drug-administration-for-crinecerfont-in-congenital-adrenal-hyperplasia-302006430.html
SOURCE Neurocrine Biosciences, Inc.
Neurocrine gets FDA breakthrough therapy status for crinecerfont
Dec. 05, 2023 5:16 PM ET
Neurocrine Biosciences, Inc. (NBIX)
By: Val Brickates Kennedy, SA News Editor
Neurocrine Biosciences (NASDAQ:NBIX) said that it has received breakthrough therapy designation from the FDA for its drug candidate crinecerfont in the treatment of congenital adrenal hyperplasia.
The company plans to submit a market application with the FDA for crincerfont in 2024.
Neurocrine also said it expects to report Phase 2 data for five programs in 2024, including its drug NBI-‘568 in the treatment of schizophrenia.
ELAHERE® (mirvetuximab soravtansine-gynx)
ELAHERE® (mirvetuximab soravtansine-gynx)
ELAHERE® (mirvetuximab soravtansine-gynx)
FDA Grants Priority Review of ImmunoGen’s Supplemental Biologics License Application for ELAHERE® (mirvetuximab soravtansine-gynx) in Platinum-Resistant Ovarian Cancer
December 5, 2023 at 6:30 AM EST
Priority Review Granted with PDUFA Date of April 5, 2024
WALTHAM, Mass.--(BUSINESS WIRE)--Dec. 5, 2023-- ImmunoGen, Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, today announced that the US Food and Drug Administration (FDA) has filed the supplemental Biologics License Application (sBLA) supporting the conversion of the accelerated approval of ELAHERE® (mirvetuximab soravtansine-gynx) for the treatment of patients with folate receptor alpha (FRα)-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received one to three prior systemic treatment regimens to full approval. The application has been granted Priority Review designation with a Prescription Drug User Fee Act (PDUFA) action date of April 5, 2024.
"With the FDA’s filing of our sBLA, we are one step closer to securing full approval of ELAHERE in the US and establishing this novel ADC as the standard of care in FRα-positive platinum-resistant ovarian cancer," said Michael Vasconcelles, MD, ImmunoGen's Executive Vice President, Research, Development, and Medical Affairs. "This regulatory milestone, achieved just over one year after ELAHERE’s accelerated approval, underscores the significance of the confirmatory MIRASOL data and the broader data set seen to date with ELAHERE, as well as the urgency with which our teams worked to bring this potentially practice-changing therapy to eligible patients in need. We look forward to collaborating closely with the FDA throughout the review process."
The confirmatory Phase 3 MIRASOL trial of ELAHERE in platinum-resistant ovarian cancer forms the basis of the sBLA. Top-line data from the MIRASOL trial were disclosed in May 2023 and presented as a late-breaking abstract at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. In the MIRASOL trial, ELAHERE demonstrated statistically significant and clinically meaningful improvements in progression-free survival, objective response rate, and overall survival compared to investigator's choice (IC) of single-agent chemotherapy. ELAHERE demonstrated a tolerable safety profile compared to IC chemotherapy, consisting predominantly of low-grade ocular and gastrointestinal events.
ELAHERE was granted accelerated approval by the FDA in November 2022 based on data from the pivotal SORAYA trial. A Marketing Authorization Application for ELAHERE in Europe has been accepted by the European Medicines Agency and a New Drug Application in China has been accepted by the National Medical Products Administration of China.
ABOUT OVARIAN CANCER
Ovarian cancer is the leading cause of death from gynecological cancers in the US. Each year, roughly 20,000 patients are diagnosed, and 13,000 patients will die. Most patients present with late-stage disease and will typically undergo surgery followed by platinum-based chemotherapy. Unfortunately, the majority of patients eventually develop platinum-resistant disease, which is difficult to treat. In this setting, standard of care single-agent chemotherapies are associated with low response rates, short durations of response, and significant toxicities.
ABOUT IMMUNOGEN
ImmunoGen is developing the next generation of antibody-drug conjugates (ADCs) to improve outcomes for cancer patients. By generating targeted therapies with enhanced anti-tumor activity and favorable tolerability profiles, we aim to disrupt the progression of cancer and offer our patients more good days. We call this our commitment to TARGET A BETTER NOW™.
Learn more about who we are, what we do, and how we do it at www.immunogen.com.
ABOUT ELAHERE
ELAHERE (mirvetuximab soravtansine-gynx) is a first-in-class ADC comprising a folate receptor alpha-binding antibody, cleavable linker, and the maytansinoid payload DM4, a potent tubulin inhibitor designed to kill the targeted cancer cells.
ELAHERE is indicated for the treatment of adult patients with folate receptor-alpha (FRα) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. Select patients for therapy based on an FDA-approved test.
This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Eye problems are common with ELAHERE and can be severe. ELAHERE also can cause severe or life-threatening inflammation of the lungs that may lead to death and patients may develop nerve problems called peripheral neuropathy during treatment.
Please see full Prescribing Information, including Boxed Warning for ELAHERE.
View source version on businesswire.com: https://www.businesswire.com/news/home/20231205658270/en/
Source: ImmunoGen, Inc.
ImmunoGen bags priority review for full approval of ovarian cancer drug
Dec. 05, 2023 6:55 AM ET
By: Preeti Singh, SA News Editor
The U.S. Food and Drug Administration has granted ImmunoGen (NASDAQ:IMGN) a priority review for its supplemental biologics license application of ovarian cancer drug Elahere (mirvetuximab soravtansine-gynx).
TAR-200
Jaypirca® (pirtobrutinib)
ELAHERE® (mirvetuximab soravtansine-gynx)
Johnson & Johnson’s Investigational TAR-200 Granted U.S. FDA Breakthrough Therapy Designation for the Treatment of High-Risk Non-Muscle-Invasive Bladder Cancer
Breakthrough Therapy Designation for Novel Targeted Releasing System Based on Results from Ongoing Phase 2b SunRISe-1 Study
DECEMBER 04, 2023
RARITAN, N.J., Dec. 4, 2023 –
Johnson & Johnson announced today that the U.S. Food and Drug Administration (FDA) has granted TAR-200 Breakthrough Therapy Designation (BTD) for the potential future treatment of patients with Bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer (HR-NMIBC), who are ineligible for or elected not to undergo radical cystectomy (surgical removal of the bladder). TAR-200 is a novel investigational targeted releasing system designed to provide sustained local release of gemcitabine into the bladder. Today’s BTD marks Johnson & Johnson’s 13th such designation in oncology.
“TAR-200 represents a novel interventional approach for the treatment of localized bladder cancer where today, unfortunately, options are limited and include antiquated BCG therapy or radical cystectomy,” said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Johnson & Johnson Innovative Medicine. “This Breakthrough Therapy Designation recognizes TAR-200 as a promising advancement and marks an important step forward in our innovative focus to transform the treatment of bladder cancer.”
The BTD is supported by data from SunRISe-1 (NCT04640623), an open-label Phase 2b clinical study evaluating the safety and efficacy of TAR-200 in combination with cetrelimab, TAR-200 alone, or cetrelimab alone for BCG-unresponsive HR-NMIBC carcinoma in situ (CIS) patients, who are ineligible for or elected not to undergo radical cystectomy.1 Data from the SunRISe-1 study were featured during the 2023 European Society for Medical Oncology Annual Congress as a late-breaking mini-oral presentation (Abstract #LBA105) and interim results were presented at the 2023 American Urological Association Annual Meeting (Abstract #LBA02-03).
A U.S. FDA BTD is granted to expedite the development and regulatory review of a medicine that is intended to treat a serious or life-threatening condition and is based on preliminary clinical evidence that demonstrates the drug may have substantial improvement over available therapies on a clinically significant endpoint(s).2
About SunRISe-1
SunRISe-1 (NCT04640623) is an open-label Phase 2b clinical study evaluating the safety and efficacy of TAR-200 in combination with cetrelimab, TAR-200 alone, or cetrelimab alone for BCG-unresponsive HR-NMIBC carcinoma in situ (CIS) patients, who are ineligible for or elected not to undergo radical cystectomy. Participants were randomized to one of three cohorts: treatment with TAR-200 in combination with cetrelimab (Cohort 1), TAR-200 alone (Cohort 2), or cetrelimab alone (Cohort 3). The primary endpoint is Complete Response rate at any time point. Secondary endpoints include duration of response, overall survival, pharmacokinetics, quality of life, safety, and tolerability. Cohorts 1 and 3 were closed to further enrollment effective June 1, 2023.
About TAR-200
TAR-200 is an investigational targeted releasing system enabling controlled release of gemcitabine into the bladder, sustaining local drug exposure for weeks at a time. The safety and efficacy of TAR-200 are being evaluated in Phase 2 and Phase 3 studies in patients with muscle-invasive bladder cancer in SunRISe-2 and SunRISe-4 and NMIBC in SunRISe-1 and SunRISe-3.
About Cetrelimab
Administered intravenously, cetrelimab is an investigational programmed cell death receptor-1 (PD-1) monoclonal antibody being studied for the treatment of bladder cancer, prostate cancer, melanoma, and multiple myeloma as part of a combination regimen.
About High-Risk Non-Muscle-Invasive Bladder Cancer
High-risk non-muscle-invasive bladder cancer (HR-NMIBC) is a type of non-invasive bladder cancer that is more likely to recur or spread beyond the lining of the bladder, called the urothelium, and progress to invasive bladder cancer, compared to low- and intermediate risk NMIBC.3,4 HR-NMIBC makes up 15–44 percent of patients with NMIBC and is characterized by a high-grade, large tumor size, presence of multiple tumors and CIS. Radical cystectomy is currently recommended for NMIBC patients who are unresponsive to BCG therapy, with over 90 percent cancer-specific survival if performed before muscle-invasive progression.5,6 Given that NMIBC typically affects older patients, many may be unwilling or unable to undergo radical cystectomy.7 The high rates of recurrence and progression can pose significant morbidity and distress for patients with NMIBC.8
About Johnson & Johnson
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at https://www.jnj.com/ or at www.janssen.com/johnson-johnson-innovative-medicine. Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC and Janssen Biotech, Inc. are both Johnson & Johnson companies.
J&J gets FDA breakthrough status for TAR-200 in bladder cancer
Dec. 04, 2023 5:18 PM ET
By: Val Brickates Kennedy, SA News Editor
Johnson & Johnson (NYSE:JNJ) said the FDA has granted its therapy candidate TAR-200 breakthrough therapy designation for the treatment of high-risk non-muscle-invasive bladder cancer.
More specifically, the designation is for the product as a potential treatment for patients with Bacillus Calmette-Guerin unresponsive high-risk non-muscle-invasive bladder cancer who are ineligible or have elected not to undergo surgical removal of the bladder.
Imetelstat
Jaypirca® (pirtobrutinib)
Jaypirca® (pirtobrutinib)
Geron Announces Publication in The Lancet of Results from the IMerge Phase 3 Clinical Trial Evaluating Imetelstat in Lower Risk MDS
December 4, 2023
- Imetelstat is currently under regulatory review by the FDA and EMA for the treatment of transfusion-dependent anemia in adult patients with lower risk MDS
FOSTER CITY, Calif.--(BUSINESS WIRE)-- Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company, today announced publication in The Lancet of results from the IMerge Phase 3 trial investigating imetelstat versus placebo in patients with lower risk myelodysplastic syndromes (MDS) relapsed/refractory or ineligible for erythropoiesis stimulating agents (ESAs). The publication is available online and will be available in print at a later date.
“The Lancet’s publication of our IMerge Phase 3 manuscript is a strong validation of the importance of this study within the field, as well as a powerful way of reaching hematologists and other providers globally with these potentially practice-changing results,” said Faye Feller, M.D., Executive Vice President, Geron’s Chief Medical Officer. “Based on the highly differentiated qualities of imetelstat reported in this study, we believe that, if approved by regulatory authorities, imetelstat could substantially improve the treatment paradigm in certain patients with lower risk MDS.”
Imetelstat is currently under regulatory review by the U.S. Food and Drug Administration (FDA) and by the European Medicines Agency (EMA) for approval in transfusion dependent anemia in patients with lower risk MDS who have failed to respond or have lost response to or are ineligible for ESAs.
“I am pleased with the publication in The Lancet of what I believe are very powerful Phase 3 results with this unique mechanism of action, telomerase inhibition, where we see long-term and durable responses broadly across MDS subgroups. This includes lower risk MDS patients without ring sideroblasts (RS-), ESA-ineligible patients who have high serum EPO levels, and those with high transfusion burden, whose needs are not being met by today’s treatments,” said Uwe Platzbecker, M.D., Department of Hematology, Cellular Therapy, Hemostaseology and Infectious Diseases, Leipzig University Hospital, Leipzig, Germany, who is the lead author on the manuscript and is an IMerge investigator. “With regards to the safety results, neutropenia and thrombocytopenia were predictable and manageable, with little to no significant clinical consequences. These adverse events commonly occurred in the first three cycles and frequently resolved within two weeks.”
As previously reported, in the IMerge Phase 3 clinical trial, the primary endpoint of red blood cell transfusion independence (TI) for at least 8 consecutive weeks was significantly higher with imetelstat vs. best supportive care (placebo) (p<0.001), with median TI duration approaching one year for imetelstat 8-week TI responders. Mean hemoglobin levels in imetelstat-treated patients increased significantly (p<0.001) over time compared to placebo patients. For patients achieving 8-week TI, median increases in hemoglobin were 3.6 g/dL for imetelstat and 0.8 g/dL for placebo. Significant and clinically meaningful efficacy results were achieved across key MDS subgroups irrespective of ring sideroblast (RS) status, baseline transfusion burden and IPSS risk category. Patient-reported outcomes (PRO) data reported a sustained meaningful improvement in fatigue for imetelstat-treated patients vs. placebo. Treatment with imetelstat vs. placebo led to greater reduction in variant allele frequency (VAF) in certain genes commonly mutated in MDS, which was associated with longer TI duration and increase in hemoglobin levels. Consistent with prior imetelstat clinical experience, the most common adverse events were thrombocytopenia and neutropenia that were manageable and of short duration.
Click here to view The Lancet publication.
About IMerge Phase 3
The Phase 3 portion of the IMerge Phase 2/3 study is a double-blind, 2:1 randomized, placebo-controlled clinical trial to evaluate imetelstat in patients with IPSS Low or Intermediate-1 risk (lower risk) transfusion dependent MDS who were relapsed after, refractory to, or ineligible for, erythropoiesis stimulating agent (ESA) treatment, had not received prior treatment with either a HMA or lenalidomide and were non-del(5q). To be eligible for IMerge Phase 3, patients were required to be transfusion dependent, defined as requiring at least four units of packed red blood cells (RBCs), over an eight-week period during the 16 weeks prior to entry into the trial. The primary efficacy endpoint of IMerge Phase 3 is the rate of red blood cell transfusion independence (RBC-TI) lasting at least eight weeks, defined as the proportion of patients without any RBC transfusion for at least eight consecutive weeks since entry to the trial (8-week TI). Key secondary endpoints include the rate of RBC-TI lasting at least 24 weeks (24-week TI), the duration of TI and the rate of hematologic improvement erythroid (HI-E), which is defined under 2006 IWG criteria as a rise in hemoglobin of at least 1.5 g/dL above the pretreatment level for at least eight weeks or a reduction of at least four units of RBC transfusions over eight weeks compared with the prior RBC transfusion burden. A total of 178 patients were enrolled in IMerge Phase 3 across North America, Europe, Middle East and Asia.
About Imetelstat
Imetelstat is a novel, first-in-class investigational telomerase inhibitor exclusively owned by Geron and being developed in hematologic malignancies. Data from non-clinical studies and clinical trials of imetelstat provide strong evidence that imetelstat targets telomerase to inhibit the uncontrolled proliferation of malignant stem and progenitor cells in myeloid hematologic malignancies resulting in malignant cell apoptosis and potential disease-modifying activity. Imetelstat has been granted Fast Track designation by the U.S. Food and Drug Administration for both the treatment of adult patients with transfusion dependent anemia due to Low or Intermediate-1 risk MDS that is not associated with del(5q) who are refractory or resistant to an erythropoiesis stimulating agent, and for adult patients with Intermediate-2 or High-risk myelofibrosis (MF) whose disease has relapsed after or is refractory to janus associated kinase (JAK) inhibitor treatment. Imetelstat is currently not approved by any regulatory authority.
About Geron
Geron is a late-stage clinical biopharmaceutical company pursuing therapies with the potential to extend and enrich the lives of patients living with hematologic malignancies. Our first-in-class investigational telomerase inhibitor, imetelstat, harnesses Nobel Prize-winning science in a treatment that may alter the underlying drivers of disease. The New Drug Application (NDA) for imetelstat for the treatment of transfusion dependent anemia in patients with lower risk myelodysplastic syndromes (LR MDS) who have failed to respond or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESAs), based on the results from the Phase 3 IMerge clinical trial, is currently under review by the United States Food and Drug Administration (FDA) with a Prescription Drug User Fee Act (PDUFA) target action date of June 16, 2024. In addition, an MAA is under review in the European Union for the same proposed indication. Furthermore, Geron currently has an ongoing pivotal Phase 3 clinical trial evaluating imetelstat in relapsed/refractory myelofibrosis (MF). To learn more, visit www.geron.com or follow us on LinkedIn.
Source: Geron Corporation
Geron shares rise after positive trial results of blood disorder candidate
Dec. 04, 2023 8:53 AM ET
By: Preeti Singh, SA News Editor3 Comments
- Geron (NASDAQ:GERN) rose as much as +6% in premarket hours on Monday after it reported positive data from the Phase 3 trial of its drug candidate targeting myelodysplastic syndromes (MDS).
- The data - published in The Lancet - showed imetelstat met the primary endpoint in treating transfusion-dependent anemia in adult patients with lower risk MDS. Imetelstat is currently being reviewed by the U.S. FDA and European Medicines Agency for this indication.
- https://seekingalpha.com/news/4042795-geron-shares-rise-after-positive-trial-results-of-blood-disorder-candidate
- Geron Corporation (GERN)
- https://www.geron.com/research-and-development/imetelstat/
- https://www.geron.com/
Jaypirca® (pirtobrutinib)
Jaypirca® (pirtobrutinib)
Jaypirca® (pirtobrutinib)
Jaypirca® (pirtobrutinib) Now Approved by U.S. FDA for the Treatment of Adult Patients with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Who Have Received at Least Two Lines of Therapy, Including a BTK Inhibitor and a BCL-2 Inhibitor
December 1, 2023
The first and only non-covalent (reversible) BTK inhibitor, Jaypirca has been shown to extend the benefit of BTK inhibition
In the BRUIN Phase 1/2 trial, adult patients with CLL/SLL who have received at least two lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor, achieved an overall response rate of 72%
INDIANAPOLIS, Dec. 1, 2023 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced that the U.S. Food and Drug Administration (FDA) approved Jaypirca® (pirtobrutinib, 100 mg & 50 mg tablets) for the treatment of adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have received at least two prior lines of therapy, including a Bruton's tyrosine kinase (BTK) inhibitor and a BCL-2 inhibitor. Jaypirca was approved under the FDA's Accelerated Approval pathway based on overall response rate (ORR) and duration of response (DOR) from the open-label, single-arm, multicohort, international, Phase 1/2 BRUIN trial.1 Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.1
Jaypirca, the first and only FDA-approved non-covalent (reversible) BTK inhibitor, is a highly selective kinase inhibitor that can extend the benefit of targeting the BTK pathway in CLL/SLL patients previously treated with a covalent BTK inhibitor (ibrutinib, acalabrutinib, or zanubrutinib) and a BCL-2 inhibitor.1,2 Jaypirca utilizes a novel binding mechanism and has the largest body of evidence of any targeted therapy in patients previously treated with a BTK inhibitor.1,2
"Once patients with CLL or SLL have progressed on covalent BTK inhibitor and BCL-2 inhibitor therapies, treatments are limited and outcomes can be poor, making the approval of Jaypirca a meaningful advance and much-needed new treatment option for these patients," said William G. Wierda, M.D., Ph.D., professor, medical director, and CLL section head for the Department of Leukemia at The University of Texas MD Anderson Cancer Center. "Jaypirca offers a new treatment option and different approach to targeting BTK, providing clinical benefit for a high proportion of patients with CLL or SLL in the BRUIN Phase 1/2 trial whose disease progressed following treatment with a covalent BTK inhibitor and with a BCL-2 inhibitor."
The labeling for Jaypirca contains warnings and precautions for infections, hemorrhage, cytopenias, cardiac arrhythmias, second primary malignancies, and embryo-fetal toxicity. See Important Safety Information below and full Prescribing Information for additional information, including dosing modifications.
"This FDA approval — the second for Jaypirca in 2023 — underscores the impactful clinical benefit of continuing to leverage the BTK pathway with Jaypirca for patients with CLL or SLL as seen in the BRUIN trial," said Jacob Van Naarden, chief executive officer, Loxo@Lilly. "These first two indications for Jaypirca represent the beginning of the eventual impact that we hope Jaypirca can have for patients, and we look forward to seeing the results of the comprehensive Phase 3 development program across CLL, SLL and MCL."
"The treatment landscape for CLL has been dramatically improved by the introduction of covalent BTK inhibitors and BCL-2 inhibitors. However, most patients will unfortunately relapse eventually," said Brian Koffman, M.D., chief medical officer and executive vice president at the CLL Society. "Pirtobrutinib's approval gives patients a much-needed option and brings forward new possibilities as they continue their treatment journey."
The FDA approval is based on data from a subset of patients in the BRUIN Phase 1/2 trial. The assessment of efficacy was based on 108 patients with CLL/SLL treated with Jaypirca who were previously treated with at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor. Jaypirca 200 mg was given once daily and was continued until disease progression or unacceptable toxicity. Patients with active central nervous system (CNS) involvement by lymphoma or allogeneic hematopoietic stem cell transplantation (HSCT) within 60 days were excluded. Patients in the efficacy-eligible population had received a median of five prior lines of therapy (range: 2 to 11). The most common prior BTK inhibitors received were ibrutinib (97%), acalabrutinib (9%), and zanubrutinib (0.9%). Seventy-seven percent (77%) of patients discontinued the last BTK inhibitor for refractory or progressive disease. Efficacy was established based on ORR and DOR, as assessed by an independent review committee (IRC) using 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria.
The pooled safety analysis of the full BRUIN study population evaluated 593 patients with hematologic malignancies administered Jaypirca 200 mg daily as a single agent. In this pooled safety population, the most common adverse reactions (ARs) to Jaypirca therapy, occurring in 20% of patients or more, including laboratory abnormalities, were decreased neutrophil count, decreased hemoglobin, fatigue, decreased lymphocyte count, musculoskeletal pain, decreased platelet count, diarrhea, COVID-19, bruising, and cough.
The safety of Jaypirca was evaluated in the BRUIN trial in 110 patients with CLL/SLL, with 98% receiving at least two prior lines of systemic therapy, including a BTK inhibitor and a BCL-2 inhibitor. Sixty percent (60%) of these patients were exposed to Jaypirca for at least one year, and 14% were exposed for at least two years. ARs led to dose reductions in 3.6%, treatment interruption in 42%, and permanent discontinuation of Jaypirca in 9% of patients. ARs that resulted in permanent discontinuation of Jaypirca in more than 1% of patients included second primary malignancy, COVID-19, and sepsis. Serious ARs occurred in 56% of patients who received Jaypirca. Serious ARs occurring in greater than or equal to 5% of patients were pneumonia (18%), COVID-19 (9%), sepsis (7%), and febrile neutropenia (7%).
Lilly is committed to delivering on the requirements of the FDA's Accelerated Approval pathway, including the completion of confirmatory studies supporting traditional approval as soon as possible. The Phase 3 randomized confirmatory trial intended to convert this approval to traditional approval is BRUIN CLL-321, which reached its target number of progression-free survival (PFS) events and met its primary endpoint. Topline results were shared with the FDA in November 2023, although these data have not yet been formally reviewed. BRUIN CLL-321 is a randomized Phase 3 trial comparing pirtobrutinib monotherapy versus the investigator's choice of either idelalisib in combination with rituximab or bendamustine in combination with rituximab in patients with CLL/SLL who have been treated with at least a BTK inhibitor. These data will be presented at an upcoming medical meeting. Jaypirca is not approved for use in the BRUIN CLL-321 population.
This is the second FDA-approved indication for Jaypirca following the January 2023 Accelerated Approval for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor.
Loxo@Lilly is studying Jaypirca in CLL/SLL in multiple Phase 3 studies. Details on the trials can be found by visiting clinicaltrials.gov.
See Important Safety Information below and full Prescribing Information for additional information.
Click here to view the CLL infographic.
Click to view the Jaypirca product photos: 100 mg and 50 mg.
Click here to view the Jaypirca logo.
About the BRUIN Phase 1/2 Trial
The BRUIN Phase 1/2 clinical trial is the ongoing first-in-human, global, multi-center evaluation of Jaypirca in patients with hematologic malignancies, including chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and mantle cell lymphoma (MCL).
The trial includes a Phase 1 dose-escalation phase, a Phase 1b combination arm, and a Phase 2 dose-expansion phase. The primary endpoint of the Phase 1 study is maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D). Secondary endpoints include safety, pharmacokinetics (PK), and preliminary efficacy measured by overall response rate (ORR) for monotherapy. The primary endpoint of the Phase 1b study is safety of the drug combinations. The secondary endpoints are PK and preliminary efficacy measured by ORR for the drug combinations. The primary endpoint for the Phase 2 study is ORR as determined by an independent review committee (IRC). Secondary endpoints include ORR as determined by investigator, best overall response (BOR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety, and PK.
About Jaypirca® (pirtobrutinib)
Jaypirca (pirtobrutinib, formerly known as LOXO-305) (pronounced jay-pihr-kaa) is a highly selective (300 times more selective for BTK versus 98% of other kinases tested in preclinical studies), non-covalent (reversible) inhibitor of the enzyme BTK.2 BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including mantle cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma.3,4 Jaypirca is a U.S. FDA-approved oral prescription medicine, 100 mg or 50 mg tablets taken as a once-daily 200 mg dose with or without food until disease progression or unacceptable toxicity.
About Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
CLL and SLL are forms of slow-growing non-Hodgkin lymphoma that develop from white blood cells known as lymphocytes.5,6 CLL is one of the most common types of leukemia in adults.5 In the U.S., CLL accounts for about one-quarter of the new cases of leukemia and there are approximately 18,740 new cases of CLL diagnosed this year.5,7 SLL is identical to CLL from a pathologic and immunophenotypic standpoint, with the main difference between them being the location of the cancer cells.5 In CLL, the cancer cells are present in the blood, and in SLL, the cancer cells are found in the lymph nodes.5
INDICATIONS FOR JAYPIRCA
Jaypirca is a kinase inhibitor indicated for the treatment of
- Adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor.
- Adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.
These indications are approved under accelerated approval based on response rate. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Please see Prescribing Information and Patient Information for Jaypirca.
About Lilly
Lilly unites caring with discovery to create medicines that make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help more than 51 million people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges, redefining diabetes care, treating obesity and curtailing its most devastating long-term effects, advancing the fight against Alzheimer's disease, providing solutions to some of the most debilitating immune system disorders, and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/newsroom or follow us on Facebook, Instagram and LinkedIn. P-LLY
Jaypirca® is a registered trademark owned by or licensed to Eli Lilly and Company, its subsidiaries, or affiliates.
PP-PT-US-0760 12/2023
© Lilly USA, LLC 2023. ALL RIGHTS RESERVED.
FDA grants second accelerated approval to Lilly's Jaypirca
Dec. 01, 2023 6:35 PM ET
By: Val Brickates Kennedy, SA News Editor1 Comment
Eli Lilly (NYSE:LLY) said the FDA has granted accelerated approval for its drug Jaypirca for the treatment of chronic lymphocytic leukemia or small lymphocytic leukemia in patients who have received at least two prior therapies, including a BTK inhibitor and a BCL-2 inhibitor.
https://seekingalpha.com/news/4042556-fda-grants-second-accelerated-approval-to-lilly-jaypirca
SGX945 (dusquetide)
Telisotuzumab-Vedotin (Teliso-V)
Telisotuzumab-Vedotin (Teliso-V)
Soligenix Receives FDA IND Clearance for Phase 2 Clinical Trial of Dusquetide in the Treatment of Aphthous Ulcers in Behçet's Disease
Pipeline Expansion of Novel Innate Defense Regulator Technology
PRINCETON, N.J., Nov. 30, 2023 /PRNewswire/ --
Soligenix, Inc. (Nasdaq: SNGX)
(Soligenix or the Company), a late-stage biopharmaceutical company focused on developing and commercializing products to treat rare diseases where there is an unmet medical need, announced today that the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application for a Phase 2a clinical trial entitled, "Pilot Study of SGX945 (Dusquetide) in the Treatment of Aphthous Ulcers in Behçet's Disease." The study is designed to evaluate the safety and efficacy of SGX945 (dusquetide) and is expected to begin patient enrollment in the second half of 2024.
"We are pleased to have received FDA clearance on our SGX945 Phase 2 pilot trial in aphthous ulcers of Behçet's disease," stated Christopher J. Schaber, PhD, President and Chief Executive Officer of Soligenix. "Our previous studies with dusquetide in oral mucositis have clearly validated the biologic activity in aphthous ulcers induced by chemotherapy and radiation. Given the role of the innate immune system in ulcers associated with Behçet's Disease, and the unmet medical need particularly for more severe ulcers such as genital and leg ulcers, we believe that dusquetide may offer significant relief to patients. We are excited to expand dusquetide's development into different innate immune-related inflammatory conditions such as Behçet's disease, as a component of our long-term strategy to enhance the value of this unique compound. Behçet's disease is an unmet medical need, with up to 18,000 people in the U.S., 80,000 in Europe, 350,000 people in Turkey and as many as 1 million people worldwide affected by this incurable disease. Given our promising results with aphthous ulcers in oral mucositis, we are hopeful dusquetide will have a role to play in helping underserved patients suffering from this difficult to treat and chronic disease."
Under this IND, the pilot clinical trial of SGX945 will be an open-label study that will enroll approximately 25 patients age 18 years or older with mild to moderate Behçet's disease active oral and/or genital ulcers. Patients will receive SGX945 as a twice weekly 4-minute intravenous (IV) infusion for 4 weeks. Efficacy endpoints will include the extent of lesion clearance, timeline to lesion clearance, and patient reported quality of life indices.
About Dusquetide
Dusquetide (the active ingredient in SGX945 and SGX942 in development for oral mucositis) is an innate defense regulator (IDR), a new class of short, synthetic peptides. It has a novel mechanism of action whereby it modulates the body's reaction to both injury and infection towards an anti-inflammatory, anti-infective, and tissue healing response. IDRs have no direct antibiotic activity but, by modulating the host's innate immune system responses, increase survival after infections caused by a broad range of bacterial Gram-negative and Gram-positive pathogens. It also accelerates resolution of tissue damage following exposure to a variety of agents including bacterial pathogens, trauma, and chemo- and/or radiation therapy. Preclinical efficacy and safety have been demonstrated in numerous animal disease models including mucositis, colitis, macrophage activation syndrome (MAS) as well as bacterial infections, including melioidosis. In addition, potential anti-tumor activity has been demonstrated in multiple in vitro and in vivo xenograft studies.
Dusquetide has demonstrated safety and tolerability in a Phase 1 clinical study in 84 healthy human volunteers. In Phase 2 and 3 clinical studies with SGX942 in over 350 subjects with oral mucositis due to chemoradiation therapy for head and neck cancer, positive efficacy results were demonstrated, including potential long-term ancillary benefits.
Soligenix has a strong intellectual property position in the IDR technology platform, including composition of matter for dusquetide and related analogs. Dusquetide was developed pursuant to discoveries made by Professors B. Brett Finlay, PhD and Robert Hancock, PhD of the University of British Columbia, Canada.
About Behçet's Disease
Behçet's Disease (BD) is commonly known as an inflammatory disorder of the blood vessels (vasculitis). Often first diagnosed in young adults, it's effects and severity will wax and wane over time. Major signs and symptoms usually include mouth sores (approximately 95% of patients), skin rashes and lesions (approximately 50% of patients), genital sores (approximately 50% of patients), leg ulcers (approximately 40% of patients) and eye inflammation (approximately 15% of patients). It is a painful disease, directly impacting the patient's quality of life and ability to productively engage in life activities, including work.
BD is thought to be an auto-immune disease with both genetic and environmental factors. It is most common along the "Silk Road" in the Middle East and East Asia, including Turkey, Iran, Japan and China. There are approximately 18,000 known cases of BD in the U.S. and 80,000 in Europe. There are as many as 1,000,000 people worldwide living with BD.
There is no cure for BD, rather treatments are prescribed to manage symptoms. Treatments may include both maintenance therapies and those specifically addressing flares (e.g., mouth ulcers, genital ulcers and leg ulcers). Corticosteroids are generally applied topically to sores and as eyedrops and may also be given systemically to reduce inflammation. Although used frequently, they have limited efficacy over the long-term and have significant side effects that become more concerning with more chronic use. Genital ulcers are often associated with significant genital scarring while leg ulcers can result in a post-thrombotic syndrome. Other treatments for BD flares involve suppressing the immune system with drugs (e.g., cyclosporine or cyclophosphamide). These drugs come with a higher risk of infection, liver and kidney problems, low blood counts and high blood pressure. Finally, anti-inflammatory drugs are also used, including anti-TNF medications. The only approved drug in BD is apremilast, which is used as a maintenance therapy to prevent formation of oral ulcers. Unfortunately, apremilast is associated with both high cost and side effects including diarrhea, nausea, upper respiratory tract infection and headache.
About Soligenix, Inc.
Soligenix is a late-stage biopharmaceutical company focused on developing and commercializing products to treat rare diseases where there is an unmet medical need. Our Specialized BioTherapeutics business segment is developing and moving toward potential commercialization of HyBryte™ (SGX301 or synthetic hypericin sodium) as a novel photodynamic therapy utilizing safe visible light for the treatment of cutaneous T-cell lymphoma (CTCL). With a successful Phase 3 study completed, regulatory approval is being sought and commercialization activities for this product candidate are being advanced initially in the U.S. Development programs in this business segment also include expansion of synthetic hypericin (SGX302) into psoriasis, our first-in-class innate defense regulator (IDR) technology, dusquetide (SGX942) for the treatment of inflammatory diseases, including oral mucositis in head and neck cancer, and (SGX945) in Behçet's Disease. The Company also is developing proprietary formulations of oral beclomethasone 17,21-dipropionate (BDP) for the prevention/treatment of gastrointestinal (GI) disorders characterized by severe inflammation such as pediatric Crohn's disease (SGX203).
Our Public Health Solutions business segment includes active development programs for RiVax®, our ricin toxin vaccine candidate, as well as our vaccine programs targeting filoviruses (such as Marburg and Ebola) and CiVax™, our vaccine candidate for the prevention of COVID-19 (caused by SARS-CoV-2). The development of our vaccine programs incorporates the use of our proprietary heat stabilization platform technology, known as ThermoVax®. To date, this business segment has been supported with government grant and contract funding from the National Institute of Allergy and Infectious Diseases (NIAID), the Defense Threat Reduction Agency (DTRA) and the Biomedical Advanced Research and Development Authority (BARDA).
For further information regarding Soligenix, Inc., please visit the Company's website at https://www.soligenix.com and follow us on LinkedIn and Twitter at @Soligenix_Inc.
SOURCE SOLIGENIX, INC.
Soligenix wins FDA nod to conduct trial for rare disease therapy
Nov. 30, 2023 2:00 PM ET
By: Dulan Lokuwithana, SA News Editor1 Comment
- Nano-cap biotech Soligenix (NASDAQ:SNGX) gained over 200% on Thursday after announcing that the U.S. FDA greenlighted its Investigational New Drug (IND) application for SGX945 (dusquetide), a synthetic peptide targeted at a rare disease called Behçet's Disease.
- https://seekingalpha.com/news/4041946-soligenix-stock-gains-fda-clears-rare-disease-trial
- Soligenix, Inc. (SNGX)
- https://www.soligenix.com/pipeline-programs/
- https://www.soligenix.com/
Telisotuzumab-Vedotin (Teliso-V)
Telisotuzumab-Vedotin (Teliso-V)
Telisotuzumab-Vedotin (Teliso-V)
November 29, 2023
AbbVie Announces Positive Topline Results from Phase 2 LUMINOSITY Trial Evaluating Telisotuzumab-Vedotin (Teliso-V) for Patients with Previously Treated Non-Small Cell Lung Cancer (NSCLC)
- Open a printable version of this page
- Email the URL of this page to a friend
- LUMINOSITY trial demonstrated compelling clinical benefits across key endpoints
- Teliso-V is an investigational first-in-class, c-Met protein directed antibody-drug conjugate (ADC) being studied in patients with previously treated non-small cell lung cancer (NSCLC) with c-Met overexpression
- Data from the study will be presented at a future medical meeting and we will discuss with global health authorities the potential to support an accelerated approval
NORTH CHICAGO, Ill., Nov. 29, 2023 /PRNewswire/ -- AbbVie (NYSE: ABBV) announced today topline results from the single-arm Phase 2 LUMINOSITY trial evaluating telisotuzumab-vedotin (Teliso-V) in patients with c-Met protein overexpression, epidermal growth factor receptor (EGFR) wild type, advanced/metastatic nonsquamous non-small cell lung cancer (NSCLC). The results demonstrated a compelling overall response rate per independent central review (ICR) of 35 percent and 23 percent across c-Met High and c-Met Intermediate patients respectively.
In addition, other endpoints demonstrated meaningful clinical outcomes including median duration of response per ICR of 9 months and 7.2 months and a median overall survival of 14.6 months and 14.2 months across c-Met High and c-Met Intermediate patients respectively.
The safety profile of Teliso-V was consistent with previous findings and no new safety concerns were identified. Adverse events with Teliso-V monotherapy were generally well managed and tolerated. Full data from the LUMINOSITY study will be presented at a future medical meeting and we will discuss with global health authorities the potential to support an accelerated approval.
Approximately 85% of lung cancers are classified as NSCLC1 and despite advances in treatment, lung cancer remains the leading cause of cancer-related deaths in both men and women throughout the world.2 C-Met protein overexpression is found in approximately 25% of advanced EGFR wild type NSCLC patients3 and is associated with a poor prognosis for these patients.4,5,6 Teliso-V, an investigational ADC, is being studied in this patient population who have very limited treatment options and where there are currently no approved therapies.
"The results of the Phase 2 LUMINOSITY trial are encouraging for those patients with non-small cell lung cancer with c-Met overexpression as there is a critical need for better care and additional therapy options for them," said Ross Camidge, MD, PhD, University of Colorado Cancer Center, United States, and Principal Investigator for the trial. "Today's announcement also provides confidence as we continue to enroll patients into the Phase 3 TeliMET NSCLC-01 trial and expand our understanding of Teliso-V's potential."
"Results from the Phase 2 LUMINOSITY trial mark an important step forward for AbbVie's mission to advance new oncology treatments across our ADC program targeting solid tumor types with critical patient needs," said Roopal Thakkar, M.D., senior vice president, development and regulatory affairs and chief medical officer, AbbVie.
Teliso-V is being evaluated as a monotherapy in patients with previously treated c-Met overexpressing EGFR wild type nonsquamous NSCLC in the randomized Phase 3 study TeliMET NSCLC-01, which is currently enrolling.
Teliso-V has also been granted several designations around the world including Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) and Taiwanese health authorities, SAKIGAKE designation in Japan by the Ministry of Health, Labour and Welfare (MHLW), as well as being awarded an Innovation Passport by the UK's Medicines and Healthcare products Regulatory Agency (MHRA).
About Telisotuzumab-Vedotin (Teliso-V)
Teliso-V is an investigational first-in-class, c-Met protein directed antibody-drug conjugate (ADC) targeting patients with c-Met overexpressing tumors. C-Met is a receptor tyrosine kinase that is overexpressed in many solid tumors including NSCLC. Teliso-V is being evaluated as a monotherapy in patients with previously treated c-Met overexpressing EGFR wild type non squamous NSCLC in the randomized Phase 3 study TeliMET NSCLC-01, which is currently enrolling. In addition, it is being evaluated in combination with osimertinib in the ongoing Phase 1 study M14-237, and as a monotherapy in the Phase 2 LUMINOSITY study. Further information on clinical trials for Teliso-V is available at https://clinicaltrials.gov/. Currently there are no approved cancer therapies specifically for patients with c-Met overexpressing NSCLC. Teliso-V is not approved by any regulatory authority and its safety and efficacy have not been established.
About the LUMINOSITY trial
The LUMINOSITY trial (M14-239), is an ongoing Phase 2 study designed to identify the target NSCLC populations that overexpress c-Met best suited for Teliso-V monotherapy in the second line or third line setting, and then to expand the groups to further evaluate efficacy in the selected populations. The endpoints include overall response rate (ORR), duration of response (DoR), disease control rate (DCR) and progression-free survival (PFS) per independent central review (ICR) as well as overall survival (OS).
About AbbVie in Oncology
At AbbVie, we are committed to transforming standards of care for multiple blood cancers while advancing a dynamic pipeline of investigational therapies across a range of cancer types. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potentially breakthrough medicines. We are evaluating more than 20 investigational medicines in over 300 clinical trials across some of the world's most widespread and debilitating cancers. As we work to have a remarkable impact on people's lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit www.abbvie.com/oncology.
About AbbVie
AbbVie's mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas – immunology, oncology, neuroscience, and eye care – and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on LinkedIn, Facebook, Instagram, X (formerly Twitter), and YouTube.
SOURCE AbbVie
https://www.abbvie.com/science/pipeline.html
ABBV Dividend History
https://www.nasdaq.com/market-activity/stocks/abbv/dividend-history
KarXT (xanomeline-trospium)
Telisotuzumab-Vedotin (Teliso-V)
KarXT (xanomeline-trospium)
Karuna Therapeutics Announces U.S. Food and Drug Administration Accepts New Drug Application for KarXT for the Treatment of Schizophrenia
November 29, 2023
Prescription Drug User Fee Act (PDUFA) action date is September 26, 2024 If approved, KarXT would represent the first new pharmacological approach to treating schizophrenia in several decades The application is supported by positive data from the EMERGENT clinical trial program showing KarXT is associated with significant improvements in schizophrenia symptoms
BOSTON--(BUSINESS WIRE)--
Nov. 29, 2023--
Karuna Therapeutics, Inc.
(NASDAQ: KRTX), a biopharmaceutical company driven to discover, develop, and deliver transformative medicines for people living with psychiatric and neurological conditions, today announced the U.S. Food and Drug Administration (FDA) has accepted its New Drug Application (NDA) for KarXT (xanomeline-trospium) for the treatment of schizophrenia in adults. The application has been granted a Prescription Drug User Fee Act (PDUFA) date of September 26, 2024. “We are pleased the NDA for KarXT has been accepted, and we look forward to working with the FDA during the review process,” said Bill Meury, president and chief executive officer of Karuna Therapeutics. “There is a significant need for new treatment options for serious mental illness. If approved, KarXT could be one of the more important new product introductions in neuropsychiatry by providing a novel pharmacological approach for the treatment of schizophrenia.” “Schizophrenia’s disabling symptoms pose significant challenges to navigating crucial aspects of life, including developing relationships, maintaining employment, and securing safe housing,” said Gordon Lavigne, M.Ed., chief executive officer, Schizophrenia & Psychosis Action Alliance. “Diagnosis marks the beginning of an often long and tiresome search for effective and tolerable treatment options. The nature and magnitude of side effects often play a pivotal role in whether someone continues treatment, which is often crucial to minimize the risk of relapse and realize the life-altering benefits of long-term treatment. Potential approval of a pharmacologically distinct treatment option would be a welcome innovation for people living with schizophrenia.” The NDA submission is supported by efficacy and long-term safety data from the EMERGENT program, the clinical program evaluating KarXT as a treatment for schizophrenia. The EMERGENT program includes the three completed positive EMERGENT-1, EMERGENT-2, and EMERGENT-3 trials evaluating the efficacy and safety of KarXT compared to placebo, and the EMERGENT-4 and EMERGENT-5 trials evaluating the long-term safety of KarXT. In all three placebo-controlled trials, KarXT met its primary endpoint, demonstrating statistically significant and clinically meaningful improvements in symptoms of schizophrenia compared to placebo as measured by Positive and Negative Syndrome Scale (PANSS) total score. KarXT was found to be generally well tolerated, with the most common adverse events being cholinergic in nature and mild to moderate in severity. Notably, KarXT was not associated with common side effects of currently available antipsychotics, including weight gain, somnolence, and movement disorders. “KarXT focuses on a novel pathway through muscarinic receptors to indirectly modulate dopamine signaling in key brain circuits, and in clinical trials completed to date KarXT has demonstrated the much-needed combination of strong tolerability and clinically meaningful symptom reduction,” remarked Rishi Kakar, M.D., chief scientific officer and medical director of Segal Trials, and investigator in the EMERGENT program. “This decision by the FDA marks an important step in working toward a new chapter in the standard of care for those facing the immense, daily struggle of this serious mental illness.” About KarXT KarXT (xanomeline-trospium) is an investigational muscarinic antipsychotic in development for the treatment of schizophrenia and psychosis related to Alzheimer’s disease. Through its novel mechanism of action, KarXT acts as a dual M1/M4 muscarinic acetylcholine receptor agonist in the central nervous system, which is thought to improve positive, negative, and cognitive symptoms of schizophrenia. Unlike existing treatments, KarXT does not directly block dopamine receptors, representing a potential new approach to treating schizophrenia. About Schizophrenia Schizophrenia is a persistent and often disabling mental illness impacting how a person thinks, feels, and behaves, and affects nearly 24 million people worldwide, including 2.8 million people in the U.S. It is characterized by three symptom domains: positive symptoms (hallucinations and delusions), negative symptoms (difficulty enjoying life and withdrawal from others), and cognitive impairment (deficits in memory, concentration, and decision-making). In part due to limitations with current treatments, people living with schizophrenia often struggle to maintain employment, live independently, and manage relationships. While current treatments can be effective in managing select symptoms, approximately 30% of people do not respond to therapy, with an additional 50% experiencing only a partial improvement in symptoms or unacceptable side effects. About Karuna Karuna Therapeutics is a biopharmaceutical company driven to discover, develop, and deliver transformative medicines for people living with psychiatric and neurological conditions. At Karuna, we understand there is a need for differentiated and more effective treatments that can help patients navigate the challenges presented by serious mental illness. Utilizing our extensive knowledge of neuroscience, we are harnessing the untapped potential of the brain in pursuit of novel pathways to develop medicines that make meaningful differences in peoples’ lives. For more information, please visit www.karunatx.com.
View source version on businesswire.com: https://www.businesswire.com/news/home/20231129152646/en/
Source: Karuna Therapeutics, Inc.
FDA accepts Karuna Therapeutics schizophrenia drug for review
Nov. 29, 2023 7:16 AM ET
Karuna Therapeutics, Inc. (KRTX)
By: Preeti Singh, SA News Editor
The U.S. Food and Drug Administration has accepted Karuna Therapeutics' (NASDAQ:KRTX) new drug application for its lead candidate, KarXT.
KarXT (xanomeline-trospium) is an investigational muscarinic antipsychotic in development for the treatment of schizophrenia and psychosis related to Alzheimer's disease.
The application is backed by positive data from the EMERGENT clinical trial program showing KarXT is associated with significant improvements in schizophrenia symptoms.
https://seekingalpha.com/news/4041063-fda-accepts-karuna-therapeutics-schizophrenia-drug-for-review
ARCT-032
Epcoritamab (EPKINLY®/TEPKINLY®)
KarXT (xanomeline-trospium)
Arcturus Therapeutics Receives Orphan Drug Designation from the U.S. FDA for ARCT-032, for the Treatment of Cystic Fibrosis
November 27, 2023 at 8:30 AM EST
First cystic fibrosis patient in Phase 1b study successfully completed two administrations of ARCT-032
On track to share interim Phase 1b data in H1 2024
SAN DIEGO--(BUSINESS WIRE)--Nov. 27, 2023-- Arcturus Therapeutics Holdings Inc. (the “Company”, “Arcturus”, Nasdaq: ARCT), a global late-stage clinical messenger RNA medicines company focused on the development of infectious disease vaccines and opportunities within liver and respiratory rare diseases, today announced the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation for the Company’s product candidate ARCT-032 to treat cystic fibrosis (CF).
The FDA’s Office of Orphan Products Development grants orphan status to drugs being developed to treat, prevent, or diagnose a rare disease or condition affecting fewer than 200,000 people in the United States. The designation provides significant incentives to promote the development of the drug including the potential for market exclusivity for seven years upon FDA approval, eligibility for tax credits for qualified clinical trials, waiver of Prescription Drug User Fee Act Application fee, and eligibility to receive regulatory guidance from the FDA in the design of an overall drug development plan.
“Orphan Drug Designation is a very important regulatory milestone in our development plan for ARCT-032,” said Joseph Payne, President, and Chief Executive Officer of Arcturus Therapeutics. "We are executing diligently to accelerate ARCT-032 as a potential new treatment option for people with cystic fibrosis.”
The first CF patient in our Phase 1b study successfully completed two administrations of ARCT-032. We remain on track to share interim Phase 1b data in H1 2024.
About Cystic Fibrosis
Cystic fibrosis is a life-shortening disease with a worldwide distribution. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene result in a reduction or absence of CFTR protein and/or function in the airways, causing insufficient chloride transport to maintain airway surface homeostasis. CF mucus is more difficult to clear, thus clogging the airways and leading to infection, inflammation, respiratory failure, or other life-threatening complications. Currently approved CFTR modulator therapies are designed to increase function of the CFTR channel to help reduce symptoms yet are ineffective in some people with CF because of their underlying mutations.
About ARCT-032
ARCT-032 utilizes Arcturus' LUNAR® lipid-mediated aerosolized platform to deliver CFTR messenger RNA to the lungs. Expression of a functional copy of the CFTR mRNA in the lungs of people with CF has the potential to restore CFTR activity and mitigate the downstream effects that cause progressive lung disease. The ARCT-032 program is supported by preclinical data in rodents, ferrets and primates, as well as demonstrating restoration of CFTR expression and function in human bronchial epithelial cells.
About Arcturus Therapeutics
Founded in 2013 and based in San Diego, California, Arcturus Therapeutics Holdings Inc. (Nasdaq: ARCT) is a global late-stage clinical mRNA medicines and vaccines company with enabling technologies: (i) LUNAR® lipid-mediated delivery, (ii) STARR® mRNA Technology (sa-mRNA) and (iii) mRNA drug substance along with drug product manufacturing expertise. The Company has an ongoing global collaboration for innovative mRNA vaccines with CSL Seqirus, and a joint venture in Japan, ARCALIS, focused on the manufacture of mRNA vaccines and therapeutics. Arcturus’ pipeline includes RNA therapeutic candidates to potentially treat ornithine transcarbamylase deficiency and cystic fibrosis, along with its partnered mRNA vaccine programs for SARS-CoV-2 (COVID-19) and influenza. Arcturus’ versatile RNA therapeutics platforms can be applied toward multiple types of nucleic acid medicines including messenger RNA, small interfering RNA, circular RNA, antisense RNA, self-amplifying RNA, DNA, and gene editing therapeutics. Arcturus’ technologies are covered by its extensive patent portfolio (patents and patent applications issued in the U.S., Europe, Japan, China, and other countries). For more information, visit www.ArcturusRx.com. In addition, please connect with us on Twitter and LinkedIn.
View source version on businesswire.com: https://www.businesswire.com/news/home/20231127768908/en/
Source: Arcturus Therapeutics Holdings Inc.
Arcturus cystic fibrosis therapy gets orphan drug status
Nov. 27, 2023 11:36 AM ET
Arcturus Therapeutics Holdings Inc. (ARCT)
By: Preeti Singh, SA News Editor
- Arcturus Therapeutics (NASDAQ:ARCT) on Monday announced that its drug candidate ARCT-032 has been granted orphan drug designation by the U.S. Food and Drug Administration to treat cystic fibrosis (CF).
- The first CF patient successfully completed two administrations of ARCT-032 as part of a Phase 1b study. The biotech firm is on track to share interim from the study in the first half of 2024.
- https://seekingalpha.com/news/4040412-arcturus-cystic-fibrosis-therapy-gets-orphan-drug-status
- Arcturus Therapeutics Holdings Inc. (ARCT)
- https://arcturusrx.com/
Epcoritamab (EPKINLY®/TEPKINLY®)
Epcoritamab (EPKINLY®/TEPKINLY®)
Epcoritamab (EPKINLY®/TEPKINLY®)
November 27, 2023
AbbVie Announces U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) Updates for Epcoritamab (EPKINLY®/TEPKINLY®) for the Treatment of Relapsed/Refractory Follicular Lymphoma
- Open a printable version of this page
- Email the URL of this page to a friend
- Updates are supported by data from the Phase 1/2 EPCORE™ NHL-1 clinical trial
NORTH CHICAGO, Ill., Nov. 27, 2023 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced updates from the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) for epcoritamab, an investigational T-cell engaging bispecific antibody administered subcutaneously, for relapsed or refractory (R/R) follicular lymphoma (FL).
The FDA has granted Breakthrough Therapy Designation (BTD) to epcoritamab-bysp (EPKINLY®) for the treatment of adult patients with R/R FL after two or more therapies. Additionally, the EMA has validated a Type II application for epcoritamab (TEPKINLY®) for the same indication. If approved, R/R FL would become the second conditionally approved indication for epcoritamab in the European Union.
"The FDA granted BTD and validated European application are an important step in our commitment to improving the lives of patients with relapsed/refractory follicular lymphoma, a complex blood cancer with limited treatment options," said Mariana Cota Stirner, M.D., Ph.D., vice president, therapeutic area head for hematology, AbbVie. "Together with Genmab, we are continuing to investigate epcoritamab as a potential core therapy for multiple B-cell malignancies, including diffuse large B-cell lymphoma and now follicular lymphoma."
These updates were supported by previously announced results from the Phase 1/2 EPCORE™ NHL-1 clinical trial evaluating the safety and preliminary efficacy of subcutaneous epcoritamab in 128 adult patients with relapsed, progressive or refractory CD20+ mature B-cell non-Hodgkin's lymphoma (NHL), including FL. Data from the FL cohort of the trial, including an optimized dosing schedule allowing for outpatient administration, will be presented at the upcoming Annual Meeting and Exposition of the American Society of Hematology (ASH) in December 2023.
BTD may expedite the development and review of investigational medicines by the FDA for serious or life-threatening diseases in cases where preliminary clinical evidence shows that a therapy may provide substantial improvements over available therapies.1 EMA validation confirms that the submitted regulatory application is complete and initiates the scientific review process by the EMA's Committee for Medicinal Products for Human Use (CHMP).
FL is typically an indolent, or slow-growing, form of NHL that arises from B-cell lymphocytes.2 It is the second most common form of NHL overall, accounting for 20 percent to 30 percent of all NHL cases globally.3 Although FL is an indolent lymphoma, it is considered incurable with current standard of care therapies.4,5
Epcoritamab is being co-developed by AbbVie and Genmab as part of the companies' oncology collaboration. The companies will share commercial responsibilities in the U.S. and Japan, with AbbVie responsible for further global commercialization.
About the Phase 1/2 EPCORE™ NHL-1 Trial
EPCORE™ NHL-1 is an open-label, multi-center safety and preliminary efficacy trial of epcoritamab that consists of three parts: a Phase 1 first-in-human, dose escalation part; a Phase 2a expansion part; and a Phase 2a dose optimization part. The trial was designed to evaluate subcutaneous epcoritamab in adult patients with relapsed, progressive or refractory CD20+ mature B-cell non-Hodgkin's lymphoma (NHL), including follicular lymphoma (FL). In the Phase 2a expansion part, additional patients are being enrolled to further explore the safety and efficacy of epcoritamab in three cohorts of patients with different types of relapsed or refractory (R/R) B-cell NHLs who have limited therapeutic options. The dose optimization part evaluates the potential for alternative step-up dosing regimens to help further minimize Grade 2 cytokine release syndrome (CRS) and mitigate Grade ≥3 CRS. The application for BTD included additional data from this cohort of patients. The primary endpoint of the expansion part was overall response rate as assessed by an independent review committee. Secondary efficacy endpoints included duration of response, complete response rate, duration of complete response, progression-free survival, and time to response as determined by the Lugano criteria. Overall survival, time to next therapy, and rate of minimal residual disease negativity were also evaluated as secondary efficacy endpoints.
About Epcoritamab
Epcoritamab is an investigational IgG1-bispecific antibody created using Genmab's proprietary DuoBody® technology and administered subcutaneously. Genmab's DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response toward target cell types. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B cells and induces T-cell-mediated killing of CD20+ cells.6
Epcoritamab (approved under the brand name EPKINLY® in the United States and TEPKINLY® in the European Union) has received regulatory approval in adults with certain types of large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL), globally. EPKINLY is approved under the FDA's Accelerated Approval program based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Use of epcoritamab in FL is not approved in the U.S. or in the EU. AbbVie will continue to pursue regulatory submissions for epcoritamab across international markets.
Genmab and AbbVie continue to evaluate the use of epcoritamab as a monotherapy, and in combination, across lines of therapy in a range of hematologic malignancies. This includes three ongoing Phase 3, open-label, randomized trials including a trial evaluating epcoritamab as a monotherapy in patients with R/R DLBCL (NCT: 04628494) compared to investigator's choice chemotherapy, a Phase 3 trial evaluating epcoritamab in combination with R-CHOP in adult patients with newly diagnosed DLBCL (NCT: 05578976), and a Phase 3 clinical trial evaluating epcoritamab in combination with rituximab and lenalidomide (R2) in patients with R/R FL (NCT: 05409066). Epcoritamab is not approved to treat patients with newly diagnosed DLBCL or with FL. The safety and efficacy of epcoritamab has not been established for these investigational uses. Please visit clinicaltrials.gov for more information.
EPKINLY® (epcoritamab-bysp) U.S. USES AND IMPORTANT SAFETY INFORMATION
USE
EPKINLY is a prescription medicine used to treat adults with certain types of diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma that has come back (relapsed) or that did not respond to previous treatment (refractory), and who have received 2 or more treatments for their cancer.
EPKINLY is approved based on patient response data. A study is ongoing to confirm the clinical benefit of EPKINLY. It is not known if EPKINLY is safe and effective in children.
About AbbVie in Oncology
At AbbVie, we are committed to transforming standards of care for multiple blood cancers while advancing a dynamic pipeline of investigational therapies across a range of cancer types. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potential breakthrough medicines. We are evaluating more than 20 investigational medicines in over 300 clinical trials across some of the world's most widespread and debilitating cancers. As we work to have a remarkable impact on people's lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit www.abbvie.com/oncology and our Blood Cancer Press Kit page.
About AbbVie
AbbVie's mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas – immunology, oncology, neuroscience, and eye care – and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on LinkedIn, Facebook, Instagram, X (formerly Twitter), and YouTube.
SOURCE AbbVie
AbbVie-Genmab lymphoma drug gets FDA breakthrough designation
Nov. 27, 2023 8:03 AM ET
By: Preeti Singh, SA News Editor3 Comments
- AbbVie (NYSE:ABBV) and Genmab (GMAB) said on Monday their investigational lymphoma drug candidate epcoritamab has received breakthrough therapy designation from the U.S. FDA.
- The breakthrough drug designation is for treatment of relapsed or refractory follicular lymphoma. Additionally, European Medicines Agency has validated a type 2 application for the same indication. If approved, this would be the second conditional nod for epcoritamab in the EU.
- https://seekingalpha.com/news/4040271-abbvie-genmab-lymphoma-drug-gets-fda-breakthrough-designation
- AbbVie Inc. (ABBV), GMAB
- https://www.abbvie.com/
- https://www.epkinly.com/
VLA1553
Epcoritamab (EPKINLY®/TEPKINLY®)
Epcoritamab (EPKINLY®/TEPKINLY®)
EMA Accepts Valneva’s Chikungunya Vaccine Marketing Authorization Application for Accelerated Assessment
November 27, 2023
Saint-Herblain (France),
November 27, 2023 – Valneva SE (Nasdaq: VALN; Euronext Paris: VLA), a specialty vaccine company, today announced that the European Medicines Agency (EMA) has performed a technical validation of the Marketing Authorization Application (MAA) for Valneva’s single-shot chikungunya vaccine candidate VLA1553 and has determined that all essential regulatory elements required for scientific assessment were included in the application. The MAA was granted accelerated assessment[1] last month by EMA’s Committee for Medicinal Products for Human Use (CHMP) based on the vaccine candidate’s “major interest for public health and therapeutic innovation”[2].
Accelerated assessment reduces the timeframe for EMA’s CHMP to review a MAA once it is accepted for review from 210 days under the standard review procedure to 150 days. This does not, however, include clock stops when applicants must provide additional information during the review process, which is common in review procedures.
Juan Carlos Jaramillo, MD, Chief Medical Officer of Valneva, commented, “We welcome EMA’s MAA review acceptance and will work closely with them to bring VLA1553 to market. Chikungunya virus, or CHIKV, has already spread to over 110 countries and the risk of chikungunya spreading in Europe is relatively high due to the possibility of infected travelers[3]. No vaccine or specific treatments are currently available for this debilitating disease which therefore constitutes an unmet medical need. Following approval of VLA1553 in the United States[4], we will continue to work diligently to bring VLA1553 to other territories as soon as possible.”
VLA1553 received approval from the U.S. Food and Drug Administration (FDA)[5] at the beginning of the month under the brand name IXCHIQ®. In the U.S., the vaccine is indicated for the prevention of disease caused by the chikungunya virus (CHIKV) in individuals 18 years of age and older who are at increased risk of exposure to CHIKV.
Mid-November, Valneva also reported positive pivotal Phase 3 immunogenicity data in adolescents for VLA1553 which are intended to support label extension in this age group[6]. The trial is also expected to support licensure of the vaccine in Brazil, which would be the first potential approval for use in endemic populations.
About Chikungunya
Chikungunya is a mosquito-borne viral disease caused by the chikungunya virus (CHIKV), a Togaviridae virus, transmitted by Aedes mosquitoes. Infection leads to symptomatic disease in up to 97% of humans after four to seven days following the mosquito bite[7]. While mortality with CHIKV is low, morbidity is high, and the global market for vaccines against chikungunya is estimated to exceed $500 million annually by 2032[8]. Clinical symptoms include acute onset of fever, debilitating joint and muscle pain, headache, nausea, rash and chronic arthralgia. Chikungunya virus often causes sudden large outbreaks with high attack rates, affecting one-third to three-quarters of the population in areas where the virus is circulating. The high-risk areas of infection for travelers are places where chikungunya virus-carrying mosquitos are endemic, including the Americas, parts of Africa, and Southeast Asia, and the virus has spread to more than 110 countries[9]. Between 2013 and 2023, more than 3.7 million cases were reported in the Americas[10] and the economic impact is considered to be significant. The medical and economic burden is expected to grow as the CHIKV primary mosquito vectors continue to spread geographically. In Europe, there is no preventive vaccines or effective treatments available and, as such, chikungunya is considered a major public health threat.
About VLA1553
VLA1553 is a live-attenuated, single dose investigational vaccine candidate targeting the chikungunya virus, which has spread to over 110 countries[11]. It has been designed by deleting a part of the chikungunya virus genome.
Valneva reported final data from the pivotal Phase 3 trial of VLA1553 in March 2022[12], final lot-to-lot consistency results in May 2022[13], positive twelve-month persistence data in December 2022[14] and positive pivotal Phase 3 data in adolescents in November 2023[15].
To make VLA1553 more accessible to Low- and Middle-Income Countries (LMIC), Valneva and Instituto Butantan in Brazil signed an agreement in January 2021 for the development, manufacturing and marketing of VLA1553[16]. The collaboration falls within the framework of the agreement signed between CEPI and Valneva in July 2019[17], which provides funding of up to $24.6 million with support from the European Union’s Horizon 2020 program.
VLA1553 received FDA approval in November 2023 under the brand name IXCHIQ® and is indicated for the prevention of disease caused by CHIKV in individuals 18 years of age and older who are at increased risk of exposure to CHIKV. Continued approval of IXCHIQ® in the United States is contingent upon verification of clinical benefit in confirmatory studies.
VLA1553 was also granted PRIority MEdicine (PRIME) designation and accelerated assessment by the European Medicines Agency (EMA) in 2020 and 2023 respectively.
The Company intends to commercialize this vaccine by leveraging its existing manufacturing and commercial operations.
About Valneva SE
We are a specialty vaccine company that develops, manufactures, and commercializes prophylactic vaccines for infectious diseases addressing unmet medical needs. We take a highly specialized and targeted approach, applying our deep expertise across multiple vaccine modalities, focused on providing either first-, best- or only-in-class vaccine solutions.
We have a strong track record, having advanced multiple vaccines from early R&D to approvals, and currently market two proprietary travel vaccines as well as certain third-party vaccines leveraging our established commercial infrastructure.
Revenues from our growing commercial business help fuel the continued advancement of our vaccine pipeline. This includes the only Lyme disease vaccine candidate in advanced clinical development, which is partnered with Pfizer, potentially the world’s first vaccine against the chikungunya virus, as well as vaccine candidates against the Zika virus and other global public health threats.
Valneva chikungunya vaccine to go through accelerated review in Europe
Nov. 27, 2023 4:41 AM ET
By: Preeti Singh, SA News Editor
French specialty vaccine company Valneva (NASDAQ:VALN) announced on Monday that the European Medicines Agency (EMA) has accepted the marketing authorization application for its chikungunya vaccine for accelerated assessment.
The EU regulator determined that all essential regulatory elements required for scientific assessment were included in the application.
Valneva’s single-shot chikungunya vaccine candidate VLA1553 will go through an accelerated assessment, which reduces the timeframe for review from 210 days under the standard process to 150 days.
biotecHOPE™ 2023
oral cyclin-dependent kinase 2 (CDK2) inhibitor
oral cyclin-dependent kinase 2 (CDK2) inhibitor
oral cyclin-dependent kinase 2 (CDK2) inhibitor
BEIGENE AND ENSEM THERAPEUTICS ANNOUNCE PARTNERSHIP TO ADVANCE DIFFERENTIATED CDK2 INHIBITOR
BeiGene and Ensem Therapeutics Announce Partnership to Advance Differentiated CDK2 Inhibitor
BASEL, Switzerland & BEIJING & CAMBRIDGE, Mass. & WALTHAM, Mass.–(BUSINESS WIRE)–BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global biotechnology company, and Ensem Therapeutics, Inc. (ENSEM), a biotechnology company focusing on high-value and difficult-to-drug oncology targets, today announced an agreement for BeiGene to acquire an exclusive global license to an Investigational New Drug (IND) application-ready oral cyclin-dependent kinase 2 (CDK2) inhibitor.
“We are committed to developing novel molecules with the potential to transform the therapeutic landscape for cancer patients, and this partnership fits well with our strategic focus on breast cancer as an area with tremendous unmet need for innovative treatment options,” said Lai Wang, Ph.D., Global Head of R&D at BeiGene. “This CDK2 inhibitor from ENSEM complements our internally discovered Phase 1 CDK4 inhibitor, which has the potential to improve upon current CDK4/6 inhibitors in some breast cancer patients, and strengthens our early development pipeline in breast cancer and other solid tumors. We are excited to work with ENSEM to bring this molecule into the clinic in the near future.”
Under the terms of the agreement, ENSEM will receive an upfront payment, and will be eligible for additional payments upon the achievement of certain development, regulatory, and commercial milestones, totaling up to $1.33 billion, in addition to tiered royalties.
“We are pleased to partner with BeiGene on the development of this differentiated CDK2 inhibitor,” said Shengfang Jin, Ph.D., President and Chief Executive Officer at ENSEM. “We believe BeiGene is the right partner to advance our first IND-ready asset due to their wealth of expertise in bringing innovative cancer therapies to patients globally. This partnership validates the capabilities of ENSEM’s drug discovery and development team and the ability to rapidly advance potential best-in-class or first-in-class molecules utilizing our Kinetic Ensemble® platform. We look forward to progressing our additional pipeline programs to help patients in need and supporting BeiGene’s important work to take this therapy into clinical trials.”
About Ensem Therapeutics
ENSEM is a pioneering drug discovery and development company that leverages its unique Kinetic Ensemble® platform to develop innovative small molecule precision medicines for oncology. ENSEM integrates computational and AI deep learning methodologies with advanced experimental techniques to identify non-obvious binding pockets and accelerate structure-based drug design, with a focus on high-value and difficult-to-drug targets.
For more information, please visit www.ensemtx.com, or engage with us on LinkedIn.
About BeiGene
BeiGene is a global biotechnology company that is discovering and developing innovative oncology treatments that are more affordable and accessible to cancer patients worldwide. With a broad portfolio, we are expediting development of our diverse pipeline of novel therapeutics through our internal capabilities and collaborations. We are committed to radically improving access to medicines for far more patients who need them. Our growing global team of more than 10,000 colleagues spans five continents, with administrative offices in Basel, Beijing, and Cambridge, U.S. To learn more about BeiGene, please visit www.beigene.com and follow us on LinkedIn and X (formerly known as Twitter).
BeiGene inks $1.33B deal with Ensem Therapeutics for cancer drug
Nov. 21, 2023 7:11 AM ET
By: Dulan Lokuwithana, SA News Editor
- BeiGene (NASDAQ:BGNE) on Tuesday agreed to pay more than $1B to acquire an exclusive global license for a cancer candidate developed by Waltham, Massachusetts-based biotech Ensem Therapeutics.
- Privately held Ensem has yet to file an Investigational New Drug (IND) application for the candidate identified as an oral cyclin-dependent kinase 2 (CDK2) inhibitor.
- https://seekingalpha.com/news/4039015-beigene-inks-billion-dollar-deal-cancer-drug?mailingid=33439730&messageid=2900&serial=33439730.515&utm_campaign=rta-stock-news&utm_content=link-1&utm_medium=email&utm_source=seeking_alpha&utm_term=33439730.515
- BeiGene, Ltd. (BGNE)
- https://ensemtx.com/science/pipeline/
- https://ensemtx.com/
- https://www.beigene.com/
- BEIGENE, LTD. (6160)
- https://www.hkex.com.hk/Market-Data/Securities-Prices/Equities/Equities-Quote?sym=6160&sc_lang=en
YORVIPATH® (palopegteriparatide)
oral cyclin-dependent kinase 2 (CDK2) inhibitor
oral cyclin-dependent kinase 2 (CDK2) inhibitor
Ascendis Pharma Announces European Commission Approval of YORVIPATH® (palopegteriparatide) for the Treatment of Adults with Chronic Hypoparathyroidism
November 20, 2023 at 8:00 AM EST
- YORVIPATH (developed as TransCon PTH) is a parathyroid hormone (PTH) replacement therapy indicated for the treatment of adults with chronic hypoparathyroidism
- Ascendis plans its first EU launch of YORVIPATH in Germany in January 2024
COPENHAGEN, Denmark, Nov. 20, 2023 (GLOBE NEWSWIRE) -- Ascendis Pharma A/S (Nasdaq: ASND) today announced that the European Commission (EC) has granted marketing authorization for YORVIPATH® (palopegteriparatide) as replacement therapy indicated for the treatment of adults with chronic hypoparathyroidism. YORVIPATH is a prodrug of parathyroid hormone (PTH 1-34) administered once daily. Ascendis plans its first European Union (EU) launch of YORVIPATH in January 2024 in Germany.
“Each patient living with chronic hypoparathyroidism faces serious health and quality of life concerns,” said Professor Lorenz C. Hofbauer, Professor of Medicine, Geriatrics, and Endocrinology, Technical University of Dresden. “To treat the underlying cause of disease, these patients need new treatment options that go beyond the limits and risks of conventional therapy, which today consists of oral calcium and active vitamin D.”
The EC approval follows the positive opinion adopted on September 14, 2023 by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommending approval of YORVIPATH.
“By focusing on patient need and using science to drive our decisions, we have brought YORVIPATH – our second approved TransCon product – from concept through EU marketing authorization in only eight years and we are preparing to launch it in Germany this coming January,” said Jan Mikkelsen, President and Chief Executive Officer at Ascendis Pharma. “Knowing the urgent need that many patients and physicians have expressed for new treatment options, we will continue our work to make YORVIPATH widely available.”
TransCon PTH will be marketed in the EU as YORVIPATH, a parathyroid hormone (PTH) replacement therapy indicated for the treatment of adults with chronic hypoparathyroidism. Treatment should be initiated and monitored by physicians or qualified healthcare professionals experienced in the diagnosis and management of patients with hypoparathyroidism. TransCon PTH is in development for adults with hypoparathyroidism in the United States, Japan, and other countries.
About Hypoparathyroidism
Hypoparathyroidism is an endocrine disease caused by insufficient levels of PTH, the primary regulator of calcium/phosphate balance in the body, acting directly on bone and kidneys and indirectly on intestines. Hypoparathyroidism is considered chronic if it persists >6 months following surgery per the 2016 Endocrine Society Guidelines, 2019 Canadian and International Consensus Statement, and 2022 European Society of Endocrinology Consensus Statement. Individuals with hypoparathyroidism may experience a range of severe and potentially life-threatening short-term and long-term complications, including neuromuscular irritability, renal complications, extra-skeletal calcifications, and cognitive impairment. Postsurgical hypoparathyroidism accounts for the majority of cases (78%), with other etiologies that include autoimmune disorders, familial disorders, and idiopathic causes.
About Ascendis Pharma A/S
Ascendis Pharma is applying its innovative platform technology to build a leading, fully integrated biopharma company focused on making a meaningful difference in patients’ lives. Guided by its core values of patients, science and passion, the company uses its TransCon technologies to create new and potentially best-in-class therapies. Ascendis is headquartered in Copenhagen, Denmark and has additional facilities in Germany (Heidelberg and Munich) and the United States (Palo Alto and Redwood City, California, and Princeton, New Jersey). Please visit ascendispharma.com to learn more.
Ascendis, Ascendis Pharma, the Ascendis Pharma logo, the company logo, TransCon, and YORVIPATH® are trademarks owned by the Ascendis Pharma group. © November 2023 Ascendis Pharma A/S.
Source: Ascendis Pharma
Ascendis receives EU approval for hypoparathyroidism drug
Nov. 21, 2023 9:32 AM ET
By: Val Brickates Kennedy, SA News Editor
Ascendis Pharma (ASND) has received EU approval for its drug palopegteriparatide for the treatment of chronic hypoparathyroidism in adults.
The drug will be marketed under the name Yorvipath. The company plans to launch the drug first in Germany in January.
Last week, Ascendis resubmitted its application for FDA approval of the product, which is also known as TransCon PTH.
https://seekingalpha.com/news/4039124-ascendis-receives-eu-approval-for-hypoparathyroidism-drug
https://ascendispharma.com/pipeline/endocrinology/transcon-pth/
ANAVEX®2-73 (Blarcamesine)
oral cyclin-dependent kinase 2 (CDK2) inhibitor
ANAVEX®2-73 (Blarcamesine)
Anavex Initiates Regulatory Submission of Oral Blarcamesine for Alzheimer’s Disease
to the European Medicines Agency (EMC)
NEW YORK – November 20, 2023
Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq: AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders announced today that representatives of Anavex met with team members of the European Medicines Agency (EMA).
These meetings discussed the debilitating pathology of Alzheimer’s disease and Anavex’s blarcamesine (ANAVEX®2-73) Alzheimer’s disease clinical program results, including data obtained in the ANAVEX®2-73-AD-004 study.
Pursuant to the discussion at the meetings, Anavex initiated the process for submitting a Marketing Authorisation application to the EMA with the submission of the Centralised Procedure request with the goal of the Authorisation allowing direct access to the market of the European Union for oral blarcamesine for the treatment of Alzheimer’s disease.
Anavex’s goal is to take care of patients in a patient-centric way with the preference for convenient oral treatment options for Alzheimer’s disease not requiring complex logistics resources and added personnel for drug administration and monitoring for brain edema and brain bleeds.
Severe symptoms in relation to Amyloid-Related Imaging Abnormalities (ARIA) is a known risk factor for Alzheimer’s patients taking the class of drugs called monoclonal antibodies, and requires constant and repeated MRI examination, for which not all regions in Europe are currently sufficiently prepared and equipped for in addition to the requirement to address affordability and inequalities in patient access within European Union countries. [1],[2]
“We look forward to working together with the team from EMA,” said David Goldberger, RPh, MLS, Senior Vice President of Regulatory Affairs at Anavex. “We continue to work towards fulfilling our purpose of improving patients' lives with oral blarcamesine not requiring any complex additional procedures for the treatment of people with Alzheimer’s disease.”
There are an estimated 7 million people in Europe with Alzheimer’s disease, a number expected to double by 2030, according to the European Brain Council. [3]
The World Health Organization (WHO) estimated the cost in Europe of caring for people with dementia, including Alzheimer's disease, at $439 billion, or $31,144 per person in 2019. That includes hospital care, medicines, diagnostics, informal caregiver time, community services, and long-term care facility costs. [4],[5]
“There remains an urgent need for convenient once-daily oral treatment options for Alzheimer’s disease, and Anavex is moving forward to potentially addressing the preference for simple patient-centered administrations and shared decision-making,” said Christopher U Missling, PhD, President and Chief Executive Officer at Anavex.
In addition to significant improvement in dementia symptoms, blarcamesine demonstrated a reduction of pathological aggregation of amyloid in early Alzheimer’s disease as well as a reduction of brain volume loss, a well-known marker of neurodegeneration.
Data from the blarcamesine in Alzheimer’s disease Phase 2b/3 randomized clinical trial will be published in an upcoming peer-reviewed journal.
About Anavex Life Sciences Corp.
Anavex Life Sciences Corp. (Nasdaq: AVXL) is a publicly traded biopharmaceutical company dedicated to the development of novel therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders, including Alzheimer's disease, Parkinson's disease, Rett syndrome, and other central nervous system (CNS) diseases, pain, and various types of cancer. Anavex's lead drug candidate, ANAVEX®2-73 (blarcamesine), has successfully completed a Phase 2a and a Phase 2b/3 clinical trial for Alzheimer's disease, a Phase 2 proof-of-concept study in Parkinson's disease dementia, and both a Phase 2 and a Phase 3 study in adult patients with Rett syndrome. ANAVEX®2-73 is an orally available drug candidate that restores cellular homeostasis by targeting sigma-1 and muscarinic receptors. Preclinical studies demonstrated its potential to halt and/or reverse the course of Alzheimer's disease. ANAVEX®2-73 also exhibited anticonvulsant, anti-amnesic, neuroprotective, and anti-depressant properties in animal models, indicating its potential to treat additional CNS disorders, including epilepsy. The Michael J. Fox Foundation for Parkinson's Research previously awarded Anavex a research grant, which fully funded a preclinical study to develop ANAVEX®2-73 for the treatment of Parkinson's disease. ANAVEX®3-71, which targets sigma-1 and M1 muscarinic receptors, is a promising clinical-stage drug candidate demonstrating disease-modifying activity against the major hallmarks of Alzheimer's disease in transgenic (3xTg-AD) mice, including cognitive deficits, amyloid, and tau pathologies. In preclinical trials, ANAVEX®3-71 has shown beneficial effects on mitochondrial dysfunction and neuroinflammation. Further information is available at www.anavex.com. You can also connect with the Company on Twitter, Facebook, Instagram, and LinkedIn.
Anavex gains as EU filing for Alzheimer’s drug starts
Nov. 20, 2023 2:04 PM ET
Anavex Life Sciences Corp. (AVXL)
By: Dulan Lokuwithana, SA News Editor2 Comments
- Anavex Life Sciences (NASDAQ:AVXL) traded higher on Monday after the company started filings to seek EU regulatory clearance for its oral Alzheimer's candidate blarcamesine (ANAVEX 2-7https://seekingalpha.com/news/4038761-anavex-stock-gains-eu-filing-alzheimers-drug-starts3).
- Anavex Life Sciences Corp. (AVXL)
- https://www.anavex.com/
- https://www.anavex.com/therapeutic-candidates
MN-166 (ibudilast)
Truqap (capivasertib) plus Faslodex
ANAVEX®2-73 (Blarcamesine)
MediciNova Announces New Data and Results of a Phase 2 Clinical Trial of MN-166 (ibudilast) in Glioblastoma Presented at the 28th Annual Meeting of the Society for Neuro-Oncology
LA JOLLA, Calif., Nov. 19, 2023 (GLOBE NEWSWIRE) -- MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ Global Market (NASDAQ:MNOV) and the Standard Market of the Tokyo Stock Exchange (Code Number: 4875), today announced that MediciNova’s collaborator, Justin Lathia PhD, Co-Director of the Brain Tumor Research and Therapeutic Development Center of Excellence at Cleveland Clinic Lerner Research Institute, and Professor, Department of Molecular Medicine at Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, and Patrick Wen, Director at the Center for Neuro-Oncology at Dana-Farber Cancer Institute, Professor of Neurology, Harvard Medical School, presented new data and results of a Phase 2 clinical trial of MN-166 (ibudilast) in glioblastoma (GBM) patients at the 28th Annual Meeting of the Society for Neuro-Oncology (SNO) held November 15 - 19, 2023 in Vancouver, Canada. The presentation also included data from preclinical studies which evaluated the combination of MN-166 (ibudilast) and anti-PD1 or anti-PD-L1 therapy in GBM models.
The primary endpoints of this Phase 2 clinical trial were safety and tolerability of MN-166 (ibudilast) and temozolomide (TMZ) combination treatment and efficacy of the combination treatment defined as progression-free survival rate at 6 months using the RANO criteria. MN-166 (ibudilast) and TMZ combination treatment was safe and well-tolerated, and no unexpected adverse effects were reported.
The highlights of the presentation are as follows:
Phase II clinical trial and immunohistochemistry study
- The trial enrolled a total of 62 patients, including 36 newly diagnosed GBM (new GBM) patients and 26 recurrent GBM patients
- Study participants’ mean age at screening was 58.9 years old for new GBM and 59.6 years old for recurrent GBM
- 39% of patients were female in both groups
- 94% of new GBM patients and 100% of recurrent GBM patients were Caucasian
- All of the subjects received TMZ and MN-166 (ibudilast) treatment
- Progression-Free Survival at 6 months (PFS6) was 44% for new GBM and 31% for recurrent GBM
- Immunohistochemistry evaluation was performed for the patients whose pre-treatment tumor tissue samples were available from resected tumors at the initial surgery or biopsy to evaluate MIF (macrophage migration inhibitory factor), pERK, Ki67, CD3, CD11b, and CD74
- CD3 expression was a good predictor for tumor progression at five months in recurrent glioblastoma subjects treated with MN-166 (ibudilast) and TMZ as subjects with progression had higher CD3 tumor infiltration than subjects with no progression (p<0.05)
Preclinical GBM model studies
- C57BL/6 mice were intracranially injected with SB28 tumor cells at 4 weeks of life and then treated with either isotype control, vehicle control, MN-166 (ibudilast), anti-PD1, anti-PDL1 or a combination therapy
- Median survival was 17 days for the vehicle and 28 days for the anti-PD1 inhibitor treatment alone. The addition of MN-166 (ibudilast) to the anti-PD1 inhibitor treatment significantly extended survival to a median of 66 days (p<0.001) for the combination therapy.
- Median survival was 18 days for the vehicle and 26 days for the anti-PD-L1 inhibitor treatment alone. The addition of MN-166 (ibudilast) to the anti-PD-L1 inhibitor treatment significantly extended survival to a median of 34 days (p<0.05) for the combination therapy.
Kazuko Matsuda, M.D., Ph.D., M.P.H., Chief Medical Officer of MediciNova, Inc., commented, “We are very pleased to report the positive safety and efficacy results from the first GBM clinical trial of MN-166. GBM’s rapid progression and resistance to therapy poses a serious challenge to the medical community. Evaluation of MN-166 (ibudilast) as an adjuvant therapy with TMZ in GBM patients was generally safe and well tolerated. For the PFS6 primary efficacy endpoint, recurrent GBM patients showed a higher PFS6 rate compared to most historical studies. Moreover, the preclinical studies presented at this meeting support our postulation that adding MN-166 (ibudilast) to existing therapies, e.g., TMZ, anti-PD1 or anti-PD-L1, improves survival more than the individual therapies alone. We are excited by the findings presented by our esteemed collaborators and look forward to completing the full data analysis from the GBM clinical trial. We are eager to evaluate MN-166 (ibudilast) in combination with anti-PD1 and anti-PD-L1 therapies in a future clinical trial. MediciNova is grateful to the patients and families for their invaluable participation in our trial.”
About MN-166 (ibudilast)
MN-166 (ibudilast) is a small molecule compound that inhibits phosphodiesterase type-4 (PDE4) and inflammatory cytokines, including macrophage migration inhibitory factor (MIF). It is in late-stage clinical development for the treatment of neurodegenerative diseases such as ALS (amyotrophic lateral sclerosis), progressive MS (multiple sclerosis), and DCM (degenerative cervical myelopathy); and is also in development for glioblastoma, Long COVID, CIPN (chemotherapy-induced peripheral neuropathy), and substance use disorder. In addition, MN-166 (ibudilast) was evaluated in patients that are at risk for developing acute respiratory distress syndrome (ARDS).
About MediciNova
MediciNova, Inc. is a clinical-stage biopharmaceutical company developing a broad late-stage pipeline of novel small molecule therapies for inflammatory, fibrotic, and neurodegenerative diseases. Based on two compounds, MN-166 (ibudilast) and MN-001 (tipelukast), with multiple mechanisms of action and strong safety profiles, MediciNova has 11 programs in clinical development. MediciNova’s lead asset, MN-166 (ibudilast), is currently in Phase 3 for amyotrophic lateral sclerosis (ALS) and degenerative cervical myelopathy (DCM) and is Phase 3-ready for progressive multiple sclerosis (MS). MN-166 (ibudilast) is also being evaluated in Phase 2 trials in Long COVID and substance dependence. MN-001 (tipelukast) was evaluated in a Phase 2 trial in idiopathic pulmonary fibrosis (IPF) and a second Phase 2 trial in non-alcoholic fatty liver disease (NAFLD) is ongoing. MediciNova has a strong track record of securing investigator-sponsored clinical trials funded through government grants.
Source: MediciNova, Inc.
MediciNova spikes on potential of lead asset in brain cancer
Nov. 20, 2023 6:44 AM ET
By: Dulan Lokuwithana, SA News Editor
- MediciNova (NASDAQ:MNOV) added ~19% pre-market Monday after announcing new mid-stage data to indicate the safety and efficacy of its lead candidate, MN-166, as a combination regimen against brain cancer glioblastoma (GBM).
- Citing a recent data readout presented at a medical event in Canada, MediciNova (MNOV) said that 44% of new GBM patients who received MN-166 (ibudilast) with cancer medicine temozolomide (TMZ) remained alive without cancer progression (progression-free survival) at six months.
- The La Jolla, California-based biotech said the progression-free survival rate for recurrent GBM patients stood at 31%.
- https://seekingalpha.com/news/4038508-medicinova-stock-gains-potential-glioblastoma-therapy
- MediciNova, Inc. (MNOV)
- https://medicinova.com/clinical-development/core/mn-166/
- https://medicinova.com/
Truqap (capivasertib) plus Faslodex
Truqap (capivasertib) plus Faslodex
Truqap (capivasertib) plus Faslodex
Truqap (capivasertib) plus Faslodex approved in the US for patients with advanced HR-positive breast cancer
PUBLISHED
17 November 2023
First-in-class AKT inhibitor has potential to reshape treatment for breast cancer
patients with specific biomarker alterations (PIK3CA, AKT1 or PTEN)
Approval based on CAPItello-291 results which showed this combination reduced the
risk of disease progression or death by 50% vs. Faslodex alone in the
biomarker-altered population
AstraZeneca’s Truqap (capivasertib) in combination with Faslodex (fulvestrant) has been approved in the US for the treatment of adult patients with hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer with one or more biomarker alterations (PIK3CA, AKT1 or PTEN). Eligible patients will have progressed on at least one endocrine-based regimen in the metastatic setting or experienced recurrence on or within 12 months of completing adjuvant therapy.
The approval by the Food and Drug Administration (FDA) was based on the results from the CAPItello-291 Phase III trial published earlier this year in The New England Journal of Medicine.1 In the trial, Truqap in combination with Faslodex reduced the risk of disease progression or death by 50% versus Faslodex alone in patients with tumours harbouring PI3K/AKT pathway biomarker alterations (based on hazard ratio of 0.50, 95% confidence interval 0.38-0.65; p=<0.001; median progression-free survival (PFS) 7.3 versus 3.1 months).
Breast cancer is the most common cancer and one of the leading causes of cancer-related death worldwide.2 HR-positive breast cancer (expressing estrogen or progesterone receptors, or both), is the most common subtype, with more than 65% of tumours considered HR-positive and HER2-low or HER2-negative.3 Collectively, mutations in PIK3CA, AKT1 and alterations in PTEN occur frequently, affecting up to 50% of patients with advanced HR-positive breast cancer.4-6 Endocrine therapies are widely used in this setting, but many patients develop resistance to 1st-line cyclin-dependent kinase (CDK) 4/6 inhibitors and estrogen receptor-targeting therapies, underscoring the need for additional endocrine therapy-based options.7
Komal Jhaveri, MD, Medical Oncologist, Memorial Sloan Kettering Cancer Center (MSK), US, said: “Patients with advanced HR-positive breast cancer typically experience tumour progression or resistance with widely used first-line endocrine therapies and there is an urgent need to extend the effectiveness of these approaches. The combination of capivasertib and fulvestrant, a first-of-its-kind combination, provides a much-needed new treatment option for up to half of patients in this setting with these specific biomarkers, offering the potential to delay disease progression and provide more time with their disease under control.”
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “The rapid US approval of Truqap reinforces the important role of the PI3K/AKT pathway in HR-positive breast cancer and the critical need to test patients at the time of diagnosis, as up to fifty per cent have tumours with these alterations. As a first-in-class medicine, this approval provides a critical new option for patients in the US with this specific type of disease and we look forward to bringing Truqap to the many breast cancer patients who can benefit across the globe.”
In the CAPItello-291 trial, the safety profile of Truqap plus Faslodex was similar to that observed in previous trials evaluating this combination.1
Concurrently with this approval, the FDA also approved a companion diagnostic test to detect relevant alterations (PIK3CA, AKT1 and PTEN).
The US regulatory submission was granted Priority Review and reviewed under Project Orbis, which provides a framework for concurrent submission and review of oncology medicines among participating international partners. As part of Project Orbis, Truqap plus Faslodex is also under review by regulatory authorities in Australia, Brazil, Canada, Israel, Singapore, Switzerland and the UK.
Regulatory applications for Truqap in combination with Faslodex are also currently under review in China, the European Union, Japan and several other countries.
Financial considerations
Following this approval in the US, Astex Therapeutics is eligible to receive a milestone payment from AstraZeneca on first commercial sale of the drug in the US as well as royalties on future sales in line with the agreement between the two companies.
Notes
HR-positive breast cancer
Breast cancer is the most common cancer and one of the leading causes of cancer-related death worldwide.2 More than two million patients were diagnosed with breast cancer in 2020, with nearly 685,000 deaths globally.2 In the US, more than 290,000 patients are expected to be diagnosed in 2023, with more than 43,000 deaths.8
HR-positive breast cancer (expressing estrogen or progesterone receptors, or both), is the most common subtype of breast cancer with more than 65% of tumours considered HR-positive and HER2-low or HER2-negative.3 Collectively, mutations in PIK3CA, AKT1 and alterations in PTEN occur frequently, affecting up to 50% of patients with advanced HR-positive breast cancer.4-6
The growth of HR-positive breast cancer cells is often driven by estrogen receptors (ER), and endocrine therapies that target ER-driven disease are widely used as first-line treatment in the advanced setting, and often paired with CDK4/6 inhibitors.7,9,10 However, resistance to CDK4/6 inhibitors and current endocrine therapies develops in many patients with advanced disease.9 Once this occurs, treatment options are limited – with chemotherapy being the current standard of care – and survival rates are low with 30% of patients anticipated to live beyond five years after diagnosis.3,9,11
The optimisation of endocrine therapy and overcoming resistance to enable patients to continue benefiting from these treatments, as well as identifying new therapies for those who are less likely to benefit, are active areas of focus for breast cancer research.
CAPItello-291
CAPItello-291 is a Phase III, double-blind, randomised trial evaluating the efficacy of Truqap in combination with Faslodex versus placebo plus Faslodex for the treatment of locally advanced (inoperable) or metastatic HR-positive, HER2-low or negative (immunohistochemistry (IHC) 0 or 1+, or IHC 2+/in-situ hybridisation (ISH)-negative) breast cancer.
The global trial enrolled 708 adult patients with histologically confirmed HR-positive, HER2-low or negative breast cancer whose disease has recurred or progressed during or after aromatase inhibitor therapy, with or without a CDK4/6 inhibitor, and up to one line of chemotherapy for advanced disease. The trial has dual primary endpoints of PFS in the overall patient population and in a population of patients whose tumours have qualifying alterations in the PI3K/AKT pathway (PIK3CA, AKT1 or PTEN genes). In the trial, approximately 40% of tumours had these alterations and approximately 70% of patients received a prior CDK4/6 inhibitor.
Truqap
Truqap (capivasertib) is a first-in-class, potent, adenosine triphosphate (ATP)-competitive inhibitor of all three AKT isoforms (AKT1/2/3). Truqap 400mg is administered twice daily according to an intermittent dosing schedule of four days on and three days off. This was chosen in early phase trials based on tolerability and the degree of target inhibition.
Truqap is currently being evaluated in Phase III trials for the treatment of multiple subtypes of breast cancer and in other tumour types either as monotherapy or in combination with established treatments. The ongoing clinical research programme is focused on tumours reliant on signalling via the PI3K/AKT pathway, and in tumours harbouring biomarker alterations in this pathway.
Truqap was discovered by AstraZeneca subsequent to a collaboration with Astex Therapeutics (and its collaboration with the Institute of Cancer Research and Cancer Research Technology Limited).
Faslodex
Faslodex is an endocrine therapy indicated for the treatment of estrogen receptor-positive, locally advanced or metastatic breast cancer in postmenopausal women not previously treated with endocrine therapy, or with disease relapse on or after adjuvant anti-estrogen therapy, or disease progression on anti-estrogen therapy.
In the US, EU and Japan, Faslodex is also approved in combination with CDK4/6 inhibitors for the treatment of women with HR-positive, HER2-negative advanced or metastatic breast cancer, whose cancer has progressed after endocrine medicine. Faslodex represents a hormonal treatment approach that helps to slow tumour growth by blocking and degrading the estrogen receptor – a key driver of disease progression.
Faslodex is approved as monotherapy or in combination with medicines from various drug classes including CDK4/6, PI3K and AKT inhibitors for the treatment of patients with HR-positive advanced breast cancer and is being evaluated in combination with medicines from other drug classes.
AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge, and redefine, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.
AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment.
With Enhertu (trastuzumab deruxtecan), a HER2-directed antibody drug conjugate (ADC), AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive and HER2-low metastatic breast cancer and are exploring its potential in earlier lines of treatment and in new breast cancer settings.
In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines Faslodex and Zoladex (goserelin) and aims to reshape the HR-positive space with first-in-class AKT inhibitor, Truqap, and next-generation SERD and potential new medicine camizestrant. AstraZeneca is also collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan, in this setting.
PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in these settings and to explore its potential in earlier disease.
To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is evaluating the potential of datopotamab deruxtecan alone and in combination with immunotherapy Imfinzi (durvalumab), Truqap in combination with chemotherapy, and Imfinzi in combination with other oncology medicines, including Lynparza and Enhertu.
AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.
The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.
AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Social Media @AstraZeneca.
AstraZeneca gets FDA nod for breast cancer drug
Nov. 17, 2023 7:44 AM ET
By: Preeti Singh, SA News Editor
- AstraZeneca (NASDAQ:AZN) has received U.S. FDA approval for the use of Truqap (capivasertib) in combination with fulvestrant to treat advanced hormone receptor (HR)-positive breast cancer.
- https://seekingalpha.com/news/4038168-astrazeneca-gets-fda-nod-for-breast-cancer-drug
- AstraZeneca PLC (AZN)
- https://www.astrazeneca.com/
CASGEVY™ (exagamglogene autotemcel)
Truqap (capivasertib) plus Faslodex
Truqap (capivasertib) plus Faslodex
Nov 16, 2023
Vertex and CRISPR Therapeutics Announce Authorization of the First CRISPR/Cas9 Gene-Edited Therapy, CASGEVY™ (exagamglogene autotemcel), by the United Kingdom MHRA for the Treatment of Sickle Cell Disease and Transfusion-Dependent Beta Thalassemia
- First regulatory authorization of a CRISPR-based gene-editing therapy in the world –
- CASGEVY is indicated for the treatment of sickle cell disease in patients 12 years of age and older with recurrent vaso-occlusive crises who have the βS/βS, βS/β+ or βS/β0 genotype, for whom hematopoietic stem cell transplantation is appropriate and a human leukocyte antigen matched related hematopoietic stem cell donor is not available -
- CASGEVY is indicated for the treatment of transfusion‑dependent beta thalassemia in patients 12 years of age and older for whom hematopoietic stem cell transplantation is appropriate and a human leukocyte antigen matched related hematopoietic stem cell donor is not available -
BOSTON & ZUG, Switzerland--(BUSINESS WIRE)--Nov. 16, 2023-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) and CRISPR Therapeutics (Nasdaq: CRSP) announced today that the United Kingdom (U.K.) Medicines and Healthcare products Regulatory Agency (MHRA) has granted conditional marketing authorization for CASGEVY™ (exagamglogene autotemcel [exa-cel]), a CRISPR/Cas9 gene-edited therapy, for the treatment of sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT).
CASGEVY has been authorized for the treatment of eligible patients 12 years of age and older with SCD with recurrent vaso-occlusive crises (VOCs) or TDT, for whom a human leukocyte antigen (HLA) matched related hematopoietic stem cell donor is not available. There are an estimated 2,000 patients eligible for CASGEVY in the U.K.
“Today is a historic day in science and medicine: this authorization of CASGEVY in Great Britain is the first regulatory authorization of a CRISPR-based therapy in the world,” said Reshma Kewalramani, M.D., Chief Executive Officer and President of Vertex.
“I hope this represents the first of many applications of this Nobel Prize winning technology to benefit eligible patients with serious diseases,” said Samarth Kulkarni, Ph.D., Chairman and Chief Executive Officer of CRISPR Therapeutics.”
In two global clinical trials of CASGEVY in SCD and TDT, the trials met their respective primary outcome of becoming free from severe VOCs or transfusion independent for at least 12 consecutive months. Once achieved, these benefits are potentially expected to be life-long. The safety profile of 97 SCD and TDT patients treated to date with CASGEVY in these ongoing studies is generally consistent with myeloablative conditioning with busulfan and hematopoietic stem cell transplant.
“This authorization offers a new option for eligible patients who are waiting for innovative therapies, and I look forward to patients having access to this therapy as quickly as possible,” said Professor Josu de la Fuente, Principal Investigator in the CLIMB-111 and CLIMB-121 studies, Professor of Practice (Cellular & Gene Therapy) at Imperial College London, and Consultant Haematologist at Imperial College Healthcare NHS Trust.
In the U.K., exa-cel was granted an Innovation Passport under the Innovative Licensing and Access Pathway (ILAP) from the MHRA, and Vertex is already working closely with national health authorities to secure access for eligible patients as quickly as possible.
About Sickle Cell Disease
Sickle cell disease (SCD) is an inherited blood disorder that affects the red blood cells, which are essential for carrying oxygen to all organs and tissues of the body. SCD causes severe pain, organ damage and shortened life span due to misshapen or “sickled” blood cells. People with SCD can experience painful blood vessel blockages, also known as vaso-occlusive crises (VOCs), that can lead to acute chest syndrome, stroke, jaundice and symptoms of heart failure. Individuals may also experience anemia, which can result in end-organ damage and premature death. VOCs are the hallmark of SCD, often resulting in severe and debilitating pain. Current standard treatment options for SCD are largely symptomatic treatments and do not adequately address the burden of disease or alleviate the need for chronic care. Most often, treatment is focused on relieving pain, minimizing organ damage, maintaining hydration and addressing fevers, requiring medication and sometimes monthly blood transfusions and frequent hospital visits. The only cure for SCD today is a stem cell transplant from a matched donor, but this option is only available to a small fraction of people living with SCD. SCD requires lifelong treatment and significant use of health care resources, and ultimately results in reduced life expectancy and reduced lifetime earnings and productivity. In the U.K., the mean age of death for people living with SCD is around 40.
About Beta Thalassemia
Beta thalassemia is an inherited blood disorder that affects the red blood cells, which are essential for carrying oxygen to all organs and tissues of the body. A lack of red blood cells, also known as anemia, is the primary manifestation of beta thalassemia. Because of this anemia, people living with beta thalassemia may experience fatigue and shortness of breath, and infants may develop failure to thrive, jaundice and feeding problems. Complications of beta thalassemia can also include an enlarged spleen, liver and/or heart; misshapen bones; and delayed puberty. Treatment for beta thalassemia is personalized and depends on the severity of disease that each person experiences. Many people have to get regular blood transfusions to deliver healthy donated blood to their body. This requires many hospital visits and can also lead to an unhealthy buildup of iron. Today, stem cell transplant from a matched donor is a curative option but is only available to a small fraction of people living with beta thalassemia. Beta thalassemia requires lifelong treatment and significant use of health care resources, and ultimately results in reduced life expectancy, decreased quality of life and reduced lifetime earnings and productivity. In the U.K., the mean age of death for people living with TDT is around 55.
About CASGEVY™ (exagamglogene autotemcel [exa-cel])
CASGEVY™ is a genetically modified autologous CD34+ cell enriched population that contains human hematopoietic stem and progenitor cells edited ex vivo by CRISPR/Cas9 at the erythroid-specific enhancer region of the BCL11A gene.
The latest data from the ongoing pivotal trials was presented at the European Hematology Association Congress in June 2023.
Exa-cel is also under review by the European Medicines Agency, the Saudi Food and Drug Authority, and the U.S. Food and Drug Administration (FDA). The FDA has granted Priority Review for SCD and Standard Review for TDT and assigned Prescription Drug User Fee Act (PDUFA) target action dates of December 8, 2023, and March 30, 2024, respectively.
About Conditional Marketing Authorizations
Conditional marketing authorizations (CMAs) are for medicines that fulfill a significant unmet medical need such as being for serious and life-threatening diseases, where no satisfactory treatment methods are available or where the medicine offers a major therapeutic advantage. A CMA is granted where comprehensive clinical data is not yet complete, but it is judged that such data will become available soon. CMAs are valid for one year and renewable annually with ongoing regulatory review of data.
About the Vertex and CRISPR Collaboration
Vertex and CRISPR Therapeutics entered into a strategic research collaboration in 2015 focused on the use of CRISPR/Cas9 to discover and develop potential new treatments aimed at the underlying genetic causes of human disease. Exa-cel represents the first treatment to emerge from the joint research program. Under an amended collaboration agreement, Vertex now leads global development, manufacturing and commercialization of exa-cel and splits program costs and profits worldwide 60/40 with CRISPR Therapeutics.
About Vertex
Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has approved medicines that treat the underlying causes of multiple chronic, life-shortening genetic diseases — cystic fibrosis, sickle cell disease and transfusion-dependent beta thalassemia — and continues to advance clinical and research programs in these diseases. Vertex also has a robust clinical pipeline of investigational therapies across a range of modalities in other serious diseases where it has deep insight into causal human biology, including APOL1-mediated kidney disease, acute and neuropathic pain, type 1 diabetes and alpha-1 antitrypsin deficiency.
Vertex was founded in 1989 and has its global headquarters in Boston, with international headquarters in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia and Latin America. Vertex is consistently recognized as one of the industry's top places to work, including 14 consecutive years on Science magazine's Top Employers list and one of Fortune’s 100 Best Companies to Work For. For company updates and to learn more about Vertex's history of innovation, visit www.vrtx.com or follow us on LinkedIn, Facebook, Instagram, YouTube and Twitter/X.
About CRISPR Therapeutics
CRISPR Therapeutics is a leading gene editing company focused on developing transformative gene-based medicines for serious diseases using its proprietary CRISPR/Cas9 platform. CRISPR/Cas9 is a revolutionary gene editing technology that allows for precise, directed changes to genomic DNA. CRISPR Therapeutics has established a portfolio of therapeutic programs across a broad range of disease areas including hemoglobinopathies, oncology, regenerative medicine and rare diseases. To accelerate and expand its efforts, CRISPR Therapeutics has established strategic collaborations with leading companies including Bayer, Vertex Pharmaceuticals and ViaCyte, Inc. CRISPR Therapeutics AG is headquartered in Zug, Switzerland, with its wholly-owned U.S. subsidiary, CRISPR Therapeutics, Inc., and R&D operations based in Boston, Massachusetts and San Francisco, California, and business offices in London, United Kingdom. For more information, please visit www.crisprtx.com.
CRISPR THERAPEUTICS® standard character mark and design logo are trademarks and registered trademarks of CRISPR Therapeutics AG. All other trademarks and registered trademarks are the property of their respective owners.
View source version on businesswire.com: https://www.businesswire.com/news/home/20231115290500/en/
Source: Vertex Pharmaceuticals Incorporated
UK approves world-first sickle cell gene-editing therapy from Vertex-Crispr
Nov. 16, 2023 5:43 AM ET
CRISPR Therapeutics AG (CRSP), VRTX
By: Preeti Singh, SA News Editor13 Comments
The UK's Medicines and Healthcare products Regulatory Agency (MHRA) has approved exagamglogene autotemcel or exa-cel, a CRISPR/Cas9 gene-edited therapy developed by CRISPR Therapeutics (NASDAQ:CRSP) and Vertex Pharma (NASDAQ:VRTX) for sickle cell disease.
The drug will be marketed as Casvegy in the UK for the treatment of sickle cell disease and transfusion-dependent beta thalassemia in patients 12 years or older. This marks the first regulatory approval of a CRISPR-based gene-editing therapy in the world.
CRISPR Therapeutics AG (CRSP), VRTX
View printer-friendly version
PDF Version
Vertex and CRISPR Therapeutics Announce Authorization of the First CRISPR/Cas9 Gene-Edited Therapy, CASGEVY™ (exagamglogene autotemcel), by the United Kingdom MHRA for the Treatment of Sickle Cell Disease and Transfusion-Dependent Beta Thalassemia
- First regulatory authorization of a CRISPR-based gene-editing therapy in the world –
- CASGEVY is indicated for the treatment of sickle cell disease in patients 12 years of age and older with recurrent vaso-occlusive crises who have the βS/βS, βS/β+ or βS/β0 genotype, for whom hematopoietic stem cell transplantation is appropriate and a human leukocyte antigen matched related hematopoietic stem cell donor is not available -
- CASGEVY is indicated for the treatment of transfusion‑dependent beta thalassemia in patients 12 years of age and older for whom hematopoietic stem cell transplantation is appropriate and a human leukocyte antigen matched related hematopoietic stem cell donor is not available -
BOSTON & ZUG, Switzerland--(BUSINESS WIRE)--Nov. 16, 2023-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) and CRISPR Therapeutics (Nasdaq: CRSP)
Augtyro™ (repotrectinib)
Augtyro™ (repotrectinib)
Augtyro™ (repotrectinib)
U.S. Food and Drug Administration Approves Augtyro™ (repotrectinib), a Next-Generation Tyrosine Kinase Inhibitor (TKI), for the Treatment of Locally Advanced or Metastatic ROS1-Positive Non-Small Cell Lung Cancer (NSCLC)
11/15/2023
CATEGORY:
The approval is based on the pivotal TRIDENT-1 trial, in which Augtyro successfully achieved a high objective response rate and durable response1
Augtyro adds to Bristol Myers Squibb’s growing and differentiated NSCLC portfolio, expanding the company’s presence in precision medicine
PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced that the U.S. Food and Drug Administration (FDA) approved Augtyro™ (repotrectinib) for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC).1 Administered as an oral therapy, Augtyro is a tyrosine kinase inhibitor (TKI) targeting ROS1 oncogenic fusions.1
The approval is based on the TRIDENT-1 study, an open-label, single-arm, Phase 1/2 trial that evaluated Augtyro in TKI-naïve and TKI-pretreated patients.2 In TKI-naïve patients (n=71), the primary endpoint of objective response rate (ORR), defined as the percentage of people treated within a certain period of time whose tumor size decreased (partial response) or who no longer have signs of cancer (complete response),was 79% (95% Confidence Interval [CI]: 68 to 88).1,3 The median duration of response (mDOR) was 34.1 months. Among patients pretreated with one prior ROS1 TKI and no prior chemotherapy (n=56), the ORR was 38% (95% CI: 25 to 52) and the mDOR was 14.8 months.1 Among those who had measurable central nervous system (CNS) metastases at baseline, responses in intracranial lesions were observed in 7 of 8 TKI-naïve patients (n=71) and 5 of 12 of those who were TKI-pretreated (n=56).1
“New treatment options continue to be needed for patients with ROS1 fusion-positive NSCLC that support important clinical goals, including achieving durable therapeutic responses,” said Jessica J. Lin, MD, TRIDENT-1 primary investigator and attending physician at the Center for Thoracic Cancers at Massachusetts General Hospital and Assistant Professor of Medicine at Harvard Medical School.4,5,6,7 “Based on the data we have seen in the TRIDENT-1 trial, repotrectinib has the potential to become a new standard of care option for patients with locally advanced or metastatic ROS1 fusion-positive lung cancer.”1
Augtyro is associated with the following Warnings & Precautions: central nervous system (CNS) effects, interstitial lung disease (ILD)/pneumonitis, hepatotoxicity, myalgia with creatine phosphokinase elevation, hyperuricemia, skeletal fractures, and embryo-fetal toxicity.1 Please see Important Safety Information below.
“While progress has been made in the treatment of NSCLC over the past decade, there is still a need to address this particularly difficult-to-treat form of the disease with innovative science and a targeted approach,” said Samit Hirawat, MD, executive vice president, chief medical officer, Global Drug Development, Bristol Myers Squibb.6,7 “As the only approved next-generation TKI for ROS1-positive NSCLC patients, Augtyro builds on our legacy of delivering transformational therapies for patients with thoracic cancers.”6,8,9
“ROS1-positive NSCLC patients and their families face a stressful journey because our cancer can be difficult to treat, especially when it spreads to the brain,” said Janet Freeman-Daily, co-founder and president of The ROS1ders, a patient advocacy organization.10 “Today’s approval brings a new treatment option for the ROS1-positive patient community, which gives us hope for more time with loved ones.”
Augtyro is designed to minimize interactions that can lead to certain forms of treatment resistance in ROS1-positive metastatic NSCLC patients.6,8,11 It is expected to be available to patients in the U.S. in mid-December 2023. Bristol Myers Squibb thanks the patients and investigators involved in the TRIDENT-1 clinical trial program.
About TRIDENT-1
TRIDENT-1 is a global, multicenter, single-arm, open-label, multi-cohort Phase 1/2 clinical trial evaluating the safety, tolerability, pharmacokinetics and anti-tumor activity of repotrectinib in patients with advanced solid tumors, including non-small cell lung cancer (NSCLC).1,2 Phase 1/2 includes patients with locally advanced or metastatic solid tumors harboring ROS1 fusions.2 Additional analyses of the trial are still being conducted; asymptomatic central nervous system (CNS) metastases are allowed.1,2 The trial excludes patients with symptomatic brain metastases, among other exclusion criteria.1 Phase 1 of the trial included the dose escalation that determined the recommended Phase 2 dose.2
Phase 2 of the trial has a primary endpoint of overall response rate (ORR).1,2 Key secondary endpoints include duration of response (DOR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1) as assessed by Blinded Independent Central Review (BICR), progression-free survival (PFS), and intracranial response in six distinct expansion cohorts, including tyrosine kinase inhibitor (TKI)-naïve and TKI-pretreated patients with ROS1-positive locally advanced or metastatic NSCLC.1,2
In TRIDENT-1, of the 79% (95% Confidence Interval [CI]: 68 to 88) of TKI-naïve patients who responded to treatment, 6% experienced complete responses and 73% experienced partial responses.1 The median duration of response (mDOR) was 34.1 months.1 Of the 38% (95% CI: 25 to 52) of TKI-pretreated patients (n=56) who responded to treatment, 5% experienced complete responses and 32% experienced partial responses and the mDOR was 14.8 months.1 Among those who had measurable CNS metastases at baseline as assessed by BICR, responses in intracranial lesions were observed in 7 of 8 TKI-naïve patients (n=71) and in 5 of 12 of those who were TKI-pretreated (n=56).1
The FDA-approved dosing for Augtyro is 160 mg orally once daily for 14 days, then increased to 160 mg twice daily until disease progression or unacceptable toxicity.1
Select Safety Profile From TRIDENT-1
Permanent discontinuation of Augtyro occurred in 8% of patients.1 Augtyro dosage was interrupted due to an adverse reaction in 48% of patients, and dose reductions due to an adverse event occurred in 35% of patients.1 Serious adverse reactions occurred in 33% of patients who received Augtyro.1 Serious adverse reactions in ≥2% of patients included pneumonia (5.7%), dyspnea (3.8%), pleural effusion (3.4%) and hypoxia (3%).1 Fatal adverse reactions occurred in 4.2% of patients who received Augtyro, including death, pneumonia, pneumonia aspiration, cardiac arrest, sudden cardiac death, cardiac failure, sudden death, hypoxia, dyspnea, respiratory failure, tremor, and disseminated intravascular coagulation.1 The most common (≥20%) adverse reactions were dizziness (63%), dysgeusia (48%), peripheral neuropathy (47%), constipation (36%), dyspnea (30%), ataxia (28%), fatigue (24%), cognitive disorders (23%), and muscular weakness (21%).1 Grade 3 dizziness occurred in 1.9% of patients.1 The most common and serious adverse reactions and fatal events were evaluated in 264 patients who received the Phase 2 recommended dose of Augtyro in TRIDENT-1.1
About Lung Cancer
Lung cancer is the leading cause of cancer deaths in the United States.12 The two main types of lung cancer are non-small cell and small cell.12 Non-small cell lung cancer (NSCLC) represents up to 85% of diagnoses.12 Survival rates vary depending on the stage and type of the cancer when diagnosed.13 ROS1 fusions are rare and occur in about 1-2% of patients with NSCLC.10 With a median age of 50, patients with tumors that are ROS1-positive tend to be younger than the average lung cancer patient, more often female than male and may have little to no smoking history.10ROS1-positive lung cancer tends to be aggressive and can often spread to the brain.10ROS1 tyrosine kinase inhibitor (TKI) therapy is the current standard of care for patients with a tumor harboring this gene alteration.4
INDICATION
AUGTYROTM (repotrectinib) is indicated for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC).
Please see U.S. Full Prescribing Information for AUGTYRO
Bristol Myers Squibb: Creating a Better Future for People with Cancer
Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine and, through innovative digital platforms, are turning data into insights that sharpen their focus. Deep understanding of causal human biology, cutting-edge capabilities and differentiated research programs uniquely position the company to approach cancer from every angle.
Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. As a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.
About Bristol Myers Squibb’s Patient Access Support
Bristol Myers Squibb remains committed to providing assistance so that cancer patients who need our medicines can access them and expedite time to therapy.
BMS Access Support®, the Bristol Myers Squibb patient access and reimbursement program, is designed to help appropriate patients initiate and maintain access to BMS medicines during their treatment journey. BMS Access Support offers benefit investigation, prior authorization assistance, as well as co-pay assistance for eligible, commercially insured patients. More information about our access and reimbursement support can be obtained by calling BMS Access Supportat 1-800-861-0048 or by visiting www.bmsaccesssupport.com.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.
Source: Bristol Myers Squibb
Multimedia Files:
Download:Download original 99 KB 1505 x 211Download thumbnail 5 KB 200 x 28Download lowres 15 KB 480 x 67Download square 23 KB 250 x 250
FDA approves Bristol Myers lung cancer drug repotrectinib: report
Nov. 15, 2023 5:39 PM ET
Bristol-Myers Squibb Company (BMY)
By: Val Brickates Kennedy, SA News Editor2 Comments
The FDA has reportedly approved Bristol Myers Squibb’s (NYSE:BMY) drug repotrectinib for the treatment of a type of non-small cell lung cancer.Reuters reported late Wednesday that the drug was approved. The FDA had been expected to decide on whether to approve the product by Nov. 27.The agency accepted Bristol Myers’ application for repotrectinib in May. The drugmaker was seeking to have the drug approved for the treatment of advanced or metastatic ROS 1-positive non-small cell lung cancer.Bristol Myers acquired repotrectinib through its $4.1B buyout of Turning Point Therapeutics in 2022.
SCI-110
Augtyro™ (repotrectinib)
Augtyro™ (repotrectinib)
November 15, 2023 8:01 AM
SciSparc Celebrates Major Breakthrough: Positive Results Show its Treatment has a Remarkable Impact on Alzheimer's Agitation
Phase IIa trial outcome indicates the potential for a new way to help Alzheimer’s patients’ agitation
Tel-Aviv, Nov. 15, 2023 (GLOBE NEWSWIRE) -- SciSparc Ltd. (NASDAQ: SPRC), a specialty, clinical-stage pharmaceutical company focusing on the development of therapies to treat disorders of the central nervous system (the “Company” or “SciSparc”), unveiled positive topline results from its investigator-initiated Phase IIa trial at the Sophie & Abraham Stuchynski Israeli Alzheimer’s Medical Center (IMCA). The trial results indicated that SciSparc’s proprietary SCI-110 provided a safe and effective solution for alleviating agitation in elderly Alzheimer's patients who participated.
Agitation is a devastating symptom of Alzheimer's Disease (AD), afflicting nearly all patients as the disease progresses, and imposing tremendous suffering and caregiving burdens. Existing treatments, including off-label medications, have questionable efficacy and come with notable side effects.
SciSparc’s open-label Phase IIa trial, conducted at IMCA, encompassed 18 AD patients grappling with agitation. It aimed to assess the safety, tolerability, and effectiveness of SCI-110, administered orally twice daily. The results not only met primary endpoints regarding tolerability and adverse events but also demonstrated SCI-110's potential to alleviate agitation without side effects.
Importantly, patients treated with SCI-110 were free of delirium, oversedation, hypotension, or falls, demonstrating its potential safety and suitability for elderly patients. Moreover, when measured by the Cohen Mansfield Agitation Inventory (CMAI), our treatment led to a significant 23% reduction in agitation symptoms. These results were further corroborated by the Edinburgh Feeding Evaluation in Dementia Scale, which showed a decline in eating and feeding difficulties.
“We are thrilled with these outcomes, as they signify a monumental potential in enhancing the lives of AD patients. Our commitment to pioneering innovative treatments with a global impact has never been clearer," said Dr. Adi Zuloff- Shani, Chief Technologies Officer of SciSparc.
The trial, titled "Phase IIa Open Label Trial to Evaluate the Safety, Tolerability and Efficacy Trend of SCI-110 in Patients with Alzheimer's Disease and Agitation," was conducted at IMCA under the guidance of Dr. Alexander Kaplan, MD, a board-certified geriatrician and principal investigator. This single-arm, open-label trial saw each subject receiving SCI-110 twice daily via oral administration, with follow-up for up to 39 days.
SCI-110 is a unique combination of FDA-Approved Dronabinol and the Company’s proprietary CannAmide™ formulation, creating a powerful solution for AD patients. SciSparc’s cannabinoid-centric approach enhances efficacy which allows lowering cannabinoid dose leading to a decrease in side effects compared to standalone cannabinoids.
AD is an urgent global health concern, and existing treatments fall short of meeting the needs of patients. SciSparc is committed to changing this reality and providing hope to millions worldwide.
About SciSparc Ltd. (NASDAQ: SPRC)
SciSparc Ltd. is a specialty clinical-stage pharmaceutical company led by an experienced team of senior executives and scientists. SciSparc’s focus is on creating and enhancing a portfolio of technologies and assets based on cannabinoid pharmaceuticals. With this focus, the Company is currently engaged in the following drug development programs based on THC and/or non-psychoactive cannabidiol (CBD): SCI-110 for the treatment of Tourette Syndrome, for the treatment of Alzheimer's disease and agitation; SCI-160 for the treatment of pain; and SCI-210 for the treatment of autism spectrum disorder and status epilepticus. The Company also owns a controlling interest in a subsidiary whose business focusses on the sale of hemp-based products on the Amazon.com marketplace.
News Provided by GlobeNewswire via QuoteMedia
SciSparc stock rallies 67% on positive results for Alzheimer's drug
Nov. 15, 2023 9:36 AM ET
By: Val Brickates Kennedy, SA News Editor
SciSparc (NASDAQ:SPRC) stock rallied 67% in early action Wednesday after the Israeli biotech reported positive results from a Phase 2a study for its drug candidate SCI-110 in the treatment of agitation in Alzheimer’s patients.
SciSparc said the study met its primary endpoints on tolerability and adverse events, along with demonstrating potential to alleviate agitation without side effects in elderly patients.
https://seekingalpha.com/news/4036992-scisparc-stock-rallies-on-positive-results-for-alzheimers-drug
CM-101
Augtyro™ (repotrectinib)
CardiAMP Heart Failure II study protocol
Chemomab Therapeutics Receives FDA Fast Track Designation for CM-101 for the Treatment of Primary Sclerosing Cholangitis
—CM-101's Unique Dual Anti-Fibrotic and Anti-Inflammatory Activity Has Disease Modifying Potential in this Poorly Treated Condition—
—CM-101's Phase 2 SPRING Trial in PSC is Advancing Towards Completion of Enrollment with Top-line Readout Expected in 2H 2024—
TEL AVIV, Israel, Nov. 15, 2023 /PRNewswire/ --
Chemomab Therapeutics Ltd. (Nasdaq: CMMB) (Chemomab), a clinical stage biotechnology company focused on the discovery and development of innovative therapeutics for fibro-inflammatory diseases with high unmet need, today announced that the U.S. Food and Drug Administration (FDA) has granted CM-101 Fast Track designation for the treatment in adult patients of primary sclerosing cholangitis (PSC), a fibrotic liver disease that can result in liver transplant, cancer and early death.
Fast Track is a process developed by the FDA to facilitate and expedite the development of new treatments that demonstrate a potential to address unmet medical needs in serious or life-threatening conditions. Programs with Fast Track designation can benefit from early and more frequent interactions with the FDA during the clinical development process. Therapeutic candidates with Fast Track designation may also be eligible for priority review and accelerated approval if supported by clinical data.
"This FDA Fast Track designation is an important validation of CM-101's potential to have a major impact on this devastating disease that attacks people in their prime years and lacks any approved treatments," said Adi Mor, PhD, co-founder, Chief Executive Officer and Chief Scientific Officer of Chemomab. "We designed the CM-101 Phase 2 SPRING trial to be supportive of a registrational trial in patients with PSC, and we welcome the enhanced opportunities for working closely with the FDA and for acceleration of the development and review process provided by Fast Track status."
There are no FDA-approved treatments for PSC. CM-101 is a first-in-class monoclonal antibody that neutralizes the soluble protein CCL24, which in preclinical and clinical studies has been associated with key pathways underlying PSC pathophysiology. CM-101's dual anti-inflammatory and anti-fibrotic activity, which is designed to break the vicious cycle driving these pathways, has demonstrated the potential for disease modifying activity in preclinical and early clinical studies of PSC-related processes.
Chemomab Chief Medical Officer Matt Frankel, MD, added, "Promising biomarker and elastography results from our Phase 2a liver fibrosis study in nonalcoholic steatohepatitis (NASH) patients reported earlier this year reinforced our optimism about the therapeutic potential of CM-101. There are common fibrosis pathways in NASH and PSC, and CM-101's relevance to PSC is supported by extensive preclinical and patient sample studies. We also are encouraged by robust patient enrollment in the SPRING trial, which speaks to the high unmet need experienced by these patients. We look forward to continuing our work with PSC patients, their clinicians and the FDA to expedite advancement of CM-101 as a potential treatment for this terrible disease."
Chemomab's Phase 2 SPRING trial (NCT04595825) is a double-blind, placebo-controlled study assessing the safety and tolerability of CM-101 in PSC patients. The trial is also measuring a wide range of relevant biomarkers and physiological parameters. Patient enrollment in the trial is advancing towards completion and Chemomab anticipates reporting a top-line readout in the second half of 2024.
About CM-101
CM-101 is a monoclonal antibody that neutralizes CCL24, a soluble protein that helps drive the inflammatory and fibrotic pathways central to many fibro-inflammatory diseases. CCL24's role as a therapeutic target has been validated in extensive preclinical studies and Chemomab researchers have demonstrated preclinical proof-of-concept for CM-101 in multiple animal and patient sample studies. CM-101 was safe and well tolerated in Phase 1 and Phase 2 clinical trials to date. In a Phase 1b study it improved liver biomarkers, decreased liver stiffness and demonstrated a favorable PK and target engagement profile in patients with nonalcoholic fatty liver disease (NAFLD). Data from a completed Phase 2a liver fibrosis trial in NASH patients (NCT05824156) reported earlier this year showed consistent, positive improvements in key inflammatory and fibrogenesis-related biomarkers, including several that may serve as a potential bridge to activity in PSC. CM-101 has Orphan Drug designation from the FDA and Europe's EMA and is currently being evaluated in PSC patients in the Phase 2 SPRING trial.
About Primary Sclerosing Cholangitis
PSC is a rare, progressive liver disease, characterized by inflammation and fibrosis (scarring) of the bile ducts. Eventually, it can lead to cirrhosis of the liver and liver failure. PSC also increases the risk of various cancers, which account for about half of PSC deaths. PSC affects an estimated 30,000 patients in the U.S. and about 80,000 worldwide. The disease can occur in all ages, genders and races, but is more common in men and is typically diagnosed in patients in their 40s. The underlying cause of PSC is unknown, but about 75% of individuals with PSC also have inflammatory bowel disease. Currently there are no FDA or EMA-approved therapies for patients with PSC. Liver transplant is common in advanced cases, but even then, PSC re-occurs in about 20% of transplanted patients. There is a high unmet need for therapeutic options to address the symptoms and modify the progression of this devastating illness.
Forward Looking Statements
This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act. These forward-looking statements include, among other things, statements regarding the clinical development pathway for CM-101; the length, duration and impact of the war in Israel on Chemomab's business and operations; the future operations of Chemomab and its ability to successfully initiate and complete clinical trials and achieve regulatory milestones; the nature, strategy and focus of Chemomab; the development and commercial potential and potential benefits of any product candidates of Chemomab; and that the product candidates have the potential to address high unmet needs of patients with serious fibrosis-related diseases and conditions. Any statements contained in this communication that are not statements of historical fact may be deemed to be forward-looking statements. These forward-looking statements are based upon Chemomab's current expectations. Forward-looking statements involve risks and uncertainties. Because such statements deal with future events and are based on Chemomab's current expectations, they are subject to various risks and uncertainties and actual results, performance or achievements of Chemomab could differ materially from those described in or implied by the statements in this presentation, including those found under the caption "Risk Factors" and elsewhere in Chemomab's filings and reports with the SEC. Chemomab expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in Chemomab's expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based, except as required by law.
About Chemomab Therapeutics Ltd.
Chemomab is a clinical stage biotechnology company developing innovative therapeutics for fibro-inflammatory diseases with high unmet need. Based on the unique and pivotal role of CCL24 in promoting fibrosis and inflammation, Chemomab developed CM-101, a monoclonal antibody designed to neutralize CCL24 activity. In preclinical and clinical studies, CM-101 appears safe, with the potential to treat multiple severe and life-threatening fibro-inflammatory diseases. Chemomab has reported encouraging results from three clinical trials of CM-101 in patients, including a Phase 1b trial in NAFLD patients, a Phase 2a liver fibrosis trial in NASH patients and an investigator-initiated study in patients with severe lung injury. The CM-101 program for the treatment of systemic sclerosis is Phase 2-ready and a Phase 2 trial in primary sclerosing cholangitis patients is ongoing, with top-line data expected in the second half of 2024. For more information about Chemomab, visit chemomab.com.
SOURCE Chemomab Therapeutics, Ltd.
Chemomab jumps on FDA Fast Track tag for liver disease therapy
Nov. 15, 2023 7:55 AM ET
Chemomab Therapeutics Ltd. (CMMB)
By: Dulan Lokuwithana, SA News Editor
- Chemomab Therapeutics (NASDAQ:CMMB) added ~90% pre-market Wednesday after Israel-based biotech said that the U.S. FDA granted fast-track designation for its liver disease candidate CM-101.
- The regulator has issued the designation for CM-101’s use in treating adults with primary sclerosing cholangitis (PSC), a rare fibrotic liver disease.
- https://seekingalpha.com/news/4036883-chemomab-stock-jumps-fda-fast-track-tag
- Chemomab Therapeutics Ltd. (CMMB)
- https://www.chemomab.com/pipeline/
- https://www.chemomab.com/#
CardiAMP Heart Failure II study protocol
CardiAMP Heart Failure II study protocol
CardiAMP Heart Failure II study protocol
BioCardia Announces FDA Approval of CardiAMP Heart Failure II Protocol for Autologous Cell Therapy for Ischemic Heart Failure
Nov. 14, 2023 7:15 AM ET
Q3: 2023-11-08 Earnings Summary
Transcript
Press Release10-Q
EPS of -$0.12 misses by $0.01 | Revenue of $357.00K (68.40% Y/Y) beats by $318.50K
SUNNYVALE, Calif., Nov. 14, 2023 (GLOBE NEWSWIRE) -- BioCardia, Inc. (BCDA) [Nasdaq: BCDA], a developer of cellular and cell-derived therapeutics for the treatment of cardiovascular and pulmonary diseases, today announced the Food and Drug Administration (FDA) approval of its Phase III clinical trial of its CardiAMP autologous cell therapy for the treatment of patients with ischemic heart failure.
BioCardia announces that the Food and Drug Administration (FDA) has approved its proposed CardiAMP Heart Failure II study protocol. The currently ongoing CardiAMP Heart Failure trial has completed enrollment and it is anticipated that the final data analyses will be reported in Q4 2024. In an interim analysis of available data to date for study patients followed up through two years, those having N-terminal pro B-type natriuretic peptide (NT-proBNP) levels consistent as demarcating heart failure (>500 pg/ml) at screening-baseline showed meaningful clinical improvements over controls, including a 59% relative risk reduction in heart death and a 54% relative risk reduction of Major Adverse Cardiovascular or Cerebrovascular events (MACCE). Further, all clinical outcome measures evaluated at follow-up for this interim subset favored cell therapy over guideline directed medical therapy, including having improved quality-of-life as measured using the Minnesota Living with Heart Failure Questionnaire, reduced NT-proBNP levels, greater walk distance as measured using the 6-minute walk distance test, and improved cardiac measures such as left ventricular ejection fraction and left ventricular end systolic and end diastolic volumes. Statistical significance (p<0.05) was noted for both the reduced heart death equivalents measure (p=0.028) and the improved quality of life measure (p=0.016).
The FDA has approved the proposed CardiAMP Heart Failure II study which includes an eligibility requirement that patients demonstrate a pre-specified NT-proBNP level at baseline. The proposed primary efficacy endpoint is also modified from that in the currently ongoing study. The CardiAMP Heart Failure II endpoint is a similar hierarchical composite assessment but consists of all-cause death, the cardiac death equivalents of heart transplant and left ventricular assist device (LVAD) implantation, heart failure hospitalizations, worsening heart failure events treated as an outpatient, and change in quality-of-life, with a follow-up duration ranging from a minimum of 12 to a maximum of 24 months. Statistical power calculations using the interim data analyses support a modestly sized clinical trial would demonstrate efficacy if the interim data it is based on is representative of future study patients enrolled into the trial. Additional modifications from the ongoing trial include enhancements to simplify clinical site logistics and reduce costs of the study. Medicare’s reimbursement support for the trial currently in place for both the control and treatment arms is anticipated to significantly offset clinical costs of the trial.
“CardiAMP Heart Failure II has strong support from our clinical investigators who have reviewed the interim trial results in detail and have first-hand knowledge of this great unmet clinical need,” said Peter Altman, PhD., BioCardia’s President and Chief Executive Officer. “We expect that we can perform this study efficiently at world class clinical centers based on the extensive experience of the ongoing trial and its positive clinical outcomes.”
About the CardiAMP Cell Therapy Program
CardiAMP Cell Therapy – FDA designated as a Breakthrough therapy – uses a patient’s own (autologous) bone marrow cells delivered to the heart in a minimally invasive, catheter-based procedure to potentially stimulate the body’s natural healing response. The CardiAMP Heart Failure II Trial builds on positive clinical experience with this autologous cell therapy in almost 200 patients and has potential to provide the primary evidence to support FDA approval and marketing registration. The trial is supported by the Maryland Stem Cell Research Fund and the Centers for Medicare and Medicaid Services. CAUTION - Limited by United States law to investigational use.
About BioCardia®
BioCardia, Inc., headquartered in Sunnyvale, California, is developing cellular and cell-derived therapeutics for the treatment of cardiovascular and pulmonary disease. CardiAMP™ autologous and NK1R+ allogeneic cell therapies are the Company’s biotherapeutic platforms that enable four product candidates in development. BioCardia also partners with other biotherapeutic companies to provide its delivery systems and development support to their programs studying therapies for the treatment of heart failure, chronic myocardial ischemia and acute myocardial infarction. For more information visit: www.BioCardia.com.
Source: BioCardia, Inc. 2023 GlobeNewswire, Inc.
NTLA-2002
CardiAMP Heart Failure II study protocol
Zilebesiran
Intellia Therapeutics Receives European Union Orphan Drug Designation for NTLA-2002, an Investigational In Vivo CRISPR Genome Editing Treatment for Hereditary Angioedema
November 14, 2023
CAMBRIDGE, Mass., Nov. 14, 2023 (GLOBE NEWSWIRE) -- Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading clinical-stage genome editing company focused on developing potentially curative single-dose therapeutics leveraging CRISPR-based technologies, today announced that the European Commission (EC) has granted orphan drug designation to NTLA-2002 for the treatment of hereditary angioedema (HAE). NTLA-2002 is an in vivo CRISPR-based investigational therapy designed to prevent potentially life-threatening swelling attacks in people with HAE.
“The European Union orphan drug designation for NTLA-2002 represents another important milestone for Intellia as we continue to make rapid progress in the development of a novel, potential one-time treatment for people with hereditary angioedema,” said Intellia President and Chief Executive Officer John Leonard, M.D. “We are on track to complete enrollment of the Phase 2 portion of the study in the coming weeks, which will bring us one step closer to our goal of delivering a potentially life-changing treatment for people who suffer from this serious and debilitating disease.”
Orphan drug designation in the European Union (EU) is granted by the EC based on a positive opinion issued by the European Medicines Agency (EMA) Committee for Orphan Medicinal Products. To qualify for orphan drug designation, a candidate therapy must be intended for the treatment, prevention or diagnosis of a life-threatening or chronically debilitating disease that occurs in not more than five in 10,000 people in the EU. The designation provides regulatory, financial and commercial incentives to develop therapies for rare diseases where there are either no satisfactory treatment options or significant benefit to those affected by the disease.
Intellia has received five special regulatory designations for NTLA-2002. NTLA-2002 was also granted Orphan Drug Designation and RMAT Designation by the U.S. Food and Drug Administration (FDA), the Innovation Passport by the U.K. Medicines and Healthcare products Regulatory Agency (MHRA), as well as PRIME designation by the EMA.
About the NTLA-2002 Clinical Program
Intellia’s global Phase 1/2 study is evaluating the safety, tolerability, activity, pharmacokinetics and pharmacodynamics of NTLA-2002 in adults with Type I or Type II hereditary angioedema (HAE). This includes the measurement of plasma kallikrein protein levels and activity, as well as HAE attack rate. The Phase 1 portion of the study is an open-label, single-ascending dose design used to identify two dose levels of NTLA-2002 for further evaluation in the Phase 2, randomized, placebo-controlled portion of the study. The Phase 1/2 study will identify the dose of NTLA-2002 for use in future studies. Visit clinicaltrials.gov (NCT05120830) for more details.
About NTLA-2002
Based on Nobel-prize winning CRISPR/Cas9 technology, NTLA-2002 is the first single-dose investigational treatment being explored in clinical trials for the potential to continuously reduce kallikrein activity and prevent attacks in people living with hereditary angioedema (HAE). NTLA-2002 is a wholly owned investigational CRISPR therapeutic candidate designed to inactivate the kallikrein B1 (KLKB1) gene, which encodes for prekallikrein, the kallikrein precursor protein. NTLA-2002 is Intellia’s second investigational CRISPR therapeutic candidate to be administered systemically, by intravenous infusion, to edit disease-causing genes inside the human body with a single dose of treatment. Intellia’s proprietary non-viral platform deploys lipid nanoparticles to deliver to the liver a two-part genome editing system: guide RNA specific to the disease-causing gene and messenger RNA that encodes the Cas9 enzyme, which together carry out the precision editing.
About Hereditary Angioedema
Hereditary angioedema (HAE) is a rare, genetic disorder characterized by severe, recurring and unpredictable inflammatory attacks in various organs and tissues of the body, which can be painful, debilitating and life-threatening. It is estimated that one in 50,000 people are affected by HAE, and current treatment options often include life-long therapies, which may require chronic intravenous (IV) or subcutaneous (SC) administration as often as twice per week, or daily oral administration to ensure constant pathway suppression for disease control. Despite chronic administration, breakthrough attacks still occur. Kallikrein inhibition is a clinically validated strategy for the preventive treatment of HAE attacks.
About Intellia Therapeutics
Intellia Therapeutics, a leading clinical-stage genome editing company, is developing novel, potentially curative therapeutics leveraging CRISPR-based technologies. To fully realize the transformative potential of CRISPR-based technologies, Intellia is pursuing two primary approaches. The company’s in vivo programs use intravenously administered CRISPR as the therapy, in which proprietary delivery technology enables highly precise editing of disease-causing genes directly within specific target tissues. Intellia’s ex vivo programs use CRISPR to create the therapy by using engineered human cells to treat cancer and autoimmune diseases. Intellia’s deep scientific, technical and clinical development experience, along with its robust intellectual property portfolio, have enabled the company to take a leadership role in harnessing the full potential of genome editing to create new classes of genetic medicine. Learn more at intelliatx.com. Follow us on X (formerly known as Twitter) @intelliatx.
Forward-Looking Statements
This press release contains “forward-looking statements” of Intellia Therapeutics, Inc. (“Intellia” or the “Company”) within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, but are not limited to, express or implied statements regarding Intellia’s beliefs and expectations regarding: the safety, efficacy, success and advancement of its clinical program for NTLA-2002 for the treatment of hereditary angioedema (“HAE”) pursuant to its clinical trial applications and investigational new drug application, including its ability to complete enrollment of the Phase 2 portion of the study in the coming weeks, and its ability to deliver a potentially life-changing treatment for people with HAE.
Source: Intellia Therapeutics, Inc.
Intellia angioedema drug candidate gets EU orphan drug status
Nov. 14, 2023 8:03 AM ET
Intellia Therapeutics, Inc. (NTLA)
By: Preeti Singh, SA News Editor
- Intellia Therapeutics (NASDAQ:NTLA) said on Tuesday its NTLA-2002 drug candidate for hereditary angioedema has received orphan drug designation from the EU.
- NTLA-2002 is an in vivo CRISPR-based investigational therapy aimed at treating swelling attacks in hereditary angioedema patients.
- https://seekingalpha.com/news/4036212-intellia-angioedema-drug-candidate-gets-eu-orphan-drug-status?mailingid=33359350&messageid=2900&serial=33359350.1723&utm_campaign=rta-stock-news&utm_content=link-1&utm_medium=email&utm_source=seeking_alpha&utm_term=33359350.1723
- Intellia Therapeutics, Inc. (NTLA)
- https://www.intelliatx.com/
- https://www.intelliatx.com/pipeline/
Zilebesiran
CardiAMP Heart Failure II study protocol
Zilebesiran
Alnylam Presents Positive Results from the KARDIA-1 Phase 2 Dose-Ranging Study of Zilebesiran, an Investigational RNAi Therapeutic in Development for the Treatment of Hypertension in Patients at High Cardiovascular Risk
Nov 11, 2023
– Zilebesiran Met Primary Endpoint Demonstrating Up to 16.7 mmHg Placebo-Adjusted Reduction of 24-Hour Mean Systolic Blood Pressure at Three Months of Treatment –
– Study Met Key Secondary Endpoints Showing Consistent and Sustained Reductions of Systolic Blood Pressure and Durable Tonic Blood Pressure Control Through Month 6 –
– Data Support Quarterly or Biannual Dosing –
– Zilebesiran Demonstrated an Encouraging Safety and Tolerability Profile in Adult Patients with Mild-to-Moderate Hypertension –
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Nov. 11, 2023-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced positive results from the KARDIA-1 Phase 2 study of zilebesiran, an investigational RNAi therapeutic targeting liver-expressed angiotensinogen (AGT) in development for the treatment of patients with hypertension and high cardiovascular risk. The study results were presented during the American Heart Association (AHA) Scientific Sessions being held in Philadelphia, Pennsylvania from November 11-13, 2023. The Company previously announced positive topline results from the KARDIA-1 study in September 2023.
The KARDIA-1 study achieved its primary endpoint, with single doses of zilebesiran demonstrating clinically significant reductions in 24-hour mean systolic blood pressure (SBP) measured by ambulatory blood pressure monitoring (ABPM) at Month 3 across all doses, with the 150 mg, 300 mg, and 600 mg doses achieving placebo-adjusted reductions of 14.1 mmHg, 16.7 mmHg, and 15.7 mmHg, respectively (all p-values less than 0.0001). The study also met key secondary endpoints across all doses, including demonstration of durable efficacy out to 6 months. At the 150 mg Q6M, 300 mg Q6M, 300 mg Q3M, and 600 mg Q6M doses, zilebesiran showed placebo-adjusted reductions in 24-hour mean SBP measured by ABPM of 11.1 mmHg, 14.5 mmHg, 14.1 mmHg, and 14.2 mmHg, respectively, at Month 6 (all p-values less than 0.0001). Zilebesiran demonstrated an encouraging safety and tolerability profile that the Company believes supports continued development.
“These KARDIA-1 results are impressive, showing that in a diverse group of patients with mild-to-moderate hypertension, zilebesiran can safely achieve clinically significant reductions in systolic blood pressure and tonic blood pressure control administered subcutaneously with either quarterly or bi-annual dosing,” said Professor George L. Bakris, M.D., Board-Certified Hypertension Specialist and Director of the American Heart Association Comprehensive Hypertension Center, University of Chicago Medicine. “I continue to be encouraged and optimistic that zilebesiran has the potential to become not only a novel treatment for hypertension but also a transformative therapy to lower cardiovascular and renal risk in patients with hypertension, an area where new and innovative therapies are desperately needed.”
KARDIA-1 Study Results
The KARDIA-1 Phase 2 study is a randomized, double-blind, placebo-controlled, multi-center global dose-ranging study designed to evaluate the efficacy and safety of subcutaneously administered zilebesiran as monotherapy in adults with mild-to-moderate hypertension.
The study enrolled 394 adults representing a diverse patient population, of which more than 40% were female and nearly 25% were Black, with untreated hypertension or who were on stable therapy with one or more anti-hypertensive medications. Any patients taking prior antihypertensive medications completed at least a two- to four-week wash-out before randomization. Patients were randomized to one of five treatment arms: 150 mg zilebesiran once every six months (Q6M); 300 mg zilebesiran Q6M; 300 mg zilebesiran once every three months (Q3M); 600 mg zilebesiran Q6M; or placebo.
The primary endpoint was the change from baseline in 24-hour mean SBP at Month 3, assessed by ABPM. Key secondary endpoints in this study include additional measures of blood pressure reduction at Month 3 and Month 6, and the proportion of patients achieving treatment response criteria at Month 6, defined as 24-hour mean ambulatory SBP <130 mmHg and/or reduction ≥20 mmHg without additional antihypertensive medications.
Zilebesiran demonstrated an encouraging safety profile through Month 6. Serious adverse events were reported in 6.7% of patients in the placebo group and 3.6% of patients in the zilebesiran groups. There was one death due to cardiopulmonary arrest in a zilebesiran-treated patient that was considered unrelated to study drug. Drug-related adverse events (AEs) reported in more than 5% of patients in any zilebesiran arm were injection site reaction (ISR) occurring in 6.3% of patients and hyperkalemia in 5.3% of patients. No drug-related AEs were classified as serious or severe. ISR and hyperkalemia AEs were mostly mild and transient. No hyperkalemia events were associated with acute kidney injury or led to study drug discontinuation. Four patients had drug-related AEs leading to an investigator decision to discontinue zilebesiran. These AEs included orthostatic hypotension (n=2), blood pressure elevation (n=1), and ISR (n=1). Hypotension AEs were mild or moderate, non-serious, and transient. A single event in the zilebesiran 300 mg Q3M group was treated with normal saline. Clinically relevant AEs of acute renal failure, hepatic AEs, hypotension, and hyperkalemia of any relatedness were reported in 1.3%, 3.0%, 4.3%, and 6.3% of patients receiving zilebesiran, and 0%, 1.3%, 1.3%, and 2.7% of patients receiving placebo.
“The totality of the data presented at the American Heart Association Scientific Sessions gives us confidence in zilebesiran’s potentially differentiated profile and its ability to transform the treatment landscape for patients with uncontrolled hypertension who are at high risk of future cardiovascular events,” said Simon Fox, Ph.D., Vice President, Zilebesiran Program Lead at Alnylam. “We look forward to sharing topline results from the KARDIA-2 Phase 2 study, designed to evaluate the efficacy and safety of zilebesiran when used in combination with one other antihypertensive medication in patients with mild-to-moderate hypertension, in early 2024.”
To view the KARDIA-1 Phase 2 results presented at AHA, please visit Capella.
About Zilebesiran
Zilebesiran is an investigational, subcutaneously administered RNAi therapeutic targeting angiotensinogen (AGT) in development for the treatment of hypertension in high unmet need populations. AGT is the most upstream precursor in the Renin-Angiotensin-Aldosterone System (RAAS), a cascade which has a demonstrated role in blood pressure (BP) regulation and its inhibition has well-established anti-hypertensive effects. Zilebesiran inhibits the synthesis of AGT in the liver, potentially leading to durable reductions in AGT protein and ultimately, in the vasoconstrictor angiotensin (Ang) II. Zilebesiran utilizes Alnylam's Enhanced Stabilization Chemistry Plus (ESC+) GalNAc-conjugate technology, which enables infrequent subcutaneous dosing with increased selectivity and the potential to achieve tonic blood pressure control demonstrating consistent and durable blood pressure reduction throughout a 24-hour period, sustained up to six months after a single dose of zilebesiran. The safety and efficacy of zilebesiran have not been established or evaluated by the FDA, EMA or any other health authority. Zilebesiran is being co-developed and co-commercialized by Alnylam and Roche.
About Hypertension
Uncontrolled hypertension is the chronic elevation of blood pressure (BP), defined by the 2017 ACC/AHA guidelines as ≥130 mmHg systolic blood pressure (SBP) and ≥80 mmHg diastolic blood pressure (DBP). More than one billion people worldwide live with hypertension.i Approximately one in three adults are living with hypertension worldwide, with up to 80% of individuals remaining uncontrolled despite the availability of several classes of oral anti-hypertensive treatments. Despite the availability of anti-hypertensive medications, there remains a significant unmet medical need, especially given the poor rates of adherence to existing daily oral medications, resulting in inconsistent BP control and an increased risk for stroke, heart attack and premature death.ii In particular, there are a number of high unmet need settings where novel approaches to hypertension warrant additional development focus, including patients with poor medication adherence and in patients with high cardiovascular risk.
About RNAi
RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as “a major scientific breakthrough that happens once every decade or so,” and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines known as RNAi therapeutics is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA) – the genetic precursors – that encode for disease-causing or disease pathway proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.
About Alnylam Pharmaceuticals
Alnylam Pharmaceuticals (Nasdaq: ALNY) has led the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare and prevalent diseases with unmet need. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach yielding transformative medicines. Since its founding in 2002, Alnylam has led the RNAi Revolution and continues to deliver on a bold vision to turn scientific possibility into reality. Alnylam’s commercial RNAi therapeutic products are ONPATTRO® (patisiran), AMVUTTRA® (vutrisiran), GIVLAARI® (givosiran), OXLUMO® (lumasiran), and Leqvio® (inclisiran), which is being developed and commercialized by Alnylam’s partner, Novartis. Alnylam has a deep pipeline of investigational medicines, including multiple product candidates that are in late-stage development. Alnylam is executing on its “Alnylam P5x25” strategy to deliver transformative medicines in both rare and common diseases benefiting patients around the world through sustainable innovation and exceptional financial performance, resulting in a leading biotech profile. Alnylam is headquartered in Cambridge, MA. For more information about our people, science and pipeline, please visit www.alnylam.com and engage with us on X (formerly Twitter) at @Alnylam, or on LinkedIn, Facebook, or Instagram.
View source version on businesswire.com: https://www.businesswire.com/news/home/20231111731245/en/
Alnylam Pharmaceuticals, Inc.
Source: Alnylam Pharmaceuticals, Inc.
Alnylam reports positive Phase 2 data for hypertension drug
Nov. 13, 2023 9:17 AM ET
Alnylam Pharmaceuticals, Inc. (ALNY)
By: Preeti Singh, SA News Editor
- Alnylam Pharmaceuticals (NASDAQ:ALNY) has announced positive results from the Phase 2 study of zilebesiran, its investigational drug for hypertension.
- Zilebesiran met its primary endpoint of clinically significant reductions in 24-hour mean systolic blood pressure at three months of treatment across all dosage levels. The drug is being tested for the treatment of patients with hypertension and high cardiovascular risk.
- https://seekingalpha.com/news/4035503-alnylam-reports-positive-phase-2-data-for-hypertension-drug
- Alnylam Pharmaceuticals, Inc. (ALNY)
- https://capella.alnylam.com/wp-content/uploads/2021/06/2021-RNAi-Roundtables-Zilebesiran_FINAL.pdf
- https://www.alnylam.com/
biotecHOPE™ 2023
LP-310
KRAZATI® (adagrasib)
LP-310
November 10, 2023 8:00 AM
FDA Grants Orphan Designation for Lipella's LP-310 Drug Candidate for Oral Graft-versus-Host Disease
PR Newswire
Lipella Pharmaceuticals' LP-310 clinical stage asset is formulated for delivering active agents to the oral cavity for diseases of the mouth including oral lichen planus and oral graft-versus-host disease
PITTSBURGH , Nov. 10, 2023 /PRNewswire/ --
Lipella Pharmaceuticals Inc. (Nasdaq: LIPO) , a clinical stage pharmaceutical company addressing serious diseases with significant unmet need based in Pittsburgh, PA , announced today that it has been granted "Orphan Drug Designation" from the U.S. Food and Drug Administration (FDA) for its drug candidate, LP-310, which has been designed for the treatment of oral Graft-versus-Host Disease (GvHD).
LP-310 is Lipella's clinical stage pipeline asset intended to be indicated for inflammatory diseases of the oral cavity, including oral lichen planus and oral GvHD.
LP-310 liposomal tacrolimus is a proprietary oral rinse formulation of Lipella's lead drug candidate, LP-10. Lipella recently received FDA clearance for a Phase 2a clinical trial to evaluate LP-310's safety and efficacy in patients with symptomatic oral lichen planus, which currently has no FDA approved treatment, and can severely impact a patient's quality of life.
Dr. Jonathan Kaufman , Ph.D., Chief Executive Officer of Lipella, said, "We are very pleased to have received Orphan Drug Designation for LP-310 in oral GvHD. This designation is an example of the way we build value, pursuing all available resources that can de-risk and accelerate our clinical research programs. Our collaborative practice with the FDA is critical to our ability to increase the value of all of our clinical assets. We look forward to advancing this drug as a potential treatment for this painful complication of chronic GvHD."
Dr. Michael Chancellor , Chief Medical Officer at Lipella, said, "GvHD occurs when donor immune cells attack the recipient's body tissues after an allogeneic tissue or bone marrow transplant. GvHD affects approximately 30,000 Americans and oral GvHD contributes significantly to morbidity in cancer survivors. Morbidity of oral GvHD encompasses significant oral pain and discomfort, making it difficult for patients to eat, drink and speak. In addition, the risk of oral cavity infection, fibrosis and even oral cancer increases. Oral GvHD affects patients' quality of life and is a great unmet need in cancer survivors."
The FDA's "Orphan Drug Designation" program provides orphan status to drugs and biologics that are intended for the treatment, prevention or diagnosis of a rare disease or condition that affects fewer than 200,000 people in the United States . Orphan Drug Designation qualifies sponsors for incentives, including tax credits for qualified clinical trials, exemption from user fees and a potential seven years of market exclusivity after approval.
Lipella's LP-10 was previously granted Orphan Drug Designation by the FDA, making LP-310 the second of Lipella's leading product candidates to receive this designation.
About LP-310
LP-310 liposomal tacrolimus is a proprietary oral rinse formulation of Lipella's lead drug candidate, LP-10.
About Graft-versus-Host Disease
Graft-Versus-Host Disease (GvHD) occurs when donor bone marrow or stem cells attack the recipient following a treatment for leukemia, lymphoma, and other hematological cancers. Acute GvHD most commonly affects the skin, liver, and the gastrointestinal tract, while chronic GvHD affects the skin, mouth, eyes, lungs, stomach, bowel and liver, as well as other organs. Oral lichen planus can occur as a single manifestation of chronic GvHD.
About Lipella Pharmaceuticals Inc.
Lipella Pharmaceuticals Inc. is a clinical stage pharmaceutical company with a focus on capital efficient therapeutic development opportunities, including the proprietary repositioning of generics for rare, morbid diseases that currently have no adequate treatments. Additional information is available at www.lipella.com .
View original content to download multimedia: https://www.prnewswire.com/news-releases/fda-grants-orphan-designation-for-lipellas-lp-310-drug-candidate-for-oral-graft-versus-host-disease-301984199.html
SOURCE Lipella Pharmaceuticals Inc.
Lipella's oral GvHD drug candidate gets orphan designation
Nov. 10, 2023 9:13 AM ET
Lipella Pharmaceuticals Inc. (LIPO)
By: Preeti Singh, SA News Editor
Lipella Pharmaceuticals (NASDAQ:LIPO) said on Friday the U.S. FDA granted orphan drug designation to its LP-310 clinical stage candidate for oral graft-versus-host disease (GvHD).
LP-310 aims to treat inflammatory diseases of the oral cavity including oral lichen planus and GvHD. It is a proprietary oral rinse formulation of Lipella's lead drug candidate, LP-10.
https://seekingalpha.com/news/4034986-lipellas-oral-gvhd-drug-candidate-gets-orphan-designation
https://seekingalpha.com/news/4034986-lipellas-oral-gvhd-drug-candidate-gets-orphan-designation
LYL845
KRAZATI® (adagrasib)
LP-310
Lyell Immunopharma Receives FDA Orphan Drug Designation for LYL845 for the Treatment of Melanoma
November 9, 2023 at 4:05 PM EST
SOUTH SAN FRANCISCO, Calif., Nov. 09, 2023 (GLOBE NEWSWIRE) -- Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical‑stage T-cell reprogramming company advancing a diverse pipeline of cell therapies for patients with solid tumors, today announced that the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation to LYL845, an investigational tumor infiltrating lymphocyte (TIL) product candidate for the treatment of patients with stage IIB-IV melanoma.
“There remains a high unmet medical need for patients with advanced melanoma and we believe LYL845 has the potential for differentiated potency and durability needed to deliver better outcomes for patients with melanoma as well as other solid tumors where TIL therapy has not yet been widely effective,” said Lynn Seely, M.D., Lyell’s President and CEO. “We are pleased to have received Orphan Drug Designation for LYL845 in advanced melanoma and look forward to presenting initial clinical data from this program next year.”
LYL845, an autologous TIL product candidate enhanced with Lyell’s Epi-R™ manufacturing protocols, is currently being investigated in a Phase 1 clinical trial in patients with relapsed or refractory metastatic or locally advanced melanoma, non-small cell lung cancer (NSCLC), and colorectal cancer (CRC). In nonclinical studies, LYL845 TIL expanded with Epi-R exhibit characteristics that have previously been associated with improved clinical response rate, including a higher percentage of cytotoxic T cells and stemness phenotypes. LYL845 TIL have also demonstrated enhanced T-cell potency and maintenance of tumor-reactive polyclonality in nonclinical experiments. Initial data from Lyell’s ongoing Phase 1 clinical trial are expected in 2024.
The FDA's Orphan Drug Designation program provides orphan status to drugs or biologics intended for the prevention, diagnosis, or treatment of diseases that affect fewer than 200,000 people in the United States. Sponsors of medicines that are granted Orphan Drug Designation are entitled to certain incentives, including tax credits for qualified clinical trials, prescription drug user-fee exemptions, and potential seven-year marketing exclusivity upon FDA approval.
Phase 1 Trial Design (NCT05573035)
The Phase 1 clinical trial is an open-label, dose-escalation trial for patients with relapsed and/or refractory metastatic or locally advanced melanoma with expansion cohorts for patients with melanoma, NSCLC, and CRC. The primary objective of the trial is to determine safety, tolerability and a recommended phase 2 dose range of LYL845. The secondary objective is to determine antitumor activity as evaluated by response rates, duration of response, progression-free survival and overall survival. Exploratory biomarkers of T-cell stemness will also be assessed.
About Melanoma
Melanoma of the skin is among the most common cancers in the United States. It is one of the most common cancers in young adults and especially in young women. It is estimated there are over 100,000 new cases of melanoma diagnosed in the United States per year. Melanoma arises due to genetic mutations in melanocytes, the pigment producing cells, which can be found in the skin, eye, inner ear and leptomeninges, and represents the most aggressive and the deadliest form of skin cancer. Although melanoma accounts for only ~1% of all dermatologic cancers, it is responsible for ~80% of deaths from skin cancer, with only ~14% of patients with advanced melanoma surviving for five years.
About LYL845
LYL845 is an investigational autologous TIL product enhanced with Epi-R manufacturing protocols for patients with relapsed and/or refractory metastatic or locally advanced melanoma, NSCLC and CRC. In nonclinical studies, Epi-R creates polyclonal populations of T cells that demonstrate properties of durable stemness and anti-tumor functionality. Durable stemness is the ability of T cells to persist and self-renew to drive durable tumor cytotoxicity.
TIL products are created by expanding T cells taken from the patient’s own tumor. Previous clinical experiences suggest that the efficacy of adoptive transfer of ex vivo expanded TILs is largely driven by specific recognition of mutated tumor neoantigens specific to each patient. To date, broad efficacy of TIL therapies has been limited by variable and often poor product quality, lack of stemness or potential durability of expanded TILs, failure to maintain polyclonality of TILs during production, and failure to enrich the TIL product with tumor-reactive T cells. TIL products manufactured using Lyell’s Epi-R manufacturing protocol aim to overcome these challenges. Nonclinical studies supporting the development of LYL845 suggest Epi-R technology improves TIL products by maintaining properties of durable stemness, which leads to superior ex vivo cell expansion and product qualities, maintenance of tumor reactive clones, and enhanced polyclonality.
About Lyell
Lyell is a clinical-stage T-cell reprogramming company advancing a diverse pipeline of cell therapies for patients with solid tumors. Lyell is currently enrolling a Phase 1 clinical trial evaluating a ROR1-targeted CAR T-cell therapy in patients with relapsed refractory triple-negative breast cancer and non-small cell lung cancer (NSCLC) and a second Phase 1 clinical trial evaluating reprogrammed tumor infiltrating lymphocytes (TIL) in patients with advanced melanoma, NSCLC and colorectal cancer. The technologies powering its product candidates are designed to address barriers that limit consistent and long-lasting responses to cell therapy for solid tumors: T-cell exhaustion and lack of durable stemness, which includes the ability to persist and self-renew to drive durable tumor cytotoxicity. Lyell is applying its proprietary ex vivo genetic and epigenetic reprogramming technologies to address these barriers in order to develop new medicines with improved durable clinical outcomes. Lyell is based in South San Francisco, California with facilities in Seattle and Bothell, Washington. To learn more, please visit www.lyell.com.
Lyell gets FDA orphan drug designation for melanoma drug candidate
Nov. 09, 2023 5:32 PM ET
Lyell Immunopharma, Inc. (LYEL)
By: Val Brickates Kennedy, SA News Editor
Lyell Immunopharma (NASDAQ:LYEL) said that it has received orphan drug designation from the FDA for its drug candidate LYL845 in the treatment of Stage IIB to Stage IV melanoma.
The product is currently in Phase 1 testing for the treatment of advanced melanoma, non-small cell lung cancer and colorectal cancer. Initial data from the trial is expected in 2024.
Lyell Immunopharma, Inc. (LYEL)
https://lyell.com/pdf/FINAL_SUBMITTED_Pre_Clinical_LYL845%20Poster_77x43.3inches_R6.pdf
KRAZATI® (adagrasib)
KRAZATI® (adagrasib)
IXCHIQ (Chikungunya Vaccine, Live)
Mirati Therapeutics Receives Positive Opinion from CHMP for KRAZATI (adagrasib) as a Targeted Treatment Option for Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) with a KRASG12C Mutation Following a Re-Examination Procedure
November 10, 2023
SAN DIEGO, Calif. and ZUG, Switzerland, Nov. 10, 2023 /PRNewswire/ -- Mirati Therapeutics, Inc.® (NASDAQ: MRTX), a commercial stage biotechnology company, today announced that following a re-examination procedure, the Company has received a positive opinion from the European Medicine Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) on KRAZATI® (adagrasib) as a targeted treatment option for adult patients with KRASG12C -mutated advanced non-small cell lung cancer (NSCLC) and disease progression after at least one prior systemic therapy.
"Today's positive opinion from the CHMP for KRAZATI marks an important step on the path to providing access to a potentially best-in-class therapeutic option to patients living with this difficult-to-treat disease," Alan Sandler, M.D., chief medical officer, Mirati Therapeutics, Inc. "We look forward to approval from the European Commission and the opportunity to positively impact the lives of eligible patients living in the European Union."
"This is an important day for the oncology community as we step closer to a new therapeutic option being available to patients living with KRASG12C mutated NSCLC in the European Union," said Martin Reck, MD, PhD, Lung Clinic Grosshansdorf, Germany. "Every patient has a slightly different case so as more options become available physicians will better be able to tailor their treatment for each patient."
About KRAZATI® (adagrasib)
Mirati has risen to meet one of the most challenging mutations in cancer research by developing KRAZATI, a highly selective and potent oral small-molecule inhibitor of KRASG12C.
Intentionally designed to meet the challenge of KRASG12C, adagrasib is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12C-mutated cancers, as the KRASG12C protein regenerates every 24−48 hours.1Adagrasib has shown clinically to be a CNS penetrant, which may be important given that CNS metastases frequently occur in NSCLC and lead to poor prognosis.2,3,4
The FDA provided KRAZATI Accelerated Approval (Subpart H), allowing for the approval of drugs that treat serious conditions, and that fill an unmet medical need based on surrogate endpoints. KRAZATI was also granted a conditional marketing authorization by the United Kingdom's Medicines and Healthcare Products Regulatory Agency (MHRA) on November 3, 2023.
Adagrasib continues to be evaluated as monotherapy and in combination with other anti-cancer therapies in patients with advanced KRASG12C-mutated solid tumors, including NSCLC, colorectal cancer, and pancreatic cancer. For more information, visit Mirati.com/science.
About the KRYSTAL-1 Study
KRYSTAL-1 is an open-label Phase 1/2 multiple-expansion cohort trial evaluating adagrasib as monotherapy and in combination with other anti-cancer therapies in patients with advanced solid tumors harboring the KRASG12C mutation.
About KRASG12C in NSCLC
Lung cancer is one of the most common cancers worldwide, accounting for 2.21 million new cases and 1.8 million deaths worldwide in 2020.5 Lung cancer consists of NSCLC in approximately 85% of cases and small cell lung cancer (SCLC) in approximately 15% of cases.6 KRASG12C is the most common KRAS mutation in NSCLC, present in approximately 14% of patients with lung adenocarcinoma, and is a biomarker mutation of poor prognosis.1,3
About Mirati Therapeutics, Inc.
Mirati Therapeutics, Inc. is a commercial stage biotechnology company whose mission is to discover, design and deliver breakthrough therapies to transform the lives of patients with cancer and their loved ones. The company is relentlessly focused on bringing forward therapies that address areas of high unmet need, including lung cancer, and advancing a pipeline of novel therapeutics targeting the genetic and immunological drivers of cancer. Unified for patients, Mirati's vision is to unlock the science behind the promise of a life beyond cancer.
For more information about Mirati, visit us at Mirati.com or follow us on Twitter, LinkedIn, and Facebook.
View original content to download multimedia:https://www.prnewswire.com/news-releases/mirati-therapeutics-receives-positive-opinion-from-chmp-for-krazati-adagrasib-as-a-targeted-treatment-option-for-patients-with-advanced-non-small-cell-lung-cancer-nsclc-with-a-krasg12c-mutation-following-a-re-examination-proce-301984690.html
SOURCE Mirati Therapeutics, Inc.
Mirati lung cancer therapy endorsed in EU
Nov. 10, 2023 7:53 AM ET
Mirati Therapeutics, Inc. (MRTX)AMGN, BMY
By: Dulan Lokuwithana, SA News Editor
Mirati Therapeutics (NASDAQ:MRTX) announced Friday that an expert panel of the EU drug regulator, the European Medicines Agency (EMA), endorsed its KRAS inhibitor KRAZATI (adagrasib) as a targeted therapy for certain cases of lung cancer.
Issuing a so-called positive opinion, EMA’s Committee for Medicinal Products for Human Use (CHMP) has endorsed the anti-tumor medication as a late-line option for adults with KRASG12C -mutated advanced non-small cell lung cancer (NSCLC).
The decision comes after the CHMP reexamined Mirati’s (MRTX) request to review the treatment. In July, the panel issued a negative opinion on its bid to receive a conditional marketing authorization for Krazati.
https://seekingalpha.com/news/4034902-mirati-lung-cancer-therapy-endorsed-eu
IXCHIQ (Chikungunya Vaccine, Live)
IXCHIQ (Chikungunya Vaccine, Live)
IXCHIQ (Chikungunya Vaccine, Live)
Valneva Announces U.S. FDA Approval of World’s First Chikungunya Vaccine, IXCHIQ®
November 10, 2023
Saint-Herblain (France),
November 10, 2023 – Valneva SE (Nasdaq: VALN; Euronext Paris: VLA), a specialty vaccine company, today announced that the U.S. Food and Drug Administration (FDA) has approved IXCHIQ®, Valneva’s single-dose, live-attenuated vaccine indicated for the prevention of disease caused by chikungunya virus (CHIKV) in individuals 18 years of age and older who are at increased risk of exposure to CHIKV. This indication is approved under accelerated approval based on anti-CHIKV neutralizing antibody titers. Continued approval for this indication is contingent upon verification of clinical benefit in confirmatory studies.
The Company will hold an analyst call and a webcast at 3:00pm CET or 9:00am EDT on Monday, November 13, 2023. The link will be available on the Company’s investor page. Please refer to this link Investors – Valneva.
As sponsor of the first chikungunya vaccine approved in the U.S., Valneva has received a Priority Review Voucher (PRV) from the FDA, which it intends to monetize to help finance its research and development (R&D) programs.
With this U.S. approval, IXCHIQ® becomes the world’s first licensed chikungunya vaccine available to address this unmet medical need and the third vaccine Valneva[1] has brought from early R&D to approval. Valneva reported final pivotal Phase 3 data for the vaccine in March 2022 showing a 98.9% seroresponse rate at 28 days with a single vaccination[2] and final lot-to-lot consistency results in May 2022[3]. IXCHIQ®-induced seroresponse was sustained over time with a 96.3% seroresponse rate six months post-vaccination2. Valneva will continue to evaluate antibody persistence for at least five years[4]. The Company’s pivotal Phase 3 results were published in the Lancet in June 2023.
Choose one of the links below to access the full press release.
FDA approves Valneva's world-first chikungunya vaccine
Nov. 10, 2023 4:26 AM ET
By: Preeti Singh, SA News Editor3 Comments
Valneva (NASDAQ:VALN) announced on Friday its Ixchiq single-dose, live-attenuated vaccine against the chikungunya virus was approved by the U.S. FDA.
Ixchiq is the world's first vaccine against the virus. It is approved for individuals 18 years of age and older with an increased risk of exposure to chikungunya.
Phase 3 data for the vaccine showed a 98.9% seroresponse rate at 28 days with a single vaccination and a 96.3% seroresponse rate six months post-vaccination. Valneva (VALN) will continue to evaluate antibody persistence for at least five years.
https://seekingalpha.com/news/4034782-fda-approves-valnevas-world-first-chikungunya-vaccine
FRUZAQLA™ (fruquintinib)
IXCHIQ (Chikungunya Vaccine, Live)
FRUZAQLA™ (fruquintinib)
Takeda Receives U.S. FDA Approval of FRUZAQLA™ (fruquintinib) for Previously Treated Metastatic Colorectal Cancer
November 8, 2023Share
- FRUZAQLA is the First Targeted Therapy Approved for Metastatic Colorectal Cancer (mCRC) Regardless of Biomarker Status or Prior Types of Therapies in More Than a Decade
- FRUZAQLA Plus Best Supportive Care Demonstrated Significant Improvements in Overall Survival, with Corresponding Improvements in Progression Free Survival, Versus Placebo Plus Best Supportive Care in Two Phase 3 Clinical Trials
- FRUZAQLA Demonstrated a Manageable Safety Profile in Previously Treated Patients with mCRC Across Both Trials
OSAKA, Japan and CAMBRIDGE, Massachusetts, November 8, 2023 – Takeda (TSE:4502/NYSE:TAK) today announced that the U.S. Food and Drug Administration (FDA) has approved FRUZAQLA™ (fruquintinib), an oral targeted therapy for adults with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type and medically appropriate, an anti-EGFR therapy. FRUZAQLA is the first and only selective inhibitor of all three VEGF receptor kinases approved in the U.S. for previously treated mCRC regardless of biomarker status.1,2 This approval was received under Priority Review more than 20 days ahead of the scheduled PDUFA date of November 30, 2023.
"There is a pressing need for new treatments for individuals with metastatic colorectal cancer, who have had limited options and continue to face poor outcomes. FRUZAQLA is the first novel chemotherapy-free treatment option approved for patients in the U.S. regardless of biomarker status in more than a decade,” said Teresa Bitetti, president of the Global Oncology Business Unit at Takeda. “For far too long, healthcare providers and patients have had limited options when selecting a therapy for metastatic colorectal cancer. FRUZAQLA has the potential to offer a significant survival benefit to patients without negatively impacting their quality of life.”
The approval of FRUZAQLA is based on data from two large Phase 3 trials: the multi-regional FRESCO-2 trial, data from which were published in The Lancet, along with the FRESCO trial conducted in China, data from which were published in JAMA. The trials investigated FRUZAQLA plus best supportive care versus placebo plus best supportive care in patients with previously treated mCRC. Both FRESCO and FRESCO-2 met their primary and key secondary efficacy endpoints and showed consistent benefit among a total of 734 patients treated with FRUZAQLA. Safety profiles were consistent across trials.
“Patients with metastatic disease are often fragile and fatigued – due to both their condition as well as the therapies they have been exposed to. An oral, chemotherapy-free option that offers a survival benefit despite treatment with prior therapies is a critical need for treating metastatic colorectal cancer,” said Cathy Eng, M.D., FACP, at Vanderbilt University Medical Center. “Colorectal cancer is a highly heterogeneous disease, making it difficult to bring advancements to patients whose cancer has metastasized. I look forward to being able to offer a new solution to appropriate patients.”
In the United States, approximately 153,000 new cases of CRC will be diagnosed in 2023, representing 7.8% of all new cancer cases.3,4 Approximately 70% of patients with CRC will experience metastatic disease, whether at diagnosis or after treatment. Metastases are the main cause of CRC-related mortality.5,6
“We have witnessed firsthand the physical and emotional toll metastatic colorectal cancer has on patients, their families and their care teams,” said Michael Sapienza, Chief Executive Officer, at Colorectal Cancer Alliance. “We are encouraged to see the continued progress in providing new options to patients.”
The data from FRESCO and FRESCO-2 also supported the EU marketing authorization application (MAA) for fruquintinib, which was validated and accepted for review by the European Medicines Agency (EMA) in June 2023. A submission to the Japan Pharmaceuticals and Medical Devices Agency (PMDA) also took place in September 2023.
About FRUZAQLA™ (fruquintinib)
FRUZAQLA (fruquintinib) is a selective oral inhibitor of VEGFR -1, -2 and -3. VEGFR inhibitors play a pivotal role in blocking tumor angiogenesis. FRUZAQLA was designed to have enhanced selectivity that limits off-target kinase activity, allowing for high drug exposure, sustained target inhibition, and flexibility for the potential use as part of combination therapy. FRUZAQLA has demonstrated a manageable safety profile and is being investigated in combinations with other anti-cancer therapies. Fruquintinib was approved for marketing by the China National Medical Products Administration (NMPA) in September 2018 and commercially launched in China in November 2018 under the brand name ELUNATE®. In addition, a marketing authorization application (MAA) from the European Medicines Agency (EMA) was validated and accepted for review in June 2023, and a submission to the Japan Pharmaceuticals and Medical Devices Agency (PMDA) took place in September 2023. Takeda has the exclusive worldwide license to further develop, commercialize, and manufacture fruquintinib outside of mainland China, Hong Kong and Macau. Fruquintinib is developed and marketed in China by HUTCHMED.
https://www.hutch-med.com/pipeline-and-products/our-pipeline/
Please see FRUZAQLA (fruquintinib) full Prescribing Information
About CRC
CRC is a cancer that starts in either the colon or rectum. According to the International Agency for Research on Cancer, CRC is the third most prevalent cancer worldwide, associated with more than 935,000 deaths in 2020.7 In the U.S., it is estimated that 153,000 patients will be diagnosed with CRC and 53,000 deaths from the disease will occur in 2023.3 In Europe, CRC was the second most common cancer in 2020, with approximately 520,000 new cases and 245,000 deaths. In Japan, CRC was the most common cancer, with an estimated 148,000 new cases and 60,000 deaths in 2020.7 Although early-stage CRC can be surgically resected, metastatic CRC remains an area of high unmet need with poor outcomes and limited treatment options. Some patients with metastatic CRC may benefit from personalized therapeutic strategies based on molecular characteristics; however, most patients have tumors that do not harbor actionable mutations.8,9,10,11,12
About the Phase 3 FRESCO-2 Trial
The FRESCO-2 study is a multi-regional clinical trial conducted in the U.S., Europe, Japan and Australia investigating FRUZAQLA (fruquintinib) plus best supportive care vs placebo plus best supportive care in patients with previously treated metastatic CRC (NCT04322539). The study met its primary and key secondary endpoints, demonstrating that treatment with FRUZAQLA resulted in statistically significant and clinically meaningful improvement in overall survival (OS) and progression-free survival (PFS). The safety profile of FRUZAQLA in FRESCO-2 was consistent with previously reported FRUZAQLA studies. Results from the study were presented at ESMO in September 2022 and subsequently published in The Lancet.13,14
The Phase 3 FRESCO and FRESCO-2 trials supported the marketing authorization application (MAA) from the European Medicines Agency (EMA) for fruquintinib, which was validated and accepted for review in June 2023. A submission to the Japan Pharmaceuticals and Medical Devices Agency (PMDA) also took place in September 2023.
About Takeda
Takeda is focused on creating better health for people and a brighter future for the world. We aim to discover and deliver life-transforming treatments in our core therapeutic and business areas, including gastrointestinal and inflammation, rare diseases, plasma-derived therapies, oncology, neuroscience and vaccines. Together with our partners, we aim to improve the patient experience and advance a new frontier of treatment options through our dynamic and diverse pipeline. As a leading values-based, R&D-driven biopharmaceutical company headquartered in Japan, we are guided by our commitment to patients, our people and the planet. Our employees in approximately 80 countries and regions are driven by our purpose and are grounded in the values that have defined us for more than two centuries. For more information, visit www.takeda.com.
Takeda wins FDA nod for colorectal cancer therapy
Nov. 09, 2023 7:21 AM ET
Takeda Pharmaceutical Company Limited (TAK), HCM, HMDCF
By: Dulan Lokuwithana, SA News Editor
- The U.S. FDA has greenlighted Fruzaqla (fruquintinib), an oral cancer therapy marketed by Takeda Pharmaceutical (NYSE:TAK) and Chinese pharma Hutchmed (NASDAQ:HCM), as a late-line treatment for adults with metastatic colorectal cancer ((mCRC)).
- https://seekingalpha.com/news/4033909-takeda-wins-fda-nod-colorectal-cancer-therapy?mailingid=33309169&messageid=2900&serial=33309169.678&utm_campaign=rta-stock-news&utm_content=link-1&utm_medium=email&utm_source=seeking_alpha&utm_term=33309169.678
- Takeda Pharmaceutical Company Limited (TAK), HCM, HMDCF
- https://www.takeda.com/
- https://assets-dam.takeda.com/image/upload/v1698295227/Global/Investor/Financial-Results/FY2023/Q2/qr2023_q2_Pipeline_table_en.pdf
- https://www.hutch-med.com/pipeline-and-products/our-pipeline/
tarcocimab tedromer
IXCHIQ (Chikungunya Vaccine, Live)
FRUZAQLA™ (fruquintinib)
Kodiak reboots tarcocimab tedromer development program following strong positive results in Phase 3 diabetic retinopathy GLOW study and following dialogue with US regulatory authorities on a regulatory pathway for BLA submission
November 6, 2023 at 5:00 AM ESTDownload PDF
- Primary endpoint and all key secondary endpoints met with high statistical significance in GLOW study.
- With 6-month dosing of all patients, tarcocimab and the ABC platform continue to demonstrate differentiated durability.
- Following dialogue with US regulatory authorities, Kodiak plans to conduct one additional pivotal study with a commercial formulation of tarcocimab.
- New regulatory strategy could support a single Biologics License Application (BLA) for macular edema following retinal vein occlusion (RVO), wet age-related macular degeneration (wAMD) and non-proliferative diabetic retinopathy (NPDR).
- Kodiak believes that it has sufficient capital to fund a comprehensive KSI-501 clinical program in parallel.
PALO ALTO, Calif., Nov. 6, 2023 /PRNewswire/ -- Kodiak Sciences Inc. (NASDAQ: KOD) today announced that its Phase 3 GLOW superiority study evaluating tarcocimab tedromer 5 mg in moderately severe to severe NPDR met its one-year primary endpoint.
"This is the first time that 6-month dosing in all patients succeeded in treating diabetic retinopathy which we believe is a meaningful and clinically relevant achievement", said Dr. J. Pablo Velazquez-Martin, Senior Vice President of Clinical Sciences at Kodiak Sciences. "We think that the consistency of the data across all endpoints, where tarcocimab significantly improved the diabetic eye disease status and, importantly, significantly prevented sight-threatening complications, is remarkable," continued, Dr. Velazquez-Martin. "The GLOW data reinforce the durability potential of tarcocimab and the antibody biopolymer conjugate platform (ABC Platform) in the management of retinal vascular diseases."
"We think that durability remains the most clinically relevant unmet patient need," said Dr. Victor Perlroth, CEO of Kodiak. "We now have three successful phase 3 pivotal studies with tarcocimab tedromer across three different retinal vascular and exudative diseases: wet AMD, RVO and NPDR. In recent discussions with the FDA, which included the GLOW data, we believe we have a clear regulatory pathway requiring one additional positive study to support a single BLA submission for all three indications," continued Dr. Perlroth.
"We have actionable learnings from the tarcocimab clinical program that we used to develop an enhanced commercial formulation of tarcocimab that balances free antibody and conjugated antibody to improve manufacturability and, importantly, to improve usability by reducing injection time from 7-10 seconds to 2-3 seconds. This formulation has already been manufactured at commercial scale and is ready for use in clinical trials. After evaluation of the Phase 3 data across the tarcocimab program and based on conversations with members of the retina community, we believe our commercial tarcocimab formulation could be an important future therapeutic option. As a result, we have decided to run another pivotal study with the intent to file a single BLA for RVO, wet AMD and NPDR. This enhancement to the ABC Platform is also being implemented in our first-in-class anti-IL-6 and anti-VEGF bispecific, KSI-501 ABC," Dr. Perlroth concluded.
Kodiak paused further development of tarcocimab last summer after its GLEAM and GLIMMER studies in diabetic macular edema did not meet their primary endpoint, in order to evaluate learnings from its pivotal BEACON study in patients with macular edema due to retinal vein occlusion and from its GLOW study.
The company believes that the one-year head-to-head BEACON results and primary endpoint and key secondary endpoint GLOW results support the development of three attractive clinical prospects: enhanced tarcocimab ABC, enhanced bispecific KSI-501 ABC, and our KSI-501 bispecific free protein (not conjugated) and that Kodiak has on hand sufficient capital to further develop in parallel all three of these prospects.
Dr. Perlroth added, "Kodiak thanks the GLOW investigators and patients whose participation and commitment helped us to generate strong data in GLOW and thus to recognize the continued importance for patients of our ABC Platform and our platform-derived medicines."
About the GLOW Study Results
First time results from GLOW were presented at the American Academy of Ophthalmology retina subspecialty day on November 3, 2023. View original content: https://ir.kodiak.com/static-files/ee94e5bd-da6e-4038-b00c-1956c72e5c72.
The Phase 3 GLOW study investigated an every 24-week tarcocimab dosing regimen for all subjects, versus sham, in patients with moderately-severe and severe NPDR without DME.
At one year, GLOW met its primary endpoint of the proportion of patients with at least a 2-step improvement on the Diabetic Retinopathy Severity Scale (DRSS) score, a grading system measuring the degree of retinopathy. Tarcocimab achieved a 29-fold increased response rate ratio, with 41.1% of evaluable patients on tarcocimab demonstrating at least 2-step improvement versus 1.4% of evaluable patients in the sham group (p less than 0.0001). Visual acuity and retinal anatomy were improved and stable with tarcocimab on its extended-dosing intervals.
GLOW also met all key secondary endpoints, including greater reductions in the proportion of patients developing sight-threatening complications (such as diabetic macular edema and proliferative diabetic retinopathy), versus sham, demonstrating an 89% decreased risk, achieving 21.0% versus 2.3% (p less than 0.0001). Tarcocimab also showed a 95% risk reduction in the development of DME, versus sham, from 13.7% on sham versus 0.7% on tarcocimab.
After the occurrence of a sight-threatening complication, all subjects were rescued with open-label tarcocimab, where subjects received two loading doses once monthly followed by continued every 12-week dosing. In patients developing sight-threatening complications, the initial visual acuity decrease and retinal anatomy worsening were both rapidly controlled and then stabilized with every 12-week dosing of tarcocimab.
The rates of serious ocular adverse events and intraocular inflammation in patients treated with tarcocimab and sham were similar in both groups.
About the GLOW Study Design
The Phase 3 GLOW study is a global, multi-center, randomized pivotal superiority study designed to evaluate the efficacy and safety of tarcocimab tedromer in treatment-naïve patients with moderately severe to severe NPDR. Patients are randomized to receive either tarcocimab every six months after initiating doses given at baseline, 8 weeks and 20 weeks into the study, or to receive sham injections. The primary endpoint is at one year. Outcomes include changes in diabetic retinopathy severity, measured on a standardized photographic grading scale, and the proportion of tarcocimab treated patients who developed a sight threatening complication due to diabetic retinopathy. Additional information about GLOW (also called Study KS301P106) can be found on www.clinicaltrials.gov under Trial Identifier NCT05066230 (https://clinicaltrials.gov/show/NCT05066230).
About the Primary Endpoint of ≥2-Step Improvement on the Diabetic Retinopathy Severity Scale (DRSS)
Derived from The Early Treatment Diabetic Retinopathy Study (ETDRS), the diabetic retinopathy severity scale (DRSS) is a systematic grading system developed to predict the risk of progression from NPDR to proliferative diabetic retinopathy (PDR). The DRSS characterizes retinopathy based on assessment of abnormalities in seven defined fields of fundus photographs. The scale divides diabetic retinopathy into levels ranging from absent to severe proliferative diabetic retinopathy. This scale is the most widely used standard for grading degrees of retinopathy in clinical studies.
About the Key Secondary Endpoint of Reducing Sight Threatening Complications
Approximately eight million people in the U.S. live with Diabetic Retinopathy (DR), a common complication of diabetes characterized by damage to the blood vessels in the retina. Diabetic retinopathy occurs when blood vessels in the retina are damaged by chronic high blood sugar levels caused by diabetes. DR is the leading cause of blindness among working-age American adults. The disease generally starts as NPDR and often has no warning signs or symptoms. Over time, patients with NPDR are at risk of suffering sight-threatening complications, including diabetic macular edema (DME), a swelling of the macula (the part of the retina responsible for central fine vision) and proliferative diabetic retinopathy (PDR) in which abnormal blood vessels grow on the surface of the retina and into the vitreous cavity. Sight-threatening complications can lead to severe vision loss in patients.
About Kodiak Sciences Inc.
Kodiak (Nasdaq: KOD) is a biopharmaceutical company committed to researching, developing and commercializing transformative therapeutics to treat high-prevalence retinal diseases. We are focused on bringing new science to the design and manufacture of next generation retinal medicines to prevent and treat the leading causes of blindness globally. Our antibody biopolymer conjugate platform, or ABC Platform™ is at the core of Kodiak's discovery engine. Kodiak's first investigational medicine, tarcocimab tedromer, is a novel anti-VEGF antibody biopolymer conjugate explored for the treatment of retinal vascular diseases. Kodiak's second clinical program, KSI-501, built from a first-in-class bispecific protein targeting both IL-6 (anti-IL-6 antibody) and VEGF (VEGF-trap), is intended to treat both orphan and high prevalence retinal diseases. Kodiak is based in Palo Alto, CA. For more information, please visit www.kodiak.com.
SOURCE Kodiak Sciences Inc.
Kodiak says Phase 3 trial for lead asset met key goals
Nov. 06, 2023 7:00 AM ET
By: Dulan Lokuwithana, SA News Editor
Kodiak Sciences (NASDAQ:KOD) announced Monday that its Phase 3 GLOW study for its lead candidate, tarcocimab tedromer, for a form of diabetic eye disease, reached its main goals with statistical significance.
However, citing discussions with the U.S. FDA, the company said it will conduct one more pivotal study to support a marketing application for the candidate.
https://seekingalpha.com/news/4030804-kodiak-stock-falls-phase-3-data-lead-asset
Barzolvolimab
Barzolvolimab
Barzolvolimab
Celldex Therapeutics Announces Positive Topline Results from Barzolvolimab Phase 2 Study in Chronic Spontaneous Urticaria
Nov 6, 2023
PDF Version(opens in a new tab)
-Barzolvolimab met primary endpoint with clinically meaningful and statistically significant decreases in urticaria disease activity across multiple dose groups-
-Mean change from baseline to week 12 in UAS7 of -23.87 in 300 mg q8w dose group and -23.02 in 150 mg q4w dose group-
-Barzolvolimab was generally well tolerated with a favorable safety profile-
-Treatment will continue to 52 weeks; results support further development of barzolvolimab in Phase 3 CSU studies-
- Company to host webcast call today at 8:00 am ET-
HAMPTON, N.J., Nov. 06, 2023 (GLOBE NEWSWIRE) -- Celldex Therapeutics, Inc. (NASDAQ:CLDX) announced today positive topline results from the Company’s Phase 2 clinical trial of barzolvolimab in patients with moderate to severe chronic spontaneous urticaria (CSU) refractory to antihistamines, including patients who received prior biologics. Barzolvolimab is a humanized monoclonal antibody that specifically binds the receptor tyrosine kinase KIT with high specificity and potently inhibits its activity, which is required for mast cell function and survival. CSU is characterized by the occurrence of hives or wheals for 6 weeks or longer without identifiable specific triggers or causes. Treatment options for patients with CSU are limited and there are no approved therapies for patients who do not respond to omalizumab.
"We are thrilled to share these positive results which we believe further establish barzolvolimab as a potential transformative treatment option for patients suffering with CSU," commented Anthony S. Marucci, President and Chief Executive Officer of Celldex Therapeutics. "These data reinforce barzolvolimab's unique mechanism targeting a key underlying pathway of the disease. Based on the strength of these results, which included patients refractory to omalizumab, we are excited to continue the development of this program and move towards registrational trials. We would like to thank the patients and investigators for their participation in this trial and look forward to presenting full 12 week data from this study at an upcoming medical meeting.”
Data from the 208 patients randomized in the study showed that barzolvolimab achieved the primary efficacy endpoint, with a statistically significant mean change from baseline to week 12 of UAS7 (urticaria activity score) compared to placebo. Barzolvolimab demonstrated rapid, durable and clinically meaningful responses in patients with moderate to severe CSU refractory to antihistamines, including patients with prior omalizumab treatment. Demographics and baseline disease characteristics were well balanced across treatment groups.
Approximately 20% of enrolled patients received prior treatment with omalizumab. These patients experienced a similar clinical benefit as the overall treated population within their individual dosing groups.
Barzolvolimab was generally well tolerated with a favorable safety profile. Most adverse events were mild to moderate in severity; through 12 weeks, the most common treatment emergent adverse events in barzolvolimab treated patients were hair color changes (9%), urticaria (9%) and neutropenia (8%). The rate of infections was similar between barzolvolimab-treated patients and placebo with no apparent association between neutropenia and infections.
Phase 2 Study Design
The randomized, double-blind, placebo-controlled, parallel group Phase 2 study is evaluating the efficacy and safety profile of multiple dose regimens of barzolvolimab in patients with CSU who remain symptomatic despite antihistamine therapy, to determine the optimal dosing strategy. 208 patients were randomly assigned on a 1:1:1:1 ratio to receive subcutaneous injections of barzolvolimab at 75 mg every 4 weeks, 150 mg every 4 weeks, 300 mg every 8 weeks or placebo during a 16-week placebo-controlled treatment period. After 16 weeks, patients then enter a 36-week active treatment period, in which patients not already randomized to barzolvolimab at 150 mg every 4 weeks or 300 mg every 8 weeks are randomized 1:1 to receive one of these two dose regimens; patients already randomized to these treatment arms remain on the same regimen as during the placebo-controlled treatment period. After 52 weeks, patients then enter a follow-up period for an additional 24 weeks. The primary endpoint of the study is mean change in baseline to Week 12 in UAS7. Secondary endpoints include other assessments of safety and clinical activity including ISS7, HSS7 and AAS7.
For additional information on this trial (NCT05368285), please visit www.clinicaltrials.gov(opens in a new tab)
Webcast and Conference Call
The Company will host a conference call/webcast today to discuss the results at 8:00 a.m. ET. The event will be webcast live and can be accessed by going to the "Events & Presentations " page under the "Investors & Media” section of the Celldex Therapeutics website at www.celldex.com. The call can also be accessed by dialing (646) 307-1963 or (800) 715-9871 (toll free). The conference ID is 3272134.
About Celldex Therapeutics, Inc.
Celldex is a clinical stage biotechnology company leading the science at the intersection of mast cell biology and the development of transformative therapeutics for patients. Our pipeline includes antibody-based therapeutics which have the ability to engage the human immune system and/or directly affect critical pathways to improve the lives of patients with severe inflammatory, allergic and autoimmune and other devastating diseases. Visit www.celldex.com(opens in a new tab).
Source: Celldex Therapeutics, Inc.
Celldex jumps premarket on positive topline results from urticaria drug study
Nov. 06, 2023 7:03 AM ET
Celldex Therapeutics, Inc. (CLDX)
By: Preeti Singh, SA News Editor
- Celldex Therapeutics (NASDAQ:CLDX) was trading as much as +40% in premarket hours on Monday after it reported positive topline results from the phase 2 study for its urticaria drug candidate.
- Barzolvolimab is being tested as a treatment for chronic spontaneous urticaria, and the latest results showed it met the primary endpoint with clinically meaningful and statistically significant decreases in urticaria disease across multiple dose groups.
- https://seekingalpha.com/news/4030808-celldex-jumps-premarket-on-positive-topline-results-from-urticaria-drug-study
- Celldex Therapeutics, Inc. (CLDX)
- https://www.globenewswire.com/news-release/2023/11/06/2773880/24180/en/Celldex-Therapeutics-Announces-Positive-Topline-Results-from-Barzolvolimab-Phase-2-Study-in-Chronic-Spontaneous-Urticaria.html
- https://celldex.com/pipeline/overview/therapeutic-areas/
CART-ddBCMA
Barzolvolimab
Barzolvolimab
Arcellx Announces Oral Presentation for Its CART-ddBCMA Phase 1 Trial in Patients with Relapsed or Refractory Multiple Myeloma at the 65th ASH Annual Meeting and Exposition
November 2, 2023
-- Abstract released today is from a June 2, 2023 data cut --
-- Median duration of response, progression free survival, and overall survival rate not reached with median follow-up after CART-ddBCMA infusion of 22 months --
-- A more recent data cut will be shared during the oral presentation with a median follow-up of 26.5 months --
-- Company to host a live webcast event with an expert panel of clinicians --
REDWOOD CITY, Calif., Nov. 2, 2023 /PRNewswire/ -- Arcellx, Inc. (NASDAQ: ACLX), a biotechnology company reimagining cell therapy through the development of innovative immunotherapies for patients with cancer and other incurable diseases, today announced that new clinical data from its Phase 1 study of CART-ddBCMA in patients with relapsed or refractory multiple myeloma will be presented at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition taking place December 9-12, 2023 in San Diego, California. The data in the ASH abstract published today is from a June 2, 2023 data cut. The oral presentation at ASH will be on Monday, December 11, 2023 at 5 p.m. PT and will include new data with a median follow-up of 26.5 months. The company will also have a medical affairs booth (#748) in Hall E of the San Diego Convention Center.
As detailed in the abstract (#1023), 38 patients were evaluable for efficacy and safety analysis as of the June 2, 2023 cutoff date, based on a median follow-up of 22 months following treatment. These evaluable patients comprised the dose escalation cohorts for the first dose level (100 (+/- 20) million CAR+ T cells, n=6) and the second dose level (300 (+/- 20) million CAR+ T cells, n=6), and a dose expansion cohort at 100 (+/- 20) million CAR+ T cells (n=26). The median dose administered to patients in the first dose level and dose expansion cohorts was 115 million CAR+ T cells. All patients evaluable for this analysis have poor prognostic factors with 38 of 38 (100%) patients triple-refractory, 26 of 38 (68%) penta-refractory, and 34 of 38 (89%) refractory to last-line of treatment by International Myeloma Working Group (IMWG) criteria. Additionally, 9 of 38 patients (24%) patients had high tumor burden with >60% bone marrow plasma (BMPC) cells, 13 of 38 patients (34%) patients had extramedullary disease (EMD), and 11 of 38 (29%) patients had high-risk cytogenetics (Del 17p, t(14;16), t(4;14)) at baseline. At baseline, 24 of 38 (63%) had at least one high risk clinical feature, defined as presence of EMD, BMPC >60% or B2M >5.5. All 38 patients had at least three prior lines of therapy.
The interim CART-ddBCMA Phase 1 clinical results (June 2, 2023 cutoff date) demonstrate deep and durable responses in patients with poor prognostic factors.
All Patients:
Of the 38 evaluable patients with a median follow-up of 22 months
- 100% overall response rate (ORR) achieved in all patients per IMWG criteria
- 29 of 38 evaluable patients achieved a complete response (CR) or a stringent complete response (sCR) (> CR rate, 76%)
- 35 patients achieved a very good partial response or higher (>VGPR rate, 92%)
Median duration of response, progression free survival (PFS), and overall survival were not reached at the time of the June 2, 2023 data cut because 25 of 38 (66%) evaluable patients had ongoing responses.
The Kaplan-Meier method estimated PFS rates for 6, 12, and 18 months were 92%, 74%, and 67% respectively. Durable responses were also observed in patients with high-risk features (EMD, BMPC ≥60%, or B2M ≥5.5 mg/L at baseline) and high-risk cytogenetics.
CART-ddBCMA dosed at RP2D (115 million (+/- 10) CAR+ T cells) continues to be well-tolerated at the time of the data cut:
- Adverse events with CART-ddBCMA, including CRS and ICANS, were manageable
- No tissue-targeted toxicities were observed
- No cases of delayed neurotoxicity events or parkinsonian symptoms were observed
ASH Presentation Details:
Title: Phase 1 Study of CART-ddBCMA for the Treatment of Patients with Relapsed and/or Refractory Multiple Myeloma: Results from at Least 1-Year Follow-up in All Patients
Speaker: Matthew J. Frigault, M.D., Clinical Director of the Cellular Therapy Service at Massachusetts General Cancer Center, and Assistant Professor at Harvard Medical School
Session Name: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: CAR-T Cell Therapies for Multiple Myeloma and B Cell Lymphomas
Session Date: Monday, December 11, 2023
Session Time: 4:30 - 6:00 p.m. PT (CART-ddBCMA oral presentation will be at 5 p.m. PT)
Location: San Diego Convention Center, Room 6A, San Diego, California
Publication Number: 1023
Webcast Event:
Arcellx will host a live webcast event with an expert panel of clinicians to discuss the clinical results on Monday, December 11, 2023 at 8 p.m. PT. The event will be accessible from Arcellx's website at www.arcellx.com in the Investors section. A replay of the webcast will be archived and available for 30 days following the event.
About Multiple Myeloma
Multiple Myeloma (MM) is a type of hematological cancer in which diseased plasma cells proliferate and accumulate in the bone marrow, crowding out healthy blood cells and causing bone lesions, loss of bone density, and bone fractures. These abnormal plasma cells also produce excessive quantities of an abnormal immunoglobulin fragment, called a myeloma protein (M protein), causing kidney damage and impairing the patient's immune function. Multiple myeloma is the third most common hematological malignancy in the United States and Europe, representing approximately 10% of all hematological cancer cases and 20% of deaths due to hematological malignancies. The median age of patients at diagnosis is 69 years with one-third of patients diagnosed at an age of at least 75 years. Because MM tends to afflict patients at an advanced stage of life, patients often have multiple co-morbidities and toxicities that can quickly escalate and become life-endangering.
About CART-ddBCMA
CART-ddBCMA is Arcellx's BCMA-specific CAR-modified T-cell therapy utilizing the company's novel BCMA-targeting binding domain for the treatment of patients with relapsed or refractory multiple myeloma. CART-ddBCMA is currently in a Phase 2 study. Arcellx's proprietary binding domains are novel synthetic proteins designed to bind specific therapeutic targets. CART-ddBCMA has been granted Fast Track, Orphan Drug, and Regenerative Medicine Advanced Therapy Designations by the U.S. Food and Drug Administration.
About Arcellx, Inc.
Arcellx, Inc. is a clinical-stage biotechnology company reimagining cell therapy by engineering innovative immunotherapies for patients with cancer and other incurable diseases. Arcellx believes that cell therapies are one of the forward pillars of medicine and Arcellx's mission is to advance humanity by developing cell therapies that are safer, more effective, and more broadly accessible. Arcellx's lead product candidate, CART-ddBCMA, is being developed for the treatment of relapsed or refractory multiple myeloma (rrMM) in a Phase 2 pivotal trial. CART-ddBCMA has been granted Fast Track, Orphan Drug, and Regenerative Medicine Advanced Therapy designations by the U.S. Food and Drug Administration.
Arcellx is also advancing its dosable and controllable CAR-T therapy, ARC-SparX, through two clinical-stage programs: a Phase 1 study of ACLX-001 for rrMM, initiated in the second quarter of 2022; and ACLX-002 in relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome, initiated in the fourth quarter of 2022. For more information on Arcellx, please visit www.arcellx.com. Follow Arcellx on X (formerly known as Twitter) (@arcellx) and LinkedIn.
About Arcellx and Kite Pharma Collaboration Arcellx and Kite, a Gilead Company, formed a global strategic collaboration to co-develop and co-commercialize Arcellx's CART-ddBCMA candidate for the treatment of patients with relapsed or refractory multiple myeloma currently in a pivotal Phase 2 study. Kite and Arcellx will jointly advance and commercialize the CART-ddBCMA asset in the United States, and Kite will commercialize the product outside the U.S.
Cision View original content to download multimedia:https://www.prnewswire.com/news-releases/arcellx-announces-oral-presentation-for-its-cart-ddbcma-phase-1-trial-in-patients-with-relapsed-or-refractory-multiple-myeloma-at-the-65th-ash-annual-meeting-and-exposition-301975098.html
SOURCE Arcellx, Inc.
Arcellx jumps after data for Gilead-partnered multiple myeloma drug
Nov. 02, 2023 12:44 PM ET
By: Dulan Lokuwithana, SA News Editor
- Shares of Arcellx (NASDAQ:ACLX) traded higher on Thursday after the immunotherapy developer released data from a Phase 1 trial for its multiple myeloma therapy, CART-ddBCMA, developed in partnership with Gilead Sciences (NASDAQ:GILD).
- Citing an abstract published in connection with the upcoming meeting of the American Society of Hematology (ASH), Arcellx (ACLX) reported over 76% complete response rate for the treatment.
- https://seekingalpha.com/news/4029397-arcellx-stock-jumps-data-gilead-partnered-lead-drug
- Arcellx, Inc. (ACLX), GILD
- https://www.arcellx.com/
- https://www.arcellx.com/pipeline-focus-area/
Felzartamab
Barzolvolimab
Felzartamab
2023.11.02
Felzartamab Granted Breakthrough Therapy Designation by U.S. Food and Drug Administration (FDA) for Primary Membranous Nephropathy (PMN)
- FDA granted Breakthrough Therapy Designation for felzartamab in PMN upon positive clinical data from M-PLACE, a Phase 2 study led by I-Mab partner HI-Bio
- I-Mab has full development and commercialization rights of felzartamab in Greater China for all indications, with Phase 3 multiple myeloma data expected in 2024, followed by a planned BLA submission
ROCKVILLE, MD, U.S. and SHANGHAI, China, November 2, 2023 – I-Mab (Nasdaq: IMAB) (the “Company”), a global biotechnology company focused on bringing highly differentiated medicines to patients around the world through the discovery, development, and commercialization of novel immunotherapies and biologics, and HI-Bio, a clinical-stage biotechnology company developing targeted therapies for patients with severe immune-mediated diseases (IMDs), today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) for felzartamab, an investigational CD38 antibody, for the treatment of primary membranous nephropathy (PMN).
“The FDA’s decision to grant felzartamab Breakthrough Therapy designation is recognition of the promising data we have collected to date, as well as an acknowledgement of the need for major advances over available therapies in the treatment of patients with PMN,” said Dr. Uptal Patel, Chief Medical Officer of HI-Bio. “We believe that the cellular depletion strategy with felzartamab in PMN is applicable to many more immune-mediated diseases driven by antibodies produced in CD38+ plasma cells. For that reason, we are currently developing felzartamab in multiple diseases including PMN, IgA nephropathy, antibody-mediated rejection and lupus nephritis.”
The FDA selectively grants Breakthrough Therapy Designation to expedite the development and review of drugs that are intended to treat a serious or life-threatening condition, and preliminary clinical evidence indicates the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).
The designation for felzartamab was based on clinical data submitted to the FDA, including results from M-PLACE, a Phase 1b/2a proof-of-concept, open-label study. The final analysis of the M-PLACE study has been accepted as an oral presentation at the American Society of Nephrology (ASN) Kidney Week 2023 Annual Meeting (Abstract TH-OR27), taking place November 1–5, 2023, by Brad Rovin, M.D., Director of the Division of Nephrology at Ohio State University.
I-Mab has the full rights to develop and commercialize felzartamab for all indications in Greater China which encompasses Mainland China, Hong Kong, Macau, and Taiwan. I-Mab is evaluating felzartamab in oncology and autoimmune diseases. I-Mab is currently conducting a Phase 3 registrational study of felzartamab in combination with lenalidomide and dexamethasone as a second-line treatment for multiple myeloma (MM) in China with progression-free survival (PFS) as the primary endpoint, with a projected read-out in 2024, followed by a planned BLA submission.
“We are excited about the potential therapeutic benefit of felzartamab through this Breakthrough Therapy Designation by the FDA, following the Orphan Drug Designation received in May,” said Dr. Andrew Zhu, President of I-Mab. “This designation represents an important milestone for I-Mab, our partner HI-Bio, and the PMN community as we continue to evaluate felzartamab as an innovative immunotherapy for multiple indications, including cancers and autoimmune diseases.”
###
About Primary Membranous Nephropathy (PMN)
PMN is a rare autoantibody-mediated autoimmune kidney disease and a leading cause of nephrotic syndrome (NS) in adults worldwide. Disease onset and diagnosis typically occurs between 40 and 50 years of age, with 80% of patients presenting with nephrotic syndrome (i.e., edema, >3.5 g/day proteinuria, hypoalbuminemia). PMN is characterized by a thickening of the glomerular basement membrane (GBM) due to the formation and deposition of immune complexes in this space between podocytes and the glomerular endothelium of the kidney.
Approximately 80% of PMN cases arise due to autoantibodies that recognize the phospholipase A2 receptor (PLA2R) antigen expressed on podocytes. Anti-PLA2R is both a diagnostic and prognostic biomarker, and total aPLA2R antibody level has been shown to be a biomarker for prognosis of outcome in patients with PMN. Other autoantibodies have been identified in patients with PMN including anti-THSD7A, NELL-1 and Sema3B, further supporting the role of antibody-secreting plasma cells in the pathophysiology of PMN. CD38+ long-lived plasma cells and plasmablasts are a main source of autoantibodies.
There are no approved therapies for PMN. The current standard of care comprises off-label use of supportive care measures (e.g., angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, statins, and diuretics), conventional immunosuppressive treatments (ISTs) (e.g. cyclophosphamide combined with steroids and calcineurin inhibitors) or B-cell depleting agents (e.g. anti-CD20 antibodies). However, these treatments are not effective in all patients, with a significant proportion of patients not achieving remission or relapsing. In addition, conventional immunosuppressive treatments are associated with a high risk of toxicity.
About Felzartamab
Felzartamab is an investigational therapeutic human monoclonal antibody directed against CD38, a protein expressed on mature plasma cells. The antibody is directed against CD38 on the surface of multiple myeloma cells, which has been characterized as one of the most strongly and uniformly expressed antigens on the surface of malignant plasma cells. According to its suggested mode of action, the antibody recruits cells of the body’s immune system to kill the tumor through antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). The antibody does not involve complement dependent cytotoxicity, or CDC, an additional immune mechanism involved in tumor cell killing. Scientific research suggests that an anti-CD38 antibody may have therapeutic potential also in other cancers as well as autoimmune diseases. Based on a licensing agreement between MorphoSys and I-Mab signed in November 2017, I-Mab owns the exclusive rights for development and commercialization of felzartamab for all indications in Greater China, which encompasses Mainland China, Hong Kong, Macao, and Taiwan. HI-Bio in-licensed felzartamab from MorphoSys in June 2022, and holds exclusive worldwide rights for felzartamab with the exception of Greater China.
About I-Mab
I-Mab (Nasdaq: IMAB) is a global biotechnology company focused on bringing highly differentiated medicines to patients around the world through the discovery, development, and commercialization of novel immunotherapies and biologics. I-Mab’s innovative pipeline is driven by internal R&D’s Fast-to-Proof-of-Concept, Fast-to-Market development strategies, and through global partnerships. For more information, please visit https://www.i-mabbiopharma.com and follow us on LinkedIn, Twitter, and WeChat.
I-Mab gains FDA breakthrough tag for kidney disease therapy
Nov. 02, 2023 10:07 AM ET
By: Dulan Lokuwithana, SA News Editor1 Comment
I-Mab (NASDAQ:IMAB) traded higher pre-market Thursday after the U.S. FDA issued the agency's breakthrough therapy designation for its CD38-targeting monoclonal antibody felzartamab to treat a kidney disease called primary membranous nephropathy.
PMN is an autoimmune disease characterized by a thickening of the kidney tissue, the glomerular basement membrane. It typically occurs between 40 and 50 years of age.
The FDA's Breakthrough Therapy designation aims to speed up the development and review of treatments targeted at serious or life-threatening conditions.
With the full features of the designation, a breakthrough therapy developer can receive intensive regulatory guidance with potential eligibility for the FDA's priority review.
A Phase 3 registrational trial is currently underway in China to study felzartamab in combination with lenalidomide and dexamethasone as a second-line therapy for multiple myeloma.
I-Mab (IMAB) develops felzartamab in partnership with South San Francisco, California-based biotech Hi-Bio which in-licensed the treatment from German biotech MorphoSys (NASDAQ:MOR) (OTCPK:MPSYF) in June 2022
https://seekingalpha.com/news/4029210-i-mab-gains-fda-breakthrough-tag-kidney-disease-therapy
Mavorixafor
Novel CELMoD™ Agent CC- 92480 Mezigdomide in Combination with Selinexor
Felzartamab
X4 Pharmaceuticals Announces FDA Acceptance with Priority Review of U.S. NDA for Mavorixafor in WHIM Syndrome
October 31, 2023
FDA sets a Prescription Drug User Fee Act (PDUFA) target action date of April 30, 2024
If the NDA is approved, company eligible to receive a Priority Review Voucher (PRV) resulting from mavorixafor’s rare pediatric designation in WHIM syndrome
NDA supported by positive results from global, pivotal 4WHIM Phase 3 clinical trial
BOSTON, Oct. 31, 2023 (GLOBE NEWSWIRE) -- X4 Pharmaceuticals (Nasdaq: XFOR), a company driven to improve the lives of people with rare diseases of the immune system, today announced that the United States Food and Drug Administration (FDA) has accepted for filing the company’s New Drug Application (NDA) for once-daily, oral mavorixafor to treat individuals aged 12 and older with WHIM (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis) syndrome, a rare, primary immunodeficiency. The FDA granted Priority Review of the mavorixafor NDA, establishing a goal of six months review from the date of acceptance and assigning a Prescription Drug User Fee Act (PDUFA) target action date of April 30, 2024.
“The FDA’s acceptance of our mavorixafor NDA with priority review represents yet another significant step forward towards a potential treatment for those with WHIM syndrome, a rare disease for which there are currently no approved therapies,” said Paula Ragan, Ph.D., President and Chief Executive Officer of X4 Pharmaceuticals. “We look forward to working closely with the FDA throughout the NDA review process with the goal of bringing mavorixafor to people with WHIM syndrome as quickly as possible.”
Mavorixafor is an investigational small-molecule antagonist of the CXCR4 receptor being developed as a once-daily oral therapy for WHIM syndrome and certain chronic neutropenic disorders. For the WHIM syndrome indication, mavorixafor has been granted Breakthrough Therapy Designation, Fast Track Designation, and Rare Pediatric Disease (RPD) Designation in the U.S., and Orphan Drug Status in both the U.S. and European Union. Upon FDA approval of a product with RPD designation, the sponsor can receive a Priority Review Voucher that can be used to obtain priority review for a subsequent application or sold to another drug sponsor.
The NDA is supported by the results of the global, pivotal, 4WHIM Phase 3 clinical trial of once-daily, oral mavorixafor in individuals with WHIM syndrome. The 4WHIM trial met its primary endpoint of time above threshold for absolute neutrophil count (TAT-ANC) vs. placebo (p<0.0001), a key secondary endpoint, and was generally well tolerated in the trial, with no treatment-related serious adverse events reported and no discontinuations for safety events. The 4WHIM data also revealed that mavorixafor treatment resulted in reductions in the rate, severity, and duration of infections in trial participants versus placebo. These and additional 4WHIM Phase 3 data were published in oral presentations at the annual meetings of both the Clinical Immunology Society (CIS) and European Hematology Association (EHA).
About WHIM Syndrome
WHIM syndrome is a rare, inherited, combined immunodeficiency disease caused by reduced mobilization and trafficking of white blood cells from the bone marrow due to over-signaling of the CXCR4/CXCL12 pathway. WHIM syndrome is named for its four common clinical findings: Warts, Hypogammaglobulinemia, Infections, and Myelokathexis, although not all patients experience all symptoms, and not all symptoms are required for a diagnosis. People with WHIM syndrome characteristically have very low blood levels of neutrophils (neutropenia) and lymphocytes (lymphopenia), and as a result, experience frequent, recurrent infections with a high risk of lung disease and refractory warts from underlying human papillomavirus (HPV) infection. Those with WHIM syndrome may also have limited antibody production due to low levels of immunoglobulin and an increased risk of developing certain types of cancer.
About the 4WHIM Phase 3 Clinical Trial
The 4WHIM Phase 3 clinical trial was a global, randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the efficacy and safety of oral, once-daily mavorixafor in people with genetically confirmed WHIM syndrome. The trial enrolled 31 participants aged 12 and older who received either mavorixafor (n=14) or placebo (n=17) orally once daily for 52 weeks. An open-label extension phase of the clinical trial is ongoing (NCT03995108).
About X4 Pharmaceuticals
X4 Pharmaceuticals is a late-stage clinical biopharmaceutical company driven to improve the lives of people with rare diseases of the immune system. Our lead clinical candidate is mavorixafor, a small molecule antagonist of chemokine receptor CXCR4 that is being developed as an oral, once-daily therapy across a variety of immunodeficiencies, including WHIM (Warts, Hypogammaglobulinemia, Infections, and Myelokathexis) syndrome and certain chronic neutropenic disorders. Following successful completion of a global, pivotal, Phase 3 clinical trial, we are seeking U.S. approval of oral, once-daily mavorixafor for the treatment of people aged 12 years and older with WHIM syndrome. We are also currently planning a Phase 3 clinical program evaluating mavorixafor in certain chronic neutropenic disorders. We continue to leverage our insights into CXCR4 and immune system biology at our corporate headquarters in Boston, Massachusetts and at our research center of excellence in Vienna, Austria. For more information, please visit our website at www.x4pharma.com.
Source: X4 Pharmaceuticals
X4 shares jump as FDA accepts priority review of pediatric WHIM drug
Oct. 31, 2023 10:35 AM ET
X4 Pharmaceuticals, Inc. (XFOR)
By: Preeti Singh, SA News Editor
- X4 Pharmaceuticals (NASDAQ:XFOR) shares popped +14% on Tuesday after the company said its drug mavorixafor was accepted by the US FDA with priority review for a rare pediatric designation.
- Mavorixafor is a once-daily oral drug candidate aimed at treating patients 12 years or older with warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome - a rare, primary immunodeficiency.
- https://seekingalpha.com/news/4026969-x4-shares-jump-as-fda-accepts-priority-review-of-pediatric-whim-drug
- X4 Pharmaceuticals, Inc. (XFOR)
- https://www.x4pharma.com/
- https://www.x4pharma.com/pipeline/
Novel CELMoD™ Agent CC- 92480 Mezigdomide in Combination with Selinexor
Novel CELMoD™ Agent CC- 92480 Mezigdomide in Combination with Selinexor
Novel CELMoD™ Agent CC- 92480 Mezigdomide in Combination with Selinexor
Karyopharm Announces Clinical Trial Collaboration with Bristol Myers Squibb to Evaluate Novel CELMoD™ Agent CC- 92480 Mezigdomide in Combination with Selinexor in Patients with Relapsed/Refractory Multiple Myeloma
— Phase 1b/2 Trial Will Investigate Mezigdomide in Combination with Selinexor in Patients with Relapsed/Refractory Multiple Myeloma Progressing after T-cell Immunotherapies –
— Expected to be Initiated 1H 2024 –
NEWTON, Mass., Oct. 30, 2023 /PRNewswire/ -- Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that it has entered into a clinical trial collaboration and supply agreement with Bristol-Myers Squibb (NYSE: BMY) to evaluate the company's proprietary investigational cereblon E3 ligase modulator (CELMoD™) agent mezigdomide in combination with Karyopharm's selinexor, an approved first-in-class inhibitor of Exportin 1 (XPO1), plus dexamethasone in patients with relapsed/refractory multiple myeloma.
This trial will evaluate mezigdomide in combination with selinexor doses of either 40mg or 60mg plus dexamethasone in patients who have prior exposure to immunomodulatory (IMiD®) drug agents, proteasome inhibitors, and anti-CD38 monoclonal antibody treatment. All patients must have received at least two prior lines of therapy, and either have progressed after or are not eligible to receive CAR-T or bispecific antibody treatment.
"This is an important collaboration with Bristol Myers Squibb to explore this novel and entirely oral combination in patients who have progressed following T-cell engaging therapy. This trial will also evaluate mezigdomide-selinexor plus dexamethasone in patients with relapsed/refractory multiple myeloma who need an effective alternative to T-cell therapies," said Richard Paulson, MBA, President and Chief Executive Officer of Karyopharm. "Pre-clinical studies with selinexor and mezigdomide post T-cell mediated therapies provide a scientific rationale for this novel combination to potentially prevent/reverse T-cell exhaustion and improve outcomes for more of these patients. We look forward to initiating the trial in the first half of 2024."
"Despite multiple treatment advances, there is a growing need for new combinations, particularly those that are all-oral, accessible and that have novel mechanisms to help treat patients with relapsed and refractory multiple myeloma," said Paul Richardson, M.D., the RJ Corman Professor of Medicine, Dana Farber Cancer Institute, and senior investigator of the study. "Pre-clinical data suggests the combination of a selective inhibitor of nuclear export (SINE), such as selinexor, with potent cereblon E3 ligase modulators , such as mezigdomide, may spare T-cell function while showing potential activity against resistant myeloma. This particular combination represents an innovative and promising approach to treating relapsed and refractory multiple myeloma with the convenience of an all-oral approach. We look forward to learning more about its potential in triple-class exposed patients, as well as in those who've experienced [anti-]BCMA and T-cell directed treatment failure."
The primary endpoints of this trial are to assess the objective response rate (ORR) and the clinical benefit rate (CBR). Key secondary endpoints include progression-free survival (PFS), overall survival (OS) and duration of response (DOR). In addition, the trial will evaluate dynamic changes in T-cell populations and activity as patients undergo treatment. Under the terms of the agreement with Bristol Myers Squibb, Karyopharm will sponsor the trial as a new arm of Karyopharm's Phase 1b/2 STOMP trial and Bristol Myers Squibb will supply the study's clinical drug mezigdomide.
About XPOVIO® (selinexor)
XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor and the first of Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds to be approved for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved in the U.S. and marketed by Karyopharm in multiple oncology indications, including: (i) in combination with Velcade® (bortezomib) and dexamethasone (XVd) in patients with multiple myeloma after at least one prior therapy; (ii) in combination with dexamethasone in patients with heavily pre-treated multiple myeloma; and (iii) in patients with diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. XPOVIO (also known as NEXPOVIO® in certain countries) has received regulatory approvals in various indications in a growing number of ex-U.S. territories and countries, including but not limited to the European Union, the United Kingdom, China, South Korea, Canada, Israel and Taiwan. XPOVIO and NEXPOVIO is marketed by Karyopharm's partners, Antengene, Menarini, Neopharm and FORUS, in China, South Korea, Singapore, Australia, Hong Kong, Germany, Austria, Israel and Canada.
Please refer to the local Prescribing Information for full details.
Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high unmet need cancer indications, including in endometrial cancer and myelofibrosis.
For more information about Karyopharm's products or clinical trials, please contact the Medical Information department at:
Tel: +1 (888) 209-9326
Email: medicalinformation@karyopharm.com
About Mezigdomide
Cereblon E3 ligase modulators (CELMoD™) are a class of oral immunomodulatory therapeutics that are designed to stimulate the immune system and directly kill cancer cells by inducing the degradation of tumor-promoting proteins. Bristol Myers Squibb is investigating a novel CELMoD™ agent, mezigdomide, for multiple myeloma that was intentionally designed to improve upon the demonstrated efficacy of the IMiD agents, along with manageable tolerability, ease of administration, and the potential to improve patient outcomes. Mezigdomide co-opts cereblon to rapidly induce degradation of target proteins Ikaros and Aiolos, thus inhibiting tumor cell proliferation, promoting tumor cell death, and inducing immune-stimulatory effects.
About Karyopharm Therapeutics
Karyopharm Therapeutics Inc. (Nasdaq: KPTI) is a commercial-stage pharmaceutical company pioneering novel cancer therapies. Since its founding, Karyopharm has been an industry leader in oral Selective Inhibitor of Nuclear Export (SINE) compound technology, which was developed to address a fundamental mechanism of oncogenesis: nuclear export dysregulation. Karyopharm's lead SINE compound and first-in-class, oral exportin 1 (XPO1) inhibitor, XPOVIO® (selinexor), is approved in the U.S. and marketed by the Company in three oncology indications and has received regulatory approvals in various indications in a growing number of ex-U.S. territories and countries, including Europe and the United Kingdom (as NEXPOVIO®) and China. Karyopharm has a focused pipeline targeting multiple high unmet need cancer indications, including in multiple myeloma, endometrial cancer, myelodysplastic neoplasms and myelofibrosis. For more information about our people, science and pipeline, please visit www.karyopharm.com, and follow us on Twitter at @Karyopharm and LinkedIn.
Please see the Medication Guide and the full Prescribing Information for XPOVIO.
XPOVIO® and NEXPOVIO® are registered trademarks of Karyopharm Therapeutics Inc. Any other trademarks referred to in this release are the property of their respective owners.
SOURCE Karyopharm Therapeutics Inc.
Karyopharm, Bristol Myers to evaluate drug combination for treatment of multiple myeloma
Oct. 30, 2023 1:54 PM ET
Karyopharm Therapeutics Inc. (KPTI), BMY
By: Anuron Mitra, SA News Editor
Karyopharm Therapeutics (NASDAQ:KPTI) on Monday said it would collaborate with Bristol Myers Squibb (NYSE:BMY) to assess a combination of their drugs in patients with multiple myeloma, a type of white blood cell cancer.
Karyopharm Therapeutics Inc. (KPTI), BMY
LOQTORZI™ (toripalimab-tpzi)
Novel CELMoD™ Agent CC- 92480 Mezigdomide in Combination with Selinexor
Novel CELMoD™ Agent CC- 92480 Mezigdomide in Combination with Selinexor
Coherus and Junshi Biosciences Announce FDA Approval of LOQTORZI™ (toripalimab-tpzi) in All Lines of Treatment for Recurrent or Metastatic Nasopharyngeal Carcinoma (NPC)
– LOQTORZI is the first and only FDA-approved treatment for NPC –
– Indicated in combination with chemotherapy for 1st line treatment and as monotherapy for patients with disease progression on or after platinum containing chemotherapy, irrespective of PD-L1 status –
– Conference today at 4:30 p.m. Eastern Daylight Time –
REDWOOD CITY, Calif. and SHANGHAI, China, Oct. 27, 2023 (GLOBE NEWSWIRE) -- Coherus BioSciences, Inc. (“Coherus”, NASDAQ: CHRS), and Shanghai Junshi Biosciences Co., Ltd. (Junshi Biosciences, HKEX: 1877; SSE: 688180) today announced that the U.S. Food and Drug Administration (FDA) approved LOQTORZI™ (toripalimab-tpzi) in combination with cisplatin and gemcitabine for the first-line treatment of adults with metastatic or recurrent locally advanced NPC, and as monotherapy for the treatment of adults with recurrent, unresectable, or metastatic NPC with disease progression on or after platinum-containing chemotherapy. The approval was based on results of the JUPITER-02 Phase 3 study and the POLARIS-02 Phase 2 study and is irrespective of a patient’s PD-L1 status. LOQTORZI is a next-generation, programmed death receptor-1 (PD-1) monoclonal antibody that blocks PD-1 ligands PD-L1 and PD-L2 with high potency at a unique site on the PD-1 receptor, enabling the immune system to activate and kill the tumor.
In the JUPITER-02 Phase 3 study, LOQTORZI combined with chemotherapy significantly improved progression-free survival (PFS), reducing the risk of disease progression or death by 48% compared to chemotherapy alone. LOQTORZI also demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS), with treatment resulting in a 37% reduction in the risk of death versus chemotherapy alone.
The safety profile of LOQTORZI was consistent with the PD-1 inhibitor class. The incidence of Grade ≥3 adverse events (AEs) (89.7% vs 90.2%) and fatal AEs (3.4% vs 2.8%) was similar between the two arms. AEs leading to discontinuation of LOQTORZI versus placebo (11.6% vs 4.9%), immune-related adverse events (irAEs) (54.1% vs. 21.7%), and Grade ≥3 irAEs (9.6% vs. 1.4%) were more frequent in the LOQTORZI arm.
In the POLARIS-02 clinical study LOQTORZI demonstrated durable antitumor activity in patients with recurrent or metastatic NPC who failed previous chemotherapy, with an objective response rate (ORR) of 20.5%, a disease control rate (DCR) of 40.0%, and a median OS of 17.4 months with an acceptable safety profile.
NPC is an aggressive cancer that starts in the nasopharynx, the upper part of the throat behind the nose and near the base of skull. Due to the location of the primary tumor, surgery is rarely an option, and patients with localized disease are treated primarily with radiation and chemotherapy. LOQTORZI is the first FDA-approved agent for NPC patients.
“LOQTORZI’s first approval is a pivotal event for Coherus as an innovative oncology company. As a next generation PD-1 inhibitor it is the keystone of our I-O strategy to extend cancer patient survival as shown with the impressive results in NPC,” said Denny Lanfear, Chairman and Chief Executive Officer of Coherus. “We are particularly excited to now turn our attention to developing LOQTORZI across multiple tumor types in combination with I-O agents that target the tumor microenvironment, such as our IL27-targeted antibody, casdozokitug, and our CCR8 inhibitor CHS-114, potentially greatly expanding the number of cancer patients achieving improved survival benefit.”
“Today’s FDA approval of LOQTORZI is very encouraging for those living with NPC who currently have very limited treatment options and are in need of new therapies to treat this aggressive and life-threatening form of cancer,” said Jong Chul Park, M.D., Assistant Professor, Harvard Medical School and attending physician at the Center for Head and Neck Cancers at Massachusetts General Hospital Cancer Center. “LOQTORZI is a new treatment option that has demonstrated the ability to significantly improve PFS and OS and should quickly emerge as the new standard of care when used in combination with chemotherapy.”
The recommended LOQTORZI dose with cisplatin and gemcitabine is 240 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months. The recommended LOQTORZI dose as a single agent for previously treated NPC is 3 mg/kg every two weeks until disease progression or unacceptable toxicity.
LOQTORZI is expected to be available in the United States in Q1 2024.
“The impressive results from JUPITER-02 and POLARIS-02 have provided conclusive evidence that establishes toripalimab, in combination with chemotherapy or as monotherapy, as the standard therapy for advanced NPC,” said Professor Ruihua Xu of Sun Yat-sen University Cancer Center, the principal investigator of JUPITER-02 and POLARIS-02. “This great achievement was only made possible through the solid foundation laid by countless oncology experts over decades of in-depth research, as well as the selfless dedication of the patients and research teams involved in our toripalimab studies. We hope that this promising therapy will close the treatment gap for international NPC patients struggling to find effective therapies, bringing them renewed hope for better survival.”
“We’re excited to reach another significant company milestone of ‘going overseas’,” said Dr. Ning LI, Chief Executive Officer of Junshi Biosciences. “Following etesevimab, toripalimab has become Junshi Biosciences’ second product to receive FDA approval for commercialization—an achievement that will further enhance the company’s international presence. Currently, the establishment of toripalimab’s global commercialization network is in progress, and the network aims to span over 50 countries. In accordance with the company’s ‘In China, For Global’ strategy, we will continue working with our collaborators to promote the commercialization of toripalimab in other regions, in order to provide innovative and high-quality drugs from China to more patients overseas.”
About JUPITER-02
JUPITER-02 is the largest randomized, double-blind, placebo-controlled, international, multi-center Phase 3 clinical study to evaluate a checkpoint inhibitor plus chemotherapy for the first-line treatment of recurrent or metastatic NPC.
Two hundred eighty-nine patients with advanced NPC who had received no prior chemotherapy for recurrent/metastatic disease were randomized 1:1 to receive LOQTORZI (toripalimab-tzpi) 240 mg or placebo in combination with gemcitabine 1000 mg/m2 (days 1 and 8) and cisplatin 80 mg/m2 (day 1) of every three-week treatment cycle, followed by toripalimab-tzpi or placebo monotherapy every 3 weeks until disease progression, intolerable toxicity, or completion of two years of treatment. JUPITER-02 included all eligible patients regardless of PD-L1 status and histologies.
In this study, LOQTORZI met the primary endpoint, demonstrating a significant improvement in PFS (assessed by a Blinded Independent Review Committee (BIRC)) compared to the chemotherapy alone arm with toripalimab-tzpi, reducing the risk of disease progression or death by 48% (HR=0.52 [95% CI: 0.36, 0.74; P<0.0003). Improvement in PFS was observed irrespective of PD-L1 status.
LOQTORZI demonstrated a statistically significant and clinically meaningful improvement in OS with treatment resulting in a 37% reduction in the risk of death versus chemotherapy alone. Median OS has not been reached in the LOQTORZI arm versus 33.7 months for chemotherapy treatment alone (HR=0.63 [95% CI 0.45-0.89]; P=0.0083).
LOQTORZI also demonstrated an improvement in ORR, duration of response (DoR), and DCR. In the study, 77% of patients treated with LOQTORZI experienced a complete or partial response (19% and 58% respectively) and the median duration of response was 10 months in the LOQTORZI arm versus 5.7 months in the chemotherapy alone arm.
About LOQTORZI Solutions
Coherus is committed to supporting patients with programs for zero out-of-pocket costs or patient assistance for eligible patients so that they may benefit from a proven PD-1 immunotherapy, with less financial burden.
Our robust patient support services include:
- Reimbursement support
- Patient support
- Access support
Commitment to the NPC community
Given the limited resources available to patients and caregivers contending with NPC, Coherus has launched a new educational community resource, NPCFacts.com, which includes detailed information about the types of NPC as well as its causes, diagnosis, and treatment options.
In addition to education about nasopharyngeal carcinoma, the website includes links to patient-advocacy organizations providing additional resources, including the Head and Neck Cancer Alliance, Support for People with Oral Head and Neck Cancer, and Thyroid Head and Neck Cancer Foundation.
The website includes a companion website for healthcare professionals treating patients with NPC, including educational resources and opportunities for peer-to-peer education.
About NPC
NPC is a type of aggressive cancer that starts in the nasopharynx, the upper part of the throat behind the nose and near the base of the skull. NPC is rare in the United States, with an annual incidence of fewer than one per 100,000. The five-year survival rate for all patients diagnosed with NPC is approximately 60%, however, those who are diagnosed with advanced disease have a five-year survival rate of approximately 49%.
Due to the location of the primary tumor, surgery is rarely an option, and patients with localized disease are treated primarily with radiation and chemotherapy. Patients treated with chemotherapy alone experience poor prognosis: only 20% experience one-year PFS; up to 50% developed distant metastasis during their disease course; and low median OS of 29 months.
LOQTORZI™ is the first FDA-approved therapy for NPC and will represent a new standard of care for treating the disease when used in combination with cisplatin and gemcitabine in the first line setting or as monotherapy in the second line or greater setting.
About LOQTORZI™ (toripalimab-tpzi)
LOQTORZI is a next generation anti-PD-1 monoclonal antibody that blocks PD-L1 binding to the PD-1 receptor at a unique site with high affinity and activates antitumor immunity demonstrating improvement in the overall survival of cancer patients in several tumor types.
INDICATIONS AND IMPORTANT SAFETY INFORMATION
INDICATIONS
LOQTORZI (toripalimab-tpzi) is indicated:
- In combination with cisplatin and gemcitabine, for the first-line treatment of adults with metastatic or with recurrent, locally advanced nasopharyngeal carcinoma (NPC).
- As a single agent, for the treatment of adults with recurrent unresectable or metastatic NPC with disease progression on or after a platinum-containing chemotherapy.
Please see Prescribing Information for LOQTORZI and Medication Guide
Conference Call Information
When: Friday, October 27, 2023, starting at 4:30 p.m. Eastern Time / 1:30 p.m. Pacific Time
To access the conference call, please pre-register through the following link to receive dial-in information and a personal PIN to access the live call: https://register.vevent.com/register/BI5e94411d336341ba89d7e9eed804e892
Please dial-in 15 minutes early to ensure a timely connection to the call.
Webcast Link: https://edge.media-server.com/mmc/p/hpvx6oka
A replay of the webcast will be archived on the “Investors” section of the Coherus website at http://investors.coherus.com.
About Coherus BioSciences
Coherus is a commercial-stage biopharmaceutical company focused on the research, development and commercialization of innovative immunotherapies to treat cancer. Coherus is developing an innovative immuno-oncology pipeline that will be synergistic with its proven commercial capabilities in oncology.
Coherus’ immuno-oncology pipeline includes multiple antibody immunotherapy candidates focused on enhancing the innate and adaptive immune responses to enable a robust immunologic response and enhance outcomes for patients with cancer. Casdozokitug is a novel anti-IL-27 antibody currently being evaluated in Phase 1/2 clinical trials in lung and liver cancer. CHS-114 is a highly selective, competitively positioned, ADCC-enhanced anti-CCR8 antibody currently in a Phase 1/2 study as a monotherapy in patients with advanced solid tumors.
Coherus’ earlier-stage immuno-oncology pipeline targets immune-suppressive mechanisms, including CHS-006, a TIGIT-targeted antibody, being evaluated in a Phase 1/2 clinical trial in combination with LOQTORZI in patients with advanced solid tumors, and CHS-1000, a preclinical program targeting the novel pathway ILT4.
Coherus markets UDENYCA® (pegfilgrastim-cbqv), a biosimilar of Neulasta®, CIMERLI® (ranibizumab-eqrn), a biosimilar of Lucentis®, YUSIMRY™ (adalimumab-aqvh), a biosimilar of Humira® and expects to launch LOQTORZI (toripalimab-tpzi), a novel next generation PD-1 inhibitor, in the U.S. in Q1 2024.
About Junshi Biosciences
Founded in December 2012, Junshi Biosciences (HKEX: 1877; SSE: 688180) is an innovation-driven biopharmaceutical company dedicated to the discovery, development, and commercialization of innovative therapeutics. The company has established a diversified R&D pipeline comprising more than 50 drug candidates, with five therapeutic focus areas covering cancer, autoimmune, metabolic, neurological, and infectious diseases. Four of the company’s innovations have already reached the Chinese or international markets, one of which is China’s first self-developed anti-PD-1 monoclonal antibody, toripalimab. Additionally, more than 30 drugs are currently in clinical development. During the COVID-19 pandemic, Junshi Biosciences actively shouldered the social responsibilities of a Chinese pharmaceutical company through its involvement in developing etesevimab, MINDEWEI®, and other novel therapies for the prevention and treatment of COVID-19.
With a mission of “providing patients with world-class, trustworthy, affordable, and innovative drugs”, Junshi Biosciences is “In China, For Global.” At present, the company has approximately 3,000 employees in the United States (California and Maryland) and China (Shanghai, Suzhou, Beijing, Guangzhou, etc). For more information, please visit: http://junshipharma.com.
A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/0309b960-26f3-48b4-97a8-2076d70bbb71
LOQTORZI™ (toripalimab-tpzi)
LOQTORZI™ (toripalimab-tpzi) carton
Source: Coherus BioSciences, Inc.
Junshi-Coherus' Loqtorzi cancer drug wins FDA approval
Oct. 30, 2023 6:50 AM ET
Coherus BioSciences, Inc. (CHRS), SHJBF
By: Preeti Singh, SA News Editor
The US Food and Drug Administration has granted approval for Loqtorzi (toripalimab-tpzi) to Shanghai Junshi Biosciences (OTCPK:SHJBF) and its US partner Coherus BioSciences for the treatment of nasopharyngeal carcinoma (NPC).
https://seekingalpha.com/news/4026141-junshi-coherus-loqtorzi-cancer-drug-wins-fda-approval
Coherus BioSciences, Inc. (CHRS), SHJBF
biotecHOPE™ 2023
ELAHERE (MIRVETUXIMAB SORAVTANSINE)
ELAHERE (MIRVETUXIMAB SORAVTANSINE)
ELAHERE (MIRVETUXIMAB SORAVTANSINE)
mmunoGen Announces European Medicines Agency Acceptance of Marketing Authorization Application for Mirvetuximab Soravtansine in Platinum-Resistant Ovarian Cancer
October 27, 2023 at 6:30 AM EDT
WALTHAM, Mass.--(BUSINESS WIRE)--Oct. 27, 2023-- ImmunoGen, Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, today announced that the European Medicines Agency (EMA) has accepted the Marketing Authorization Application (MAA) for mirvetuximab soravtansine (ELAHERE®) for the treatment of patients with folate receptor alpha (FRα)-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer.
"The acceptance of our MAA is another important regulatory milestone in the next chapter of ELAHERE’s story as we work diligently to deliver this new treatment option to patients with platinum-resistant ovarian cancer globally," said Michael Vasconcelles, MD, ImmunoGen's Executive Vice President, Research, Development, and Medical Affairs. "As the first novel medicine to have demonstrated an overall survival benefit in platinum-resistant ovarian cancer compared to chemotherapy in a Phase 3 clinical trial, we are pleased to initiate the review process that moves us one step closer to providing access to ELAHERE for eligible patients in Europe. We look forward to working closely with the EMA throughout the review process and to potentially bring this novel ADC to Europe as early as 2024."
The MAA is supported by positive data from the Phase 3 MIRASOL trial of ELAHERE in platinum-resistant ovarian cancer, which was disclosed in May 2023 and subsequently presented as a late-breaking abstract at the 2023 American Society of Clinical Oncology Annual Meeting. In the MIRASOL trial, ELAHERE demonstrated statistically significant and clinically meaningful improvements in progression-free survival, objective response rate, and overall survival compared to investigator's choice (IC) of single-agent chemotherapy. ELAHERE demonstrated a tolerable safety profile compared to IC chemotherapy consisting predominantly of low-grade ocular and gastrointestinal events.
ELAHERE was approved by the US Food and Drug Administration in November 2022.
ABOUT OVARIAN CANCER
Ovarian cancer is the leading cause of death from gynecological cancers worldwide. Each year, more than 66,000 patients are diagnosed and 45,000 patients will die in the United States and Europe combined. Most patients present with late-stage disease and will typically undergo surgery followed by platinum-based chemotherapy. Unfortunately, the majority of patients eventually develop platinum-resistant disease, which is difficult to treat.
ABOUT IMMUNOGEN
ImmunoGen is developing the next generation of antibody-drug conjugates (ADCs) to improve outcomes for cancer patients. By generating targeted therapies with enhanced anti-tumor activity and favorable tolerability profiles, we aim to disrupt the progression of cancer and offer our patients more good days. We call this our commitment to TARGET A BETTER NOW™.
Learn more about who we are, what we do, and how we do it at www.immunogen.com.
ABOUT ELAHERE (MIRVETUXIMAB SORAVTANSINE)
ELAHERE (mirvetuximab soravtansine-gynx) is a first-in-class ADC comprising a folate receptor alpha-binding antibody, cleavable linker, and the maytansinoid payload DM4, a potent tubulin inhibitor designed to kill the targeted cancer cells.
ELAHERE is indicated for the treatment of adult patients with folate receptor-alpha (FRα) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. Select patients for therapy based on an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
The prescribing information includes a boxed warning. ELAHERE can cause severe ocular toxicities, including visual impairment, keratopathy, dry eye, photophobia, eye pain, and uveitis. Conduct an ophthalmic exam including visual acuity and slit lamp exam prior to initiation of ELAHERE, every other cycle for the first 8 cycles, and as clinically indicated. Administer prophylactic artificial tears and ophthalmic topical steroids. Withhold ELAHERE for ocular toxicities until improvement and resume at the same or reduced dose. Discontinue ELAHERE for Grade 4 ocular toxicities.
Serious adverse reactions occurred in 31% of patients. The most common (≥2%) serious adverse reactions were intestinal obstruction (8%), ascites (4%), infection (3%), and pleural effusion (3%). Fatal adverse reactions occurred in 2% of patients, including small intestinal obstruction (1%) and pneumonitis (1%).The most common (≥20%) adverse reactions, including laboratory abnormalities, were vision impairment, fatigue, increased aspartate aminotransferase, nausea, increased alanine aminotransferase, keratopathy, abdominal pain, decreased lymphocytes, peripheral neuropathy, diarrhea, decreased albumin, constipation, increased alkaline phosphatase, dry eye, decreased magnesium, decreased leukocytes, decreased neutrophils, and decreased hemoglobin.
Please see full Prescribing Information,
including Boxed Warning for ELAHERE.
Source: ImmunoGen, Inc.
ImmunoGen's ovarian cancer medication accepted for EU review
Oct. 27, 2023 7:38 AM ET
By: Preeti Singh, SA News Editor
The European Medicines Agency (EMA) has accepted marketing authorization application for ImmunoGen's (NASDAQ:IMGN) cancer medication.
ELAHERE (mirvetuximab soravtansine-gynx), which is indicated for the treatment of adult patients with folate receptor-alpha (FRα) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, is now up for EMA review. The company hopes to bring this novel treatment to Europe as early as 2024.
The latest authorization is supported by positive data from the Phase 3 MIRASOL trial of ELAHERE in platinum-resistant ovarian cancer, where it showed statistically significant and clinically meaningful improvements in progression-free survival, objective response rate, and overall survival compared to investigator's choice of single-agent chemotherapy.
https://seekingalpha.com/news/4025624-immunogens-ovarian-cancer-medication-accepted-for-eu-review
DB-OTO
ELAHERE (MIRVETUXIMAB SORAVTANSINE)
ELAHERE (MIRVETUXIMAB SORAVTANSINE)
October 26, 2023 at 4:00 PM EDT
REGENERON SHARES PRELIMINARY RESULTS SHOWING GENE THERAPY IMPROVES AUDITORY RESPONSES IN CHILD WITH PROFOUND GENETIC HEARING LOSS
Global Phase 1/2 CHORD trial investigating otoferlin gene therapy (DB-OTO) represents Regeneron’s first auditory program and is currently enrolling patients
DB-OTO is part of a growing pipeline of genetic medicines for hearing loss and other therapeutic areas that are being advanced by the company
TARRYTOWN, N.Y., Oct. 26, 2023 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced preliminary, positive safety and efficacy results from the first patient (<2 years of age) dosed in the Phase 1/2 CHORD trial investigating otoferlin gene therapy (DB-OTO) in children with profound genetic hearing loss due to mutations of the otoferlin gene.
“The children who are being enrolled in CHORD are often born with profound hearing loss due to mutations in a single gene, otoferlin, which essentially turns off their auditory circuits,” said Professor Manohar Bance, M.B., an ear surgeon and principal trial investigator at Cambridge University Hospitals NHS Foundation Trust in the United Kingdom. “Cochlear implants are the current standard of care but are unable to replicate the full complexity and range of sound. With these very preliminary DB-OTO results, we now have encouraging evidence that this gene therapy may be able to help turn these auditory circuits back on. We look forward to following this child and others further to determine if DB-OTO gene therapy can restore clinically meaningful hearing as they are learning to interact with the world.”
In the trial, the child received an intracochlear injection of DB-OTO in one ear. At planned follow-ups, the child experienced improvements in auditory responses through week 6 compared to baseline, per auditory brainstem response (ABR) and behavioral (pure tone) audiometry. ABR, a clinically accepted physiologic measure of hearing sensitivity, is often absent in those with classic otoferlin-related hearing loss and was absent in both ears of the child at baseline. There were no concerning safety signals through week 6 following treatment.
Congenital hearing loss (hearing loss present at birth) is a significant unmet medical need with no approved pharmacologic treatment options that affects approximately 1.7 out of every 1,000 children born in the U.S. While hearing loss caused by mutations of the otoferlin gene is ultra-rare, the majority of permanent, congenital hearing loss cases diagnosed in developed countries are sensorineural and result from a single gene defect, making them suitable targets for gene therapy.
“These preliminary DB-OTO results provide early and encouraging proof-of-concept for the treatment of otoferlin-related hearing loss, as well as our pipeline of gene therapies to address more common forms of genetic hearing loss and other therapeutic areas,” said Christos Kyratsous, Ph.D., Senior Vice President of Research and co-head of Genetic Medicines at Regeneron. “The ongoing CHORD trial is our first clinical-stage auditory program, and we are incredibly grateful to the investigators and the family of this child for embarking on this breakthrough trial. We remain committed to advancing this research and hope these results mean that children with genetic hearing loss will eventually be able to benefit from the revolutionary promise of gene therapies like DB-OTO.”
DB-OTO was originally developed under a collaboration between Regeneron and Decibel Therapeutics that was initially established in 2017, with an extension announced in 2021. In September 2023, Regeneron acquired Decibel Therapeutics, cementing this long-standing collaboration. In addition to the DB-OTO development program, other clinical efforts include AAV.103 for people with GJB2-related hearing loss and AAV.104 for people with stereocilin (STRC)-related hearing loss.
The potential use of DB-OTO for otoferlin-related hearing loss is currently under clinical development, and its safety and efficacy have not been evaluated by any regulatory authority.
About the CHORD Trial
The CHORD trial (NCT# 05788536) is a Phase 1/2 first-in-human, multicenter, open-label trial to evaluate the safety, tolerability, and preliminary efficacy of DB-OTO in pediatric patients with otoferlin mutations.
Currently enrolling children across sites in the U.S., United Kingdom and Spain (<18 years of age; staggered by age in the U.S.), CHORD is being conducted in two parts. In the initial dose-escalation cohort (Part A), patients will receive a single intracochlear injection of DB-OTO in one ear, while in expansion cohort (Part B), patients will receive single intracochlear injections of DB-OTO in both ears at the selected dose from Part A.
Additional information about the trial, including enrollment, can be obtained by contacting clinicaltrials@decibeltx.com or 1-617-370-8701.
About DB-OTO
DB-OTO is an investigational cell-selective, adeno-associated virus (AAV) gene therapy designed to provide durable, physiological hearing to individuals with profound, congenital hearing loss caused by mutations of the otoferlin gene. The treatment aims to deliver a working copy of the faulty otoferlin gene using a modified, non-pathogenic virus that is delivered via an injection into the cochlea under general anesthesia (similar to the procedure used for cochlear implantation). In this gene therapy, the introduced otoferlin gene is under the control of a proprietary cell-specific Myo15 promoter, which is intended to restrict expression only to the cells that normally express otoferlin.
DB-OTO received Orphan Drug and Rare Pediatric Disease designations from the U.S. Food and Drug Administration in 2021. In the European Union, Orphan Drug Designation was granted by the European Medicines Agency in 2023.
About Regeneron
Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led for 35 years by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous FDA-approved treatments and product candidates in development, almost all of which were homegrown in our laboratories. Regeneron’s medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, hematologic conditions, infectious diseases and rare diseases.
Regeneron is accelerating and improving the traditional drug development process through its proprietary VelociSuite® technologies, such as VelocImmune®, which uses unique genetically humanized mice to produce optimized fully human antibodies and bispecific antibodies, and through ambitious research initiatives such as the Regeneron Genetics Center®, which is conducting one of the largest genetics sequencing efforts in the world.
For additional information about Regeneron, please visit www.regeneron.com or follow Regeneron on LinkedIn.
Source: Regeneron Pharmaceuticals, Inc.
Regeneron's hearing loss gene therapy shows positive outcomes in trial
Oct. 27, 2023 7:02 AM ET
Regeneron Pharmaceuticals, Inc. (REGN)
By: Preeti Singh, SA News Editor
Regeneron (NASDAQ:REGN) on Friday announced positive results from a trial investigating its otoferlin gene therapy (DB-OTO) in children with profound genetic hearing loss due to mutations of the otoferlin gene.
DB-OTO is an investigational cell-selective, adeno-associated virus gene therapy designed to provide durable, physiological hearing to individuals with congenital hearing loss caused by otoferlin gene mutations.
Preliminary data from the first patient (<2 years of age) dosed in the Phase 1/2 CHORD trial showed positive safety and efficacy results. The study marks Regeneron's (REGN) first auditory program and is currently enrolling patients.
Regeneron Pharmaceuticals, Inc. (REGN)
https://www.regeneron.com/pipeline-medicines/investigational-pipeline
Pemvidutide
ELAHERE (MIRVETUXIMAB SORAVTANSINE)
influenza vaccine (qIRV (22/23)) and bivalent BNT162b2
Altimmune Granted Fast Track Designation By FDA For Pemvidutide For The Treatment Of Non-Alcoholic Steatohepatitis (NASH)
October 26, 2023 at 7:30 AM EDT
GAITHERSBURG, Md., Oct. 26, 2023 (GLOBE NEWSWIRE) -- Altimmune, Inc. (Nasdaq: ALT), a clinical-stage biopharmaceutical company, today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to its clinical program investigating pemvidutide for the treatment of NASH.
NASH is a serious, potentially life-threatening condition that is a leading cause of liver failure and liver transplantation globally. NASH is a growing public health concern, and there are currently no approved treatments. The Fast Track designation is designed to facilitate the development and expedite the review of new drugs intended to treat serious conditions and address unmet medical needs.
“The FDA’s decision was informed by the results of Altimmune’s studies including its Phase 1b randomized, placebo-controlled study of pemvidutide in subjects with non-alcoholic fatty liver disease (NAFLD), which showed class-leading relative reductions in liver fat and non-invasive markers of hepatic inflammation and a favorable safety and tolerability profile,” said Vipin K. Garg, Ph.D., President and CEO of Altimmune. “The Fast Track designation reflects Altimmune’s commitment to patients with NASH and efforts to find safe and effective treatments for this condition.”
The efficacy and safety of pemvidutide in NASH are being evaluated in IMPACT, a Phase 2b randomized, placebo-controlled biopsy-driven trial that is being conducted at approximately 60 sites in the U.S. Approximately 190 subjects with and without diabetes are being enrolled. Key efficacy endpoints are NASH resolution and fibrosis improvement at 24 weeks of treatment, with subjects followed for an additional 24 weeks to a total of 48 weeks for safety and biomarker responses. In addition to IMPACT, the efficacy and safety of pemvidutide in obesity is being evaluated in MOMENTUM, a Phase 2b, randomized, placebo-control trial that is being conducted at approximately 30 sites in the U.S. An interim analysis of 160 subjects completing 24 weeks of treatment was reported in Q1 2023, and full results of 391 subjects receiving up to 48 weeks of treatment are expected later this quarter.
About Pemvidutide
Pemvidutide is a novel, investigational, peptide-based GLP-1/glucagon dual receptor agonist in development for the treatment of obesity and NASH. Activation of the GLP-1 and glucagon receptors is believed to mimic the complementary effects of diet and exercise on weight loss, with GLP-1 suppressing appetite and glucagon increasing energy expenditure. Glucagon is also recognized as having direct effects on hepatic fat metabolism, leading to rapid reductions in levels of liver fat. Pemvidutide incorporates the EuPort™ domain, a proprietary technology that increases its serum half-life for weekly dosing while likely slowing the entry of pemvidutide into the bloodstream, which may improve its tolerability.
https://altimmune.com/pemvidutide/
About Altimmune
Altimmune is a clinical-stage biopharmaceutical company focused on developing innovative next-generation therapeutics for the treatment of obesity and liver diseases. The Company’s lead product candidate, pemvidutide, is a GLP-1/glucagon dual receptor agonist that is being developed for the treatment of obesity and NASH. In addition, Altimmune is developing HepTcell™, an immunotherapeutic designed to achieve a functional cure for chronic hepatitis B. For more information, please visit www.altimmune.com.
Follow @Altimmune, Inc. on LinkedIn
Follow @AltimmuneInc on Twitter
Source: Altimmune, Inc
Altimmune gains after FDA fast track status for NASH therapy
Oct. 26, 2023 8:38 AM ET
By: Dulan Lokuwithana, SA News Editor1 Comment
- Altimmune (NASDAQ:ALT) advanced ~9% pre-market Thursday after announcing that the U.S. FDA granted the Fast Track designation for the company’s GLP-1 receptor agonist, pemvidutide, as a treatment for the liver disorder Non-Alcoholic Steatohepatitis (NASH).
- https://seekingalpha.com/news/4024890-altimmune-stock-fda-fast-track-status-nash-drug
- Altimmune, Inc. (ALT)
- https://altimmune.com/pemvidutide/
- https://altimmune.com/
influenza vaccine (qIRV (22/23)) and bivalent BNT162b2
influenza vaccine (qIRV (22/23)) and bivalent BNT162b2
influenza vaccine (qIRV (22/23)) and bivalent BNT162b2
Pfizer and BioNTech Announce Positive Topline Data for mRNA-based Combination Vaccine Program Against Influenza and COVID-19
26 October 2023
- Lead formulations evaluated in the Phase 1/2 study demonstrated robust immune responses to influenza A, influenza B, and SARS-CoV-2 strains
- Safety profile of the mRNA-based combination vaccine candidates consistent with the companies’ COVID-19 vaccine
- The companies plan to start a pivotal Phase 3 trial in the coming months
NEW YORK and MAINZ, GERMANY, October 26, 2023 — Pfizer Inc. (NYSE: PFE) and BioNTech SE (Nasdaq: BNTX) today announced positive topline results from a Phase 1/2 study (NCT05596734) evaluating the safety, tolerability and immunogenicity of mRNA-based combination vaccine candidates for influenza and COVID-19 among healthy adults 18 to 64 years of age. In the clinical trial, the vaccine candidates were compared to a licensed influenza vaccine and the companies’ Omicron BA.4/BA.5-adapted bivalent COVID-19 vaccine given at the same visit. The data from the trial showed that the companies' lead formulations demonstrated robust immune responses to influenza A, influenza B, and SARS-CoV-2 strains.
“We are encouraged by these early results in our Phase 1/2 study of our combination vaccine candidates against influenza and COVID-19. This vaccine has the potential to lessen the impact of two respiratory diseases with a single injection and may simplify immunization practices for providers, patients, and healthcare systems all over the world,” said Annaliesa Anderson, PhD, FAAM, Senior Vice President and Head, Vaccine Research and Development at Pfizer. “mRNA-based vaccines have demonstrated their ability to induce robust antibody and T-cell responses, and we look forward to starting Phase 3 clinical development. Today’s results are an important achievement towards our ambition of providing a broad portfolio of respiratory combination vaccines.”
“Studies of confirmed viral infections suggest that COVID-19 adopts a seasonal pattern with peaks in fall and winter, similar to other respiratory diseases. Co-infections as well as consecutive respiratory infection during this period can further increase the risk of severe illness,” said Prof. Ugur Sahin, MD, CEO and Co-founder of BioNTech. “Combination vaccines have the potential to become a mainstay of routine vaccination against respiratory diseases, especially for the vaccination of populations who have a higher risk of severe illness.”
The topline results of the ongoing trial demonstrated that the combination formulations evaluated had a safety profile consistent with the safety profile of the companies’ COVID-19 vaccine. Immunogenicity results induced by lead formulations in the companies’ phase 1/2 trial showed point estimates for Geometric Mean Titer (GMT) ratios that were consistent with the criteria applied to regulatory approved vaccines against the respective influenza and SARS-CoV-2 strains. Point estimates for GMT ratios for all matched influenza vaccine strains with lead formulations were >1 relative to a licensed Quadrivalent Influenza Vaccine (QIV) given concomitantly with the Pfizer-BioNTech COVID-19 vaccine. A pivotal Phase 3 trial evaluating these lead formulations is expected to be initiated in the coming months. Data from the Phase 1/2 trial will be published in a peer-reviewed journal.
Pfizer and BioNTech previously announced that their mRNA-based combination vaccine candidate for influenza and COVID-19 received Fast Track Designation from the U.S. Food and Drug Administration (FDA).
About Respiratory Diseases
SARS-CoV-2 led to a global pandemic with more than 6.5 million deathsi and a severe socio-economic burden worldwide.ii While vaccinations can help address the disease, COVID-19 is expected to remain a circulating, severe respiratory disease, requiring adjustments of vaccines to variants of concern. This is reminiscent of influenza, another respiratory disease that requires repeated vaccinations due to its genomic instability resulting in modifications of the surface protein hemagglutinin. Each year, influenza results in up to one billion infections, five million hospitalizations, and 650,000 deaths worldwide.iii
INDICATION, AUTHORIZED USE AND IMPORTANT SAFETY INFORMATION
INDICATION
COMIRNATY® (COVID-19 Vaccine, mRNA) is a vaccine for use in people 12 years of age and older to protect against coronavirus disease 2019 (COVID-19).
You can also report side effects to Pfizer Inc. at www.pfizersafetyreporting.com or by calling 1-800-438-1985.
Please click here for full Prescribing Information for COMIRNATY.
AUTHORIZED USE
Pfizer-BioNTech COVID-19 Vaccine (2023-2024 Formula)* is FDA authorized under Emergency Use Authorization (EUA) to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 6 months through 11 years of age.
*Hereafter referred to as Pfizer-BioNTech COVID-19 Vaccine
EMERGENCY USE AUTHORIZATION
Pfizer-BioNTech COVID-19 Vaccine has not been approved or licensed by FDA, but has been authorized for emergency use by FDA, under an EUA to prevent Coronavirus Disease 2019 (COVID-19) for use in individuals aged 6 months through 11 years of age. The emergency use of this product is only authorized for the duration of the declaration that circumstances exist justifying the authorization of emergency use of the medical product under Section 564(b) (1) of the FD&C Act unless the declaration is terminated or authorization revoked sooner.
Please click here for Pfizer-BioNTech COVID-19 Vaccine Healthcare Providers Fact Sheet and Vaccine Recipient and Caregiver EUA Fact Sheet.
About Pfizer: Breakthroughs That Change Patients’ Lives
At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 170 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.Pfizer.com. In addition, to learn more, please visit us on www.Pfizer.com and follow us on Twitter at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.
About BioNTech
Biopharmaceutical New Technologies (BioNTech) is a next generation immunotherapy company pioneering novel therapies for cancer and other serious diseases. The Company exploits a wide array of computational discovery and therapeutic drug platforms for the rapid development of novel biopharmaceuticals. Its broad portfolio of oncology product candidates includes individualized and off-the-shelf mRNA-based therapies, innovative chimeric antigen receptor (CAR) T cells, several protein-based therapeutics, including bispecific immune checkpoint modulators, targeted cancer antibodies and antibody-drug conjugate (ADC) therapeutics, as well as small molecules. Based on its deep expertise in mRNA vaccine development and in-house manufacturing capabilities, BioNTech and its collaborators are developing multiple mRNA vaccine candidates for a range of infectious diseases alongside its diverse oncology pipeline. BioNTech has established a broad set of relationships with multiple global pharmaceutical collaborators, including Duality Biologics, Fosun Pharma, Genentech, a member of the Roche Group, Genevant, Genmab, OncoC4, Regeneron, Sanofi and Pfizer.
For more information, please visit www.BioNTech.com.
Pfizer, BioNTech post early-stage data for COVID-flu combo shot
Oct. 26, 2023 8:11 AM ET
By: Dulan Lokuwithana, SA News Editor2 Comments
- Pfizer (NYSE:PFE) and BioNTech (NASDAQ:BNTX) announced Thursday plans to run a pivotal Phase 3 trial for their mRNA-based combination vaccine candidates for influenza and COVID-19 after a Phase 1/2 study generated positive data.
- In the trial for healthy adults aged 18–64, the investigators compared the combo vaccine with the companies’ BA.4/BA.5-adjusted bivalent COVID shot and an unnamed licensed influenza vaccine.
- https://seekingalpha.com/news/4024859-pfizer-biontech-post-early-stage-data-covid-flu-shot
- Pfizer Inc. (PFE), BNTX
- https://www.biontech.com/int/en/home.html
- https://www.pfizer.com/
- https://www.fda.gov/vaccines-blood-biologics/comirnaty
Anavex®3-71
influenza vaccine (qIRV (22/23)) and bivalent BNT162b2
Anavex®3-71
Anavex Life Sciences Reports New Publication in Scientific Journal Demonstrating the Potential of
Anavex®3-71 Prevent Cognitive Decline in Alzheimer's Disease
ANAVEX®3-71 treatment prevents cognitive impairment, reduces amyloid, and neuroinflammation even after a long drug washout
ANAVEX®3-71 halts neurodegeneration and prevents cognitive decline in a transgenic Alzheimer’s disease model
Confirmation of Anavex’s upstream SIGMAR1 oral small molecule drug platform in Alzheimer’s disease
NEW YORK – October 25, 2023
Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq: AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders, including Alzheimer's disease, Parkinson's disease, Rett syndrome, and other central nervous system (CNS) diseases, today reported a new peer-reviewed publication in the journal Neurobiology of Aging, titled ”Early treatment with an M1 and sigma-1 receptor agonist prevents cognitive decline in a transgenic rat model displaying Alzheimer-like amyloid pathology”, featuring the orally available small molecule ANAVEX®3-71 (AF710B).[1]
This study ascertains potential disease-modifying properties of ANAVEX®3-71 (AF710B) on Alzheimer’s disease (AD) pathology and could be a drug candidate for a once daily oral preventive strategy.
ANAVEX®3-71 activates the sigma-1 receptor (SIGMAR1) and the M1 muscarinic receptor (M1R). Data suggests that activation of SIGMAR1 results in the restoration of homeostatic function within the body and is pivotal to restoring neural cell balance and promoting neuroplasticity.[2] Previous studies of ANAVEX®3-71 have demonstrated its potential to treat Alzheimer’s disease (AD)-like pathology at advanced stages of disease in animal models.[3],[4]
ANAVEX®3-71, an orally available small molecule, has already successfully completed a Phase 1 human clinical trial demonstrating good safety and tolerability signals at all doses studied.[5]
In this publication, transgenic rats that develop AD-like symptoms as they age were treated with ANAVEX®3-71 for 7-months before they developed amyloid plaques, followed by a 4-week washout period. Preventative treatment with ANAVEX®3-71 reduced levels of insoluble and soluble amyloid-beta as well as plaque deposition in the aging cortex and hippocampus, areas heavily impacted by AD. Notably, the reduction in amyloid pathology was accompanied by a reduction in inflammatory glial activity which is connected to the disease cascade in AD and other dementias. ANAVEX®3-71 treatment downregulated the proinflammatory IL-1β and IL-6 cytokines, which are known to be associated with AD. Additionally, ANAVEX®3-71 treatment boosted brain derived neurotrophic factor (BDNF) which reinforces the evidence that ANAVEX®3-71 protects neurons.
Importantly, these beneficial effects were sustained after a month-long drug washout. This differentiates ANAVEX®3-71 from other therapeutic approaches and suggests long-lasting, disease-modifying effects on AD pathology. This long-lasting effect was also observed in previous animal studies of ANAVEX®3-71 at advanced stages of the disease.
The publication is consistent with previous scientific findings, including with the more advanced drug candidate ANAVEX®2-73 (blarcamesine), which successfully completed a Phase 2b/3 study in early Alzheimer’s disease, that SIGMAR1 activation acts upstream of multiple contributors to AD and other dementias including but not limited to mitochondrial dysfunction[6], oxidative stress[7], impaired autophagy[8] and that amyloid pathology can be reduced by M1R stimulation[9].
The authors of the paper (Neurobiology of Aging 132 (2023) 220–232) from the Laboratory of Professor Cuello, MD at McGill University concluded: “This involved study could be considered as proof of principle for preventive therapies in Alzheimer’s disease and illustrates that this category of compounds, or similar effective agents, could be considered as candidates for preventive strategies to slow down the early amyloid pathology in Alzheimer’s disease, a condition that is increasingly diagnosed at preclinical stages.”
“This publication is a confirmation of the scientific depth of Anavex’s upstream SIGMAR1 platform, which gives hope to the Alzheimer’s disease community, especially for the patients, families and caregivers who fight everyday against this devastating disease for a potential disease-modifying drug candidate with a once daily oral preventive strategy. We also look forward to presenting in an upcoming major publication the complete dataset of the Phase 2b/3 Alzheimer’s disease trial of ANAVEX®2-73 (blarcamesine), a potential next-generation precision medicine convenient once daily oral Alzheimer’s disease treatment,” said Christopher U Missling, PhD, President and Chief Executive Officer of Anavex. "We are also on track within our neurodevelopmental precision medicine Rett syndrome program to release top-line data of ANAVEX®2-73-RS-003 Phase 2/3 EXCELLENCE pediatric clinical trial in the current quarter of 2023.”
About Anavex Life Sciences Corp.
Anavex Life Sciences Corp. (Nasdaq: AVXL) is a publicly traded biopharmaceutical company dedicated to the development of novel therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders, including Alzheimer's disease, Parkinson's disease, Rett syndrome, and other central nervous system (CNS) diseases, pain, and various types of cancer. Anavex's lead drug candidate, ANAVEX®2-73 (blarcamesine), has successfully completed a Phase 2a and a Phase 2b/3 clinical trial for Alzheimer's disease, a Phase 2 proof-of-concept study in Parkinson's disease dementia, and both a Phase 2 and a Phase 3 study in adult patients with Rett syndrome. ANAVEX®2-73 is an orally available drug candidate that restores cellular homeostasis by targeting sigma-1 and muscarinic receptors. Preclinical studies demonstrated its potential to halt and/or reverse the course of Alzheimer's disease. ANAVEX®2-73 also exhibited anticonvulsant, anti-amnesic, neuroprotective, and anti-depressant properties in animal models, indicating its potential to treat additional CNS disorders, including epilepsy. The Michael J. Fox Foundation for Parkinson's Research previously awarded Anavex a research grant, which fully funded a preclinical study to develop ANAVEX®2-73 for the treatment of Parkinson's disease. ANAVEX®3-71, which targets sigma-1 and M1 muscarinic receptors, is a promising clinical stage drug candidate demonstrating disease-modifying activity against the major hallmarks of Alzheimer's disease in transgenic (3xTg-AD) mice, including cognitive deficits, amyloid, and tau pathologies. In preclinical trials, ANAVEX®3-71 has shown beneficial effects on mitochondrial dysfunction and neuroinflammation. Further information is available at www.anavex.com. You can also connect with the Company on Twitter, Facebook, Instagram, and LinkedIn.
Anavex gains on preventative effects of Alzheimer’s drug
Oct. 25, 2023 3:18 PM ET
Anavex Life Sciences Corp. (AVXL)
By: Dulan Lokuwithana, SA News Editor2 Comments
- Anavex Life Sciences (NASDAQ:AVXL) announced pre-clinical data on Wednesday to highlight the potential of its Alzheimer’s candidate, ANAVEX®3-71, in preventing the cognitive decline associated with the memory-robbing disease. Shares of the New York-based biotech gained in reaction.
- Citing pre-clinical data published in the journal Neurobiology of Aging, Anavex (AVXL) said that rats with Alzheimer’s-like symptoms showed a decline in the disease biomarker amyloid beta after receiving ANAVEX 3-71.
- https://seekingalpha.com/news/4024309-anavex-stock-gains-data-alzheimers-drug
- Anavex Life Sciences Corp. (AVXL)
- https://www.anavex.com/therapeutic-candidates
- https://www.anavex.com/
BXCL501
influenza vaccine (qIRV (22/23)) and bivalent BNT162b2
Anavex®3-71
BioXcel Therapeutics Announces Positive Findings from Independent Third Party Audit of Data Integrity at TRANQUILITY II Phase 3 Trial Site
Oct 25, 2023 PDF Version
No evidence of misconduct or fraud found beyond instance previously reported1
No findings identified that impact data integrity
Company believes audit findings support reliability of positive TRANQUILITY II trial data and potential sNDA submission
NEW HAVEN, Conn., Oct. 25, 2023 (GLOBE NEWSWIRE) -- BioXcel Therapeutics, Inc. (Nasdaq: BTAI), a biopharmaceutical company utilizing artificial intelligence to develop transformative medicines in neuroscience, today announced positive findings from an independent third party audit of the data from a single site1 in its TRANQUILITY II Phase 3 trial.
Conducted by a well-regarded regulatory and quality consulting firm, the independent audit consisted of a comprehensive review of records from over 50% of subjects enrolled at the single trial site to identify any additional instance of misconduct or fraud2 and to evaluate data integrity and reliability for eligibility, safety, and efficacy data. This sample size provides 95% confidence that the data reviewed is a representative sample. Following an extensive review, the team of auditors did not identify any findings that they believe impact the data reliability or integrity, nor did they find any evidence of additional misconduct or fraud. Based on these findings, BioXcel Therapeutics believes that the positive, statistically significant TRANQUILITY II trial data announced in June 2023 potentially support a supplemental new drug application (sNDA) for BXCL501 for the acute treatment of agitation associated with dementia in probable Alzheimer’s disease.
“We believe these results of an audit by a respected, independent firm validate the integrity of data from the single site in question and add to the body of clinical evidence we intend to include in our sNDA submission,” said Vimal Mehta, Ph.D., CEO of BioXcel Therapeutics. “We recently had a Type B/Breakthrough meeting with the FDA to discuss our plans for the development of BXCL501 for the acute treatment of agitation associated with dementia in probable Alzheimer’s disease. We expect to receive the FDA meeting minutes in the first half of November, and intend to provide an update on additional steps for the TRANQUILITY program and a potential sNDA in our upcoming third quarter financial results.”
About BioXcel Therapeutics, Inc.
BioXcel Therapeutics, Inc. (Nasdaq: BTAI) is a biopharmaceutical company utilizing artificial intelligence to develop transformative medicines in neuroscience. The Company’s drug re-innovation approach leverages existing approved drugs and/or clinically validated product candidates together with big data and proprietary machine learning algorithms to identify new therapeutic indications. For more information, please visit bioxceltherapeutics.com.
Source: BioXcel Therapeutics, Inc.
BT BIOXCEL THERAPEUTICS is a registered trademark of BioXcel Therapeutics, Inc.
All other trademarks are the properties of their respective owners.
Copyright © 2023, BioXcel Therapeutics, Inc. All rights reserved.
BioXcel gains as independent audit validates Alzheimer’s trial
Oct. 25, 2023 7:31 AM ET
BioXcel Therapeutics, Inc. (BTAI)
By: Dulan Lokuwithana, SA News Editor
- BioXcel Therapeutics (NASDAQ:BTAI) added ~41% pre-market Wednesday after announcing that an independent third-party audit found no data integrity issues in the company’s TRANQUILITY II Phase 3 trial for Alzheimer’s candidate BXCL501.
- Shares of the New Haven, Connecticut, biotech fell in June despite reporting positive findings from TRANQUILITY II amid concerns about how a study site, which accounted for approximately 40% of subjects, conducted the trial.
- https://seekingalpha.com/news/4023920-bioxcel-stock-gains-audit-validates-alzheimers-trial
- BioXcel Therapeutics, Inc. (BTAI)
- https://www.bioxceltherapeutics.com/our-pipeline/
- https://www.bioxceltherapeutics.com/
BMS-986278
autogene cevumeran (BNT122, RO7198457) with the anti-PD-L1 immune checkpoint inhibitor atezolizumab
autogene cevumeran (BNT122, RO7198457) with the anti-PD-L1 immune checkpoint inhibitor atezolizumab
Bristol Myers Squibb Announces U.S. FDA Breakthrough Therapy Designation for Investigational LPA1 Antagonist for Progressive Pulmonary Fibrosis
10/24/2023CATEGORY:
Designation is based on results from the progressive pulmonary fibrosis cohort of the Phase 2 study assessing the safety and efficacy of BMS-986278 treatment versus placebo
PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for BMS-986278, a potential first-in-class, oral, lysophosphatidic acid receptor 1 (LPA1) antagonist, for the treatment of progressive pulmonary fibrosis (PPF), a devastating, life-threatening illness. Currently, there is only one therapy approved for the treatment of PPF.
The Breakthrough Therapy Designation is based on results from the global, randomized Phase 2 study that assessed the safety and efficacy of BMS-986278 treatment versus placebo in people living with idiopathic pulmonary fibrosis (IPF) and PPF. Stable background use of antifibrotics in the IPF cohort and/or select immunosuppressives in the PPF cohort were allowed. Results from the PPF cohort showed that 26 weeks of treatment with a twice-daily 60 mg dose of BMS-986278 resulted in a 69% relative reduction in the rate of decline in percent predicted forced vital capacity versus placebo. Treatment effect was consistent with or without background therapy and BMS-986278 was well tolerated, with rates of adverse events similar to placebo and low discontinuation rates. These findings were presented at the European Respiratory Society (ERS) 2023 International Congress in September 2023.
Breakthrough Therapy Designation is an FDA program intended to expedite the development and review of medicines for serious or life-threatening diseases with preliminary clinical evidence that the investigational therapy may offer substantial improvement on at least one clinically significant endpoint over available therapies.
“People living with pulmonary fibrosis face deteriorating lung function, worsening respiratory symptoms and reduced quality of life, which can ultimately lead to respiratory failure and death,” said Roland Chen, MD, senior vice president and head, Immunology, Cardiovascular and Neuroscience Development, Bristol Myers Squibb. “The FDA’s Breakthrough Therapy Designation underscores the potential of BMS-986278 as an innovative, first-in-class treatment that may redefine the standard of care for progressive pulmonary fibrosis.”
In addition to this Breakthrough Therapy Designation for PPF, the U.S. FDA has also previously granted BMS-986278 fast-track designation and orphan drug designation for the treatment of IPF. Bristol Myers Squibb is continuing the development of BMS-986278 with the global Phase 3 ALOFT program for PPF (NCT06025578) and IPF (NCT06003426).
About BMS-986278
BMS-986278 is a potential first-in-class, oral, small molecule lysophosphatidic acid receptor 1 (LPA1) antagonist currently being evaluated as a novel antifibrotic treatment for patients with idiopathic pulmonary fibrosis and progressive pulmonary fibrosis. Increased LPA levels and activation of LPA1 are involved in the pathogenesis of pulmonary fibrosis. A preclinical in vitro and in vivo study found that antagonizing LPA1 may be beneficial in treating lung injury and fibrosis.
About the BMS-986278 Phase 2 Study
The Phase 2 study was a global, randomized study in which parallel cohorts of patients with idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) received 30 mg or 60 mg of BMS-986278 or matched placebo orally twice-daily. The study consisted of a 26-week placebo-controlled treatment period, an optional 26-week active treatment extension period and a 4-week post-treatment follow-up period. Patients were permitted to take background antifibrotics in the IPF cohort and background antifibrotics and/or immunosuppressants in the PPF cohort. The primary endpoint was rate of change in percent predicted forced vital capacity (ppFVC) from baseline to Week 26 in the IPF cohort. ppFVC compares the observed FVC to that which is expected for a healthy person of the same age, gender, race and height. Rate of change in ppFVC from baseline through Week 26 in the PPF cohort was a key secondary endpoint. Patients who met prespecified blood pressure reduction criteria were to receive a dose reduction to 10 mg of BMS-986278 or matching placebo twice-daily.
More information can be found on www.clinicaltrials.gov (NCT04308681).
About Pulmonary Fibrosis
Pulmonary fibrosis is a chronic, life-threatening interstitial lung disease (ILD) that occurs when lung tissue becomes damaged and scarred, impacting how lungs function. Progressive pulmonary fibrosis (PPF) is the preferred term to describe patients who have an ILD with a progressive fibrotic phenotype. Idiopathic pulmonary fibrosis (IPF) is the most common type of progressive fibrosing ILD. As an idiopathic disease, there is no identifiable cause, and as of 2021, more than 700,000 adults are living with IPF globally.
Many people living with PPF and IPF are physically impaired, experience a progressive decline in lung function, have difficulty performing simple daily activities due to breathlessness and require continuous supplemental oxygen to ease the burden of normal breathing.
IPF is a fatal disease with a median survival time of 3-5 years following diagnosis and 5-year survival rate of approximately 45%; PPF has shown a similar prognosis. Innovation in treatment has been limited with few new therapies approved in nearly 10 years.
Bristol Myers Squibb: Pioneering Paths Forward in Immunology to Transform Patients’ Lives
Bristol Myers Squibb is inspired by a single vision – transforming patients’ lives through science. For people living with immune-mediated diseases, the debilitating reality of enduring chronic symptoms and disease progression can take a toll on their physical, emotional and social well-being, making simple tasks and daily life a challenge. Driven by our deep understanding of the immune system that spans over 20 years of experience, and our passion to help patients, the company continues to pursue pathbreaking science with the goal of delivering meaningful solutions that address unmet needs in rheumatology, gastroenterology, dermatology and pulmonology. We follow the science, aiming to tailor therapies to individual needs, improve outcomes and expand treatment options by working to identify mechanisms with the potential to achieve long-term remission – and perhaps even cures – in the future. By building partnerships with researchers, patients and caregivers to deliver innovative treatments, Bristol Myers Squibb strives to elevate patient care to new standards and deliver what matters most – the promise of living a better life.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.
Source: Bristol Myers Squibb
Multimedia Files:
Download:Download original 99 KB 1505 x 211Download thumbnail 5 KB 200 x 28Download lowres 15 KB 480 x 67Download square 7 KB 250 x 250
BMY Dividend History
https://www.nasdaq.com/market-activity/stocks/bmy/dividend-history
autogene cevumeran (BNT122, RO7198457) with the anti-PD-L1 immune checkpoint inhibitor atezolizumab
autogene cevumeran (BNT122, RO7198457) with the anti-PD-L1 immune checkpoint inhibitor atezolizumab
autogene cevumeran (BNT122, RO7198457) with the anti-PD-L1 immune checkpoint inhibitor atezolizumab
BioNTech Expands Late-Stage Clinical Oncology Portfolio with Initiation of further Phase 2 Trial with mRNA-based Individualized Neoantigen Specific Immunotherapy in New Cancer Indication
19 October 2023
- Initiation of Phase 2 builds on data from a Phase 1 clinical trial evaluating the safety and tolerability of autogene cevumeran (BNT122, RO7198457) in combination with the anti-PD-L1 immune checkpoint inhibitor atezolizumab and standard of care chemotherapy in patients with resected pancreatic ductal adenocarcinoma (PDAC)
- The Phase 2 trial is expected to enroll approximately 260 patients with PDAC at clinical trial sites initially in the United States, followed by Europe and Asia Pacific region
- This is the third later-stage trial with a product candidate based on BioNTech’s individualized cancer vaccine platform iNeST aimed at treating patients with solid tumors in a high unmet need indication
MAINZ, Germany, October 19, 2023 (GLOBE NEWSWIRE) – BioNTech SE (Nasdaq: BNTX, “BioNTech” or “the Company”) today announced that the first patient has been treated in a Phase 2 clinical trial evaluating the mRNA-based individualized neoantigen-specific immunotherapy (iNeST) candidate autogene cevumeran (also known as BNT122, RO7198457) in resected pancreatic ductal adenocarcinoma (PDAC). PDACs are solid tumors with a poor prognosis reflected in a 5-year overall survival rate of only 8-10%1,2, high recurrence rates3 and limited treatment options.
Autogene cevumeran, which is being jointly developed by BioNTech and Genentech, a member of the Roche Group, is a therapeutic, individualized cancer vaccine candidate encoding up to 20 patient-specific cancer mutations selected for their proficiency to serve as neoantigens. Neoantigens are proteins that are produced by cancer cells that differ from the proteins produced by healthy cells. The investigational treatment aims to induce a neoantigen-directed immune response against the patient’s individual tumor.
The open-label, multicenter, randomized Phase 2 trial (NCT05968326), sponsored by Genentech, will evaluate the efficacy and safety of autogene cevumeran in combination with anti-PD-L1 immune checkpoint inhibitor atezolizumab and chemotherapy compared to the current standard-of-care chemotherapy (mFOLFIRINOX). The Phase 2 study is expected to enroll 260 patients with resected PDAC, who have not received prior systemic anti-cancer treatment and showed no evidence of disease after surgery. The trial will be conducted at various sites in the United States, followed by Europe and Asia Pacific region. The primary endpoint is disease-free survival. Secondary endpoints include disease-free survival rates, overall survival, overall survival rate and safety profile.
The Phase 2 initiation is based on data from an investigator-initiated, single-center Phase 1 trial (NCT04161755) evaluating the combination of autogene cevumeran (BNT122, RO7198457), atezolizumab, and chemotherapy (mFOLFIRINOX) in patients with resected PDAC. Preliminary data of the Phase 1 trial were presented at the American Society of Clinical Oncology (“ASCO”) Annual Meeting in June 2022 and complete study results were recently published in Nature, demonstrating a favorable safety profile and substantial vaccine-induced T cell responses that may correlate with delayed PDAC recurrence.
“PDAC is a tumor type for which the relapse rate after surgery is extremely high at nearly 80%. The recent Phase 1 study has shown that individualized neoantigen vaccination is feasible for this tumor type with low mutational burden and an immunosuppressive microenvironment3. We have been evaluating cancer mutations since the start of the first clinical trial based on our mRNA technology in 2014 with the hypothesis that they could be suitable targets for individualized cancer vaccines,” said Prof. Özlem Türeci, M.D., Co-Founder and Chief Medical Officer at BioNTech. “The Phase 2 study will provide additional data whether our approach with autogene cevumeran has the potential to provide a benefit for patients in this high unmet medical need setting. Our aim is to prevent relapses and thus ensure that the disease is managed at the earliest possible stage.”
Autogene cevumeran (BNT122, RO7198457) is part of BioNTech’s and Genentech’s worldwide strategic collaboration to develop, manufacture and commercialize novel mRNA-based, individualized cancer vaccines, which was initiated in 2016. Autogene cevumeran is currently being evaluated in various solid tumor indications, including a Phase 2 trial (NCT04486378) in the adjuvant treatment of surgically resected colorectal cancer, a Phase 2 proof-of-concept study (NCT03815058) of autogene cevumeran in combination with pembrolizumab in the first-line treatment of advanced melanoma and a Phase 1a/b trial in locally advanced or metastatic tumors (NCT03289962). The Phase 2 trial of autogene cevumeran in patients with PDAC is the third later-stage trial based on BioNTech’s individualized cancer vaccine platform iNeST.
About resected pancreatic ductal adenocarcinoma (PDAC)
PDAC is amongst the leading causes of cancer-related deaths in the United States4 with approximately 90% of patients dying within two years of their diagnosis5. A combination of surgical removal and systemic cytotoxic chemotherapy has shown to improve clinical outcomes, however, even with surgical resection, the relapse rate remains high, and the 5-year overall survival is only approximately 20%6 in patients who undergo surgery followed by adjuvant chemotherapy (“ACT”) and only 8-10%1,2 in those who do not receive ACT. Thus, there is a high unmet medical need for novel therapies for patients with resected PDAC. The individualized neoantigen specific immunotherapy (“iNeST”) candidate autogene cevumeran (BNT122, RO7198457) provides a novel treatment strategy aimed to induce de-novo immune responses against cancer-specific neoantigens, recognize residual cancer cells and to prevent relapse.
About iNeST (individualized Neoantigen Specific immunoTherapy)
iNeST immunotherapies are individualized cancer therapies tailored to a specific patient’s tumor. They contain unmodified, pharmacologically optimized mRNA encoding up to 20 patient-specific neoantigens, identified using real-time next generation sequencing and bioinformatic neoantigen discovery. Neoantigens are proteins that are produced by cancer cells that differ from the proteins produced by healthy cells and are recognized by immune cells. The mRNA is encapsulated in BioNTech’s proprietary intravenous RNA-lipoplex delivery formulation which is designed to enhance stability as well as enable targeted delivery to dendritic cells. By analyzing each patient’s tumor, BioNTech is able to identify the cancer mutations that may act as neoantigens. Each individual cancer vaccine encodes for neoantigen candidates with the highest likelihood to help the immune system to recognize the cancer. For this purpose, BioNTech has developed an on-demand manufacturing process, following Good Manufacturing Practice (GMP) conditions.
An iNeST Fact Sheet and images from the iNeST manufacturing process are available in the newsroom section on BioNTech’s website at this link.
About BioNTech
Biopharmaceutical New Technologies (BioNTech) is a next generation immunotherapy company pioneering novel therapies for cancer and other serious diseases. The Company exploits a wide array of computational discovery and therapeutic drug platforms for the rapid development of novel biopharmaceuticals. Its broad portfolio of oncology product candidates includes individualized and off-the-shelf mRNA-based therapies, innovative chimeric antigen receptor (CAR) T cells, several protein-based therapeutics, including bispecific immune checkpoint modulators, targeted cancer antibodies and antibody-drug conjugate (ADC) therapeutics, as well as small molecules. Based on its deep expertise in mRNA vaccine development and in-house manufacturing capabilities, BioNTech and its collaborators are developing multiple mRNA vaccine candidates for a range of infectious diseases alongside its diverse oncology pipeline. BioNTech has established a broad set of relationships with multiple global pharmaceutical collaborators, including Duality Biologics, Fosun Pharma, Genentech, a member of the Roche Group, Genevant, Genmab, OncoC4, Regeneron, Sanofi and Pfizer.
For more information, please visit www.BioNTech.com.
BioNTech starts another Phase 2 trial for mRNA-based cancer shot
Oct. 19, 2023 12:10 PM ET
BioNTech SE (BNTX), RHHBY, RHHBFMRK
By: Dulan Lokuwithana, SA News Editor
- BioNTech (NASDAQ:BNTX) announced Thursday it dosed the first patient in another Phase 2 trial evaluating its messenger-RNA-based cancer vaccine, autogene cevumeran, developed with the Genentech unit of Swiss pharma giant Roche (OTCQX:RHHBY).
- https://seekingalpha.com/news/4022100-biontech-starts-another-phase-2-trial-mrna-based-cancer-shot
- BioNTech SE (BNTX), RHHBY, RHHBF
- https://www.biontech.com/int/en/home.html
NTLA-2001
autogene cevumeran (BNT122, RO7198457) with the anti-PD-L1 immune checkpoint inhibitor atezolizumab
NTLA-2001
Intellia Therapeutics Announces FDA Clearance of Investigational New Drug (IND) Application to Initiate a Pivotal Phase 3 Trial of NTLA-2001 for the Treatment of Transthyretin (ATTR) Amyloidosis with Cardiomyopathy
October 18, 2023 at 7:00 AM EDT
- NTLA-2001 is the first-ever investigational in vivo CRISPR-based gene editing therapy cleared to enter late-stage clinical development
CAMBRIDGE, Mass., Oct. 18, 2023 (GLOBE NEWSWIRE) -- Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading clinical-stage genome editing company focused on developing potentially curative therapies leveraging CRISPR-based technologies, today announced that the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) application for NTLA-2001 for the treatment of transthyretin (ATTR) amyloidosis with cardiomyopathy. The global Phase 3 study of NTLA-2001, an in vivo CRISPR-based gene editing candidate, is expected to initiate by year-end 2023.
“The FDA clearance of the NTLA-2001 IND application allows us to initiate a pivotal Phase 3 trial in the United States, marking the first in vivo CRISPR-based candidate to begin late-stage clinical development. This is another important step forward for Intellia and our collaborator, Regeneron, as we aim to establish a new standard of care for the treatment of ATTR amyloidosis,” said Intellia President and Chief Executive Officer John Leonard, M.D. “We are thrilled to further advance NTLA-2001 and our pipeline of investigational gene editing therapies as we embark on a new era in medicine. We look forward to sharing additional information about the Phase 3 study at our upcoming quarterly earnings webcast, being held on Thursday, November 9.”
About NTLA-2001
Based on Nobel Prize-winning CRISPR/Cas9 technology, NTLA-2001 could potentially be the first single-dose treatment for ATTR amyloidosis. NTLA-2001 is the first investigational CRISPR therapy candidate to be administered systemically, or through a vein, to edit genes inside the human body. Intellia’s proprietary non-viral platform deploys lipid nanoparticles to deliver to the liver a two-part genome editing system: guide RNA specific to the disease-causing gene and messenger RNA that encodes the Cas9 enzyme, which carries out the precision editing. Robust preclinical and clinical data, showing deep and long-lasting transthyretin (TTR) reduction following in vivo inactivation of the target gene, supports NTLA-2001’s potential as a single-administration therapeutic. Intellia leads development and commercialization of NTLA-2001 as part of a multi-target discovery, development and commercialization collaboration with Regeneron. The global Phase 1 trial is an open-label, multi-center, two-part study of NTLA-2001 in adults with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) or transthyretin amyloidosis with cardiomyopathy (ATTR-CM). The trial is now closed for enrollment. Visit clinicaltrials.gov (NCT04601051) for more details.
About Transthyretin (ATTR) Amyloidosis
Transthyretin amyloidosis, or ATTR amyloidosis, is a rare, progressive and fatal disease. Hereditary ATTR (ATTRv) amyloidosis occurs when a person is born with mutations in the TTR gene, which causes the liver to produce structurally abnormal transthyretin (TTR) protein with a propensity to misfold. These damaged proteins build up as amyloid in the body, causing serious complications in multiple tissues, including the heart, nerves and digestive system. ATTRv amyloidosis predominantly manifests as polyneuropathy (ATTRv-PN), which can lead to nerve damage, or cardiomyopathy (ATTRv-CM), which can lead to heart failure. Some individuals without the genetic mutation produce non-mutated, or wild-type TTR proteins that become unstable over time, misfolding and aggregating in disease-causing amyloid deposits. This condition, called wild-type ATTR (ATTRwt) amyloidosis, primarily affects the heart. There are an estimated 50,000 people worldwide living with ATTRv amyloidosis and between 200,000 and 500,000 people with ATTRwt amyloidosis.
About Intellia Therapeutics
Intellia Therapeutics, a leading clinical-stage genome editing company, is developing novel, potentially curative therapeutics leveraging CRISPR-based technologies. To fully realize the transformative potential of CRISPR-based technologies, Intellia is pursuing two primary approaches. The company’s in vivo programs use intravenously administered CRISPR as the therapy, in which proprietary delivery technology enables highly precise editing of disease-causing genes directly within specific target tissues. Intellia’s ex vivo programs use CRISPR to create the therapy by using engineered human cells to treat cancer and autoimmune diseases. Intellia’s deep scientific, technical and clinical development experience, along with its robust intellectual property portfolio, have enabled the company to take a leadership role in harnessing the full potential of genome editing to create new classes of genetic medicine. Learn more at intelliatx.com. Follow us on X (formerly known as Twitter) @intelliatx.
Source: Intellia Therapeutics, Inc.
Intellia cleared to start Phase 3 trial for gene editing drug
Oct. 18, 2023 7:45 AM ET
Intellia Therapeutics, Inc. (NTLA), REGN
By: Dulan Lokuwithana, SA News Editor2 Comments
- Intellia Therapeutics (NASDAQ:NTLA) said Wednesday that the U.S. FDA cleared the company’s Investigational New Drug (IND) application for NTLA-2001, allowing it to start a pivotal Phase 3 trial for the gene editing candidate in transthyretin (ATTR) amyloidosis with cardiomyopathy.
- Accordingly, the biotech and its partner, Regeneron Pharmaceuticals (NASDAQ:REGN), expect to start a global Phase 3 study for NTLA-2001 later this year for patients with cardiomyopathy linked to ATTR amyloidosis.
- https://seekingalpha.com/news/4021448-intellia-cleared-start-phase-3-trial-gene-editing-drug?mailingid=33063195&messageid=2900&serial=33063195.5857&utm_campaign=rta-stock-news&utm_content=link-1&utm_medium=email&utm_source=seeking_alpha&utm_term=33063195.5857
- Intellia Therapeutics, Inc. (NTLA), REGN
- https://www.intelliatx.com/
- https://www.intelliatx.com/pipeline/
SAGE-718
XPHOZAH® (tenapanor)
NTLA-2001
October 18, 2023
Sage Therapeutics Announces U.S. Food and Drug Administration Granted SAGE-718 Orphan Drug Designation for the Treatment of Huntington’s Disease
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Oct. 18, 2023-- Sage Therapeutics, Inc. (Nasdaq: SAGE), a biopharmaceutical company leading the way to create a world with better brain health, today announced the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation (ODD) to SAGE-718 for the treatment of Huntington’s disease (HD). SAGE-718 is in development as a potential oral therapy for cognitive disorders associated with NMDA receptor dysfunction. Multiple clinical studies are ongoing with SAGE-718 across several disease areas, including two placebo-controlled Phase 2 studies and a Phase 3 open-label safety study in the potential lead indication of HD-related cognitive impairment, as well as Phase 2 placebo-controlled studies in mild cognitive impairment (MCI) associated with Parkinson’s disease (PD) and MCI and mild dementia due to Alzheimer’s disease (AD).
“Huntington’s disease is a devastating condition that often affects patients in their prime years, and it can significantly impact a patient’s ability to live independently. Cognitive impairment is one of the most underrecognized aspects of this disease,” said Laura Gault, M.D., Ph.D., Chief Medical Officer, Sage Therapeutics. “There are currently no approved treatments to address cognitive impairment for people with HD and a growing sense of urgency among researchers and people living with HD to address cognitive impairment early so that patients can maintain independence longer. The ODD designation from the FDA provides continued momentum in our efforts to help patients and their families impacted by this aspect of HD.”
Orphan drug designation is granted by the FDA Office of Orphan Products Development to assist and encourage companies to develop safe and effective therapies for the treatment of rare diseases and disorders. Under the Orphan Drug Act, the FDA may provide grant funding towards clinical trial costs, tax advantages, FDA user-fee benefits, and the potential for seven years of market exclusivity in the United States for the drug in the orphan indication following drug approval by the FDA. The approval of an orphan designation request does not alter the standard regulatory requirements and process for obtaining marketing approval. For more information about orphan designation, please visit the FDA website at www.fda.gov.
SAGE-718 previously received Fast Track Designation from the FDA for HD, and orphan drug designation for HD by the European Medicines Agency.
About SAGE-718
SAGE-718, a first-in-class investigational NMDA receptor positive allosteric modulator (PAM), is in development as a potential oral therapy for cognitive disorders associated with NMDA receptor dysfunction, including HD, PD and AD. Sage is advancing a clinical program for SAGE-718 with multiple ongoing placebo-controlled Phase 2 studies across multiple disease areas, including its potential lead indication, cognitive impairment associated with HD, as well as cognitive impairment due to AD and PD. The Company is also conducting a Phase 3 open-label safety study in HD cognitive impairment.
About Huntington’s disease and cognition
HD is a rare, inherited neurodegenerative disease that progresses over time and affects up to an estimated 40,000 adults in the U.S. each year. Cognitive impairment can severely affect people with HD. There are currently no treatment options available to improve the cognitive effects of the disease.
About Sage Therapeutics
Sage Therapeutics is a biopharmaceutical company fearlessly leading the way to create a world with better brain health. Our mission is to pioneer solutions to deliver life-changing brain health medicines, so every person can thrive. For more information, please visit http://www.sagerx.com.
View source version on businesswire.com: https://www.businesswire.com/news/home/20231018464957/en/
Source: Sage Therapeutics, Inc.
Sage granted FDA orphan tag for Huntington’s disease therapy
Oct. 18, 2023 11:28 AM ET
Sage Therapeutics, Inc. (SAGE)
By: Dulan Lokuwithana, SA News Editor1 Comment
- Sage Therapeutics (NASDAQ:SAGE) announced Wednesday that the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation for its NMDA receptor modulator SAGE-718 as a treatment for Huntington’s disease, a neurodegenerative condition.
- An oral experimental therapy, SAGE-718, is currently undergoing studies for cognitive disorders linked to NMDA receptor dysfunction.
- https://seekingalpha.com/news/4021587-sage-granted-fda-orphan-tag-huntingtons-disease-therapy
- Sage Therapeutics, Inc. (SAGE)
- https://www.sagerx.com/
- https://www.sagerx.com/programs-research/pipeline
XPHOZAH® (tenapanor)
XPHOZAH® (tenapanor)
XPHOZAH® (tenapanor)
FDA Approves XPHOZAH® (tenapanor), a First-in-Class Phosphate Absorption Inhibitor
XPHOZAH has been approved to reduce serum phosphorus in adults with chronic kidney disease (CKD) on dialysis as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy
XPHOZAH blocks the absorption of phosphate with a single tablet taken twice daily
Commercial launch underway with product expected to be available in November
Ardelyx to host conference call tomorrow, October 18 at 8:00 am ET
WALTHAM, Mass., Oct. 17, 2023 (GLOBE NEWSWIRE) -- Ardelyx, Inc. (Nasdaq: ARDX), a biopharmaceutical company founded with a mission to discover, develop and commercialize innovative, first-in-class medicines that meet significant unmet medical needs, today announced that the U.S. Food and Drug Administration (FDA) has approved XPHOZAH® (tenapanor), the first and only phosphate absorption inhibitor, indicated to reduce serum phosphorus in adults with chronic kidney disease (CKD) on dialysis as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy. XPHOZAH is a single tablet taken twice daily that offers a first-in-class mechanism of action that blocks phosphate absorption through its primary pathway.
“The approval of XPHOZAH is an important milestone for patients on dialysis, their families and the nephrology care community, as it represents a new mechanism and new option for patients who, despite treatment with phosphate binders, continue to have elevated phosphorus. It is also a significant accomplishment for everyone at Ardelyx,” said Mike Raab, president and chief executive officer of Ardelyx. “Since the founding of the company in 2007, we have been steadfast in our commitment to the kidney community, and today’s approval reinforces the compelling clinical profile and potential benefit that XPHOZAH may provide for so many patients. This therapy was born in our labs in 2008, and to now see it becoming available for patients is truly a testament to the dedication, outstanding execution, and sense of mission of the Ardelyx team. This approval is also a tribute to the patients, families, physicians and clinical trial personnel who participated in the development of XPHOZAH. There is a high level of anticipation and enthusiasm for the launch of XPHOZAH from the kidney community, and our world-class team will enter the marketplace well positioned with a first-in-class product.”
Dr. Glenn Chertow, professor of medicine, Stanford University, added, “Hyperphosphatemia management has been a persistent clinical challenge, as the majority of patients receiving maintenance dialysis are unable to consistently achieve target serum phosphate concentrations despite treatment with phosphate binders. XPHOZAH is not a phosphate binder. XPHOZAH is a phosphate absorption inhibitor. In patients not adequately responding to phosphate binder therapy, XPHOZAH has been shown to help increase the proportion of patients achieving target serum phosphate concentrations. I believe XPHOZAH can advance the care of patients with hyperphosphatemia, providing a new treatment option with a complementary mechanism of action.”
Clinical Data Supporting XPHOZAH
FDA approval of XPHOZAH is based on a comprehensive development program, including a diverse population of more than 1,000 patients in three Phase 3 clinical trials evaluating the efficacy and safety of XPHOZAH, as monotherapy and in combination with phosphate binder therapy, all of which met their primary and key secondary endpoints (PHREEDOM, BLOCK and AMPLIFY). Data from the three clinical trials demonstrated that XPHOZAH significantly reduced elevated serum phosphorus in patients receiving maintenance hemodialysis.
Diarrhea, which occurred in 43 to 53 percent of patients, was the only adverse reaction reported in at least five percent of XPHOZAH-treated patients with CKD on dialysis across trials. The majority of diarrhea events in the XPHOZAH-treated patients were reported to be mild-to-moderate in severity and resolved over time, or with dose reduction. Diarrhea was typically reported soon after initiation but could occur at any time during treatment with XPHOZAH. Severe diarrhea was reported in five percent of XPHOZAH-treated patients in these trials.
Ardelyx also completed two open-label clinical trials (OPTIMIZE and NORMALIZE) to evaluate different options for integrating XPHOZAH into clinical practice.
Ardelyx Commitment to Patient Access
Ardelyx is committed to setting new standards in product innovation and to setting new standards for patient support. Ardelyx will integrate XPHOZAH into its established patient services program, ArdelyxAssist™. ArdelyxAssist is an innovative, digital-forward patient services program that provides access and affordability support for patients, with integration into medical office work processes and connectivity to patients and health care providers.
Conference Call Details
The company will host a conference call tomorrow, October 18, 2023, at 8:00 am ET to discuss today's announcement. To participate in the conference call, please dial (844) 481-2838 (domestic) or (412) 317-1858 (international) and ask to be joined into the Ardelyx call. A webcast of the call can also be accessed by visiting the Investor page of the company's website, www.ardelyx.com, and will be available on the website for 30 days following the call.
About XPHOZAH® (tenapanor)
XPHOZAH, discovered and developed by Ardelyx, is a first-in-class, phosphate absorption inhibitor with a differentiated mechanism of action that acts locally in the gut to inhibit the sodium hydrogen exchanger 3 (NHE3), thereby reducing phosphate absorption through the paracellular pathway, the primary pathway of phosphate absorption. XPHOZAH is a single tablet, taken twice daily. Diarrhea was the most common side effect experienced by patients taking XPHOZAH in clinical trials. Please see additional full Prescribing Information.
About Hyperphosphatemia
Hyperphosphatemia is a serious condition, defined as resulting in elevated levels of phosphate in the blood, which affects the vast majority of the 550,000 patients in the United States with chronic kidney disease (CKD) on maintenance dialysis. The kidneys are responsible for eliminating excess phosphate and as kidney function declines, phosphate is not adequately eliminated from the body. As a result, hyperphosphatemia is a nearly universal condition among people with CKD on maintenance dialysis, with internationally recognized KDIGO treatment guidelines that recommend lowering elevated phosphate levels toward the normal range (2.5-4.5mg/dL).
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
XPHOZAH is contraindicated in:
- Pediatric patients under 6 years of age
- Patients with known or suspected mechanical gastrointestinal obstruction
INDICATION
XPHOZAH (tenapanor), 30 mg BID, is indicated to reduce serum phosphorus in adults with chronic kidney disease (CKD) on dialysis as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy.
For additional safety information, please see full Prescribing Information.
About Ardelyx, Inc.
Ardelyx was founded with a mission to discover, develop and commercialize innovative, first-in-class medicines that meet significant unmet medical needs. Ardelyx has two commercial products approved in the United States, IBSRELA® (tenapanor) and XPHOZAH® (tenapanor) as well as early-stage pipeline candidates. Ardelyx has agreements for the development and commercialization of tenapanor outside of the U.S. Kyowa Kirin has received approval for PHOZEVEL® (tenapanor) for hyperphosphatemia in Japan. A New Drug Application for tenapanor for hyperphosphatemia has been submitted in China with Fosun Pharma. Knight Therapeutics commercializes IBSRELA in Canada. For more information, please visit https://ardelyx.com/ and connect with us on X (formerly known as Twitter), LinkedIn and Facebook.
Source: Ardelyx, Inc.
Ardelyx granted FDA nod for kidney disease therapy
Oct. 18, 2023 7:26 AM ET
By: Dulan Lokuwithana, SA News Editor7 Comments
Update 07.26 AM EST: Adds latest share price move
- The U.S. Food and Drug Administration (FDA) has approved Xphozah (tenapanor), an oral phosphate absorption inhibitor developed by Ardelyx (NASDAQ:ARDX), to reduce serum phosphorus in adults with chronic kidney disease (CKD) on dialysis.
- Accordingly, the Xphozah will be available in the U.S. for twice-daily use as an add-on therapy for those patients with an inadequate response to phosphate binders or who are intolerant of phosphate binder therapy.
- https://seekingalpha.com/news/4021409-ardelyx-wins-fda-nod-kidney-disease-drug
- Ardelyx, Inc. (ARDX)
- https://xphozah-hcp.com/
- https://ardelyx.com/
Mirikizumab
XPHOZAH® (tenapanor)
XPHOZAH® (tenapanor)
Lilly's Mirikizumab Helped Patients with Crohn's Disease Achieve Long-Term Remission in Phase 3 Trial
October 12, 2023
Mirikizumab demonstrated clinical remission and endoscopic response for patients with moderately to severely active Crohn's disease through 52 weeks
The study achieved the coprimary endpoints and all major secondary endpoints versus placebo
This successful Phase 3 trial will be the basis of global regulatory submissions for Crohn's disease
INDIANAPOLIS, Oct. 12, 2023 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) announced today that mirikizumab (an investigational interleukin-23p19 antagonist) met the co-primary and all major secondary endpoints compared to placebo in VIVID-1, a Phase 3 study evaluating the safety and efficacy of mirikizumab for the treatment of adults with moderately to severely active Crohn's disease. The double-blind, treat-through trial included mirikizumab, placebo and active control (ustekinumab) arms.
Crohn's disease is a form of inflammatory bowel disease (IBD) that can cause systemic inflammation manifested as abdominal pain, diarrhea, fever and weight loss. It can lead to intestinal obstruction, fibrosis and other complications.
In VIVID-1, all patients in the active treatment arms from the 12-week induction period continued with their original therapy into the maintenance portion of the study up to Week 52. Placebo patients who did not achieve clinical response at Week 12 (nonresponders) were switched to blinded mirikizumab treatment.
The study included co-primary endpoints, which were:
- Proportion of participants achieving clinical response by patient reported outcomes (PRO)* at Week 12 and clinical remission (defined as a Crohn's Disease Activity Index [CDAI] Total Score <150) at Week 52 compared to placebo
- In the mirikizumab arm, a statistically higher proportion achieved clinical response at Week 12 and clinical remission at Week 52 compared to placebo (45.4% versus 19.6%, p<0.000001)
- Proportion of participants achieving clinical response by PRO at Week 12 and endoscopic response (defined as ≥50% reduction from baseline in Simple Endoscopic Score – Crohn's Disease [SES-CD] Total Score) at Week 52 compared to placebo
- In the mirikizumab arm, a statistically higher proportion achieved clinical response at Week 12 and endoscopic response at Week 52 compared to placebo (38.0% versus 9.0%, p<0.000001)
In this double-blind placebo and active controlled trial – the first reported for an IL-23p19 antibody – mirikizumab achieved all individual and composite major secondary endpoints at Week 52 compared to placebo (p<0.000001). Notably, of the patients who received mirikizumab, 54.1% achieved clinical remission at Week 52 compared to 19.6% of patients who received placebo (p<0.000001). In addition, for the endpoint of clinical remission (defined as CDAI <150), mirikizumab demonstrated non-inferiority versus ustekinumab (non-inferiority margin of 10%). For the endpoint of endoscopic response (≥50% reduction from baseline in SES-CD Total Score) at Week 52, mirikizumab did not achieve superiority to ustekinumab although results with mirikizumab were numerically higher, particularly in the non-multiplicity controlled bio-failed population.
"I'm excited by these results, which showed more than half of patients on mirikizumab achieved clinical remission as measured by CDAI at one year. Furthermore, mirikizumab demonstrated robust efficacy across subgroups and particularly in patients for whom prior biologic therapy had failed," said Lotus Mallbris, M.D., Ph.D., senior vice president of immunology development at Lilly. "Many people are seeking relief from their uncontrolled Crohn's disease, including those still experiencing symptoms with available therapies such as TNF inhibitors. Helping patients achieve long-term clinical remission is what inspires us to develop innovative treatments for inflammatory bowel diseases, including Crohn's disease and ulcerative colitis."
The overall safety was consistent with the known safety profile of mirikizumab. The frequency of serious adverse events was greater in placebo than mirikizumab. The most common treatment-emergent adverse events reported among patients treated with mirikizumab were COVID-19, anemia, arthralgia, headache and upper respiratory tract infection. Additional adverse events of interest reported among patients treated with mirikizumab included infections, injection-site reactions, hypersensitivity, liver enzyme elevations, depression and suicidal thoughts. No major adverse cardiac events were observed in the mirikizumab arm.
With these data, Lilly plans to submit a marketing application for mirikizumab in Crohn's disease to the Food and Drug Administration (FDA), followed by submissions to other regulatory agencies around the world, in 2024. Full data from the Phase 3 VIVID program will be disclosed in publications and at upcoming congresses.
*Clinical response by PRO is defined as ≥30% decrease in stool frequency and/or abdominal pain, and neither score worse than baseline.
About Mirikizumab
Mirikizumab is an interleukin-23p19 antagonist that is currently indicated for the treatment of moderately to severely active ulcerative colitis (UC) in Japan, Germany, the United Kingdom and Canada. Mirikizumab selectively targets the p19 subunit of IL-23 and inhibits the IL-23 pathway. Inflammation due to over-activation of the IL-23 pathway plays a critical role in the pathogenesis of UC and Crohn's disease.
About Lilly
Lilly unites caring with discovery to create medicines that make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help more than 51 million people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges, redefining diabetes care, treating obesity and curtailing its most devastating long-term effects, advancing the fight against Alzheimer's disease, providing solutions to some of the most debilitating immune system disorders, and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news or follow us on Facebook, Instagram, Twitter and LinkedIn. P-LLY
View original content to download multimedia:https://www.prnewswire.com/news-releases/lillys-mirikizumab-helped-patients-with-crohns-disease-achieve-long-term-remission-in-phase-3-trial-301954471.html
SOURCE Eli Lilly and Company
LLY Dividend History
https://www.nasdaq.com/market-activity/stocks/lly/dividend-history
https://seekingalpha.com/symbol/LLY
https://www.lilly.com/discovery/research-and-scientific-discovery
biotecHOPE™ 2023
ELREXFIOTM (elranatamab-bcmm) injection
ELREXFIOTM (elranatamab-bcmm) injection
ELREXFIOTM (elranatamab-bcmm) injection
Pfizer’s ELREXFIO™ Receives Positive CHMP Opinion for Relapsed and Refractory Multiple Myeloma
Friday, October 13, 2023 - 06:00amShare
ELREXFIO is an off-the-shelf (ready-to-use) BCMA-directed immunotherapy that induces deep and durable responses with a manageable tolerability profile, as well as convenient subcutaneous dosing
NEW YORK, OCTOBER 13, 2023 – Pfizer Inc. (NYSE:PFE) today announced the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion, recommending marketing authorization for ELREXFIO™ (elranatamab). ELREFXIO is a targeted immunotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma (RRMM) who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody and have demonstrated disease progression on the last therapy. ELREXFIO was evaluated through the EMA PRIME scheme, a program that supports the development of medicines that target an unmet medical need, and through Orphan Drug Designation. The European Commission (EC), which authorizes central marketing approvals in the European Union (EU), will take a legally binding decision based on the CHMP recommendation and is expected to make a final decision in the coming months. If granted, the decision will apply to all 27 EU member states plus Iceland, Liechtenstein, and Norway.
“People with multiple myeloma are prone to relapse and resistance, and they often have no choice but to recycle treatment classes as they go through successive rounds of therapy. Efficacious and tolerable new treatments are desperately needed, especially in later-line care,” said MagnetisMM clinical trial investigator Mohamad Mohty, M.D., Ph.D., Professor of Hematology and Head of the Hematology and Cellular Therapy Department at the Saint-Antoine Hospital and Sorbonne University, Paris, France. “With its generally manageable safety profile and clinically meaningful and durable responses among hard-to-treat patients, ELREXFIO offers a new tool in the fight against relapse and resistance.”
ELREXFIO is a subcutaneously delivered B-cell maturation antigen (BCMA)-CD3-directed bispecific antibody (BsAb) immunotherapy that binds to BCMA on myeloma cells and CD3 on T-cells, bringing them together and activating the T-cells to kill myeloma cells. The CHMP recommendation is based on data from cohort A of the Phase 2 MagnetisMM-3 study (NCT04649359) showing meaningful responses among heavily pretreated RRMM patients (at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody) who received ELREXFIO as their first BCMA-directed therapy. In an analysis of these patients (n=123) at 15 months, the objective response rate was 61%, with a 72% probability of maintaining a response at 15 months. These data were recently published in Nature Medicine.
The results from MagnetisMM-3 also established once-every-other-week dosing with ELREXFIO for responding patients after 24 weeks of weekly therapy, which means less time at the clinic and potentially greater long-term treatment tolerability. Among responding patients who switched to every-other-week dosing at least six months prior to the data cut-off date (n=50), 80% maintained or improved their response after the switch, with 38% attaining a complete response (CR) or better after the switch.
“We discovered and developed ELREXFIO as an off-the-shelf (ready-to-use) fixed-dose option with a subcutaneous administration to be broadly accessible as quickly as possible,” said Chris Boshoff, Chief Oncology Research and Development Officer and Executive Vice President, Pfizer. “We’re excited at the possibility of ELREXFIO reaching people with multiple myeloma that have relapsed and refractory disease across Europe. We’re also exploring the use of ELREXFIO in earlier lines of therapy to potentially help even more people with multiple myeloma.”
The extensive MagnetisMM clinical development program is investigating ELREXFIO’s use across the entire spectrum of patients with multiple myeloma, from those with newly diagnosed multiple myeloma to RRMM. Ongoing registrational-intent trials are exploring ELREXFIO both as monotherapy and in combination with standard or novel therapies. These include MagnetisMM-5 in the double-class exposed setting, MagnetisMM-6 in newly diagnosed patients who are ineligible for stem cell transplant, and MagnetisMM-7 in newly diagnosed patients after transplant.
The most common adverse reactions to ELREXFIO are cytokine release syndrome (CRS) (58%), anemia (54%), neutropenia (45%), fatigue (44%), upper respiratory tract infection (39%), injection site reaction (38%), diarrhoea (38%), pneumonia (37%), thrombocytopenia (36%), lymphopenia (30%), decreased appetite (27%), rash (26%), joint pain (arthralgia) (25%), fever (pyrexia) (27%), hypokalemia (23%), nausea (21%), and dry skin (21%). Serious adverse reactions are pneumonia (31%), sepsis (15%), CRS (13%), anemia (6%), upper respiratory tract infection (5%), urinary tract infection (3%), febrile neutropenia (3%), dyspnea (2%), and pyrexia (2%).
ELREXFIO received approval from the U.S. Food and Drug Administration (FDA) in August 2023 under the FDA’s Accelerated Approval Program, which allows for earlier approval of drugs that treat serious conditions and fill an unmet medical need. The FDA review was also conducted under Project Orbis, a framework for the concurrent submission and review of oncology drugs among international partners to potentially expedite approvals. ELREXFIO has been approved under Project Orbis in Switzerland, and four other countries (Brazil, Canada, Australia, and Singapore) are participating. The UK Medicines and Healthcare Products Regulatory Agency (MHRA) has granted ELREXFIO Innovative Medicine Designation and the Innovation Passport, for the treatment of MM.
About Multiple Myeloma
Multiple myeloma (MM) is an aggressive and currently incurable blood cancer that affects plasma cells made in the bone marrow. Healthy plasma cells make antibodies that help the body fight infection.1 MM is the second most common type of blood cancer, with over 50,000 new cases diagnosed annually in Europe and 176,000 new cases diagnosed globally each year.2,3 About half of those diagnosed with MM won’t survive beyond five years, and most will receive four or more lines of therapy due to relapse.4 While disease trajectory varies for each person, relapses are nearly inevitable.5 Real-world evidence shows that people with RRMM often become resistant to the three main classes of treatment – proteasome inhibitors, immunomodulatory agents and anti-CD38 monoclonal antibodies – after just a few rounds of therapy, and re-treating with these classes was common.6 The goal of therapy for people with RRMM is to achieve disease control with acceptable toxicity and improved quality of life.7
U.S. INDICATION
What is ELREXFIO?
ELREXFIO is a prescription medication used to treat adults with multiple myeloma who have already received at least four treatment regimens (including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody) to treat their multiple myeloma, and their cancer has come back or did not respond to prior treatment.
ELREXFIO is approved based on patient response. Data are not yet available to show if ELREXFIO improves survival or symptoms.
It is not known if ELREXFIO is safe and effective in children.
Please read full Prescribing Information, including BOXED WARNING, for ELREXFIO.
About Pfizer Oncology
At Pfizer Oncology, we are committed to advancing medicines wherever we believe we can make a meaningful difference in the lives of people living with cancer. Today, we have an industry-leading portfolio of 24 approved innovative cancer medicines and biosimilars across more than 30 indications, including breast, genitourinary, colorectal, blood, and lung cancers, as well as melanoma.
About Pfizer: Breakthroughs That Change Patients’ Lives
At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 170 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.Pfizer.com. In addition, to learn more, please visit us on www.Pfizer.com and follow us on Twitter at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.
DISCLOSURE NOTICE: The information contained in this release is as of October 13, 2023. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.
This release contains forward-looking information about ELREXFIO (elranatamab), a B-cell maturation antigen (BCMA) CD3-directed bispecific antibody, including its potential benefits, pending regulatory applications and the MagnetisMM clinical program to potentially expand ELREXFIO into earlier lines of treatment, as monotherapy and in combination with standard or novel therapies, and Pfizer Oncology, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, uncertainties regarding the commercial success of ELREXFIO; the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from our clinical studies; whether and when drug applications for any potential indications for ELREXFIO may be filed in any particular jurisdictions; whether and when the EMA may approve the pending application for ELREXFIO for the treatment of people with relapsed and refractory multiple myeloma (RRMM) and whether and when regulatory authorities in any jurisdictions may approve any such other applications that may be pending or filed for ELREXFIO, which will depend on myriad factors, including making a determination as to whether the product's benefits outweigh its known risks and determination of the product's efficacy and, if approved, whether ELREXFIO will be commercially successful; decisions by regulatory authorities impacting labeling, manufacturing processes, safety and/or other matters that could affect the availability or commercial potential of ELREXFIO; uncertainties regarding the impact of COVID-19 on Pfizer’s business, operations and financial results; and competitive developments.
A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2022 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information and Factors That May Affect Future Results,” as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at www.sec.gov and www.pfizer.com.
Pfizer's blood cancer drug Elrexfio backed for conditional approval in EU
Oct. 13, 2023 10:37 AM ET
By: Ravikash, SA News Editor15 Comments
A committee of the European Medicines Agency (EMA) recommended the conditional approval of Pfizer's (NYSE:PFE) Elrexfio to treat a type of blood cancer called multiple myeloma.
VELSIPITY™ (etrasimod)
ELREXFIOTM (elranatamab-bcmm) injection
ELREXFIOTM (elranatamab-bcmm) injection
U.S. FDA Approves Pfizer’s VELSIPITY™ for Adults with Moderately to Severely Active Ulcerative Colitis (UC)
Friday, October 13, 2023 - 09:00am
- Approval of oral, once-daily VELSIPITY based on favorable safety and efficacy data from the ELEVATE UC Phase 3 trials
NEW YORK--(BUSINESS WIRE)-- Pfizer Inc. (NYSE: PFE) announced today that the U.S. Food and Drug Administration (FDA) has approved VELSIPITY™ (etrasimod), an oral, once-daily, selective sphingosine-1-phosphate (S1P) receptor modulator for adults with moderately to severely active ulcerative colitis (UC). The approved recommended dose for VELSIPITY is 2 mg.
UC is a chronic and often debilitating condition1 that affects an estimated 1.25 million people in the United States.2 Symptoms of UC can include chronic diarrhea with blood and mucus, abdominal pain, and urgency.3,4 However, its impact can span beyond the physical to other aspects of life due to the chronic and unpredictable nature of symptoms.5,6
“VELSIPITY provides adults living with moderately to severely active UC the opportunity to achieve steroid-free remission with an oral, once-daily pill that has a favorable benefit-risk profile,” said Angela Hwang, Chief Commercial Officer and President of Global Biopharmaceuticals Business, Pfizer. “VELSIPITY’s FDA approval today marks a significant milestone for UC patients who need new treatments for this chronic condition and are ready to start advanced therapy.”
The U.S. FDA approval was based on results from the ELEVATE UC Phase 3 registrational program (ELEVATE UC 52 and ELEVATE UC 12) that evaluated the safety and efficacy of VELSIPITY 2 mg once-daily on clinical remission in UC patients who had previously failed or were intolerant to at least one conventional, biologic, or Janus kinase (JAK) inhibitor therapy. Nearly two-thirds of patients in ELEVATE UC 52 and ELEVATE UC 12 were naïve to biologic or JAK inhibitor therapy, and these studies were also the only studies for advanced therapies for ulcerative colitis to include patients with isolated proctitis. Both studies achieved all primary and key secondary efficacy endpoints, with a favorable safety profile consistent with previous studies of VELSIPITY.
“Because of the unpredictable nature of UC, people living with the disease can cycle through several different treatments over time. Patients may also be apprehensive about using injectable therapies, like biologics,” said Dr. Michael Chiorean, Co-Director of the IBD Center at Swedish Medical Center and an investigator in the ELEVATE Registrational Program. “It’s important to have new, effective options like VELSIPITY for those patients who may require an advanced treatment option and prefer the convenience of a once-daily pill. VELSIPITY is a proven advanced treatment with a favorable benefit-risk profile.”
“UC can affect patients differently and many people living with this disease struggle with ongoing symptoms,” said Michael Osso, President and CEO of the Crohn’s & Colitis Foundation. “The introduction of a new treatment for UC could increase options for patients, and we look forward to seeing the impact of VELSIPITY for patients across the U.S.”
In ELEVATE UC 52, clinical remission was 27.0% for patients receiving VELSIPITY compared to 7.0% for patients receiving placebo at week 12 (20.0% differential, P˂.001) and was 32.0% compared to 7.0% at week 52 (26.0% differential, P=˂.001). In ELEVATE UC 12, clinical remission was achieved among 26.0% of patients receiving VELSIPITY compared to 15.0% of patients receiving placebo (11.0% differential, P=<.05). All key secondary efficacy endpoints were met at week 12, including endoscopic improvement and mucosal healing. The safety of VELSIPITY was consistent with previous studies, with the most common adverse reactions being headache, elevated liver tests, and dizziness (incidence ≥ 5%).
Full results from the program were published by The Lancet in March 2023.
View the full Prescribing Information. If it is not currently available via this link, it will be visible as soon as possible as we work to finalize the document. Please check back for the full information shortly.
About VELSIPITY™ (Etrasimod)
VELSIPITY is a once-daily, oral, sphingosine 1-phosphate (S1P) receptor modulator that selectively binds with S1P receptor subtypes 1, 4, and 5.
Regulatory applications for VELSIPITY in ulcerative colitis have been submitted to countries around the world for review, including Canada, Australia, Mexico, Russia, Switzerland, and Singapore. The European Medicines Agency (EMA) has accepted the Marketing Authorization Application (MAA) for VELSIPITY, with a decision anticipated in the beginning of 2024.
About ELEVATE UC 52 and ELEVATE UC 12
ELEVATE UC 52 and ELEVATE UC 12 are pivotal trials that are part of the ELEVATE UC Phase 3 registrational program.7
ELEVATE UC 52 is a randomized, double-blind, placebo-controlled trial that utilized a treat-through design comprising of a 12-week induction period followed by a 40-week maintenance period. Subjects were randomized to VELSIPITY or placebo and continued on treatment without re-randomization for the entire duration of the study. Beginning at week 12, all patients could continue their randomized treatment; patients whose disease had not improved or had worsened compared to baseline could discontinue and, if eligible, enroll in an open-label extension study. The primary objective of this trial was to assess the safety and efficacy of etrasimod 2 mg once daily on clinical remission after both 12 and 52 weeks. The primary endpoint is based on the 3-domain, modified Mayo score (MMS). In ELEVATE UC 52, clinical remission was 27.0% for patients receiving etrasimod compared to 7.0% for patients receiving placebo at week 12 (20.0% differential, P˂.001) and was 32.0% compared to 7.0% at week 52 (26.0% differential, P≤˂.001). Statistically significant improvements were attained in all key secondary endpoints, including endoscopic improvement and mucosal healing at weeks 12 and 52, and corticosteroid-free remission and sustained clinical remission at week 52.
ELEVATE UC 12 is a randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of etrasimod 2 mg once-daily in subjects with moderately to severely active UC. The primary objective of this trial was to assess the safety and efficacy of etrasimod on clinical remission at 12 weeks assessed by the FDA-required, 3-domain, MMS. In ELEVATE UC 12, clinical remission was achieved among 26.0% of patients receiving etrasimod compared to 15.0% of patients receiving placebo (11.0% differential, P<.05). All key secondary endpoints were met at week 12, including endoscopic improvement and mucosal healing.
In ELEVATE UC 12, a similar proportion of patients experienced treatment-emergent adverse events (AEs) between etrasimod 2 mg and placebo treatment groups, while in ELEVATE UC 52, it was higher in the etrasimod 2 mg group compared to placebo. The proportion of patients experiencing serious AEs was similar between treatment groups in both trials. The most common treatment-emergent AEs in 3% or more of etrasimod-treated patients and greater than placebo up to week 52 in either trial were headache, elevated liver tests, worsening of UC, COVID-19 infection, dizziness, pyrexia, arthralgia, abdominal pain and nausea. Data support that initiation of etrasimod treatment does not require a complex up-titration regimen.
Nearly two-thirds of patients in ELEVATE UC 52 and ELEVATE UC 12, respectively, were naïve to biologic or JAK inhibitor therapy.
INDICATION
VELSIPITY is a prescription medicine used to treat adults with moderately to severely active ulcerative colitis. It is not known if VELSIPITY is safe and effective in children.
About Pfizer: Breakthroughs that Change Patients’ Lives
At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety, and value in the discovery, development, and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments, and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments, and local communities to support and expand access to reliable, affordable health care around the world. For more than 170 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.pfizer.com. In addition, to learn more, please visit us on www.pfizer.com and follow us on Twitter at @Pfizer and @Pfizer_News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.
View source version on businesswire.com: https://www.businesswire.com/news/home/20231012073213/en/
Source: Pfizer Inc.
Pfizer's Velsipity gets FDA nod for ulcerative colitis
Oct. 13, 2023 9:43 AM ET
By: Sinchita Mitra, SA News Editor4 Comments
- The U.S. Food and Drug Administration (FDA) approved Pfizer's (NYSE:PFE) medicine Velsipity to treat adults with moderately to severely active ulcerative colitis (UC).
- UC is an inflammatory bowel disease that leads to inflammation and ulcers in the digestive tract.
- https://seekingalpha.com/news/4020390-pfizers-velsipity-gets-fda-nod-for-ulcerative-colitis?mailingid=33017072&messageid=2900&serial=33017072.19063&utm_campaign=rta-stock-news&utm_content=link-1&utm_medium=email&utm_source=seeking_alpha&utm_term=33017072.19063
- Pfizer Inc. (PFE)
- https://www.pfizer.com/products/product-detail/velsipitytm
- https://www.velsipity.com/
Foralumab
ELREXFIOTM (elranatamab-bcmm) injection
Foralumab
Tiziana Announces Positive Qualitative Six-Month PET Scan Results With Intranasal Foralumab Treating Multiple Sclerosis Patients Diagnosed With Non-Active Secondary Progressive MS (na-SPMS)
13 October 2023
- Five out of six patients in FDA authorized Expanded Access Program are showing a qualitative reduction in microglia activation (a key biomarker being observed)
- Foralumab to advance into Phase 2 human clinical trials using the world’s only fully human intranasal anti-CD3 monoclonal antibody
- Phase 2 trial screening for na-SPMS to begin in November 2023
NEW YORK, October 13, 2023 -- Tiziana Life Sciences Ltd. (Nasdaq: TLSA) (“Tiziana” or the “Company”), a biotechnology company developing breakthrough immunomodulation therapies via novel routes of drug delivery, today announced that a reduction in activated microglia, as seen in six-month Positron Emission Tomography (PET) scans, has now been observed in a total of five of the six patients with non-active secondary-progressive multiple sclerosis (na-SPMS) treated with intranasal foralumab in its Expanded Access Program (EAP). Activated microglia are believed to play a prominent role in the pathogenesis of neuroinflammatory and neurodegenerative diseases including multiple sclerosis, Alzheimer’s disease, and amyotrophic lateral sclerosis, or ALS.
Tarun Singhal, M.B.B.S., M.D., Director of the PET Imaging Program in Neurologic Diseases, associate neurologist and nuclear medicine physician at Brigham and Women’s Hospital, a founding member of Mass General Brigham Healthcare System, and Assistant Professor of Neurology at Harvard Medical School, commented, “Upon review of the baseline and six-month PET scans of the latest cohort of four Expanded Access patients, three out of the four scans suggested a qualitative reduction in the microglial PET signal. When combined with my assessment of the first two Expanded Access patients at six-months, five of the six suggested a reduction in qualitative microglial PET signal. An example of this can be seen in the graphic below, titled, “Figure 1”, showing the deactivation of this signal in patient EA6. This is promising from an imaging standpoint, and further studies are needed to confirm these findings using additional quantitative approaches."
Howard L. Weiner, M.D., Chairman of Tiziana's Scientific Advisory Board and Co-Director of the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital added, “With six patients now dosed in our na-SPMS EA program, I feel that Dr. Singhal’s readout of the six-month PET scans strongly supports our previously announced 3-month clinical findings.”
Gabriele Cerrone, Chairman, acting CEO and founder of Tiziana Life Sciences commented, “I believe that the six-month qualitative na-SPMS PET readout by Dr. Singhal is very encouraging and will enable us to rapidly advance foralumab in Phase 2a testing to address patients afflicted with this devasting disease who currently have no FDA-approved treatments available.”
Figure 1.
About Foralumab
Activated T cells play an important role in the inflammatory process. Foralumab, the only fully human anti-CD3 monoclonal antibody (mAb), binds to the T cell receptor and dampens inflammation by modulating T cell function, thereby suppressing effector features in multiple immune cell subsets. This effect has been demonstrated in patients with COVID and with multiple sclerosis, as well as in healthy normal subjects. The non-active SPMS intranasal foralumab Phase 2 trial is expected to start screening in November of 2023. Immunomodulation by nasal anti-CD3 mAb represents a novel avenue for treatment of neuroinflammatory and neurodegenerative human diseases.[1],[2]
About Tiziana Life Sciences
Tiziana Life Sciences is a clinical-stage biopharmaceutical company developing breakthrough therapies using transformational drug delivery technologies to enable alternative routes of immunotherapy. Tiziana’s innovative nasal approach has the potential to provide an improvement in efficacy as well as safety and tolerability compared to intravenous (IV) delivery. Tiziana’s lead candidate, intranasal foralumab, which is the only fully human anti-CD3 mAb, has demonstrated a favorable safety profile and clinical response in patients in studies to date. Tiziana’s technology for alternative routes of immunotherapy has been patented with several applications pending and is expected to allow for broad pipeline applications.
For further inquiries:
Tiziana Life Sciences Ltd
[1] https://www.pnas.org/doi/10.1073/pnas.2220272120
[2] https://www.pnas.org/doi/10.1073/pnas.2309221120
Related documents
Tiziana announces positive six-month PET scan results for intranasal Alzheimer’s drug
Oct. 13, 2023 9:14 AM ET
Tiziana Life Sciences Ltd (TLSA)
By: Jaskiran Singh, SA News Editor
- Biotech Tiziana Life Sciences (NASDAQ:TLSA) Friday announced that five out of six patients in the FDA-authorized Expanded Access Program showed a qualitative reduction in microglia activation
- https://seekingalpha.com/news/4020383-tiziana-announces-positive-six-month-pet-scan-results-with-its-intranasal-foralumab
- Tiziana Life Sciences Ltd (TLSA)
- https://www.tizianalifesciences.com/drug-pipeline/foralumab/
- https://www.tizianalifesciences.com/
NVL-655
mRNA-1083
Foralumab
Nuvalent Reports Preliminary Phase 1 Clinical Data from ALKOVE-1 Trial that Support Best-In-Class Potential of NVL-655 for Patients with ALK-Positive NSCLC
Encouraging preliminary signs of activity observed in heavily pre-treated patients with ALK-positive NSCLC, including in subgroups of patients who have previously received a 2nd generation ALK TKI and lorlatinib, have brain metastases, or have single or compound ALK resistance mutationsFavorable preliminary safety profile is consistent with an ALK-selective, TRK sparing designCompany to host a conference call today, October 13, at 8:00am EDT
CAMBRIDGE, Mass., Oct. 13, 2023 /PRNewswire/ -- Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, today announced updated preliminary data from the Phase 1 dose-escalation portion of its ongoing ALKOVE-1 Phase 1/2 clinical trial of NVL-655 for patients with advanced ALK-positive non-small cell lung cancer (NSCLC) and other solid tumors. These data will be presented today at the 35th AACR-NCI-EORTC (ANE) Symposium in Boston, Massachusetts.
NVL-655 is a novel brain-penetrant ALK-selective tyrosine kinase inhibitor (TKI) created with the aim to simultaneously overcome the clinical challenges of emergent treatment resistance, brain metastases, and off-target central nervous system (CNS) adverse events associated with tropomyosin receptor kinase (TRK) inhibition that may limit the use of currently available ALK TKIs.
"Significant advancements have been made with the development of three generations of ALK TKIs, and the five ALK inhibitors that are currently FDA-approved provide important treatment options for patients with advanced ALK fusion-positive cancers. However, some limitations remain with the available therapies, ranging from association with TRK-related neurologic adverse events that can limit adequate coverage of ALK single resistance mutations to the emergence of refractory compound mutations following sequential treatment with ALK TKIs," said presenting investigator Jessica J. Lin, M.D., Assistant Professor of Medicine, Harvard Medical School and Attending Physician, Mass General Cancer Center. "These preliminary data support the potential for NVL-655 as an ALK-selective inhibitor that may combine, for the first time, potent and selective targeting of diverse ALK fusions and secondary ALK resistance mutations, including single and compound mutations involving G1202R and I1171N, brain penetrance, and the avoidance of TRK inhibition that can be dose limiting."
As of the enrollment and data cut-off date of August 8, 2023 for the preliminary data, 93 patients have been enrolled in the Phase 1 portion of the ALKOVE-1 trial across six evaluated dose levels of NVL-655 ranging from 15 mg once daily (QD) to 200 mg QD. Enrollment in the Phase 1 portion of the trial is ongoing.
Preliminary activity data as of the cut-off date were available from 51 heavily pre-treated response-evaluable NSCLC patients. The objective response rate (ORR) by RECIST 1.1 was 39% (20/51) of patients treated at all doses, of which all were partial responses (4 pending confirmation). In the subset of 41 patients treated at dose levels of 50 mg QD or higher, the ORR was 44% (18/41).
To evaluate key target characteristics of NVL-655, activity was examined in subgroups of the 51 response-evaluable patients treated at all doses, including:
- Patients with any history of CNS metastases (ORR 52%, 15/29);
- Patients with any ALK resistance mutation (ORR 54%, 15/28), including those with compound ALK mutations (ORR 56%, 9/16) and those with ALK G1202R single or compound mutations (ORR 71%, 12/17);
- The most heavily pre-treated of patients, after receiving ≥3 prior ALK TKIs including at least one 2nd generation (2G) ALK TKI (alectinib, brigatinib, or ceritinib) plus lorlatinib, and prior chemotherapy (ORR 42%, 8/19); and,
- Lorlatinib-naïve patients who had received at least one 2G +/- 1G ALK TKI (ORR 71%, 5/7).
Preliminary pharmacokinetic (PK) analyses were available for dose levels 15 mg QD to 150 mg QD. Treatment with NVL-655 resulted in exposure above target efficacy thresholds in both the periphery and in the CNS. These preliminary PK data suggest that dose levels of 50 mg QD and above may provide increased coverage of single and compound mutations in the CNS. Preliminary pharmacodynamic analysis showed that NVL-655 induced clearance of diverse ALK resistance mutation alleles across a wide dose range.
As of the cut-off date for the preliminary data, 67% (34/51) of response-evaluable patients remained on treatment with NVL-655 with duration of treatment up to 12 months (median duration of treatment of 3.4 months). All patients with tumor response continued on treatment without disease progression. NVL-655 was well-tolerated with a preliminary safety profile that was favorable and consistent with its ALK-selective, TRK sparing design.
"We are excited to present the first look at the safety and clinical activity of NVL-655 from our ALKOVE-1 clinical trial, which we believe supports the potential for NVL-655 to address each key area of its desired target product profile," said Christopher Turner, M.D., Chief Medical Officer of Nuvalent. "Across a wide dose range, NVL-655 demonstrated activity in a heavily pre-treated patient population that uniquely includes patients in the post-lorlatinib setting, with a favorable preliminary safety profile consistent with its ALK-selective, TRK sparing design. Importantly, all patients with tumor response remained on treatment without disease progression as of the data cut-off date, suggesting the potential for durable responses even in this late line population."
Dr. Turner continued, "Ultimately, we view the ability to keep patients on therapeutically relevant dose levels as a key indicator of the potential for NVL-655 to drive clinically meaningful durable responses when used earlier in the treatment paradigm. In earlier lines of therapy, potent activity against ALK as well as single or compound ALK resistance mutations in both the periphery and the brain has the potential to delay or prevent the emergence of both treatment resistance and CNS progression. Furthermore, selective inhibition of wild-type ALK and its resistance variants may minimize TRK-related CNS adverse events and other off-target toxicities that can be dose limiting. We believe that the preliminary characteristics of NVL-655 observed in this heavily pre-treated patient population support its opportunity as a potential best-in-class therapy that can move up the treatment paradigm to deliver deep and durable responses for patients with ALK-positive cancers."
"With today's data, Nuvalent has presented preliminary proof-of-concept data for both of its novel parallel lead programs in ROS1 and ALK-positive cancers in just over 5 years since the company's inception," said James Porter, Ph.D., Chief Executive Officer at Nuvalent. "We believe this achievement is a testament to the dedication of the Nuvalent team, and to our approach of collaboration with leading physician-scientists, identification of medical needs stemming from the limitations of existing therapies, and focused application of our innovative chemistry and deep expertise in structure-based drug design to develop precisely targeted therapies according to well-defined target product profiles."
Dr. Porter continued, "Most importantly, we recognize that this achievement is made possible by the patients, caregivers, and investigators who are participating in the ALKOVE-1 trial and offer our sincere gratitude. We look forward to discussions with investigators and regulators on the selection of a recommended Phase 2 dose (RP2D) and the transition to the planned Phase 2 portion of ALKOVE-1 for patients with lorlatinib-naïve and lorlatinib-treated ALK-positive NSCLC. We also look forward to using the preliminary data to guide discussions with physicians regarding potential development strategies for patients with TKI-naïve ALK-positive NSCLC as we work towards our goal of bringing new treatment options to all patients with ALK-positive cancers."
NVL-655 First-in-Human Preliminary Phase 1 Data
NVL-655 is currently being evaluated in the ALKOVE-1 Phase 1/2 clinical trial, a first-in-human study of NVL-655 in patients with advanced ALK-positive NSCLC and other solid tumors (NCT05384626). The Phase 1 dose escalation portion is enrolling ALK-positive NSCLC patients who have previously received at least one ALK TKI and patients with other ALK-positive solid tumors who have been previously treated with at least one prior systemic anticancer therapy. The primary objectives are to determine the RP2D and if applicable, the maximum tolerated dose (MTD) of NVL-655 in patients with ALK-positive solid tumors. Additional objectives include characterization of the overall safety, tolerability, and pharmacokinetic profile, and evaluation of the preliminary anti-tumor activity and intracranial activity of NVL-655.
As of the enrollment and data cut-off date of August 8, 2023 for the preliminary data, 93 patients were enrolled in the Phase 1 portion of the ALKOVE-1 trial, of which 91 patients had ALK-positive NSCLC and 58% (54/93) had a history of CNS metastases.
The patient population was heavily pre-treated:
- 100% (93/93) had received a 2G ALK TKI or lorlatinib;
- 77% (72/93) had received two or more ALK TKIs, including a 2G ALK TKI and lorlatinib;
- 44% (41/93) had received three or more ALK TKIs, including a 2G ALK TKI and lorlatinib; and,
- 46% (43/93) had an identified secondary ALK mutation, including 26% (24/93) with any compound ALK mutation.
Preliminary Activity Analysis
As of the cut-off date for the preliminary data, patients were treated in six NVL-655 dose cohorts of 15 mg, 25 mg, 50 mg, 100 mg, 150 mg, and 200 mg QD. Fifty-one patients with NSCLC were response-evaluable by investigator assessment with duration of treatment up to 12 months (median duration of treatment of 3.4 months).
Key findings include early anti-tumor activity in ALK-positive NSCLC patients, including partial responses (RECIST 1.1) in:
- Heavily pre-treated patients: An ORR of 39% (20/51) was observed in response-evaluable patients, and all patients with tumor response continued on treatment without disease progression as of the data cut-off date.
- For dose levels of 50 mg or greater, which may provide increased coverage of single and compound mutations in the CNS, an ORR of 44% (18/41) was observed.
- In patients who have likely exhausted all available treatment options (≥3 prior ALK TKIs including a 2G ALK TKI and lorlatinib), the observed ORR was 40% (10/25) regardless of prior chemotherapy and 42% (8/19) with prior chemotherapy.
- Patients with ALK single or compound resistance mutations: An ORR of 54% (15/28) was observed in patients with any ALK resistance mutation, including an ORR of 56% (9/16) in patients with compound ALK mutations, and an ORR of 71% (12/17) in patients with ALK G1202R single or compound mutations.
- Patients with CNS metastases: An ORR of 52% (15/29) was observed in patients with any history of CNS metastases. All patients with tumor response who had a history of CNS disease continued on treatment without CNS progression.
- Lorlatinib-naïve patients: Of patients who received at least one 2G +/- 1G ALK TKI and had not previously received lorlatinib, 5 of 7 (71%) responded.
Preliminary Safety, Pharmacokinetic, and Pharmacodynamic Analysis
A favorable preliminary safety profile was observed with NVL-655 treatment in the 93 patients enrolled across the dose-escalation portion of ALKOVE-1, consistent with an ALK-selective, TRK-sparing design. Most treatment-related adverse events (TRAEs) were low-grade and manageable, with the highest incidence of TRAEs being ALT increase (19%, 18/93 any grade; 6%, 6/93 ≥ Grade 3), AST increase (18%, 17/93 any grade; 4%, 4/93 ≥ Grade 3), and nausea (10%, 9/93 of which all were Grade 1 or 2). TRAEs requiring dose modification were infrequent, with 2% (2/93) discontinuations and 5% (5/93) dose reductions. There was one dose-limiting toxicity of transient asymptomatic Grade 4 CPK increase at the 200 mg QD dose level. An MTD was not reached, and the preliminary overall safety profile was consistent with avoidance of TRK-related neurotoxicities.
The observed favorable preliminary safety profile allowed for achievement of NVL-655 exposure levels above target CNS efficacy thresholds for ALK, ALK single and compound G1202R mutations, and other recalcitrant ALK single mutations such as I1171N. Favorable PK and low intra-cohort patient PK variability were observed, with dose-proportional exposure and a half-life that is supportive of once daily dosing. This preliminary PK data suggest that dose levels of 50 mg QD or greater may provide increased coverage of single and compound mutations in the CNS.
Preliminary pharmacodynamic findings by centrally confirmed ctDNA analysis showed that treatment with NVL-655 induced clearance of diverse ALK resistance mutation alleles across a wide dose range. Notably, 100% clearance was observed in 14 of 16 patients with centrally confirmed single or compound ALK G1202R or I1171X (X = N or T) mutations, of which 13 had received prior lorlatinib.
Combined with the favorable preliminary activity observed as of the data cut-off date, these data suggest that NVL-655 has opportunity as a potential best-in-class therapy that may be able to move up the treatment paradigm for patients with ALK-positive NSCLC.
The ALKOVE-1 clinical trial is continuing to enroll patients in the Phase 1 portion of the trial and is focused on further characterizing the safety, PK, and pharmacodynamic profiles, determining the RP2D, and if applicable, the MTD of NVL-655. Upon RP2D selection, the trial is designed to transition directly into the Phase 2 portion, which will evaluate the safety and activity of NVL-655 in several expansion cohorts of patients defined based on the number and type of prior anti-cancer therapies they have received. The Phase 2 cohorts are intended to support potential registration in patients with ALK-positive NSCLC who are both lorlatinib-naïve and lorlatinib-treated.
In addition to the planned Phase 2 cohorts, Nuvalent intends to use these preliminary data in patients with heavily pre-treated ALK-positive NSCLC to guide discussions with physicians that will inform development strategies in TKI-naïve ALK-positive NSCLC.
Webcast and Conference Call Information
A conference call with management will be held today at 8:00 am EDT. To access the call, please dial +1 (866) 652-5200 (domestic) or +1 (412) 317-6060 (international) at least 10 minutes prior to the start time and ask to be joined to the Nuvalent call. Accompanying slides and a live video webcast will be available in the Investors section of the Nuvalent website at https://investors.nuvalent.com/events. A replay and accompanying slides will be archived on the Nuvalent website for 30 days.
About NVL-655
NVL-655 is a novel brain-penetrant ALK-selective inhibitor created with the aim to overcome limitations observed with currently available ALK inhibitors. NVL-655 is designed to remain active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumors with the solvent front G1202R mutation or compound mutations G1202R / L1196M ("GRLM"), G1202R / G1269A ("GRGA"), or G1202R/L1198F ("GRLF"). NVL-655 has been designed for CNS penetrance to improve treatment options for patients with brain metastases. NVL-655 has been observed in preclinical studies to selectively inhibit wild-type ALK and its resistance variants over the structurally related tropomyosin receptor kinase (TRK) family to potentially avoid TRK-related CNS adverse events seen with dual TRK/ALK inhibitors and drive more durable responses for patients. NVL-655 is currently being investigated in the ALKOVE-1 clinical trial (NCT05384626), a first-in-human Phase 1/2 clinical trial for patients with advanced ALK-positive non-small cell lung cancer (NSCLC) and other solid tumors.
About Nuvalent
Nuvalent, Inc. (Nasdaq: NUVL) is a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for patients with cancer, designed to overcome the limitations of existing therapies for clinically proven kinase targets. Leveraging deep expertise in chemistry and structure-based drug design, we develop innovative small molecules that have the potential to overcome resistance, minimize adverse events, address brain metastases, and drive more durable responses. Nuvalent is advancing a robust pipeline with parallel lead programs in ROS1-positive and ALK-positive non-small cell lung cancer (NSCLC), a program in HER2 Exon 20 Insertion positive cancers, and multiple discovery-stage research programs. We routinely post information that may be important to investors on our website at www.nuvalent.com. Follow us on Twitter (@nuvalent) and LinkedIn.
SOURCE Nuvalent, Inc.
Nuvalent's drug shows promise in lung cancer patients in preliminary phase 1 data
Oct. 13, 2023 7:34 AM ET
By: Ravikash, SA News Editor
Nuvalent (NASDAQ:NUVL) said encouraging preliminary signs of activity were seen in certain heavily pre-treated patients with a type of non-small cell lung cancer (NSCLC) who received its drug NVL-655.
The company reported updated preliminary data from the phase 1 dose-escalation part of its ongoing Phase 1/2 trial, dubbed ALKOVE-1, of NVL-655 to treat patients with advanced ALK-positive NSCLC and other solid tumors.
The subgroups of patients included people who have previously received a 2nd generation ALK TKI and lorlatinib — sold as Lorbrena by Pfizer (PFE) — have brain metastases, or have single or compound ALK resistance mutations.
INO-3107
mRNA-1083
mRNA-1083
INOVIO Receives FDA Feedback that Data from Completed Phase 1/2 Trial of INO-3107 Can Be Used to Submit a BLA Under Accelerated Approval Program
October 10, 2023
DownloadPDF Format (opens in new window)
– Previously planned Phase 3 trial no longer required to support Biological License Application (BLA) submission
– If approved, INO-3107 could potentially revolutionize treatment options for patients with Recurrent Respiratory Papillomatosis (RRP), a debilitating rare disease caused by human papillomavirus (HPV)
– INO-3107 could be the first DNA medicine available in the United States and the first commercial product for INOVIO
PLYMOUTH MEETING, Pa., Oct. 10, 2023 /PRNewswire/ -- INOVIO (NASDAQ:INO), a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases, today announced that it has received feedback from the U.S. Food and Drug Administration (FDA) that data from its completed Phase 1/2 trial of INO-3107 for the treatment of RRP could support INOVIO's submission of a BLA for review under the FDA's accelerated approval program. The FDA also advised that the company's previously planned Phase 3 randomized, placebo-controlled trial would not be required to support this submission. INOVIO will be required to initiate a confirmatory trial prior to BLA submission for accelerated approval and satisfy all other FDA filing requirements. The design of the confirmatory trial has not yet been finalized. If approved, INO-3107 would be the first DNA medicine in the United States and the first INOVIO candidate to receive regulatory approval.
"Following the recent grant of Breakthrough Therapy Designation for INO-3107 for the treatment of RRP, we're grateful for the additional feedback from the FDA providing a potentially accelerated development pathway. We believe INO-3107 could become a game-changing treatment option for those suffering from RRP, a serious and often difficult-to-treat disease," said INOVIO's President and Chief Executive Officer, Dr. Jacqueline Shea. "We're now focused on streamlining our development plan to support submission of a BLA for accelerated approval. We would like to thank the patients and investigators who have participated in our trials to date."
"I commend the FDA for recognizing the immense burden RRP puts on patients and the critical need for a better standard of care," said the President of the Recurrent Respiratory Papillomatosis Foundation, Kim McClellan. "I'm thrilled by the progress being made for RRP patients who are desperate for an alternative to surgery."
INOVIO's completed Phase 1/2 open-label, multicenter trial assessed INO-3107's safety, tolerability, immunogenicity, and efficacy in patients with HPV-6 and/or HPV-11-related RRP (NCT:04398433). The trial evaluated the reduction in the number of surgical interventions in the year following initial administration of INO-3107 compared to the year prior to treatment. Patients received four doses of INO-3107 on Day 0, and Weeks 3, 6, and 9. Overall, 81.3% (26/32) of patients in the trial had a decrease in surgical interventions in the year after INO-3107 administration compared to the prior year, including 28.1% (9/32) that required no surgical intervention during or after the dosing window. Patients in the trial had a median range of 4 surgeries (2-8) in the year prior to dosing. After dosing, there was a median decrease of 3 surgical interventions (95% confidence interval -3, -2). At the outset of the study (Day 0), patients could have RRP tissue surgically removed, but any surgery performed after Day 0 during the dosing window was counted against the efficacy endpoint. Treatment with INO-3107 generated a strong immune response in the trial, inducing activated CD4 T cells and activated CD8 T cells with lytic potential. T-cell responses were also observed at Week 52, indicating a persistent cellular memory response. INO-3107 was well tolerated by participants in the trial, resulting in mostly low-grade (Grade 1) treatment-emergent adverse effects such as injection site pain and fatigue.
Data from this Phase 1/2 trial were presented earlier this year at scientific and medical conferences, including the 2023 Annual Meeting of the American Broncho-Esophageal Association (ABEA) in May and at the European Laryngological Association's Annual Meeting in June. Data from the trial was also published in May in the peer-reviewed journal, The Laryngoscope, under the title "Interim Results of a Phase 1/2 Open-Label Study of INO-3107 for HPV-6 and/or HPV-11–Associated RRP."The Laryngoscope is the official journal of the Triological Society (TRIO), the American Laryngological Association (ALA), and the ABEA.
INO-3107 is INOVIO's lead candidate and one of three clinical-stage DNA medicine candidates targeting HPV-related disease. INOVIO's DNA technology has been studied in twelve HPV-related trials, ranging from Phase 1 to Phase 3, involving more than 900 patients in 20 countries with a variety of HPV-related diseases, including RRP, HSIL (cervical, anal and vulvar) and head and neck cancers. Shared observations in these trials include the ability of DNA medicines to generate HPV antigen specific T cells and a persistent cellular memory response, viral clearance and lesion regression, and no anti-vector immune responses. All three HPV-related product candidates (INO-3107, INO-3112 and VGX-3100) have been well tolerated in these trials.
Updated Cash Guidance
INOVIO previously announced it expected its cash runway to fund the company's operations into the third quarter of 2025. The changes to the development plan for INO-3107 as a result of the FDA feedback announced today could affect that prior guidance. The company plans to provide updated cash guidance on its third quarter earnings call scheduled to take place in November.
About RRP
RRP is a debilitating and rare disease caused primarily by HPV-6 and/or HPV-11. RRP is characterized by the development of small, wart-like growths, or papillomas, in the respiratory tract. While papillomas are generally benign, they can cause severe, life-threatening airway obstruction and respiratory complications. RRP can also significantly affect quality of life for patients by affecting the voice box, limiting the ability to speak effectively. Surgery to remove papillomas is the standard of care for RRP; however, the papillomas often grow back because the underlying HPV infection has not been eradicated.
The most widely cited U.S. epidemiology data published in 1995 estimated that there were 14,000 active cases and about 1.8 per 100,000 new cases in adults each year. More recent pediatric epidemiology data cites a range of 0.5 - 0.7 per 100,000 new cases in children in the U.S. each year.
About INO-3107
INO-3107 is INOVIO's lead DNA medicine product candidate and is being developed as a potential treatment for RRP. INO-3107 is designed to elicit a targeted T cell response against HPV-6 and HPV-11, the HPV types responsible for causing RRP among other HPV-related diseases. These targeted T cells are designed to seek out and kill infected cells, with the aim of potentially preventing or slowing the growth of new papillomas. INO-3107 was designated a Breakthrough Therapy by the FDA in September 2023. INO-3107 received Orphan Drug designation from the European Commission in May 2023 and from the FDA in 2020.
About INOVIO's DNA Medicines Platform
INOVIO's DNA medicines platform has two innovative components: precisely designed DNA plasmids, delivered by INOVIO's proprietary investigational medical device, CELLECTRA®. INOVIO uses proprietary technology to design its DNA plasmids, which are small circular DNA molecules that work like software the body's cells can download to produce specific proteins to target and fight disease. INOVIO's CELLECTRA® delivery devices help ensure its DNA medicines enter the body's cells for optimal effect, without chemical adjuvants or nanoparticles and without the risk of the anti-vector response seen in viral vector platforms.
About INOVIO
INOVIO is a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases. INOVIO's technology optimizes the design and delivery of innovative DNA medicines that teach the body to manufacture its own disease-fighting tools. For more information, visit www.inovio.com.
Cision View original content:https://www.prnewswire.com/news-releases/inovio-receives-fda-feedback-that-data-from-completed-phase-12-trial-of-ino-3107-can-be-used-to-submit-a-bla-under-accelerated-approval-program-301951543.html
SOURCE INOVIO Pharmaceuticals, Inc.
Inovio gains after FDA feedback on marketing application for lead drug
Oct. 10, 2023 8:47 AM ET
Inovio Pharmaceuticals, Inc. (INO)
By: Dulan Lokuwithana, SA News Editor1 Comment
- DNA medicines company Inovio Pharmaceuticals (NASDAQ:INO) traded higher premarket Tuesday after the FDA issued positive feedback on its plans to seek U.S. marketing authorization for its lead asset INO-3107 for recurrent respiratory papillomatosis (RRP), a rare disorder.
- https://seekingalpha.com/news/4019351-inovio-stock-rises-fda-remarks-lead-drug
- Inovio Pharmaceuticals, Inc. (INO)
- https://inovio.com/
- https://inovio.com/dna-medicines-pipeline/
mRNA-1083
mRNA-1083
mRNA-1083
Moderna Announces Positive Phase 1/2 Data from mRNA-1083, the Company's Combination Vaccine Against Influenza and COVID-19
October 4, 2023
mRNA-1083 showed strong immunogenicity against influenza and COVID-19, with an acceptable reactogenicity and safety profile, compared to licensed standalone vaccines
Company to begin Phase 3 trial of mRNA-1083 in adults 50 years and above
CAMBRIDGE, MA / ACCESSWIRE / October 4, 2023 /
Moderna, Inc. (NASDAQ:MRNA) today announced positive interim results from the Phase 1/2 trial of mRNA-1083, an investigational combination vaccine against influenza and COVID-19. Moderna's investigational combination vaccines are designed to deliver value to individuals, providers and healthcare systems through higher compliance, easier administration and greater convenience.
"With today's positive results from our combination vaccine against flu and COVID-19, we continue to expand our Phase 3 pipeline," said Stéphane Bancel, Chief Executive Officer of Moderna. "Flu and COVID-19 represent a significant seasonal burden for individuals, providers, healthcare systems and economies. Combination vaccines offer an important opportunity to improve consumer and provider experience, increase compliance with public health recommendations, and deliver value for healthcare systems. We are excited to move combination respiratory vaccines into Phase 3 development and look forward to partnering with public health officials to address the significant seasonal threat posed to people by these viruses."
The ongoing Phase 1/2 clinical trial (ClinicalTrials.gov Identifier: NCT05827926) is a randomized, observer blind study evaluating the safety and immunogenicity of mRNA-1083 compared to a standard dose influenza vaccine, Fluarix, in adults 50-64 years of age and against an enhanced influenza vaccine, Fluzone HD, in adults 65-79 years of age. For both age groups, mRNA-1083 was compared against Spikevax booster.
The mRNA-1083 candidate selected to advance to Phase 3 achieved hemagglutination inhibition antibody titers similar to or greater than both licensed quadrivalent influenza vaccines and achieved SARS-CoV-2 neutralizing antibody titers similar to the Spikevax bivalent booster in the Phase 1/2 study. mRNA-1083 resulted in geometric mean titer (GMT) ratios >1.0 relative to Fluarix in adults 50-64 years of age, for all four influenza vaccine strains. GMT ratios for mRNA-1083 relative to Fluzone HD in adults 65-79 were also >1.0, for all four influenza vaccine strains. The GMT ratios of mRNA-1083 relative to Spikevax bivalent were > 0.9 in adults 50 to 64 years of age and > 1.0 in adults 65 to 79 years of age, relative to Spikevax.
Reported rates of solicited local and systemic adverse reactions after mRNA-1083 administration were similar to the standalone COVID-19 vaccine group in the trial. The majority of solicited adverse reactions were grade 1 or 2 in severity. Grade 3 solicited local or solicited systemic reactions were reported in less than 4% of participants ages 50 and above. No new safety concerns were identified for mRNA-1083 compared to the standalone vaccines.
The Company plans to begin a Phase 3 trial of mRNA-1083 in 2023 and is targeting potential regulatory approval for the combination vaccine in 2025.
Influenza epidemics occur seasonally and vary in severity each year, causing respiratory illnesses and placing a substantial burden on healthcare systems. Worldwide, influenza leads to 3-5 million cases of severe diseases and 290,000-650,000 influenza-related respiratory deaths annually, despite the availability of current influenza vaccines. Influenza affects people of all ages, but older adults are disproportionately affected by influenza and its complications. The SARS-CoV-2 virus remains a leading cause of severe illness and mortality throughout the world. Since the start of the pandemic in 2020, there have been approximately 770 million cases of COVID-19 respiratory illness and approximately seven million deaths reported globally. SARS-CoV-2 infects people of all ages, but higher rates of severe illness and death are observed among older individuals and individuals with pre-existing medical conditions.
The global influenza market volume is approximately 500-600 million doses annually with approximately 150 million doses administered in the United States. Moderna estimates the U.S. fall 2023 COVID-19 market size as likely to be 50 to 100 million doses, depending on vaccination rates. Over time, the Company anticipates the COVID-19 market will approach the influenza market in the U.S. given the burden of disease.
The Company previously announced that it expects respiratory product sales in 2027 to be in the range of $8 billion to $15 billion with corresponding respiratory product operating profit in the range of $4 billion to $9 billion.
About Moderna
In over 10 years since its inception, Moderna has transformed from a research-stage company advancing programs in the field of messenger RNA (mRNA), to an enterprise with a diverse clinical portfolio of vaccines and therapeutics across seven modalities, a broad intellectual property portfolio in areas including mRNA and lipid nanoparticle formulation, and an integrated manufacturing plant that allows for rapid clinical and commercial production at scale. Moderna maintains alliances with a broad range of domestic and overseas government and commercial collaborators, which has allowed for the pursuit of both groundbreaking science and rapid scaling of manufacturing. Most recently, Moderna's capabilities have come together to allow the authorized use and approval of one of the earliest and most effective vaccines against the COVID-19 pandemic.
Moderna's mRNA platform builds on continuous advances in basic and applied mRNA science, delivery technology and manufacturing, and has allowed the development of therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases, cardiovascular diseases and auto-immune diseases. Moderna has been named a top biopharmaceutical employer by Science for the past eight years. To learn more, visit www.modernatx.com.
SpikeVax® is a registered trademark of Moderna
Fluzone® is a registered trademark of Sanofi Pasteur
Fluarix® is a registered trademark of the GlaxoSmithKline group of companies.
SOURCE: Moderna, Inc.
View source version on accesswire.com:
https://www.accesswire.com/789816/moderna-announces-positive-phase-12-data-from-mrna-1083-the-companys-combination-vaccine-against-influenza-and-covid-19
Moderna eyes late-stage trial for COVID/flu combo shot
Oct. 04, 2023 9:25 AM ET
Moderna, Inc. (MRNA)GSK, SNY, SNYNF, GCVRZ
By: Dulan Lokuwithana, SA News Editor3 Comments
- Moderna (NASDAQ:MRNA) said Wednesday it will begin a Phase 3 trial for its combination vaccine against influenza and COVID-19 after the experimental shot, called mRNA-1083, generated positive data in a Phase 1/2 trial.
- The ongoing trial is designed to evaluate the messenger-RNA shot against licensed flu vaccines that GSK (GSK) and Sanofi (SNY) market as Fluarix and Fluzone HD, respectively, as well as Moderna’s (MRNA) COVID booster Spikevax.
- The randomized, observer-blind study enrolled adults aged 50–79 in two age groups.
- Citing interim data, Moderna (MRNA) said that the mRNA-1083 candidate chosen for Phase 3 development led to antibody levels similar to or greater than those generated from the approved flu vaccines.
- https://seekingalpha.com/news/4018156-moderna-eyes-late-stage-trial-covidflu-combo-shot
- Moderna, Inc. (MRNA)GSK, SNY, SNYNF, GCVRZ
- https://investors.modernatx.com/overview/default.aspx
- https://www.modernatx.com/research/product-pipeline
- https://www.modernatx.com/
ABBV-CLS-484
ABBV-CLS-484
ABBV-CLS-484
October 4, 2023
Nature Publishes Discovery and Preclinical Results for ABBV-CLS-484, a Potential First-in-Class PTPN2/N1 Inhibitor in Cancer Immunotherapy
NORTH CHICAGO, Ill. and SOUTH SAN FRANCISCO, Calif., Oct. 4, 2023 /PRNewswire/ -- AbbVie (NYSE: ABBV), the Broad Institute of MIT and Harvard, and Calico Life Sciences today announced the publication in Nature of the discovery and preclinical data that demonstrate investigational ABBV-CLS-484 is a potential first-in-class, orally bioavailable, PTPN2/N1 phosphatase inhibitor that enhances anti-tumor immunity. The findings, based on research conducted by AbbVie in collaboration with the Broad Institute and Calico, support the development of ABBV-CLS-484 as a promising new strategy for cancer immunotherapy.
Titled "The PTPN2/PTPN1 inhibitor ABBV-CLS-484 unleashes potent anti-tumour immunity," the paper highlights the novel structural insights and design that led to the discovery of ABBV-CLS-484 and its dual mechanism of action that targets tumor cells and suppresses their growth, as well as promotes the activation of several immune cell types to increase their anti-tumor activity.1
Researchers at the Broad previously identified protein tyrosine phosphatase non-receptor type 2 (PTPN2) and its closely related paralog PTPN1 as potential targets for cancer immunotherapy through an in vivo CRISPR screen.2 However, this challenging target class had previously been deemed "undruggable". AbbVie researchers overcame the challenges and discovered the dual PTPN2/N1 inhibitor, ABBV-CLS-484, through structure-based drug design and optimization of drug-like properties.
Discovery scientists at AbbVie, the Broad, and Calico further uncovered the biology and mechanism of action of ABBV-CLS-484. Preclinical findings presented demonstrate that ABBV-CLS-484 treatment amplifies the tumor intrinsic response to interferon and increases the activation and function of several immune cell subsets promoting cellular pathways including JAK-STAT signaling in animal models. In murine cancer models resistant to PD-1 blockade, monotherapy ABBV-CLS-484 treatment generates robust anti-tumor immunity. Through in vivo studies and single cell transcriptional profiling of tumor-infiltrating lymphocytes from ABBV-CLS-484 treated mice, the team revealed that ABBV-CLS-484 inflames the tumor microenvironment and promotes NK and CD8+ T-cell function. In T cells, mechanistically, ABBV-CLS-484 induces epigenetic and metabolic changes resulting in a unique functional state causing increased cytotoxicity and reduced T-cell exhaustion and dysfunction.
"Immunotherapies like PD-1 blockade have revolutionized cancer treatment; however, many patients do not respond well to them, and a significant unmet need remains," said Christina Baumgartner, Ph.D., co-first author and senior principal research scientist, AbbVie. "Through the extraordinary efforts of AbbVie's medicinal chemistry team to drug the undruggable, we now have a potential first-in-class PTPN2/N1 inhibitor. We're excited to share its biology and mechanism of action, and look forward to further evaluating it in the clinic."
"This study is a powerful demonstration of how collaboration can bring together diverse expertise to advance our understanding of disease biology and lead to discoveries that support new treatment strategies for people living with cancer," said Marcia Paddock, M.D., Ph.D., co-author and director of oncology new target development at Calico. "We are proud to be working with both AbbVie and the Broad Institute and look forward to sharing additional progress from our clinical studies of this novel immunotherapy."
ABBV-CLS-484 is the first active-site phosphatase inhibitor to enter clinical evaluation as a cancer therapy and is currently in an AbbVie and Calico-led Phase 1 clinical trial in solid tumors (NCT04777994).
"This is an unprecedented opportunity to evaluate how immune responses work," said Robert Manguso, Ph.D., co-senior author on the study, associate member at the Broad, and assistant professor at the Massachusetts General Hospital Center for Cancer Research and Harvard Medical School. "The ability to further explore this signaling pathway in clinical studies is really important."
About AbbVie
AbbVie's mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas – immunology, oncology, neuroscience, and eye care – and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on LinkedIn, Facebook, Instagram, X (formerly Twitter), and YouTube
About Calico
Calico (Calico Life Sciences LLC) is an Alphabet-founded research and development company whose mission is to harness advanced technologies and model systems to increase our understanding of the biology that controls human aging. Calico will use that knowledge to devise interventions that enable people to lead longer and healthier lives. To learn more about Calico, visit www.calicolabs.com. Follow @calico on LinkedIn, X (formally Twitter) and YouTube.
SOURCE AbbVie
ABBV Dividend History
https://www.nasdaq.com/market-activity/stocks/abbv/dividend-history
RGX-202
ABBV-CLS-484
ABBV-CLS-484
REGENXBIO Presents Interim Clinical Data from Phase I/II AFFINITY DUCHENNE™ Trial of RGX-202 at 28th Annual International Congress of the World Muscle Society
Oct 03, 2023 at 4:05 PM EDT
- RGX-202, a potential one-time AAV Therapeutic for the treatment of Duchenne that includes an optimized transgene for a novel microdystrophin, continues to be well-tolerated in three patients from dose level 1 (1x1014 GC/kg)
- Initial biomarker data in two patients who completed three-month assessment demonstrate robust microdystrophin expression with localization to the muscle cell membrane
- Patient aged 4.4 years old had expression level at 38.8% of control
- Trial dose escalation expected by end of 2023
- Pivotal dose determination and initiation of pivotal program anticipated in 2024
- Plan to use RGX-202 microdystrophin as a surrogate endpoint to support a Biologics License Application filing using the accelerated approval pathway
- RGX-202 development program uses commercial-ready cGMP material from the REGENXBIO Manufacturing Innovation Center
- Conference call today, Tuesday, October 3, 2023, at 4:30 p.m. ET
ROCKVILLE, Md., Oct. 3, 2023 /PRNewswire/ -- REGENXBIO Inc. (Nasdaq: RGNX) today announced additional interim safety data and initial efficacy data from the Phase I/II AFFINITY DUCHENNE™ trial of RGX-202 for the treatment of Duchenne Muscular Dystrophy (Duchenne). Results were shared at the 28th Annual International Congress of the World Muscle Society.
"Duchenne is a rare degenerative disease, and without a functional dystrophin protein, muscles progressively weaken, leading to loss of mobility and declining respiratory and cardiac function," said Olivier Danos, Ph.D., Chief Scientific Officer of REGENXBIO. "The unique construct of RGX-202, inclusive of the C-Terminal domain, has the potential to make a meaningful impact for patients and we are encouraged by these interim safety and efficacy results."
RGX-202 is an investigational one-time AAV therapeutic for Duchenne, using the NAV® AAV8 vector to deliver a transgene for a novel microdystrophin that includes the functional elements of the C-Terminal (CT) domain as well as a muscle-specific promoter to support a targeted therapy for improved resistance to muscle damage associated with Duchenne.
Data were presented from dose level 1 (1x1014 genome copies (GC)/kg body weight) of the ongoing Phase I/II AFFINITY DUCHENNE™ trial, which continues to recruit ambulatory patients (aged 4 to 11 years) and is using commercial-ready cGMP material from the REGENXBIO Manufacturing Innovation Center.
Safety Update
As of September 28, 2023, RGX-202 was reported to be well tolerated with no drug-related serious adverse events in three patients, aged 4.4, 10.6 and 6.3 years, dosed to date at dose level 1. Time of post-administration follow up ranges from three weeks to more than five months. The two patients who reached three-month follow-up have completed the immunosuppression regimen per study protocol.
Biomarker Data
Initial biomarker data from two patients who completed three-month trial assessments indicate encouraging increases in expression of RGX-202 microdystrophin from bicep muscle biopsies taken at three months following one-time administration of RGX-202. In addition, RGX-202 microdystrophin was detectable by immunofluorescence staining throughout muscle tissue at three months, with RGX-202 microdystrophin protein localized to the sarcolemma.
RGX-202 microdystrophin levels were measured using an automated and precise western blot method (Jess), and comparable results were confirmed with a proprietary liquid chromatography-mass spectrometry (LC-MS) method.
In the patient aged 4.4 years old, RGX-202 microdystrophin expression was measured to be 38.8% compared to control. A reduction from baseline in serum creatinine kinase (CK) levels of 43% was observed at ten weeks, supporting evidence of clinical improvement. Elevated CK levels are associated with muscle injury and are uniformly elevated in patients with Duchenne.
In the patient aged 10.6 years old, RGX-202 microdystrophin expression was measured to be 11.1% compared to control and a reduction from baseline in serum CK levels of 44% was observed at ten weeks.
"I am encouraged by these initial results demonstrating that RGX-202 appears to be well tolerated and leads to robust microdystrophin expression in muscle tissue, which are important early findings," said Aravindhan Veerapandiyan, M.D., Pediatric Neuromuscular Neurologist, Arkansas Children's Hospital, and primary investigator in the trial. "I know that there is still unmet need for these boys for new treatment options that have the potential to impact the trajectory of the disease."
Clinical Program Updates
REGENXBIO expects to dose patients at dose level 2 (2x1014 genome copies (GC)/kg body weight) in the Phase I/II AFFINITY DUCHENNE trial by the end of 2023. In addition, the trial protocol has been amended to accelerate the development of RGX-202, updating the dose expansion phase of the trial to begin after two patients, from the previous three patients.
Today, REGENXBIO also provided an update on a newly completed preclinical efficacy study evaluating RGX-202 manufactured using REGENXBIO's NAVXpress™ commercial-ready process at both dose levels. RGX-202 at dose level 2 showed improvement in functional performance, compared to dose level 1, as determined by forelimb muscle strength and treadmill exhaustion in mdx mice. This data further supports plans to immediately initiate dose escalation to dose level 2.
The Company expects to share initial strength and functional assessment data for both dose levels in 2024. Additionally, REGENXBIO expects to make a pivotal dose determination and initiate a pivotal program for RGX-202 in 2024.
"We are pleased to share these encouraging results and updates, enabling us to accelerate our development of RGX-202 with the goal of reaching pivotal phase faster," said Kenneth T. Mills, President and Chief Executive Officer of REGENXBIO. "We plan to scale up production of RGX-202 using commercial-ready cGMP material from the REGENXBIO Manufacturing Innovation Center to support a pivotal program in 2024, with a clear path to submit a BLA using the accelerated approval pathway, with RGX-202 microdystrophin as a surrogate endpoint for clinical benefit. This update firmly establishes RGX-202 as a key feature of our '5x'25' vision to have five gene therapies either on the market or in late-stage development by 2025."
Conference Call Details
REGENXBIO will host a conference call Tuesday, October 3 at 4:30 p.m. ET with principal investigator, Dr. Aravindhan Veerapandiyan, to discuss these results and the RGX-202 program.
Listeners can register for the webcast via this LINK. Analysts wishing to participate in the question and answer session should use this LINK. A copy of the slides being presented will be available via the Company's investor website. Those who plan on participating are advised to join 15 minutes prior to the start time. A replay of the webcast will also be available via the Company's investor website approximately two hours after the call's conclusion.
AFFINITY DUCHENNE Trial Design
The Phase I/II AFFINITY DUCHENNE trial is a multicenter, open-label dose escalation and dose expansion clinical study to evaluate the safety, tolerability and clinical efficacy of a one-time intravenous (IV) dose of RGX-202 in patients with Duchenne. In the dose evaluation phase of the trial, four ambulatory, pediatric patients (ages 4 to 11 years old) are expected to enroll in two cohorts with doses of 1x1014 genome copies (GC)/kg body weight (n=2) and 2x1014 GC/kg body weight (n=2). After an independent safety data review for each cohort, a dose expansion phase of the trial may allow for up to seven additional patients to be enrolled at each dose level (for a total of up to nine patients in each dose cohort).
The trial design consists of thorough safety measures informed by the Duchenne community and engagement with key opinion leaders, including a comprehensive, short-term, prophylactic immunosuppression regimen to proactively mitigate potential complement-mediated immunologic responses, and inclusion criteria based on dystrophin gene mutation status, including DMD gene mutations in exons 18 and above. Trial endpoints include safety, immunogenicity assessments, pharmacodynamic and pharmacokinetic measures of RGX-202, including microdystrophin protein levels in muscle, and strength and functional assessments, including the North Star Ambulatory Assessment (NSAA) and timed function tests. Initial trial sites are located in the U.S., with additional sites in Canada and Europe expected to follow.
About RGX-202
RGX-202 is designed to deliver a transgene for a novel microdystrophin that includes the functional elements of the C-Terminal (CT) domain found in naturally occurring dystrophin. Presence of the CT domain has been shown in preclinical studies to recruit several key proteins to the muscle cell membrane, leading to improved muscle resistance to contraction-induced muscle damage in dystrophic mice. Additional design features, including codon optimization and reduction of CpG content, may potentially improve gene expression, increase translational efficiency and reduce immunogenicity. RGX-202 is designed to support the delivery and targeted expression of genes throughout skeletal and heart muscle using the NAV AAV8 vector, a vector used in numerous clinical trials, and a well-characterized muscle-specific promoter (Spc5-12).
About Duchenne Muscular Dystrophy
Duchenne is a severe, progressive, degenerative muscle disease, affecting 1 in 3,500 to 5,000 boys born each year worldwide. Duchenne is caused by mutations in the Duchenne gene which encodes for dystrophin, a protein involved in muscle cell structure and signaling pathways. Without dystrophin, muscles throughout the body degenerate and become weak, eventually leading to loss of movement and independence, required support for breathing, cardiomyopathy and premature death.
About REGENXBIO Inc.
REGENXBIO is a leading clinical-stage biotechnology company seeking to improve lives through the curative potential of gene therapy. REGENXBIO's NAV Technology Platform, a proprietary adeno-associated virus (AAV) gene delivery platform, consists of exclusive rights to more than 100 novel AAV vectors, including AAV7, AAV8, AAV9 and AAVrh10. REGENXBIO and its third-party NAV Technology Platform Licensees are applying the NAV Technology Platform in the development of a broad pipeline of candidates, including late-stage and commercial programs, in multiple therapeutic areas. REGENXBIO is committed to a "5x'25" strategy to progress five AAV Therapeutics from our internal pipeline and licensed programs into pivotal-stage or commercial products by 2025.
View original content to download multimedia:
SOURCE REGENXBIO Inc.
Regenxbio up after hours on early-stage Duchenne candidate
Oct. 03, 2023 6:30 PM ET
By: Jonathan Block, SA News Editor
- Regenxbio has ticked up 2% in after-hours trading after positing encouraging data for its Duchenne muscular dystrophy candidate, RGX-202.
- The asset is a mediated adeno-associated virus using NAV AAV8 vector to deliver a transgene for a novel microdystrophin, the company says.
- Interim data presented at a medical conference Tuesday found bno reports of serious drug-related adverse events. Two out of three children reached three-month follow up.
- https://seekingalpha.com/news/4017975-regenxbio-up-after-hours-early-stage-duchenne-muscular-dystrophy-candidate
- REGENXBIO Inc. (RGNX)
- https://www.regenxbio.com/therapeutic-programs/rgx-202/
- https://www.regenxbio.com/home/
VX-880
ABBV-CLS-484
Evorpacept
Oct 3, 2023
Vertex Presents Positive, Updated VX-880 Results From Ongoing Phase 1/2 Study in Type 1 Diabetes at the European Association for the Study of Diabetes 59th Annual Meeting
- All patients treated with VX-880 in Parts A and B have follow-up data beyond Day 90 and have demonstrated islet cell engraftment and glucose-responsive insulin production -
- All patients showed improvement across all measures of glucose control, including decreases in HbA1c, increases in blood glucose time-in-range, and reduction or elimination of insulin use -
- The two patients with at least 1 year of follow-up met the criteria for the primary endpoint of elimination of severe hypoglycemic events (SHEs) and HbA1c <7.0% -
- VX-880 was generally well tolerated -
- Part C concurrent dosing well underway -
BOSTON--(BUSINESS WIRE)--Oct. 3, 2023-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today presented longer-term data on patients dosed in Parts A and B of its Phase 1/2 clinical trial of VX-880, an investigational stem cell-derived, fully differentiated islet cell therapy in people with type 1 diabetes (T1D) with impaired hypoglycemic awareness and severe hypoglycemic events (SHEs). Prior to VX-880 treatment, all six patients enrolled had long-standing T1D with no endogenous insulin secretion, required an average of 34.0 units of insulin per day, and had a history of recurrent severe hypoglycemic events (SHEs) in the year prior to screening.
All patients in Part A and B now have more than 90 days of follow-up and have demonstrated islet cell engraftment and endogenous glucose-responsive insulin production on the Day 90 mixed-meal tolerance test (MMTT). All patients demonstrated improved glycemic control across all measures, including decreases in HbA1c, improved time-in-range on continuous insulin monitoring, and reduction or elimination of exogenous insulin use.
The two patients with at least 12 months of follow-up after VX-880 infusion, who were therefore evaluable for the study’s primary efficacy endpoint, met the criteria for the primary endpoint of elimination of SHEs between Day 90 and Month 12 with an HbA1c <7.0%. The first patient achieved insulin independence at Day 270 through Month 24. This is a patient who has had T1D for nearly 42 years and prior to trial enrollment was on 34 units of daily exogenous insulin. The second patient achieved insulin independence at Day 180 through Month 12. This is a patient who has had T1D for 19 years and prior to trial enrollment was on 45.1 units of daily exogenous insulin. Starting at Month 15, this patient was started on four units of basal insulin daily, at the investigator’s discretion. After the data cut-off date, a third patient achieved insulin independence at Day 180.
VX-880 has been generally well tolerated in all patients dosed to date. The majority of adverse events (AEs) were mild or moderate, and there were no serious AEs related to VX-880 treatment. As previously reported, one subject had SHEs in the perioperative period. There have been no other SHEs in the study.
“We continue to marvel at the impressive data from the VX-880 program as evidenced by the improvements in all treated patients across all glycemic measures,” said Trevor Reichman, M.D., Department of Surgery, University of Toronto. “This represents an incredibly promising investigational therapy, one with far-reaching potential.”
“These data are particularly meaningful in the context of our overall investigational T1D program, as these same VX-880 cells are the foundation for our VX-264 cells-plus-device program, and our hypoimmune islet cell program,” said Carmen Bozic, M.D., Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex. “We are moving with urgency to bring these potentially transformative therapies to patients who are waiting.”
These data were presented during the European Association for the Study of Diabetes 59th Annual Meeting on October 3, 2023, in Hamburg, Germany as an oral presentation, “Glucose-Dependent Insulin Production and Insulin-Independence in Patients with Type 1 Diabetes Infused with Stem Cell-Derived, Fully Differentiated Islet Cells (VX-880)” (abstract/publication #449).
About Vertex T1D Programs in Clinical Development
About VX-880
VX-880 is an investigational allogeneic stem cell-derived, fully differentiated, insulin-producing islet cell therapy manufactured using proprietary technology. VX-880 is being evaluated for patients who have T1D with impaired hypoglycemic awareness and severe hypoglycemia. VX-880 has the potential to restore the body’s ability to regulate glucose levels by restoring pancreatic islet cell function, including glucose responsive insulin production. VX-880 is delivered by an infusion into the hepatic portal vein and requires chronic immunosuppressive therapy to protect the islet cells from immune rejection. The VX-880 trial has expanded to additional sites that are currently active and enrolling in the U.S., Canada, U.K., Germany, Norway, Switzerland, Italy, Netherlands, and France.
VX-880 was recently granted PRIME designation by the European Medicines Agency in March 2023, in addition to Fast Track Designation by the U.S. FDA in March 2021. PRIME designation is granted to innovative new therapies that have demonstrated the potential to significantly address an unmet medical need.
About the VX-880 Phase 1/2 Clinical Trial
The clinical trial is a Phase 1/2, multi-center, single-arm, open-label study in patients who have T1D with impaired hypoglycemic awareness and severe hypoglycemia. This study is designed as a sequential, multi-part clinical trial to evaluate the safety and efficacy of VX-880. Approximately 17 patients will be enrolled in the clinical trial. Enrollment in Part C of the study is ongoing and multiple patients have been dosed.
About VX-264
VX-264 is an investigational cell therapy in which allogeneic human stem cell-derived islets are encapsulated in a channel array device designed to shield the cells from the body’s immune system. VX-264 is designed to be surgically implanted and is currently being evaluated for patients with T1D.
About the VX-264 Phase 1/2 Clinical Trial
The clinical trial is a Phase 1/2, single-arm, open-label study in patients who have T1D. This will be a sequential, multi-part clinical trial to evaluate the safety, tolerability, and efficacy of VX-264. Approximately 17 patients will be enrolled in the global clinical trial. Enrollment is ongoing in this study.
About Type 1 Diabetes
T1D results from the autoimmune destruction of insulin-producing islet cells in the pancreas, leading to loss of insulin production and impairment of blood glucose control. The absence of insulin leads to abnormalities in how the body processes nutrients, leading to high blood glucose levels. High blood glucose can lead to diabetic ketoacidosis and, over time, to complications such as kidney disease/failure, eye disease (including vision loss), heart disease, stroke, nerve damage, and even death.
Due to the limitations and complexities of insulin delivery systems, it can be difficult to achieve and maintain balance in glucose control in people with T1D. Current standards of care do not address the underlying causes of the disease, and there are limited treatment options beyond insulin for the management of T1D; there is currently no cure for diabetes.
About Vertex
Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has multiple approved medicines that treat the underlying cause of cystic fibrosis (CF) — a rare, life-threatening genetic disease — and has several ongoing clinical and research programs in CF. Beyond CF, Vertex has a robust clinical pipeline of investigational small molecule, mRNA, cell and genetic therapies (including gene editing) in other serious diseases where it has deep insight into causal human biology, including sickle cell disease, beta thalassemia, APOL1-mediated kidney disease, acute and neuropathic pain, type 1 diabetes, and alpha-1 antitrypsin deficiency.
Founded in 1989 in Cambridge, Mass., Vertex's global headquarters is now located in Boston's Innovation District and its international headquarters is in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia, and Latin America. Vertex is consistently recognized as one of the industry's top places to work, including 13 consecutive years on Science magazine's Top Employers list and one of Fortune’s 100 Best Companies to Work For. For company updates and to learn more about Vertex's history of innovation, visit www.vrtx.com or follow us on Facebook, Twitter, LinkedIn, YouTube, and Instagram.
View source version on businesswire.com: https://www.businesswire.com/news/home/20231003786678/en/
Source: Vertex Pharmaceuticals Incorporated
Vertex updated data on diabetes candidate VX-880 encouraging
Oct. 03, 2023 7:09 PM ET
Vertex Pharmaceuticals Incorporated (VRTX)
By: Jonathan Block, SA News Editor2 Comments
- Updated data from Vertex Pharmaceuticals (NASDAQ:VRTX) type 1 diabetes candidate VX-880 indicated that reductions in HbA1c were seen in all patients on the stem cell-derived therapy.
- At 90 days, all patients on treatment demonstrated improved time-in-range on continuous insulin monitoring, and reduction or elimination of exogenous insulin use.
- https://seekingalpha.com/news/4017977-vertex-updated-data-diabetes-candidate-vx-880-encouraging
- Vertex Pharmaceuticals Incorporated (VRTX)
- https://www.vrtx.com/our-science/pipeline/
- https://www.vrtx.com/
Evorpacept
Odronextamab
Evorpacept
ALX Oncology Reports Positive Interim Phase 2 ASPEN-06 Clinical Trial Results of Evorpacept for the Treatment of Advanced HER2-Positive Gastric Cancer
-- Evorpacept is the first CD47 blocker to show activity in a global randomized study in solid tumors
-- Interim efficacy results showed the confirmed overall response rate for evorpacept combination treatment was 52% compared to 22% for control treatment
-- Company to host conference call and webcast today at 8:00 AM EDT
SOUTH SAN FRANCISCO, Calif., Oct. 03, 2023 (GLOBE NEWSWIRE) -- ALX Oncology Holdings Inc., (“ALX Oncology” or the “Company”) (Nasdaq: ALXO), an immuno-oncology company developing therapies that block the CD47 immune checkpoint pathway, today announced positive prespecified interim Phase 2 data from its ASPEN-06 clinical trial, a randomized multi-center international study evaluating evorpacept, the Company’s CD47 blocking therapeutic, in combination with trastuzumab, CYRAMZA® (ramucirumab) and paclitaxel for the treatment of patients with HER2-positive gastric/gastroesophageal junction (“GEJ”) cancer. This prespecified interim analysis represents results from 54 randomized patients with second and third line gastric/GEJ cancer, including a meaningful number of patients previously treated with ENHERTU® (trastuzumab deruxtecan) and checkpoint inhibitors. Patients were treated with evorpacept at 30 mg/kg every two weeks, mirroring the treatment cycle of trastuzumab, CYRAMZA and paclitaxel.
Phase 2 ASPEN-06 Interim Analysis Results:
- A confirmed overall response rate (“ORR”) of 52% was demonstrated for evorpacept in combination with trastuzumab + CYRAMZA + paclitaxel compared to 22% for the control group of trastuzumab + CYRAMZA + paclitaxel.
- Median duration of response (“mDOR”) was not reached for the evorpacept combination treatment arm compared to 7.4 months for the control group.
- The safety profile of evorpacept was consistent with previous clinical trials and was well-tolerated.
- These interim results compare favorably to the efficacy reported for CYRAMZA + paclitaxel in the RAINBOW study (ORR of 28% and mDOR of 4.4 months), which is the regulatory benchmark and global standard of care for second line gastric/GEJ cancer.
“The ASPEN-06 clinical trial validates the potential of evorpacept both in solid tumors and in combination with anti-cancer antibodies and these data highlight the drug’s potential as a first-in-class foundational immunotherapy,” said Sophia Randolph, M.D., Ph.D., Chief Medical Officer, ALX Oncology. “We are highly encouraged by these initial randomized efficacy and safety results in gastric cancer that build upon the activity previously seen in our first-in-human study and represent the first positive randomized clinical trial data presented for any CD47 blocker. In addition, ASPEN-06 is the first global randomized study in HER2-positive gastric cancer where prior KEYTRUDA® (pembrolizumab) and ENHERTU were allowed. We look forward to reporting the final analysis from the ongoing Phase 2 ASPEN-06 study in Q2 2024 and plan to initiate the Phase 3 portion of ASPEN-06 in late 2024.”
“These data in gastric cancer represent the first positive initial result in a randomized trial setting of blocking the CD47 immune checkpoint pathway with a CD47 blocker that has an inactive Fc effector function in order to treat patients living with advanced gastric cancer,” said Keun Wook Lee, M.D., Ph.D., Professor at Seoul National University College of Medicine and ASPEN-06 Principal Investigator. “Patients with advanced disease face poor outcomes following progression on initial treatment with HER2-directed therapy. Evorpacept could represent a breakthrough in therapy and a potential paradigm shift in the gastric cancer care continuum.”
Upcoming Clinical Milestones for Evorpacept’s Development Pipeline
- 1H 2024
- Non-Hodgkin Lymphoma - Phase 1b investigator-sponsored trial with rituximab + lenalidomide top line results (Q1/Q2 2024)
- Gastric/GEJ Cancer – Phase 2 ASPEN-06 randomized top line final results (Q2 2024)
- 2H 2024
- Head and Neck Squamous Cell Carcinoma – Phase 2 ASPEN-03 with KEYTRUDA randomized top line results
- Head and Neck Squamous Cell Carcinoma – Phase 2 ASPEN-04 with KEYTRUDA + chemotherapy randomized top line results
- Gastric/GEJ Cancer – Phase 3 ASPEN-06 study initiation
- Urothelial Carcinoma – Phase 1b ASPEN-07 with PADCEV® (enfortumab vedotin-ejfv) top line results
- Breast Cancer – Phase 1b I-SPY study with ENHERTU top line results
Conference Call on October 3 at 8:00 am EDT
The Company will host a conference call and webcast today at 8:00 AM EDT that will feature ASPEN-06 investigator Dr. Josep Tabernero, Director of the Vall d’Hebron Institute of Oncology and Head of the Medical Oncology Department at the Vall d’Hebron University Hospital in Barcelona, Spain and past President of the European Society of Medical Oncology.
To access the live conference call, please dial (800) 715-9871 (U.S./Canada) or +44.800.260.6466 (internationally) at least 10 minutes prior to the start time and refer to conference ID 7797378. The link to the live webcast of the conference call will be posted in the News & Events section (see “Events”) of the Company’s website at www.alxoncology.com. An archived replay will be accessible for 90 days following the event.
About the ASPEN-06 Study
ASPEN-06 is a randomized Phase 2 (open-label) / Phase 3 (double-blinded), multi-center international study of patients with second or third line metastatic HER2-overexpressing gastric/GEJ adenocarcinoma that has progressed on or after prior HER2-directed therapy and fluoropyrimidine- or platinum-containing chemotherapy. While trastuzumab is currently approved in combination with cisplatin or capecitabine for HER2-positive gastric/GEJ cancers, it is not yet approved with the standard-of-care of CYRAMZA + paclitaxel. The Phase 2 portion of the ASPEN-06 study is designed to enroll 122 patients who have progressed on, or after prior HER2-directed therapy and fluoropyrimidine and/or platinum-containing regimens. To determine the activity of evorpacept + trastuzumab + CYRAMZA + paclitaxel, in the Phase 2 portion of ASPEN-06, patients are randomized to receive either a four-drug combination regimen (evorpacept + trastuzumab + CYRAMZA + paclitaxel) or a three-drug combination regimen (trastuzumab + CYRAMZA + paclitaxel). This design enables the assessment of evorpacept’s contribution to the standard of care plus trastuzumab and to global standard of care, CYRAMZA + paclitaxel. Should the Phase 2 portion of the trial demonstrate proof of concept, the trial will progress to the Phase 3 portion where the evorpacept containing four-drug regimen will be tested against the two-drug global standard of care of CYRAMZA + paclitaxel.
About Gastric Cancer and Gastroesophageal Junction Cancer
Gastric cancer (“GC”) begins in the cells lining the inner wall of the stomach and spreads through the outer layers and eventually the body as it grows. GC is the fifth most common cancer worldwide and the third leading cause of cancer mortality as reported by GLOBOCAN. The American Cancer Society estimates there will be 26,500 newly diagnosed cases of GC at all stages in the U.S. in 2023, and approximately 17 percent of all GC patients have HER2-positive disease. The five-year survival rate is only 5.5 percent for those patients diagnosed with metastatic disease. GC is more common in East Asian countries, with incidence rates 4 to 10 times higher than in the U.S.
About ALX Oncology
ALX Oncology is a publicly traded, clinical-stage immuno-oncology company focused on helping patients fight cancer by developing therapies that block the CD47 immune checkpoint inhibitor and bridge the innate and adaptive immune system. ALX Oncology’s lead product candidate, evorpacept, is a next generation CD47 blocking therapeutic that combines a high-affinity CD47 binding domain with an inactivated, proprietary Fc domain. Evorpacept has demonstrated promising clinical responses across a range of hematologic and solid malignancies in combination with a number of leading anti-cancer antibodies. ALX Oncology is currently focusing on combining evorpacept with anti-cancer antibodies, ADCs, and PD-1/PD-L1 immune checkpoint inhibitors.
ALX Oncology surges on Phase 2 data for gastric cancer therapy
Oct. 03, 2023 6:56 AM ET
ALX Oncology Holdings Inc. (ALXO)LLY
By: Dulan Lokuwithana, SA News Editor
ALX Oncology (NASDAQ:ALXO) shares jumped ~67% pre-market Tuesday after the company posted results from a Phase 2 trial for its lead candidate evorpacept in a combination therapy for HER2-positive gastric/gastroesophageal junction ("GEJ") cancer.
The ASPEN-06 trial was designed to evaluate the CD47-blocker with cancer drugs, trastuzumab, paclitaxel, along with Cyramza, Eli Lilly's (LLY) vascular endothelial growth factor (VEGF) receptor antagonist.
According to the company, those who received the evorpacept-containing regimen indicated a confirmed overall response rate of 52% compared to 22% in the control group.
Patients in the evorpacept-contiaing arm didn't reach a median duration of response, while those in the control group showed a mDOR of 7.4 months.
https://seekingalpha.com/news/4017447-alx-oncology-stock-jumps-data-gastric-cancer-drug
ALX Oncology Holdings Inc. (ALXO)
Odronextamab
Odronextamab
Odronextamab
September 29, 2023 at 8:30 AM EDT
ODRONEXTAMAB BLA FOR TREATMENT OF RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA (FL) AND DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) ACCEPTED FOR FDA PRIORITY REVIEW
If approved, odronextamab would be the first and only bispecific antibody approved in both FL and DLBCL – the two most common subtypes of non-Hodgkin lymphoma
European Medicines Agency also reviewing odronextamab Marketing Authorization Application
TARRYTOWN, N.Y., Sept. 29, 2023 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced that the U.S. Food and Drug Administration (FDA) has accepted for Priority Review the Biologics License Application (BLA) for odronextamab to treat adult patients with relapsed/refractory (R/R) follicular lymphoma (FL) or R/R diffuse large B-cell lymphoma (DLBCL), who have progressed after at least two prior systemic therapies. The target action date for the FDA decision is March 31, 2024. Odronextamab is an investigational CD20xCD3 bispecific antibody designed to bridge CD20 on cancer cells with CD3-expressing T cells to facilitate local T-cell activation and cancer-cell killing.
The BLA was supported by data from a Phase 1 and pivotal Phase 2 trial (ELM-1 and ELM-2). Results from these studies investigating odronextamab in both FL and DLBCL were last presented at the 64th American Society of Hematology Annual Meeting.
The FDA previously granted odronextamab Orphan Drug Designation and Fast Track Designation for FL and DLBCL. In August, the European Medicines Agency accepted for review a Marketing Authorization Application for odronextamab for the treatment of adult patients with R/R FL or R/R DLBCL who have progressed after at least two prior systemic therapies.
FL and DLBCL are the two most common subtypes of B-cell non-Hodgkin lymphoma (B-NHL). FL is a slow-growing subtype, and although many patients are responsive to initial treatment, approximately 20% are expected to relapse within two years and have shorter remissions with each successive line of therapy. DLBCL is an aggressive subtype, with up to 50% of high-risk patients experiencing progression after first-line treatment (e.g., relapsing or refractory to treatment). As these blood cancers progress, they become increasingly hard to treat, especially in the third-line setting and beyond, leaving patients with few treatment options.
Odronextamab is currently under clinical development, and its safety and efficacy have not been fully evaluated by any regulatory authority.
About the Odronextamab Clinical Program
ELM-1 is an ongoing, open-label, multicenter Phase 1 trial to investigate the safety and tolerability of odronextamab in patients with CD20+ B-cell malignancies previously treated with CD20-directed antibody therapy, including an expansion cohort evaluating DLBCL patients who had progressed on CAR-T therapy (post-CAR-T). ELM-2 is an ongoing, open-label, multicenter pivotal Phase 2 trial investigating odronextamab in 375 patients across five independent disease-specific cohorts, including DLBCL, FL, mantle cell lymphoma, marginal zone lymphoma and other subtypes of B-NHL. The primary endpoint of ELM-2 is objective response rate according to the Lugano Classification, and secondary endpoints include complete response, progression-free survival, overall survival, duration of response, disease control rate, safety and quality of life.
Regeneron is also initiating a broad Phase 3 development program to investigate odronextamab in earlier lines of therapy and other B-NHLs, representing one of the largest clinical programs in lymphoma.
About Regeneron’s Approach to Cancer Research
At Regeneron, we’re applying more than three decades of scientific innovation with the goal of developing paradigm-changing therapies for patients with cancer.
Our portfolio is built around two foundational approaches – our approved PD-1 inhibitor Libtayo® (cemiplimab-rwlc) and investigational bispecific antibodies – which are being evaluated both as monotherapies and in combination with emerging therapeutic modalities. Together, they provide us with unique combinatorial flexibility to develop potentially synergistic treatments for a wide range of solid tumors and blood cancers.
If you are interested in learning more about our clinical trials, please contact us (clinicaltrials@regeneron.com or 1-844-734-6643) or visit our clinical trials website.
About Regeneron
Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led for 35 years by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to numerous FDA-approved treatments and product candidates in development, almost all of which were homegrown in our laboratories. Regeneron’s medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, hematologic conditions, infectious diseases and rare diseases.
Regeneron is accelerating and improving the traditional drug development process through its proprietary VelociSuite® technologies, such as VelocImmune®, which uses unique genetically humanized mice to produce optimized fully human antibodies and bispecific antibodies, and through ambitious research initiatives such as the Regeneron Genetics Center®, which is conducting one of the largest genetics sequencing efforts in the world.
For additional information about Regeneron, please visit www.regeneron.com or follow Regeneron on LinkedIn.
Source: Regeneron Pharmaceuticals, Inc.
Regeneron nabs FDA priority review for lymphoma therapy
Sep. 29, 2023 10:57 AM ET
Regeneron Pharmaceuticals, Inc. (REGN)
By: Dulan Lokuwithana, SA News Editor
- Regeneron Pharmaceuticals (NASDAQ:REGN) announced Friday that the U.S. FDA accepted its Biologics License Application (BLA) for bispecific antibody odronextamab to review it on a priority basis for certain adults with lymphoma as a late-line option.
- The BLA is aimed at securing U.S. marketing authorization for odronextamab to treat relapsed or refractory follicular lymphoma ((F.L.)) or R/R diffuse large B-cell lymphoma (DLBCL), the most common subtypes of B-cell non-Hodgkin lymphoma.
- https://seekingalpha.com/news/4016777-regeneron-nabs-fda-priority-review-lymphoma-therapy
- Regeneron Pharmaceuticals, Inc. (REGN)
- https://www.regeneron.com/
Sotatercept
Odronextamab
Odronextamab
Merck Receives Priority Review from FDA for New Biologics License Application for Sotatercept, an Activin Signaling Inhibitor to Treat Adults with Pulmonary Arterial Hypertension (PAH)
September 28, 2023 6:45 am ET
Application based on clinically meaningful results from the Phase 3 STELLAR trial
If approved, sotatercept would be the first in its class, bringing a novel approach to address a rare and progressive disease of the pulmonary arteries
RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced today that the U.S. Food and Drug Administration (FDA) has accepted for priority review a new Biologics License Application (BLA) for sotatercept, Merck’s novel investigational activin signaling inhibitor, for the treatment of adult patients with pulmonary arterial hypertension (PAH) (WHO Group 1). The FDA has set a Prescription Drug User Fee Act (PDUFA), or target action, date of March 26, 2024.
PAH is a rare, progressive and ultimately life-threatening disease characterized by the narrowing of blood vessels in the lungs, causing significant strain on the heart. The application for sotatercept is based on data from the Phase 3 STELLAR trial, in which sotatercept on top of background therapy demonstrated a statistically significant and clinically meaningful improvement in 6-minute walk distance (6MWD) and eight of nine secondary outcome measures. These results were presented at ACC.23/WCC and published in The New England Journal of Medicine.
“Despite advances in the treatment of PAH over the last two decades, there is still a significant need to improve outcomes for patients,” said Dr. Joerg Koglin, senior vice president, global clinical development, Merck Research Laboratories. “The FDA’s acceptance of this application is an exciting milestone in our journey to bring this novel activin signaling inhibitor to patients. Based on the profound improvements across primary and secondary outcome measures in the Phase 3 STELLAR trial, we believe sotatercept has the potential to transform the treatment of patients with PAH. We look forward to working closely with the FDA to bring sotatercept to patients in need.”
About STELLAR
STELLAR (NCT04576988) was a pivotal Phase 3, randomized, double-blind, placebo-controlled, multicenter, parallel-group study to evaluate the safety and efficacy of sotatercept in adult patients with PAH (WHO Group 1) being treated with background therapy with WHO Functional Class (FC) II or III. The primary endpoint of the study was exercise capacity, as measured by change from baseline in week 24 6MWD. Nine secondary endpoints, tested hierarchically in the following order, were multicomponent improvement, change in pulmonary vascular resistance (PVR), N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, improvement in WHO FC, time to clinical worsening or death, French risk score, and the PAH-SYMPACT® Physical Impacts, Cardiopulmonary Symptoms and Cognitive/Emotional Impacts domain scores; all assessed at week 24 except clinical worsening, which was assessed when the last patient completed the week 24 visit.
About pulmonary arterial hypertension (PAH)
Pulmonary arterial hypertension (PAH) is a rare, progressive and life-threatening blood vessel disorder characterized by the constriction of small pulmonary arteries and elevated blood pressure in the pulmonary circulation. Approximately 40,000 people in the U.S. are living with PAH. The disease progresses rapidly for many patients. PAH results in significant strain on the heart, leading to limited physical activity, heart failure and reduced life expectancy. The five-year mortality rate for patients with PAH is approximately 43%.
About sotatercept
Sotatercept is a potential first-in-class activin signaling inhibitor biologic being studied for the treatment of PAH (WHO Group 1). PAH is a rare disease caused by hyperproliferation of cells in the arterial walls in the lung, leading to narrowing and abnormal constriction. In pre-clinical models, sotatercept has been shown to modulate vascular cell proliferation, reversing vascular and right ventricle remodeling.
In addition to STELLAR, the sotatercept clinical development program includes multiple Phase 2 and 3 trials across a broad range of patients. Studies are underway in adult patients with PAH (WHO Group 1) at intermediate or high risk of disease progression or mortality, as well as with pulmonary hypertension due to left heart disease (WHO Group 2).
Sotatercept has been granted Breakthrough Therapy Designation and Orphan Drug designation by the U.S. Food and Drug Administration (FDA), as well as Priority Medicines designation and Orphan Drug designation by the European Medicines Agency for the treatment of PAH. Merck acquired exclusive rights to sotatercept in the pulmonary hypertension field through the acquisition of Acceleron Pharma Inc. Sotatercept is the subject of a licensing agreement with Bristol Myers Squibb.
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on Twitter,Facebook,Instagram,YouTube and LinkedIn.
Source: Merck & Co., Inc.
Merck wins FDA priority review for lung disease therapy
Sep. 28, 2023 7:06 AM ET
By: Dulan Lokuwithana, SA News Editor
- Merck (NYSE:MRK) announced Thursday that the U.S. FDA accepted its Biologics License Application (BLA) for sotatercept to review the drug on a priority basis as a treatment for pulmonary arterial hypertension (PAH), a blood vessel disorder.
- PAH is a rare condition characterized by the narrowing of tiny lung arteries and high blood pressure in the pulmonary circulation.
- The FDA has issued March 26, 2024, as the target action date to complete its review.
- The BLA is backed by data from a Phase 3 study called STELLAR in which those who received sotatercept in addition to background therapy indicated an improvement in exercise capacity, the trial's main goal as measured by 6-minute walk distance (6MWD).
- Merck (MRK) added sotatercept to its pipeline with its 2021 acquisition of Acceleron Pharma.
- https://seekingalpha.com/news/4016141-merck-wins-fda-priority-review-for-lung-disease-therapy
- Merck & Co., Inc. (MRK)
- https://www.merck.com/
- https://www.merck.com/research/product-pipeline/
MRK Dividend History
https://www.nasdaq.com/market-activity/stocks/mrk/dividend-history
biotecHOPE™ 2023
DUPIXENT® (DUPILUMAB)
Enrylaze® (JZP458) also known as JZP458 & approved as Rylaze® in the United States & Canada
Enrylaze® (JZP458) also known as JZP458 & approved as Rylaze® in the United States & Canada
September 26, 2023 at 1:29 AM EDT
DUPIXENT® (DUPILUMAB)
SBLA FOR TREATMENT OF EOSINOPHILIC ESOPHAGITIS (EOE) IN CHILDREN AGED 1 TO 11 ACCEPTED FOR FDA PRIORITY REVIEW
If approved, Dupixent would be the first and only treatment in the U.S. indicated for children aged 1 to 11 with EoE, a disease driven by type 2 inflammation that impacts the ability to eat
Of the approximately 21,000 children under the age of 12 in the U.S. currently being treated for EoE, about 9,000 do not satisfactorily respond to the unapproved therapies they have been treated with and potentially require advanced alternative therapy options
TARRYTOWN, N.Y. and PARIS, Sept. 26, 2023 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi today announced that the U.S. Food and Drug Administration (FDA) has accepted for Priority Review the supplemental Biologics License Application (sBLA) for Dupixent® (dupilumab) to treat children aged 1 to 11 years with eosinophilic esophagitis (EoE). The target action date for the FDA decision is January 31, 2024. Dupixent is the first and only treatment in the U.S. approved for children and adults aged 12 years and older with EoE, weighing at least 40kg.
The sBLA is supported by data from the Phase 3 EoE KIDS trial (Parts A and B) evaluating the efficacy and safety of Dupixent in children aged 1 to 11 with EoE. In Part A, the primary endpoint was met for the proportion of patients achieving histological disease remission (defined as peak esophageal intraepithelial eosinophil count of ≤6 eosinophils [eos]/high power field [hpf]) at 16 weeks for tiered dosing regimens based on body weight, compared to placebo. Part B was an active treatment extension period evaluating Dupixent for an additional 36 weeks and showed Dupixent maintained histologic remission for 52 weeks, a secondary endpoint. Dupixent also led to increases in body weight for age percentile, which was evaluated as an exploratory endpoint in Part A and a secondary endpoint in Part B.
Safety results in Parts A and B of the trial were generally consistent with the known safety profile of Dupixent in its FDA-approved EoE indication for children and adults aged 12 years and older who weigh at least 40kg. Adverse events more commonly observed (≥5%) with Dupixent compared to placebo were COVID-19, rash, headache, viral gastroenteritis, diarrhea and nausea.
Priority review is granted to therapies that have the potential to provide significant improvements in the treatment, diagnosis or prevention of serious conditions. The potential use of Dupixent in children with EoE aged 1 to 11 years is currently under clinical development, and its safety and efficacy have not been fully evaluated by any regulatory authority in this setting.
About Eosinophilic Esophagitis
EoE is a chronic, progressive disease driven by type 2 inflammation that damages the esophagus and prevents it from working properly. In children, common symptoms of EoE include heartburn, vomiting, abdominal discomfort, trouble swallowing, food refusal and failure to thrive. These symptoms can impact growth and development and can cause food-related fear and anxiety, which can persist through adulthood. Dietary adjustments, including the elimination of many foods, are the standard treatment for EoE, as well as the use of treatments not approved for the disease. These include proton pump inhibitors, swallowed topical corticosteroids, or in severe cases, a feeding tube, which may be used to ensure proper caloric intake and weight gain. Continuous treatment of EoE may be needed to reduce the risk of complications and disease recurrence.
About Dupixent
Dupixent, which was invented using Regeneron's proprietary VelocImmune® technology, is a fully human monoclonal antibody that inhibits the signaling of the interleukin-4 (IL-4) and interleukin-13 (IL-13) pathways and is not an immunosuppressant. The Dupixent development program has shown significant clinical benefit and a decrease in type 2 inflammation in Phase 3 trials, establishing that IL-4 and IL-13 are key and central drivers of the type 2 inflammation that plays a major role in multiple related and often co-morbid diseases. These diseases include approved indications for Dupixent, such as atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), prurigo nodularis and EoE.
Dupixent has received regulatory approvals in one or more countries around the world for use in certain patients with atopic dermatitis, asthma, CRSwNP, EoE and prurigo nodularis in different age populations. Dupixent is currently approved for one or more of these indications in more than 60 countries, including in Europe, the U.S. and Japan. More than 600,000 patients are being treated with Dupixent globally.
About Regeneron’s VelocImmune Technology
Regeneron's VelocImmune technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies. When Regeneron's co-Founder, President and Chief Scientific Officer George D. Yancopoulos was a graduate student with his mentor Frederick W. Alt in 1985, they were the first to envision making such a genetically humanized mouse, and Regeneron has spent decades inventing and developing VelocImmune and related VelociSuite® technologies. Dr. Yancopoulos and his team have used VelocImmune technology to create a substantial proportion of all original, FDA-approved or authorized fully human monoclonal antibodies. This includes REGEN-COV® (casirivimab and imdevimab), Dupixent, Libtayo® (cemiplimab-rwlc), Praluent® (alirocumab), Kevzara® (sarilumab), Evkeeza® (evinacumab-dgnb) and Inmazeb® (atoltivimab, maftivimab and odesivimab-ebgn).
Dupilumab Development Program
Dupilumab is being jointly developed by Regeneron and Sanofi under a global collaboration agreement. To date, dupilumab has been studied across more than 60 clinical trials involving more than 10,000 patients with various chronic diseases driven in part by type 2 inflammation.
In addition to the currently approved indications, Regeneron and Sanofi are studying dupilumab in a broad range of diseases driven by type 2 inflammation or other allergic processes in Phase 3 trials, including pediatric EoE, chronic spontaneous urticaria, chronic pruritus of unknown origin, chronic obstructive pulmonary disease with evidence of type 2 inflammation and bullous pemphigoid. These potential uses of dupilumab are currently under clinical investigation, and the safety and efficacy in these conditions have not been fully evaluated by any regulatory authority.
U.S. INDICATIONS
DUPIXENT is a prescription medicine used:
- to treat adults and children 6 months of age and older with moderate-to-severe eczema (atopic dermatitis or AD) that is not well controlled with prescription therapies used on the skin (topical), or who cannot use topical therapies. DUPIXENT can be used with or without topical corticosteroids. It is not known if DUPIXENT is safe and effective in children with atopic dermatitis under 6 months of age.
- with other asthma medicines for the maintenance treatment of moderate-to-severe eosinophilic or oral steroid dependent asthma in adults and children 6 years of age and older whose asthma is not controlled with their current asthma medicines. DUPIXENT helps prevent severe asthma attacks (exacerbations) and can improve your breathing. DUPIXENT may also help reduce the amount of oral corticosteroids you need while preventing severe asthma attacks and improving your breathing. DUPIXENT is not used to treat sudden breathing problems. It is not known if DUPIXENT is safe and effective in children with asthma under 6 years of age.
- with other medicines for the maintenance treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP) in adults whose disease is not controlled. It is not known if DUPIXENT is safe and effective in children with chronic rhinosinusitis with nasal polyposis under 18 years of age.
- to treat adults and children 12 years of age and older, who weigh at least 88 pounds (40 kg), with eosinophilic esophagitis (EoE). It is not known if DUPIXENT is safe and effective in children with eosinophilic esophagitis under 12 years of age and who weigh at least 88 pounds (40 kg).
- to treat adults with prurigo nodularis (PN). It is not known if DUPIXENT is safe and effective in children with prurigo nodularis under 18 years of age.
- https://www.dupixent.com/
- Please see accompanying full Prescribing Information including Patient Information.
About Regeneron
Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led for 35 years by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to nine FDA-approved treatments and numerous product candidates in development, almost all of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, hematologic conditions, infectious diseases and rare diseases.
Regeneron is accelerating and improving the traditional drug development process through our proprietary VelociSuite® technologies, such as VelocImmune®, which uses unique genetically humanized mice to produce optimized fully human antibodies and bispecific antibodies, and through ambitious research initiatives such as the Regeneron Genetics Center, which is conducting one of the largest genetics sequencing efforts in the world.
For more information, please visit www.Regeneron.com or follow @Regeneron on LinkedIn.
About Sanofi
We are an innovative global healthcare company, driven by one purpose: we chase the miracles of science to improve people's lives. Our team, across some 100 countries, is dedicated to transforming the practice of medicine by working to turn the impossible into the possible. We provide potentially life-changing treatment options and life-saving vaccine protection to millions of people globally, while putting sustainability and social responsibility at the center of our ambitions.
Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY.
Source: Regeneron Pharmaceuticals, Inc.
Regeneron, Sanofi label expansion for Dupixent under FDA priority review
Sep. 26, 2023 7:49 AM ET
Regeneron Pharmaceuticals, Inc. (REGN), SNY, GCVRZ, SNYNF
By: Dulan Lokuwithana, SA News Editor
- Regeneron (NASDAQ:REGN) and Sanofi (NASDAQ:SNY) announced Tuesday that the U.S. FDA granted priority review for a supplemental Biologics License Application ((sBLA)) targeted at expanding the label for asthma therapy Dupixent.
- The sBLA is aimed at winning FDA authorization to market Dupixent for children aged 1 to 11 years with eosinophilic esophagitis ((EoE)), an inflammatory disease that impacts the ability to eat. The monoclonal antibody is already approved in the U.S. for older children and adults with EoE.
- https://seekingalpha.com/news/4015301-regeneron-label-expansion-dupixent-under-fda-review
- Regeneron Pharmaceuticals, Inc. (REGN), SNY
- https://www.dupixent.com/
- https://www.regeneron.com/
Enrylaze® (JZP458) also known as JZP458 & approved as Rylaze® in the United States & Canada
Enrylaze® (JZP458) also known as JZP458 & approved as Rylaze® in the United States & Canada
Enrylaze® (JZP458) also known as JZP458 & approved as Rylaze® in the United States & Canada
Jazz Pharmaceuticals Receives European Commission Approval for Enrylaze® (a recombinant Erwinia asparaginase or crisantaspase) for the Treatment of Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma
September 21, 2023
DUBLIN, Sept. 21, 2023 /PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ) today announced that the European Commission (EC) has granted marketing authorization for Enrylaze® (JZP458; a recombinant Erwinia asparaginase or crisantaspase) for use as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adult and pediatric patients (1 month and older) who developed hypersensitivity or silent inactivation to E. coli-derived asparaginase.[1] Enrylaze, approved as Rylaze® in the United States and Canada, is a new Erwinia-derived asparaginase developed using a next-generation recombinant technology with a safety profile consistent with that of other asparaginase preparations.1,2,3,4,5
"Asparaginase is a core component of multi-agent chemotherapeutic regimens for the treatment of ALL, however, up to 30% of patients develop hypersensitivity to E. coli-derived asparaginase, resulting in a delay or disruption in treatment," said Professor Carmelo Rizzari, Department of Pediatrics, University of Milano-Bicocca, Head of the Pediatric Hematology Oncology Unit, Foundation IRCCS San Gerardo dei Tintori, Monza, Italy. "The ability to complete a full course of asparaginase treatment is of critical importance when treating ALL and LBL, as it is strongly linked to improved outcomes for patients. The approval of Enrylaze now provides an important option to support patients in completing their planned asparaginase treatment regimen."
Enrylaze may be given by both intravenous infusion (IV) and intramuscular injection (IM) and is dosed on either alternate days (every 48 hours) or via a Monday/Wednesday/Friday (MWF) dosing schedule.1 The use of recombinant technology to manufacture Enrylaze delivers a scalable supply – able to meet global demand, and a ready-to-use solution that avoids the need for reconstitution in the clinic.2
"This approval is a testament to Jazz's commitment to developing an Erwinia-derived asparaginase using innovative recombinant technology to deliver a scalable supply, and we look forward to making Enrylaze available to those who need it," said Robert Iannone, MD., M.S.C.E., executive vice president, global head of research and development of Jazz Pharmaceuticals. "Healthcare professionals in the European Union will now have access to a new, recombinant Erwinia-derived asparaginase with multiple dosing and administration options to address their patients' individual needs, which allows them to complete their treatment program as prescribed."
The EC approval is based on data from a Phase 2/3 trial conducted in collaboration with the Children's Oncology Group (COG) in a cohort of 228 pediatric and adult patients with ALL and LBL who have developed hypersensitivity or silent inactivation to E. coli-derived asparaginase. The study was conducted in two parts to assess the IV and IM routes of administration.1,3 The determination of efficacy was based on demonstration of the achievement and maintenance of nadir serum asparaginase activity (NSAA) levels ≥ 0.1 U/mL.1
The study showed that for the IV administration of JZP458 (a recombinant Erwinia asparaginase or crisantaspase) (25/25/50 mg/m2 MWF), the proportion of patients maintaining NSAA ≥ 0.1 U/mL at 48 hours after a dose was 89.8% (95% CI: 82.1%, 97.5%) and 40% at 72 hours post-dose (95% CI: 26.4%, 53.6%). The IM administration of JZP458 (25/25/50 mg/m2 MWF) achieved sustained asparagine activity in 95.9% of patients at 48 hours after a dose (95% CI: 90.4%, 100.0%) and 89.8% of patients at 72 hours post-dose (95% CI: 81.3%, 98.3%). The other dosing schedules were based on interpolation from pharmacokinetic (PK) and response rates observed with the very similar investigated regimens.1
Overall, the safety profile of JZP458 was consistent with the reported safety information for patients with ALL/LBL receiving asparaginase with combination chemotherapy.1,3 The most common adverse reactions were anemia, vomiting, thrombocytopenia, neutropenia, nausea, febrile neutropenia, fatigue, pyrexia, decreased appetite, transaminase increased, abdominal pain, white blood cell count decreased, headache, diarrhea, and lymphocyte count decreased. The most frequent serious adverse reactions were febrile neutropenia, pyrexia, vomiting, sepsis, medicinal product hypersensitivity, nausea, and pancreatitis.1
The European Commission approval extends to all European Union Member States, as well as Iceland, Norway, and Liechtenstein.
For a full list of side effects and information on dosage and administration, contraindications, and other precautions when using Enrylaze, please refer to the Summary of Product Characteristics for further information.
About Enrylaze® (JZP458) Enrylaze, also known as JZP458 and approved as Rylaze® in the United States and Canada, is the only recombinant Erwinia asparaginase or crisantaspase that is derived from a Pseudomonas fluorescens expression platform.2,4,5 It is approved for use as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adult and pediatric patients (1 month and older) who developed hypersensitivity or silent inactivation to E. coli-derived asparaginase products. JZP458 was approved by the U.S. Food and Drug Administration (FDA) in June 2021 for the treatment of this patient population and became commercially available in July of the same year in the U.S.4
https://www.rylazepro.com/index
About Study JZP458-201
The EC approval of Enrylaze is based on clinical data from the pivotal Phase 2/3 single-arm, open-label, multicenter, dose confirmation study evaluating 228 pediatric and adult patients with ALL or LBL who have developed hypersensitivity or silent inactivation to E. coli-derived asparaginases and have not previously received Erwinia-derived asparaginase. The study was designed to assess the safety, tolerability, and efficacy of JZP458. The determination of efficacy was measured by serum asparaginase activity (SAA) levels. The Phase 2/3 study was conducted in two parts. The first part investigated the intramuscular (IM) route of administration, including a Monday-Wednesday-Friday dosing schedule. The second investigated the dose and schedule for the intravenous (IV) route of administration.1,3
About Acute Lymphoblastic Leukemia (ALL)
Acute lymphoblastic leukemia (ALL) is a cancer of the blood and bone marrow that can progress quickly if not treated.6,7 ALL is the most common childhood malignancy, accounting for 80% of leukemia diagnoses in children, compared to 20% of adults.8 Long-term survival rates for pediatric patients have improved significantly over the last few decades, which is in part a result of crafting effective combinations of multi-agent chemotherapeutics with an asparaginase backbone.9 The estimated overall incidence of ALL and lymphoblastic lymphoma (LBL) in Europe is 1.28 per 100,000.10 The number of ALL global cases in children was 59,100 in 2017.11
Asparaginase is a core component of multi-agent chemotherapeutic regimens in ALL,12 however, up to 30% of patients develop hypersensitivity to E. coli-derived asparaginase,13 necessitating treatment discontinuation or a switch to a non-E. coli-derived asparaginase preparation.14 Patients not receiving asparaginase due to hypersensitivities and those not receiving all prescribed doses have been shown to have poor outcomes.2,15
About Lymphoblastic Lymphoma (LBL)
Lymphoblastic Lymphoma (LBL) is a rare, fast-growing, aggressive subtype of non-Hodgkin's lymphoma (NHL), which is very rare in adults and is most often seen in teenagers and young adults under the age of 35.16,17 LBL is a type of high-grade lymphoma – which means the lymphoma grows quickly with early spread to different parts of the body.17 LBL is the second most common type of NHL in childhood and adolescence, accounting for 25-35% of cases.18
About Jazz Pharmaceuticals
Jazz Pharmaceuticals plc (NASDAQ: JAZZ) is a global biopharmaceutical company whose purpose is to innovate to transform the lives of patients and their families. We are dedicated to developing life-changing medicines for people with serious diseases – often with limited or no therapeutic options. We have a diverse portfolio of marketed medicines and novel product candidates, from early- to late-stage development, in neuroscience and oncology. Within these therapeutic areas, we are identifying new options for patients by actively exploring small molecules and biologics, and through innovative delivery technologies and cannabinoid science. Jazz is headquartered in Dublin, Ireland and has employees around the globe, serving patients in nearly 75 countries. Please visit
for more information.
Jazz Pharma wins EU approval for blood cancer therapy
Sep. 22, 2023 9:29 AM ET
Jazz Pharmaceuticals plc (JAZZ)LGND
By: Dulan Lokuwithana, SA News Editor
- The European Commission has issued marketing authorization for the blood cancer therapy JZP458 developed by Jazz Pharmaceuticals (NASDAQ:JAZZ) and Ligand Pharmaceuticals (LGND).
- https://seekingalpha.com/news/4014580-jazz-pharma-wins-eu-approval-for-blood-cancer-therapy
- Jazz Pharmaceuticals plc (JAZZ)
- https://www.rylazepro.com/index
- https://www.jazzpharma.com/
TEPKINLY® (epcoritamab)
Enrylaze® (JZP458) also known as JZP458 & approved as Rylaze® in the United States & Canada
TEPKINLY® (epcoritamab)
September 25, 2023
AbbVie Announces European Commission Approval of TEPKINLY® (epcoritamab) for Adults with Relapsed or Refractory Diffuse Large B-cell Lymphoma
- TEPKINLY® (epcoritamab) is the first and only subcutaneous bispecific antibody approved as a monotherapy for adult patients with relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy
- Conditional marketing authorization approval from the European Commission is supported by data from the pivotal Phase 1/2 EPCORE™ NHL-1 clinical trial
- TEPKINLY represents AbbVie's second approved hematological cancer treatment in the European Union
NORTH CHICAGO, Ill., Sept. 25, 2023 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced that the European Commission (EC) has granted conditional marketing authorization for TEPKINLY® (epcoritamab) as a monotherapy for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy. TEPKINLY is the first and only subcutaneous T-cell engaging bispecific antibody approved for the treatment of this patient population in the European Union (EU), as well as Liechtenstein, Norway and Iceland.
DLBCL is the most common type of B-cell non-Hodgkin's lymphoma worldwide.1 While patients may have access to chemoimmunotherapy regimens to treat their disease, they face limited treatment options, with few readily available, off-the-shelf medicines, especially for those whose disease has relapsed or become refractory to prior treatments.1
"The European Commission approval of epcoritamab represents a significant milestone in our aspiration with Genmab to develop a potential core therapy for patients with B-cell malignancies, like DLBCL," said Roopal Thakkar, senior vice president, development and regulatory affairs, chief medical officer, AbbVie. "With this milestone achievement, TEPKINLY is now the second approved cancer treatment in the EU from our oncology portfolio, and AbbVie's third blood cancer medicine across the world. We remain committed to developing new innovative medicines that help improve the lives of people with hematological cancers."
This conditional approval is supported by data from the pivotal EPCORE™ NHL-1 Phase 1/2 open-label, multi-cohort, multi-center, single-arm trial evaluating the preliminary efficacy and safety of TEPKINLY in patients with R/R large B-cell lymphoma (LBCL), including its subtype DLBCL. In this study, DLBCL patients treated with TEPKINLY (N=139) achieved an overall response rate of 62 percent and a complete response rate of 39 percent. The median duration of response was 15.5 months (range: 9.7, not reached).
Results from the trial showed that TEPKINLY demonstrated a manageable safety profile across the LBCL patient cohort (N=167), which included the DLBCL patient population. The most common adverse reactions (≥ 20 percent) were cytokine release syndrome, fatigue, neutropenia, injection site reaction, musculoskeletal pain, abdominal pain, pyrexia, nausea and diarrhea.
"Relapsed or refractory DLBCL is an aggressive cancer and patients can face a difficult and emotional treatment journey. At this point in the journey, a patient may have had multiple lines of therapy and will already have experienced relapse," said Anna Sureda, M.D., Ph.D., head of clinical hematology department, Institut Català d'Oncologia – L'Hospitalet, Barcelona, Spain. "This European Commission approval represents an important moment for the DLBCL patient community and brings with it a potential opportunity for effective disease management for a condition with limited available treatment options."
Conditional marketing authorization is granted to medicines that address an unmet medical need, where the benefit of its immediate availability to patients outweighs the risk of limited data availability, and where comprehensive data will be provided.2
TEPKINLY is being co-developed by AbbVie and Genmab as part of the companies' oncology collaboration. The companies will share commercial responsibilities in the U.S. and Japan, with AbbVie responsible for further global commercialization. AbbVie will continue to pursue regulatory submissions for epcoritamab across international markets throughout the year.
About the EPCORE™ NHL-1 Trial
EPCORE™ NHL-1 evaluated epcoritamab as a monotherapy in patients with CD20+ relapsed or refractory (R/R) large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL), after two or more lines of systemic therapy.3 The study included a dose escalation part and an expansion part.3 The primary efficacy endpoint was overall response rate determined by Lugano criteria (2014) as assessed by an independent review committee.3 More information can be found on www.clinicaltrials.gov.
About TEPKINLY® (epcoritamab)
TEPKINLY is an investigational IgG1-bispecific antibody created using Genmab's proprietary DuoBody® technology. Genmab's DuoBody®-CD3 technology is designed to direct cytotoxic T-cells selectively to elicit an immune response toward target cell types. TEPKINLY is designed to simultaneously bind to CD3 on T-cells and CD20 on B-cells and induces T-cell mediated killing of CD20+ cells.4 CD20 is expressed on B-cells and is a clinically validated therapeutic target in many B-cell malignancies, including DLBCL, follicular lymphoma, mantle cell lymphoma and chronic lymphocytic leukemia.5,6
The U.S. Food and Drug Administration (FDA) approved epcoritamab under the brand name EPKINLY™ (epcoritamab-bysp) in May 2023 for the treatment of adult patients with R/R DLBCL, not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma, after two or more lines of systemic therapy. EPKINLY is approved under the FDA's Accelerated Approval program based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
EU Indications and Important Safety Information about Tepkinly® ▼ (epcoritamab)
Indications
Tepkinly (epcoritamab) as monotherapy is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy.
Important Safety Information
Contraindications
Hypersensitivity to the active substance or to any of the excipients.
This is not a complete summary of all safety information.
See Tepkinly® full Summary of Product Characteristics (SmPC) at www.ema.europa.eu
Globally, prescribing information varies; refer to the individual country product label for complete information.
Please see the Full Prescribing Information and Medication Guide, including Important Warnings.
About AbbVie in Oncology
At AbbVie, we are committed to transforming standards of care for multiple blood cancers while advancing a dynamic pipeline of investigational therapies across a range of cancer types. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potential breakthrough medicines. We are evaluating more than 20 investigational medicines in over 300 clinical trials across some of the world's most widespread and debilitating cancers. As we work to have a remarkable impact on people's lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit http://www.abbvie.com/oncology.
About AbbVie
AbbVie's mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas – immunology, oncology, neuroscience, and eye care – and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on LinkedIn, Facebook, Instagram, X (formerly Twitter), and YouTube.
SOURCE AbbVie
AbbVie's Tepkinly wins EC approval as large B-cell lymphoma therapy
Sep. 25, 2023 10:18 AM ET
By: Jonathan Block, SA News Editor
- The European Commission has approved AbbVie's Tepkinly (epcoritamab) as a third-line treatment on its own for relapsed or refractory (R/R) diffuse large B-cell lymphoma.
- The bispecific antibody is the only subcutaneous T-cell therapy approved for this population in the European Union.
- https://seekingalpha.com/news/4015084-abbvie-tepkinly-wins-ec-approval-large-b-cell-lymphoma-therapy
- AbbVie Inc. (ABBV)
- Epkinly, which was developed with Genmab (GMAB), was approved by the US FDA in January.
- https://www.us.genmab.com/
- https://www.abbvie.com/
Datopotamab deruxtecan
Datopotamab deruxtecan
TEPKINLY® (epcoritamab)
Datopotamab deruxtecan demonstrated statistically significant and clinically meaningful progression-free survival benefit in patients with HR-positive, HER2-low or negative breast cancer in TROPION-Breast01 Phase III trial
PUBLISHED22 September 2023
This announcement contains inside information
First Phase III results in breast cancer for AstraZeneca
and Daiichi Sankyo’s datopotamab deruxtecan
Plans for global regulatory submissions underway
Positive high-level results from the TROPION-Breast01 Phase III trial showed datopotamab deruxtecan (Dato-DXd) demonstrated a statistically significant and clinically meaningful improvement for the primary endpoint of progression-free survival (PFS) compared to investigator’s choice of chemotherapy in patients with inoperable or metastatic hormone receptor (HR)-positive, HER2-low or negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer previously treated with endocrine-based therapy and at least one systemic therapy.
A trend in improvement for the dual primary endpoint of overall survival (OS) was observed for datopotamab deruxtecan versus chemotherapy. Data for OS were not mature at this interim analysis and the trial will continue as planned to assess OS.
The safety profile of datopotamab deruxtecan was consistent with previous clinical trials in breast cancer with no new safety signals identified. All grade interstitial lung disease rates were low.
Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) being jointly developed by AstraZeneca and Daiichi Sankyo.
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “Today’s TROPION-Breast01 news is a significant development for patients with HR-positive, HER2-low or negative metastatic breast cancer whose tumours have become insensitive to endocrine therapy and who currently face poor outcomes. We are encouraged by these positive results.”
Ken Takeshita, MD, Global Head, Oncology R&D, Daiichi Sankyo, said: “The positive topline results from TROPION-Breast01 demonstrate the potential for datopotamab deruxtecan to become an important treatment option for patients with HR-positive, HER2-low or HER2-negative breast cancer in the second-line metastatic setting. We look forward to realising the full potential of this TROP2-directed antibody drug conjugate across breast cancer subtypes through our ongoing Phase III programme, including two trials in patients with triple-negative breast cancer.”
More than two million people worldwide are diagnosed with breast cancer each year.1 HR-positive, HER2-low or negative breast cancer is the most common subtype, accounting for more than 65% of diagnosed cases.1,2 Standard initial treatment for these patients is endocrine therapy but most patients with advanced disease will develop resistance, underscoring the need for additional options.3,4 TROP2 is a protein broadly expressed in HR-positive, HER2-low or negative breast cancer.5,6
The data will be presented at a forthcoming medical meeting and shared with health authorities.
AstraZeneca and Daiichi Sankyo have two additional Phase III trials evaluating datopotamab deruxtecan in breast cancer. TROPION-Breast02 is comparing datopotamab deruxtecan to chemotherapy in patients with previously untreated locally recurrent inoperable or metastatic triple negative breast cancer (TNBC) who are not candidates for anti-PDL1 therapy. TROPION-Breast03 is evaluating datopotamab deruxtecan with and without Imfinzi (durvalumab) versus investigator’s choice of therapy in patients with Stage I-III TNBC with residual disease after neoadjuvant therapy.
Notes
HR-positive breast cancer
Breast cancer is the most common cancer in the world and a leading cause of cancer-related death.1 More than two million breast cancer cases were diagnosed in 2020 with nearly 685,000 deaths globally.1
Breast cancer is considered HR-positive, HER2-low or negative when tumours test positive for oestrogen and/or progesterone hormone receptors and negative or low for HER2 (measured as HER2 score of IHC 0, IHC 1+ or IHC 2+/ISH-).2,7 HR-positive, HER2-low or negative breast cancer is the most common subtype, accounting for more than 65% of diagnosed cases.2 Approximately 30% of patients diagnosed with HR-positive, HER2-low or negative metastatic breast cancer are expected to live five years after their diagnosis.2
TROP2 is a protein broadly expressed in several solid tumours, including HR positive, HER2-low or negative breast cancer.5 TROP2 expression is associated with increased tumour progression and poor survival in patients with breast cancer.5,6
TROPION-Breast01
TROPION-Breast01 is global, randomised, multicentre, open-label Phase III trial evaluating the safety and efficacy of datopotamab deruxtecan versus investigator’s choice of single-agent chemotherapy (eribulin, capecitabine, vinorelbine or gemcitabine) in patients with inoperable or metastatic HR- positive, HER2-low or negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have previously progressed on or are not suitable for endocrine therapy per investigator assessment.
The dual primary endpoints of TROPION-Breast01 are PFS as assessed by blinded independent central review (BICR) and OS. Key secondary endpoints include objective response rate, duration of response, investigator-assessed PFS, disease control rate and time to first subsequent therapy.
TROPION-Breast01 enrolled more than 700 patients at sites in Asia, Europe, North America, South America and Africa. For more information visit ClinicalTrials.gov.
Datopotamab deruxtecan (Dato-DXd)
Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, datopotamab deruxtecan is one of five lead ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programmes in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.
A comprehensive development programme is underway globally with more than 12 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple tumours, including non-small cell lung cancer, triple-negative breast cancer and hormone receptor-positive, HER2-low or negative breast cancer. Beyond the TROPION programme, datopotamab deruxtecan is also being evaluated in novel combinations in several ongoing trials. AstraZeneca is also researching a potential diagnostic test to help identify patients most likely to benefit from treatment with datopotamab deruxtecan.
Daiichi Sankyo collaboration
AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise Enhertu in March 2019 and datopotamab deruxtecan in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and datopotamab deruxtecan.
AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge, and redefine, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.
AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment.
With Enhertu (trastuzumab deruxtecan), a HER2-directed ADC, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive and HER2-low metastatic breast cancer and are exploring its potential in earlier lines of treatment and in new breast cancer settings.
In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and aims to reshape the HR-positive space with next-generation SERD and potential new medicine camizestrant as well as a potential first-in-class AKT kinase inhibitor, capivasertib. AstraZeneca is also collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan, in this setting.
PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continues to research Lynparza in these settings and to explore its potential in earlier disease.
To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is evaluating the potential of datopotamab deruxtecan alone and in combination with immunotherapy Imfinzi, capivasertib in combination with chemotherapy, and Imfinzi in combination with other oncology medicines, including Lynparza and Enhertu.
AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.
The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.
AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca.
AstraZeneca PLC
AstraZeneca, Daiichi post early win in Phase 3 trial for breast cancer therapy
Sep. 22, 2023 7:25 AM ET
AstraZeneca PLC (AZN), DSKYF, DSNKY
By: Dulan Lokuwithana, SA News Editor
- AstraZeneca (NASDAQ:AZN) and Daiichi Sankyo (OTCPK:DSKYF) announced Friday that their antibody-drug conjugate datopotamab deruxtecan reached the primary endpoint in a Phase 3 trial for the commonest type of breast cancer.
- The globally run TROPION-Breast01 trial enrolled more than 700 patients with hormone receptor (HR) positive, HER2 low, or negative breast cancer, the most common cancer subtype that makes up over 65% of cases.
- https://seekingalpha.com/news/4014493-astrazeneca-posts-early-phase-3-win-breast-cancer-drug
- AstraZeneca PLC (AZN), DSKYF, DSNKY
- https://www.daiichisankyo.com/rd/pipeline/
- https://www.daiichisankyo.com/
- https://www.astrazeneca.com/
VOXZOGO® (vosoritide)
Datopotamab deruxtecan
VOXZOGO® (vosoritide)
BioMarin to Present Data Showing Long-Term Benefit of VOXZOGO® (vosoritide) on Growth in Children with Achondroplasia at 2023 European Society for Paediatric Endocrinology (ESPE) Meeting
Sep 21, 2023
Label Expansion Decisions Expected from U.S. and European Regulatory Authorities in Q4
SAN RAFAEL, Calif., Sept. 21, 2023 /PRNewswire/ -- BioMarin Pharmaceutical Inc. (Nasdaq: BMRN), a global biotechnology company dedicated to transforming lives through genetic discovery, today announced that new data on VOXZOGO® (vosoritide) in children with achondroplasia will be presented at the 61st Annual European Society for Paediatric Endocrinology (ESPE) Meeting in The Hague, Netherlands.
In an open-label, long-term Phase 2 extension study, VOXZOGO demonstrated consistent and durable growth benefits in young children with achondroplasia when initiated before the age of 5. Over a four-year period, children aged 2 years and above who received VOXZOGO exhibited a mean (average) height Z-score improvement exceeding 1 standard deviation compared to control groups and a height gain of more than 6 centimeters (cm) during this time period. Additionally, children under the age of 2 years, treated with VOXZOGO for three years, demonstrated substantial height gains, reflected in a mean height Z-score improvement of 0.79 standard deviations compared to controls and a height gain of more than 3 cm during this time period. Both groups of treated children demonstrated substantial restoration of height when compared to untreated children with achondroplasia.
VOXZOGO is currently approved in Europe in children with achondroplasia who are 2 years of age and older with open growth plates. Last week, the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending marketing authorization to expand the indication for VOXZOGO for injection to treat children with achondroplasia aged 4 months and older whose epiphyses (growth plates) are not closed. VOXZOGO is also currently approved in the United States in children with achondroplasia who are 5 years of age and older with open growth plates. The U.S. Food and Drug Administration (FDA) has set a PDUFA Target Action Date of Oct. 21, 2023, for the company's Supplemental New Drug Application (sNDA) for VOXZOGO to expand treatment in the U.S. to include children with achondroplasia under 5 years of age.
"The data presented add to the growing body of evidence demonstrating the positive effect on growth in younger children with achondroplasia who receive VOXZOGO," said Hank Fuchs, M.D., president of Worldwide Research and Development at BioMarin. "The results showed that, over the course of four years, young children treated earlier with VOXZOGO exhibited substantial gains in height, suggesting that VOXZOGO had a significant and positive impact on their growth."
New data also highlighted real-world safety and effectiveness of VOXZOGO. Results from an early access program in France found that VOXZOGO treated under real-world conditions had a safety and effectiveness profile consistent with clinical trials. After 12 months of treatment with VOXZOGO, boys demonstrated a mean (average) increase in height with a Z-score improvement of 0.3 standard deviations, and girls showed a mean increase in height with a Z-score improvement of 0.4 standard deviations.
Key VOXZOGO presentations at ESPE include:
Oral Presentations:
Real-world Safety and Effectiveness of Vosoritide: Results from an Early Access Program in France
RFC4.5
Thursday, September 21, 2023, 2:45 – 2:50 p.m., Central European Summer Time
Persistence of Growth Promoting Effects in Infants and Toddlers with Achondroplasia: Results in Children Aged Over 2 Years Old from a Phase II Extension Study with Vosoritide
FC4.6
Thursday, September 21, 2023, 3:45 – 3:55 p.m., Central European Summer Time
Poster:
Design and Objectives of the Acorn Study: A Non-Interventional Study Evaluating Long-Term Safety in Achondroplasia Patients Treated with Vosoritide
T8
Thursday, September 21, 2023, 12:55 – 2:25 p.m., Central European Summer Time
About VOXZOGO (vosoritide) for Injection
In children with achondroplasia, endochondral bone growth, an essential process by which bone tissue is created, is negatively regulated due to a gain of function mutation in fibroblast growth factor receptor 3 gene (FGFR3). VOXZOGO, a C-type natriuretic peptide (CNP) analog, represents a new class of therapy, which acts as a positive regulator of the signaling pathway downstream of FGFR3 to promote endochondral bone growth.
Through BioMarin's broad clinical development program, the company has enrolled 250 children with achondroplasia from eight countries in seven clinical studies evaluating the safety and efficacy of VOXZOGO.
VOXZOGO is approved in the U.S. and indicated to increase linear growth in pediatric patients with achondroplasia who are 5 years of age and older with open epiphyses. This indication is approved under accelerated approval based on an improvement in annualized growth velocity. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). To fulfill this post-marketing requirement, BioMarin intends to use the ongoing open-label extension studies compared to available natural history.
About Achondroplasia
Achondroplasia, the most common form of skeletal dysplasia leading to disproportionate short stature in humans, is characterized by slowing of endochondral ossification, which results in disproportionate short stature and disordered architecture in the long bones, spine, face, and base of the skull. This condition is caused by a change in the fibroblast growth factor receptor 3 gene (FGFR3), a negative regulator of bone growth.
More than 80% of children with achondroplasia have parents of average stature and have the condition as the result of a spontaneous gene mutation. The worldwide incidence rate of achondroplasia is about one in 25,000 live births. VOXZOGO is being tested in children whose growth plates are still "open," typically those under 18 years of age. Approximately 25% of people with achondroplasia fall into this category.
VOXZOGO U.S. Important Safety Information
What is VOXZOGO used for?
- VOXZOGO is a prescription medicine used to increase linear growth in children with achondroplasia who are 5 years of age and older with open growth plates (epiphyses).
- It is not known if VOXZOGO is safe and effective in children with achondroplasia under 5 years of age.
- VOXZOGO is approved under accelerated approval based on an improvement in annualized growth velocity. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.
What is the most important safety information about VOXZOGO?
- VOXZOGO may cause serious side effects including a temporary decrease in blood pressure in some patients. To reduce the risk of a decrease in blood pressure and associated symptoms (dizziness, feeling tired, or nausea), patients should eat a meal and drink 8 to 10 ounces of fluid within 1 hour before receiving VOXZOGO.
- https://www.voxzogo.com/hcp/
- Please see additional safety information in the full Prescribing Information and Patient Information.
About BioMarin
Founded in 1997, BioMarin is a global biotechnology company dedicated to transforming lives through genetic discovery. The company develops and commercializes targeted therapies that address the root cause of genetic conditions. BioMarin's unparalleled research and development capabilities have resulted in eight transformational commercial therapies for patients with rare genetic disorders. The company's distinctive approach to drug discovery has produced a diverse pipeline of commercial, clinical, and pre-clinical candidates that address a significant unmet medical need, have well-understood biology, and provide an opportunity to be first-to-market or offer a substantial benefit over existing treatment options. For additional information, please visit www.biomarin.com.
BioMarin® and VOXZOGO® are registered trademarks of BioMarin Pharmaceutical Inc.
SOURCE BioMarin Pharmaceutical Inc.
Pegozafermin
Datopotamab deruxtecan
VOXZOGO® (vosoritide)
89bio Announces U.S. FDA has Granted Breakthrough Therapy Designation for Pegozafermin in Nonalcoholic Steatohepatitis (NASH)
09/21/2023
–Supported by positive data in F2/F3 and F4 NASH patients from the ENLIVEN Phase 2b trial of pegozafermin–
–Discussions with regulatory agencies regarding the NASH Phase 3 program planned for the fourth quarter of 2023–
SAN FRANCISCO, Sept. 21, 2023 (GLOBE NEWSWIRE) -- 89bio, Inc. (Nasdaq: ETNB), a clinical-stage biopharmaceutical company focused on the development and commercialization of innovative therapies for the treatment of liver and cardiometabolic diseases, today announced that the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation (BTD) to pegozafermin in patients with nonalcoholic steatohepatitis (NASH).
“We are thrilled with this validation from the FDA awarding pegozafermin with Breakthrough Therapy Designation, which we expect will be advantageous for finalizing our Phase 3 development strategy in NASH following planned discussions with regulatory agencies in the fourth quarter of 2023,” said Rohan Palekar, Chief Executive Officer of 89bio. “We believe pegozafermin is well positioned as a leading FGF21 analog treatment option with demonstrated strong histology data, best-in-class tolerability, and dosing convenience to date. It has the potential to meet the treatment needs for F2/3 patients as well as compensated cirrhotic (F4) patients. The benefits of this designation include more comprehensive guidance from the FDA on the development program, ability to discuss innovative development plan options, access to a scientific liaison, and potential eligibility for Priority Review.”
BTD was supported by data from the ENLIVEN Phase 2b trial of pegozafermin in patients with NASH. In the study, both the 44mg every-two-week (Q2W) and 30mg weekly (QW) doses met — with high statistical significance — the primary histology endpoints per the FDA guidance regarding endpoints and statistical analysis. The 44mg Q2W and 30mg QW dose groups also demonstrated statistically significant and clinically meaningful improvements in liver fat, non-invasive markers of liver fibrosis and inflammation, and meaningful improvements in other metabolic and lipid markers. The ENLIVEN trial also included biopsy-confirmed F4 patients who were not part of the primary analysis but continued in the study. In a descriptive analysis of these data, 45% of pegozafermin-treated patients experienced at least one-stage improvement in liver fibrosis with no worsening of NASH by week 24 compared with zero out of one patient on placebo. Overall, pegozafermin was generally well-tolerated with a favorable safety profile consistent with prior studies.
BTD is an FDA program designed to expedite the development and review of product candidates intended for serious or life-threatening conditions. To qualify for this designation, preliminary clinical evidence must indicate that the product candidate may demonstrate substantial improvement over currently available options on at least one clinically significant endpoint.
About pegozafermin
Pegozafermin is a specifically engineered glycoPEGylated analog of fibroblast growth factor 21 (FGF21) being developed for the treatment of non-alcoholic steatohepatitis (NASH) and severe hypertriglyceridemia (SHTG). FGF21 is an endogenous hormone that modulates important drivers of lipid metabolism and NASH including triglyceride reduction, glycemic control, steatosis, inflammation and fibrosis. Pegozafermin was specifically engineered using a unique glycoPEGylated technology to extend the half-life while maintaining potency.
https://www.89bio.com/pipeline/#bio89-100
About 89bio
89bio is a clinical-stage biopharmaceutical company dedicated to the development of best-in-class therapies for patients with liver and cardiometabolic diseases who lack optimal treatment options. The company is focused on rapidly advancing its lead therapeutic candidate, pegozafermin, through clinical development for the treatment of non-alcoholic steatohepatitis (NASH) and severe hypertriglyceridemia (SHTG). The company is headquartered in San Francisco. For more information, visit www.89bio.com or follow the company on LinkedIn.
89bio gains FDA breakthrough status for NASH candidate
Sep. 21, 2023 8:53 AM ET
By: Dulan Lokuwithana, SA News Editor
- 89bio, Inc. (NASDAQ:ETNB) announced Thursday that the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for its lead asset pegozafermin in patients with the liver disease nonalcoholic steatohepatitis (NASH).
- The decision is backed by data from the company's ENLIVEN Phase 2b trial for NASH, in which pegozafermin at two dose levels reached the primary histology endpoints with statistical significance in line with FDA guidance.
- https://seekingalpha.com/news/4014191-89bio-gains-fda-breakthrough-status-nash-candidate
- 89bio, Inc. (ETNB)
- https://www.89bio.com/
- https://www.89bio.com/pipeline/#bio89-100
WELIREG® (belzutifan)
IZERVAY™ (avacincaptad pegol intravitreal solution)
IZERVAY™ (avacincaptad pegol intravitreal solution)
FDA Accepts for Priority Review Merck’s Supplemental New Drug Application for WELIREG® (belzutifan) in Certain Previously Treated Patients With Advanced Renal Cell Carcinoma (RCC)
September 19, 2023 6:45 am ET
Acceptance based on results from the Phase 3 LITESPARK-005 trial, which showed a statistically significant and clinically meaningful improvement in progression-free survival compared to everolimus in patients with advanced RCC that progressed following PD-1/L1 and VEGF-TKI therapies
If approved, WELIREG would provide a new, novel mechanism of action for patients with advanced RCC in need of new options
RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the U.S. Food and Drug Administration (FDA) has accepted and granted priority review for a supplemental new drug application (sNDA) seeking approval for WELIREG, Merck’s oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, for the treatment of adult patients with advanced renal cell carcinoma (RCC) following immune checkpoint and anti-angiogenic therapies. The sNDA is based on data from the LITESPARK-005 trial, in which WELIREG demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to everolimus based on a pre-specified interim analysis conducted by an independent Data Monitoring Committee. A statistically significant improvement in the trial’s key secondary endpoint of objective response rate (ORR) was also demonstrated. The FDA has set a Prescription Drug User Fee Act (PDUFA), or target action, date of January 17, 2024.
“Patients with advanced RCC whose cancer progresses following immune checkpoint and anti-angiogenic therapies face a poorer prognosis, and for those patients, there is a crucial unmet need for new options with an alternative mechanism of action,” said Dr. Marjorie Green, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories. “The FDA’s priority review designation of this application reinforces the urgency to provide new options to previously treated patients with advanced RCC, and we are committed to working closely with the FDA to bring WELIREG to these patients as quickly as possible.”
WELIREG was the first HIF-2α inhibitor therapy approved in the U.S. and is currently approved for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated RCC, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors, not requiring immediate surgery.
LITESPARK-005 is part of a comprehensive development program for WELIREG, comprised of four Phase 3 trials in RCC, including LITESPARK-011 and LITESPARK-012, evaluating WELIREG in the second-line and treatment-naïve advanced disease settings, and LITESPARK-022, evaluating WELIREG in the adjuvant setting.
About LITESPARK-005
LITESPARK-005 is a randomized, open-label Phase 3 trial (ClinicalTrials.gov, NCT04195750) evaluating WELIREG compared to everolimus for the treatment of patients with advanced RCC that has progressed after prior treatment with PD-1/L1 and VEGF-TKI therapies, in sequence or in combination. The dual primary endpoints are PFS and overall survival. Secondary endpoints include ORR, duration of response and safety. The trial enrolled 746 patients who were randomized to receive WELIREG (120 mg orally once daily) or everolimus (10 mg orally once daily).
About renal cell carcinoma
Renal cell carcinoma is by far the most common type of kidney cancer; about nine out of 10 kidney cancer diagnoses are RCCs. Renal cell carcinoma is about twice as common in men than in women. Most cases of RCC are discovered incidentally during imaging tests for other abdominal diseases. In the U.S., approximately 15% of patients with kidney cancer are diagnosed at an advanced stage.
About WELIREG® (belzutifan) 40 mg tablets, for oral use
Indication in the U.S.
WELIREG (belzutifan) is indicated for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery.
Merck’s focus on cancer
Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.
Please see Prescribing Information, including information for the Boxed Warning about embryo-fetal toxicity, for WELIREG (belzutifan) at https://www.merck.com/product/usa/pi_circulars/w/welireg/welireg_pi.pdf and Medication Guide for WELIREG at https://www.merck.com/product/usa/pi_circulars/w/welireg/welireg_mg.pdf .
Source: Merck & Co., Inc.
MRK Dividend History
https://www.nasdaq.com/market-activity/stocks/mrk/dividend-history
IZERVAY™ (avacincaptad pegol intravitreal solution)
IZERVAY™ (avacincaptad pegol intravitreal solution)
IZERVAY™ (avacincaptad pegol intravitreal solution)
Iveric Bio Announces Positive 24-Month Topline Results from Phase 3 Study of IZERVAY™ (avacincaptad pegol intravitreal solution) for Geographic Atrophy
GATHER2 24-month results met the primary objective of reducing the rate of GA growth in patients treated with IZERVAY compared to sham
IZERVAY 24-month safety data were consistent with 12-month results, with no new safety signals identified
TOKYO, Sept. 18, 2023 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, "Astellas") today announced positive 24-month topline results from the Phase 3 GATHER2 clinical trial evaluating the efficacy and safety of IZERVAY™ (avacincaptad pegol intravitreal solution), a complement C5 inhibitor for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
Topline results demonstrated that the IZERVAY monthly dosing regimen met the primary objective to significantly slow GA growth compared to sham at 24 months. Additionally, the treatment effect with the every other month dosing regimen for IZERVAY showed a similar reduction in the rate of GA growth versus sham.
Overall, safety after 24 months of treatment was consistent with previously reported 12-month data, with no new safety signals identified. There was one case of culture-positive endophthalmitis and one case of non-serious intraocular inflammation. There were no cases of occlusive or non-occlusive retinal vasculitis or ischemic neuropathy. The rate of choroidal neovascularization (CNV) was 12% in patients treated with IZERVAY and 9% in those treated with sham.
Dhaval Desai, PharmD, Senior Vice President and Chief Development Officer, Iveric Bio, An Astellas Company
"We are excited about these results, which show that IZERVAY continued to slow the rate of GA growth with a consistent safety profile after two years of treatment. We look forward to sharing results at a future scientific congress and with regulatory agencies."
IZERVAY was approved by the U.S. Food and Drug Administration on August 4, 2023, for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD) and is currently under review by the European Medicines Agency.
Astellas is reviewing potential financial impacts of these results for the fiscal year ending March 31, 2024.
About the GATHER2 Clinical Trial
GATHER2 (NCT04435366) was a randomized, double-masked, sham-controlled, multicenter Phase 3 clinical trial to evaluate the safety and efficacy of intravitreal administration of avacincaptad pegol (ACP) in 448 enrolled patients with GA secondary to AMD. ACP met its primary objective at 12 months, for which patients were randomized to receive either ACP or sham procedure monthly. In year 2 of the study, patients treated with ACP in year 1 were re-randomized to receive either ACP dosed monthly (EM, n=96) or every other month (EOM, n=93); patients who received sham in year 1 continued to receive sham in year 2 (n=203). The primary objective at 24 months was to demonstrate whether, after re-randomization at 12 months, ACP slowed the GA growth rate (slope) in the EM treatment arm compared to sham.
About IZERVAY™ (avacincaptad pegol intravitreal solution)
U.S. INDICATION
IZERVAY (avacincaptad pegol intravitreal solution) is indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD)
IMPORTANT U.S. SAFETY INFORMATION
CONTRAINDICATIONS
- IZERVAY is contraindicated in patients with ocular or periocular infections and in patients with active intraocular inflammation.
Please see full Prescribing Information for more information.
About Geographic Atrophy
Age-related macular degeneration (AMD) is the major cause of moderate and severe loss of central vision in aging adults, affecting both eyes in the majority of patients. The macula is a small area in the central portion of the retina responsible for central vision. As AMD progresses, the loss of retinal cells and the underlying blood vessels in the macula results in marked thinning and/or atrophy of retinal tissue. Geographic atrophy, associated with AMD, leads to further irreversible loss of vision in these patients.
About Astellas
Astellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+® healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into VALUE for patients. For more information, please visit our website at https://www.astellas.com/en.
About Iveric Bio
Iveric Bio, An Astellas Company, is a science-driven biopharmaceutical company focused on the discovery and development of novel treatments for retinal diseases with significant unmet medical needs. The Company is committed to having a positive impact on patients' lives by delivering high-quality, safe, and effective treatments designed to address debilitating retinal diseases including earlier stages of age-related macular degeneration. For more information on the Company, please visit www.ivericbio.com.
Apellis spikes as Astellas posts long-term data for rival product
Sep. 19, 2023 9:29 AM ET
Apellis Pharmaceuticals, Inc. (APLS), ALPMF, ALPMY
By: Dulan Lokuwithana, SA News Editor1 Comment
Apellis Pharmaceuticals (NASDAQ:APLS) added ~9% pre-market Tuesday after its rival in the eye care market, Astellas Pharma (OTCPK:ALPMF) (OTCPK:ALPMY), announced long-term data for its FDA-approved therapy, Izervay.
Astellas (OTCPK:ALPMF) added Izervay as part of its recent acquisition of U.S. biotech Iveric Bio.
https://seekingalpha.com/news/4013173-apellis-stock-spikes-astellas-posts-data-rival-drug
Apellis Pharmaceuticals, Inc. (APLS), ALPMF, ALPMY
Iveric Bio Announces Positive 24-Month Topline Results from Phase 3 Study of IZERVAY™ (avacincaptad pegol intravitreal solution) for Geographic Atrophy
September 18, 2023
– GATHER2 24-month results met the primary objective of reducing the rate of GA growth in patients treated with IZERVAY compared to sham –
– IZERVAY 24-month safety data were consistent with 12-month results, with no new safety signals identified –
TOKYO, Sept. 18, 2023 /PRNewswire/ — Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, “Astellas”) today announced positive 24-month topline results from the Phase 3 GATHER2 clinical trial evaluating the efficacy and safety of IZERVAY™ (avacincaptad pegol intravitreal solution), a complement C5 inhibitor for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).
Ojjaara (momelotinib)
IZERVAY™ (avacincaptad pegol intravitreal solution)
TransCon™ PTH (palopegteriparatide)
September 15 2023
Issued: London, UK
For media and investors only
Ojjaara (momelotinib) approved in the US as the first and only treatment indicated for myelofibrosis patients with anemia
- Approval is for use in myelofibrosis patients with anemia regardless of prior myelofibrosis therapy
- Nearly all myelofibrosis patients are estimated to develop anemia over the course of the disease, and over 30% will discontinue treatment due to anemia [1],[2],[3]
- Ojjaara addresses key manifestations of myelofibrosis, namely anemia, constitutional symptoms and splenomegaly
GSK plc (LSE/NYSE: GSK) today announced that the US Food and Drug Administration (FDA) has approved Ojjaara (momelotinib) for the treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis (post-polycythemia vera and post-essential thrombocythemia), in adults with anemia. Ojjaara is a once-a-day, oral JAK1/JAK2 and activin A receptor type 1 (ACVR1) inhibitor. To date, it is the only approved medicine for both newly diagnosed and previously treated myelofibrosis patients with anemia that addresses the key manifestations of the disease, namely anemia, constitutional symptoms, and splenomegaly (enlarged spleen).[4]
Nina Mojas, Senior Vice President, Oncology Global Product Strategy, GSK, said: “The vast majority of myelofibrosis patients eventually develop anemia, causing them to discontinue treatments and require transfusions. Given this high unmet need, we are proud to add Ojjaara to our oncology portfolio and address a significant medical need in the community. We look forward to helping improve outcomes in this difficult-to-treat blood cancer.”
Myelofibrosis is a blood cancer affecting approximately 25,000 patients in the US.[4],[5],[6] Myelofibrosis can lead to severely low blood counts, including anemia and thrombocytopenia; constitutional symptoms such as fatigue, night sweats, and bone pain; and splenomegaly. About 40% of patients have moderate to severe anemia at the time of diagnosis, and nearly all patients are estimated to develop anemia over the course of the disease.[7],[8],[9],[10] Physicians have had limited treatment options to treat myelofibrosis patients with anemia. These patients often require transfusions and more than 30% will discontinue treatment due to anemia.[3] Patients who are transfusion dependent have a poor prognosis and shortened survival.[1],11],[12],[13],[14],[15],[16],[17],[18]
Ruben A. Mesa, MD, FACP, President and Executive Director, Atrium Health Levine Cancer Center and Atrium Health Wake Forest Baptist Comprehensive Cancer Center, said: “With momelotinib we have the potential to establish a new standard of care for myelofibrosis patients with anemia. Addressing key manifestations of myelofibrosis, including anemia, constitutional symptoms and splenomegaly, makes a significant difference in the treatment regimen for these patients who have limited options to address these aspects of the disease.”
In these clinical trials, the most common adverse reactions were thrombocytopenia, hemorrhage, bacterial infection, fatigue, dizziness, diarrhea, and nausea.[19]
Kapila Viges, Chief Executive Officer, MPN (Myeloproliferative Neoplasms) Research Foundation, said: “We are thrilled to see momelotinib reach the clinic, giving patients and their physicians another option to help manage myelofibrosis. Any new treatment that takes steps toward unlocking the mysteries of this complex and chronic blood cancer represents great progress for the field.”
Momelotinib is currently not approved in any other market.
About myelofibrosis
Myelofibrosis is a rare blood cancer that results from dysregulated JAK-signal transducer and activator of transcription protein signalling and is characterized by constitutional symptoms, splenomegaly, and progressive anemia. Myelofibrosis affects approximately 25,000 patients in the US.[1],[5],[6]
About the pivotal MOMENTUM clinical trial
MOMENTUM was a phase III, global, multicenter, randomized, double-blind study investigating momelotinib versus danazol in patients with myelofibrosis who were symptomatic and anemic and had been previously treated with an approved JAK inhibitor. The trial was designed to evaluate the safety and efficacy of momelotinib for treating and reducing key hallmarks of the disease: symptoms, blood transfusions (due to anemia) and splenomegaly.[2] Results from the 24-week treatment period were presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting and subsequently published in The Lancet.[20],[21]
About the SIMPLIFY-1 clinical trial
SIMPLIFY-1 was a multicenter, randomized, double-blind, phase III study that compared the safety and efficacy of momelotinib to ruxolitinib in patients with myelofibrosis who had not received prior treatment with a JAK inhibitor. Safety and efficacy results for SIMPLIFY-1 were based upon a subset of patients with anemia (hemoglobin <10 g/dL) at baseline. The efficacy of momelotinib in the treatment of patients with myelofibrosis in SIMPLIFY-1 was based on spleen volume response (reduction by 35% or greater).
About Ojjaara (momelotinib)
Ojjaara has a differentiated mechanism of action, with inhibitory ability along three key signalling pathways: Janus kinase (JAK) 1, JAK2, and activin A receptor, type I (ACVR1).[2],[6],[22],[23] Inhibition of JAK1 and JAK2 may improve constitutional symptoms and splenomegaly.[2],[6],[23] Additionally, inhibition of ACVR1 leads to a decrease in circulating hepcidin, which is elevated in myelofibrosis and contributes to anemia.[2],[6],[22],[23]
INDICATION
OJJAARA is indicated for the treatment of intermediate or high-risk myelofibrosis (MF), including primary MF or secondary MF [post-polycythemia vera (PV) and post-essential thrombocythemia (ET)], in adults with anemia.
Please see full Prescribing Information, including Patient Information, for OJJAARA.
GSK in oncology
GSK is committed to maximizing patient survival through transformational medicines, with a current focus on breakthroughs in immuno-oncology and tumor-cell targeting therapies, and development in hematologic malignancies, gynecologic cancers and other solid tumors.
About GSK
GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com.
FDA approves GSK drug Ojjaara for myelofibrosis with anemia (update)
Sep. 18, 2023 2:09 PM ET
By: Val Brickates Kennedy, SA News Editor
GSK (NYSE:GSK) has received FDA approval for its drug Ojjaara, also known as momelotinib, for the treatment of the blood cancer myelofibrosis in patients with anemia.
https://seekingalpha.com/news/4012873-fda-approves-gsk-drug-ojjaara-for-myelofibrosis-with-anemia
TransCon™ PTH (palopegteriparatide)
TransCon™ PTH (palopegteriparatide)
TransCon™ PTH (palopegteriparatide)
Ascendis Pharma Receives Positive CHMP Opinion for TransCon™ PTH (palopegteriparatide) for Adults with Chronic Hypoparathyroidism
September 14, 2023 at 12:22 PM EDT PDF Version
- Final European Commission decision expected within 67 days after positive opinion;
if approved, first European Union launch planned in Germany in early 2024
COPENHAGEN, Denmark, Sept. 14, 2023 (GLOBE NEWSWIRE) -- Ascendis Pharma A/S (Nasdaq: ASND) today announced that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion and recommended the approval of TransCon PTH (palopegteriparatide) as a parathyroid hormone (PTH) replacement therapy indicated for the treatment of adults with chronic hypoparathyroidism. The European Commission’s final decision on the Company’s Marketing Authorisation Application is expected within 67 days after the positive opinion. TransCon PTH is a prodrug of parathyroid hormone (PTH [1-34]) administered once daily.
“We are pleased to have received this positive CHMP opinion for TransCon PTH and look forward to the final European Commission decision,” said Birgitte Volck, M.D., Ph.D., Executive Vice President, Head of Clinical Development & Medical Affairs, Endocrinology Rare Diseases at Ascendis Pharma. “Hypoparathyroidism is the last endocrine deficiency for which replacement of the missing hormone is not widely available. Based on our clinical and patient-reported data and a robust supply chain, we are confident in our ability to address the hypoparathyroidism community’s urgent need for new treatment options to safely and effectively address the burden of their disease.”
CHMP adopted its positive opinion following its review of the totality of the Company’s clinical package for TransCon PTH (palopegteriparatide), which included data from the global Phase 3 PaTHway and Phase 2 PaTH Forward trials in adult patients with hypoparathyroidism, both of which used the same drug/device combination product that Ascendis plans to make available as its commercial product, if approved. Ascendis plans its first European Union launch of TransCon PTH (palopegteriparatide), if approved, in Germany in early 2024.
About Ascendis Pharma A/S
Ascendis Pharma is applying its innovative TransCon technology platform to build a leading, fully integrated biopharma company focused on making a meaningful difference in patients’ lives. Guided by its core values of patients, science and passion, the company uses its TransCon technologies to create new and potentially best-in-class therapies. Ascendis is headquartered in Copenhagen, Denmark and has additional facilities in Germany (Heidelberg, Berlin and Munich) and the United States (Palo Alto and Redwood City, California, and Princeton, New Jersey). Please visit ascendispharma.com to learn more.
Source: Ascendis Pharma
Ascendis wins EU backing for hormone replacement therapy
Sep. 14, 2023 1:51 PM ET
By: Dulan Lokuwithana, SA News Editor
- Danish biotech Ascendis Pharma (ASND) announced Thursday that an expert panel of the EU drug regulator, the European Medicines Agency (EMA), recommended marketing authorization for its parathyroid hormone (PTH) replacement therapy, TransCon PTH.
- Adopting a so-called positive opinion, the EMA’s Committee for Medicinal Products (CHMP) has endorsed TransCon PTH as a PTH replacement therapy for adults with chronic hypoparathyroidism.
- https://seekingalpha.com/news/4011986-ascendis-stock-gains-eu-nod-hormone-therapy
- Ascendis Pharma A/S (ASND)
- https://ascendispharma.com/
- https://ascendispharma.com/pipeline/
- https://ascendispharma.us/
Blarcamesine (ANAVEX®2-73)
TransCon™ PTH (palopegteriparatide)
Blarcamesine (ANAVEX®2-73)
Anavex’s Phase 2b/3 Trial of Blarcamesine (ANAVEX®2-73) in Patients with Alzheimer’s Disease
Shows Robust Clinical Efficacy and Slows Neurodegeneration
Significant Reduction of Amyloid Beta Biomarkers of Alzheimer’s Pathology
NEW YORK – September 14, 2023
Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq: AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders announced today that a follow-on analysis of the landmark Phase 2b/3 study to treat early Alzheimer’s disease with the investigational drug blarcamesine (ANAVEX®2-73) did demonstrate a statistically significant slowing in cognitive decline associated with Alzheimer’s disease.
The clinical effect was complemented by two independent biomarkers: A significant reduction in pathological amyloid beta levels in plasma [1], as well as a significant slowing in the rate of pathological brain atrophy [2] on MRI (Magnetic Resonance Imaging) [3] scans.
The trial was a Multicenter (52 medical research centers/hospitals in 5 countries), randomized, double-blind, placebo-controlled, 48-week phase 2b/3 trial that enrolled 508 participants with early symptomatic Alzheimer disease (mild cognitive impairment/mild dementia). Participants were randomized to receive blarcamesine (n = 338) or placebo (n = 170) oral capsules once daily for 48 weeks.
All prespecified clinical endpoints were analyzed using a mixed model for repeated measures (MMRM). The MMRM analysis method is the convention used for regulatory filings and discussions with regulatory authorities are in preparation.
The trial is successful in meeting the co-primary endpoints if the significance of each endpoint is P < 0.05, or if the significance of only one co-primary endpoint is P < 0.025. If only one primary endpoint is significant at an α level of 0.025, then the secondary endpoint will be evaluated at the same level of 0.025. The trial was successful, since the differences in the least-squares mean (LSM) change from baseline to 48 weeks between the blarcamesine and placebo groups were −1.783 [95% CI, −3.314 to −0.251]; (P = 0.0226) for ADAS-Cog13, and −0.456 [95% CI, −0.831 to −0.080]; (P = 0.0175) for CDR-SB in patients with early Alzheimer’s disease.
In addition, validated biomarkers of amyloid beta pathology, plasma Aβ42/40 ratio increased significantly (P = 0.048), demonstrating strong anti-amyloid effects of blarcamesine in Alzheimer’s disease patients, while MRI revealed significant reduction in brain volume loss, including whole brain (P = 0.0005), comparing treatment to placebo. In the respective safety population, common treatment-emergent adverse events included dizziness, which was transient and mostly mild to moderate in severity, and occurred in 120 participants (35.8%) during titration and in 76 participants (25.2%) during maintenance with blarcamesine and 10 (6.0%) during titration and 9 (5.6%) during maintenance with placebo.
“There is hope that new therapies for Alzheimer’s that target the disease beyond amyloid that may slow progression of the disease for many people with the earliest forms of the disease,” said Marwan Noel Sabbagh, MD, Professor of Neurology and Chairman of the Scientific Advisory Board. “The advantage of blarcamesine (ANAVEX®2-73) is that it is a small oral molecule that exerts clinical benefits on cognition and neurodegeneration and could be appealing because of its route of administration and excellent safety profile.”
This is among the first drugs to prospectively demonstrate efficacy on biomarkers of neurodegeneration.
“These data are very exciting, particularly in a study that can demonstrate objective slowing of markers of neurodegeneration,” says Michael Weiner MD, Professor of Radiology and Biomedical Imaging, Medicine, Psychiatry, and Neurology at the University of California, San Francisco (UCSF) and Principal Investigator of the Alzheimer's Disease Neuroimaging Initiative (ADNI).
“Alzheimer’s disease is such a devastating disease that affects tens of millions worldwide, and Anavex’s clinical development is a testament to our determination to follow the science,” said Christopher U Missling, PhD, President and Chief Executive Officer of Anavex. “We like to thank all the people involved in the study for their invaluable contributions and we look forward to advancing blarcamesine as a potential new convenient orally available treatment option for Alzheimer’s disease.”
About Anavex Life Sciences Corp.
Anavex Life Sciences Corp. (Nasdaq: AVXL) is a publicly traded biopharmaceutical company dedicated to the development of novel therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders, including Alzheimer's disease, Parkinson's disease, Rett syndrome, and other central nervous system (CNS) diseases, pain, and various types of cancer. Anavex's lead drug candidate, ANAVEX®2-73 (blarcamesine), has successfully completed a Phase 2a and a Phase 2b/3 clinical trial for Alzheimer's disease, a Phase 2 proof-of-concept study in Parkinson's disease dementia, and both a Phase 2 and a Phase 3 study in adult patients with Rett syndrome. ANAVEX®2-73 is an orally available drug candidate that restores cellular homeostasis by targeting sigma-1 and muscarinic receptors. Preclinical studies demonstrated its potential to halt and/or reverse the course of Alzheimer's disease. ANAVEX®2-73 also exhibited anticonvulsant, anti-amnesic, neuroprotective, and anti-depressant properties in animal models, indicating its potential to treat additional CNS disorders, including epilepsy. The Michael J. Fox Foundation for Parkinson's Research previously awarded Anavex a research grant, which fully funded a preclinical study to develop ANAVEX®2-73 for the treatment of Parkinson's disease. ANAVEX®3-71, which targets sigma-1 and M1 muscarinic receptors, is a promising clinical stage drug candidate demonstrating disease-modifying activity against the major hallmarks of Alzheimer's disease in transgenic (3xTg-AD) mice, including cognitive deficits, amyloid, and tau pathologies. In preclinical trials, ANAVEX®3-71 has shown beneficial effects on mitochondrial dysfunction and neuroinflammation. Further information is available at www.anavex.com. You can also connect with the Company on Twitter, Facebook, Instagram, and LinkedIn.
[1] Amyloid beta levels strongly correlate with abeta plaque deposition in the brain and Alzheimer’s disease progression. [2] Brain atrophy, which is loss of brain volume is accelerated in Alzheimer’s disease. [3] Magnetic Resonance Imaging (MRI) is a non-invasive imaging technology that produces three dimensional detailed anatomical images.
Anavex Alzheimer's candidate slows cognitive decline in key study
Sep. 14, 2023 7:59 AM ET
Anavex Life Sciences Corp. (AVXL)
By: Jonathan Block, SA News Editor5 Comments
- Anavex Life Sciences' (NASDAQ:AVXL) oral drug candidate blarcamesine (ANAVEX2-73) slowed cognitive decline in a phase 2b/3 study.
- https://seekingalpha.com/news/4011760-anavex-alzheimers-candidate-blarcamesine-slows-cognitive-decline-study
- Anavex Life Sciences Corp. (AVXL)
- https://www.anavex.com/
- https://www.anavex.com/therapeutic-candidates
Resmetirom
TransCon™ PTH (palopegteriparatide)
Blarcamesine (ANAVEX®2-73)
Madrigal Pharmaceuticals Announces NDA Acceptance and Priority Review of the New Drug Application for Resmetirom for the Treatment of NASH with Liver Fibrosis
CONSHOHOCKEN, Pa., Sept. 13, 2023 (GLOBE NEWSWIRE) -- Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL), a clinical-stage biopharmaceutical company pursuing novel therapeutics for nonalcoholic steatohepatitis (NASH), today announced that the U.S. Food and Drug Administration (FDA) has accepted for review its New Drug Application (NDA) for resmetirom for the treatment of adult patients with NASH with liver fibrosis. The FDA has granted Priority Review and assigned a Prescription Drug User Fee Act date for resmetirom of March 14, 2024, the target date by which the FDA intends to complete its review and take action on the NDA. The Agency noted that it is not currently planning to hold an advisory committee meeting to discuss the application.
Resmetirom is a once daily, oral, thyroid hormone receptor (THR)-β selective agonist designed to target key underlying causes of NASH in the liver. The clinical development program for resmetirom is comprised of 18 clinical studies supporting the NDA: twelve Phase 1 studies, two Phase 2 studies, and four Phase 3 studies. Madrigal is seeking approval of resmetirom for the treatment of patients with NASH and liver fibrosis under the FDA’s accelerated approval pathway.
Bill Sibold, Chief Executive Officer of Madrigal, stated, “NASH with liver fibrosis represents a significant unmet need in healthcare today: the disease has a serious impact on patients and, without treatment, it can lead to increased risk of cirrhosis, liver failure, liver cancer, and premature mortality. Resmetirom is a liver-directed therapy that has demonstrated the potential to treat the liver fibrosis that is associated with these negative outcomes, while resolving the underlying steatohepatitis that drives the disease. The FDA’s acceptance of our NDA with priority review is an important step forward as we pursue our goal of delivering the first approved treatment to patients with NASH with liver fibrosis.”
The FDA grants Priority Review to applications for medicines that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions. A Priority Review designation means FDA’s goal is to take action on an application within 6 months (compared to 10 months under standard review).
Becky Taub, M.D., Chief Medical Officer and President of Research & Development of Madrigal, stated, “We believe that we have delivered a compelling data package to support the FDA’s benefit-risk evaluation of resmetirom for the treatment of NASH with liver fibrosis. The NDA is supported by the positive efficacy results observed in our pivotal Phase 3 trial, the large safety database we have established through the MAESTRO program, and two ongoing outcomes studies that are designed to verify clinical benefit following a potential accelerated approval. We look forward to beginning this critical next phase of the review process.”
About the Resmetirom Phase 3 Registration Program for the Treatment of NASH
Resmetirom is a once daily, oral, thyroid hormone receptor (THR)-β selective agonist designed to target key underlying causes of NASH in the liver.
Madrigal is currently conducting four Phase 3 clinical trials to demonstrate the safety and efficacy of resmetirom for the treatment of NASH: MAESTRO-NASH, MAESTRO-NAFLD-1, MAESTRO-NAFLD-OLE, and MAESTRO-NASH-OUTCOMES.
MAESTRO-NASH is a multicenter, randomized, double-blind, placebo-controlled Phase 3 study of resmetirom in patients with liver biopsy-confirmed NASH. The portion of the study designed to support a subpart H approval enrolled more than 1,000 patients with biopsy-proven NASH with fibrosis, randomized 1:1:1 to receive once-daily resmetirom 80 mg, resmetirom 100 mg, or placebo. The dual primary surrogate endpoints on biopsy were NASH resolution with ≥2-point reduction in NAS (NAFLD Activity Score), and with no worsening of fibrosis OR a 1-point decrease in fibrosis with no worsening of NAS after 52 weeks of treatment. Achievement of either primary endpoint was considered a successful trial outcome.
In December 2022, Madrigal announced that both daily oral doses of resmetirom achieved both MAESTRO-NASH primary liver biopsy endpoints. Multiple secondary endpoints were also achieved, including statistically significant reductions by resmetirom as compared with placebo in atherogenic lipids and lipoproteins, liver enzymes, fibrosis biomarkers, and imaging tests.
Resmetirom was generally safe and well-tolerated at both the 80 mg and 100 mg doses. Consistent with previous Phase 2 and Phase 3 data, the most common adverse event reported with greater frequency in the resmetirom groups versus placebo was an excess of generally mild and transient diarrhea and nausea at the beginning of therapy.
Patients enrolled in MAESTRO-NASH (approximately 1,750 total enrollment) continue on therapy after the initial 52-week treatment period for up to 54 months to accrue and measure hepatic clinical outcome events including progression to cirrhosis on biopsy (52 weeks and 54 months) and hepatic decompensation events, as well as all-cause mortality. This portion of the study is designed to generate confirmatory data that, if positive, will help verify resmetirom’s clinical benefit and support full approval.
MAESTRO-NAFLD-1 was a 52-week multicenter, randomized, placebo-controlled, double-blind Phase 3 study of resmetirom in ~1,200 patients with NAFLD, presumed NASH. MAESTRO-NAFLD-1 might be considered a “real-world” NASH study in that diagnosis was based on noninvasive measures rather than liver biopsy. The primary endpoint was to evaluate the safety and tolerability of resmetirom.
Patients in the MAESTRO-NAFLD-1 study were randomized 1:1:1:1 to receive once-daily resmetirom 80 mg, resmetirom 100 mg, or placebo in double-blind arms or resmetirom 100 mg in an open-label arm. Using noninvasive measures, MAESTRO-NAFLD-1 was designed to provide incremental safety information to support the NASH indication as well as provide additional data regarding clinically relevant key secondary efficacy endpoints to better characterize the potential clinical benefits of resmetirom on cardiovascular- and liver-related endpoints.
The primary safety endpoint of MAESTRO-NAFLD-1 and key secondary endpoints were achieved: resmetirom was safe, well-tolerated and provided statistically significant improvements in LDL-C, apolipoprotein B, triglycerides, and liver fat as measured by MRI-PDFF.
An additional open-label active treatment arm in 180 patients with early (well-compensated) NASH cirrhosis was conducted. Resmetirom was safe and well tolerated in the MAESTRO-NAFLD-1 open-label cohort of patients with well-compensated NASH cirrhosis. As observed in patients with noncirrhotic NASH, mild GI adverse events were seen at the beginning of therapy. Resmetirom reduced LDL-C, other atherogenic lipids and lipoproteins, and MRI-PDFF in patients with NASH cirrhosis and also reduced liver and spleen volume.
A separate 52 week Phase 3 clinical trial, an open-label active treatment extension study of MAESTRO-NAFLD-1 (MAESTRO-NAFLD-OLE), in about 700 patients is ongoing.
Data from the 52-week first 1,000 patient portion of MAESTRO-NASH, together with data from MAESTRO-NAFLD-1, MAESTRO-NAFLD-OLE, Phase 2 and Phase 1 data, including safety parameters, form the basis for Madrigal’s subpart H submission to FDA for accelerated approval of resmetirom for treatment of NASH with liver fibrosis.
In August 2022, Madrigal initiated MAESTRO-NASH-OUTCOMES, a randomized double-blind placebo-controlled study in approximately 700 patients with early NASH cirrhosis to allow for noninvasive monitoring of progression to liver decompensation events. A positive outcome is expected to support the full approval of resmetirom for noncirrhotic NASH, potentially accelerating the timeline to full approval. In addition, this study has the potential to support an additional indication for resmetirom in patients with well-compensated NASH cirrhosis.
About NASH
Nonalcoholic steatohepatitis (NASH) is a more advanced form of nonalcoholic fatty liver disease (NAFLD). NAFLD is estimated to afflict more than 20% of adults globally, about 30% in the United States. Of that population, 20% may have NASH.
NASH is a leading cause of liver related mortality and an increasing burden on healthcare systems globally. Additionally, patients with NASH, especially those with more advanced metabolic risk factors (hypertension, concomitant type 2 diabetes), are at increased risk for adverse cardiovascular events and increased morbidity and mortality.
In NASH, thyroid hormone beta activity in the liver is impaired, leading to a reduction in mitochondrial function and beta-oxidation of fatty acids, which in turn drive inflammation and liver fibrosis.
Once NASH progresses to significant liver fibrosis (stages F2 and F3) the risk of adverse liver outcomes increases dramatically. NASH is rapidly becoming the leading cause of liver transplantation in the U.S. There are currently no FDA-approved therapies available for the treatment of NASH.
About Madrigal Pharmaceuticals
Madrigal Pharmaceuticals, Inc. (Nasdaq: MDGL) is a clinical-stage biopharmaceutical company pursuing novel therapeutics for nonalcoholic steatohepatitis (NASH), a liver disease with high unmet medical need. Madrigal’s lead candidate, resmetirom, is a once daily, oral, thyroid hormone receptor (THR)-β selective agonist designed to target key underlying causes of NASH in the liver. For more information, visit www.madrigalpharma.com.
Source: Madrigal Pharmaceuticals, Inc.
Madrigal nabs FDA priority review for NASH drug
Sep. 13, 2023 9:58 AM ET
Madrigal Pharmaceuticals, Inc. (MDGL)
By: Dulan Lokuwithana, SA News Editor
- Madrigal Pharmaceuticals (NASDAQ:MDGL) announced Wednesday that the U.S. FDA accepted its New Drug Application (NDA) for its lead candidate resmetirom granting it the agency’s priority review for liver disease, nonalcoholic steatohepatitis (NASH).
- https://seekingalpha.com/news/4011356-madrigal-stock-gains-fda-priority-review-nash-drug
- Madrigal Pharmaceuticals, Inc. (MDGL)
- https://www.madrigalpharma.com/
- https://www.madrigalpharma.com/our-programs/resmetirom/