Moorestown, New Jersey, United States
biotecMAX™ 2023 Insight
CALQUENCE® (acalabrutinib)
Calquence granted first regulatory approval in China for adults with previously treated mantle cell lymphoma
PUBLISHED23 March 2023
23 March 2023 07:00 GMT
Across two clinical trials 82% overall response and 35% complete response rate
were observed in Chinese patients using Calquence
AstraZeneca’s Calquence (acalabrutinib), a next generation, selective Bruton’s tyrosine kinase (BTK) inhibitor, has been conditionally approved in China for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. This is the first approved indication for Calquence in China.
The conditional approval by the National Medical Products Administration (NMPA) was based on positive results from two clinical trials, including the ACE-LY-004 global Phase II trial in adults with relapsed or refractory MCL and a Phase I/ II trial in Chinese patients with relapsed or refractory MCL and other B-cell malignancies.1,2 Continued approval for this indication may be contingent upon verification of ongoing randomised controlled confirmatory trials.
MCL is typically an aggressive, rare form of non-Hodgkin lymphoma (NHL) that accounts for between 2-6% of all patients diagnosed with NHL in China. Patients are generally diagnosed around 60 years of age, often at later stages of the disease.3
Jun Zhu, Chief Physician, Department of Lymphatic Oncology, Peking University Cancer Hospital, Beijing, said: “Mantle cell lymphoma progresses rapidly and responds poorly to conventional treatment such as immunochemotherapy. Before the emergence of BTK inhibitors, there were few satisfactory treatment options for patients. The next-generation BTK inhibitor Calquence has higher target selectivity, fewer side effects, and a higher response rate compared to currently available treatments. This approval of Calquence in China can provide a new treatment option which can better benefit patients with this disease.”
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “This approval for Calquence offers people living with mantle cell lymphoma in China an effective and tolerable new treatment option to help control their disease. As the first approval in China for Calquence, it is also an exciting step forward for AstraZeneca in blood cancers, enabling us to help more patients across the globe gain access to innovative treatments.”
Results from the ACE-LY-004 Phase II trial showed at a median follow up of 15.2 months, investigator-assessed overall response rate (ORR) with Calquence was 80.6% (95% confidence interval [CI] 72.6-87.2), with a complete response (CR) achieved in 39.5% of patients with relapsed or refractory MCL (95% CI 30.9-48.7).1 Longer-term follow-up data showed at 38.1 months, patients treated with Calquence remained progression-free for a median of 22 months, with median overall survival (OS) of 59.2 months (95% CI 36.5-NE).4
Additionally, results from a Phase I/II trial conducted in China showed Calquence achieved a 82.4% ORR, with a CR achieved in 35.3% of patients with MCL based on a blinded independent central-review (BICR) analysis (95% CI 65.5-93.2). Calquence reduced the risk of disease progression or death by 51.5% (95% CI 33.3-67.0) at 12 months, with an estimated duration of response (DOR) of 65.5% (95% CI 66.6-93.3). The median DOR was not reached.2
The safety and tolerability of Calquence in these trials was consistent with that observed in previous clinical trials.1,2,4
Calquence is approved for the treatment of chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL) in the US and Japan and is approved for the treatment of CLL in the EU and in several other countries worldwide in the treatment-naïve and relapsed or refractory settings. Calquence is also approved in the US and several other countries for the treatment of adult patients with MCL who have received at least one prior therapy. Calquence is not currently approved for the treatment of MCL in Japan or the EU.
Notes
Mantle cell lymphoma (MCL)
MCL is a rare B-cell malignancy subtype and is typically clinically aggressive with a poor prognosis.3 The epidemiology of MCL in Asia is not well documented, with few published datasets describing the incidence and outcomes.3 MCL accounts for between 2-6% of all patients diagnosed with NHL China.3 Patients are generally diagnosed around 60 years of age and often at later stages of disease (Stage III or IV).3
ACE-LY-004
ACE-LY-004 is an open-label, single-arm Phase II clinical trial evaluating Calquence in adult patients with relapsed or refractory MCL.5 Patients in the trial were adults with MCL and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 or lower who had relapsed or were refractory to 1-5 prior therapies, had no prior BTK/BCL-2 inhibitor exposure, and did not require warfarin/vitamin K antagonists. Patients received oral Calquence 100mg twice-daily until progressive disease or toxicity. ORR (investigator-assessed partial response or better per Lugano classification), DOR, progression-free survival (PFS), OS and safety were assessed.1
Phase I/II trial in Chinese patients
The Phase I/II trial is an open-label, multicentre clinical trial evaluating pharmacokinetics, safety and efficacy of Calquence in adult Chinese patients with relapsed or refractory MCL and other advanced B-cell malignancies.2 In Phase I, patients with relapsed or refractory B-cell malignancies received a single dose of Calquence 100mg orally followed by a two-day washout period and subsequent treatment with Calquence 100mg orally twice daily in 28-day cycles, until progressive disease (PD) or treatment discontinuation (TD) for any other reason. In Phase II, patients with relapsed or refractory MCL and ECOG status of 2 or lower received Calquence 100mg orally twice daily in 28-day cycles until PD or TD. The primary efficacy endpoint was ORR per Lugano classification for NHL assessed by BICR. Secondary endpoints were investigator-assessed ORR, BICR- and investigator-assessed time to response, DOR, PFS, OS and adverse events. 2
Calquence
Calquence (acalabrutinib) is a next-generation, selective inhibitor of BTK. Calquence binds covalently to BTK, thereby inhibiting its activity.6 In B cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion.
Calquence is approved for the treatment of CLL and SLL in the US, approved for CLL in the EU and many other countries worldwide and approved in Japan for relapsed or refractory CLL and SLL.
As part of an extensive clinical development programme, AstraZeneca is currently evaluating Calquence in more than 20 company-sponsored clinical trials. Calquence is being evaluated for the treatment of multiple B-cell blood cancers, including CLL, MCL, diffuse large B-cell lymphoma, Waldenström’s macroglobulinaemia, marginal zone lymphoma and other haematologic malignancies.
AstraZeneca in haematology
AstraZeneca is pushing the boundaries of science to redefine care in haematology. We have expanded our commitment to patients with haematologic conditions, not only in oncology but also in rare diseases with the acquisition of Alexion, allowing us to reach more patients with high unmet needs. By applying our deep understanding of blood cancers, leveraging our strength in solid tumour oncology and delivering on Alexion’s pioneering legacy in complement science to provide innovative medicines for rare diseases, we are pursuing the end-to-end development of novel therapies designed to target underlying drivers of disease.
By targeting haematologic conditions with high unmet medical needs, we aim to deliver innovative medicines and approaches to improve patient outcomes. Our goal is to help transform the lives of patients living with malignant, rare and other related haematologic diseases, shaped by insights from patients, caregivers and physicians to have the most meaningful impact.
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 Twitter @AstraZeneca.
AstraZeneca's blood cancer drug Calquence gets conditional approval in China
Mar. 23, 2023 6:24 AM ET
By: Ravikash, SA News Editor
China' National Medical Products Administration (NMPA) granted conditional approval to AstraZeneca's (NASDAQ:AZN) Calquence to treat adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.
Upadacitinib (RINVOQ®)
March 23, 2023
AbbVie Advances Upadacitinib (RINVOQ®) to Phase 3 Clinical Trials in Systemic Lupus Erythematosus
- Results of the M19-130 (SLEek) Phase 2 trial of upadacitinib given alone or as a combination therapy (ABBV-599) met the primary endpoint of systemic lupus erythematosus (SLE) Responder Index (SRI-4) and steroid dose less than or equal to 10 mg prednisone equivalent once per day at week 24 in patients with moderately to severely active SLE1,2
- No new safety signals were identified with upadacitinib, and a similar safety profile was observed for the combination therapy (ABBV-599) as for treatment with upadacitinib alone2,3,4,5,6,7
- SLE is a complex autoimmune disorder in which the body's immune system attacks healthy tissue of the musculoskeletal system, skin, kidneys, lungs and other critical organs, leading to symptoms such as fatigue, joint pain and impaired function.8,9
NORTH CHICAGO, Ill., March 23, 2023 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced topline results from a Phase 2 study of upadacitinib (RINVOQ®, 30 mg) given alone or as combination therapy (ABBV-599) with a Bruton's Tyrosine Kinase inhibitor (elsubrutinib, 60 mg), once daily in patients with moderately to severely active systemic lupus erythematosus (SLE).1 The SLEek study met the primary endpoint of SLE Responder Index (SRI-4) and steroid dose less than or equal to 10 mg prednisone equivalent once per day at week 24 in the upadacitinib 30 mg group.1,2 Based on the results, AbbVie is advancing its clinical program of upadacitinib in SLE to Phase 3.
"Systemic lupus erythematosus is a very unpredictable life-long condition and the way it affects a patient can change over time. Therefore, there is a critical need for additional treatment options," said Roopal Thakkar, M.D., senior vice president, development and regulatory affairs and chief medical officer, AbbVie. "With a quarter-century of experience and commitment to the treatment of rheumatic diseases, our focus remains on areas of high unmet need like systemic lupus erythematosus, and we look forward to further evaluation of the potential benefits that upadacitinib could bring to patients."
A total of 341 participants enrolled in the Phase 2 study and were subsequently divided into five experimental groups according to treatment regimen (upadacitinib in combination with placebo; upadacitinib, at two different doses, combined with elsubrutinib; elsubrutinib in combination with placebo; placebo only).1 The primary outcome measure was achievement of the SRI-4 with a steroid dose less than or equal to 10 mg prednisone equivalent once daily at week 24.1 SRI-4 is defined as a greater or equal to 4-point reduction in SLE Disease Activity Index 2000 score without worsening of the overall condition or the development of significant disease activity in new organ systems.1
The safety results for the upadacitinib 30 mg arm of the study were generally consistent with the known safety profile of upadacitinib, with no new safety signals identified.2-7 Types of adverse events reported with upadacitinib combined with elsubrutinib were similar to those reported for patients treated with upadacitinib alone.2 Full results from the study will be presented at a future medical congress. Use of upadacitinib and elsubrutinib in SLE are not approved and their safety and efficacy have not been evaluated by regulatory authorities.
Additional information about the study can be found at www.clinicaltrials.gov under the identifier NCT03978520.
About Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) is a complex, multi-organ, autoimmune disorder characterized by the production of pathogenic autoantibodies and tissue deposition of immune complexes.8,9 In SLE, the body's immune system attacks healthy tissue of the musculoskeletal system, skin, kidneys, and other critical organs, leading to symptoms such as fatigue, joint pain and impaired function.8,9 The prevalence of SLE is higher in women compared to men, and SLE occurs more frequently in people of color.10,11
About RINVOQ® (upadacitinib)
Discovered and developed by AbbVie scientists, RINVOQ is a selective and reversible JAK inhibitor that is being studied in several immune-mediated inflammatory diseases.3-7,12,13,14,15,16,17,18,19 Based on enzymatic and cellular assays, RINVOQ demonstrated greater inhibitory potency for JAK-1 vs JAK-2, JAK-3 and TYK-2.3 The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness and safety is not currently known.3
Phase 3 trials of RINVOQ in rheumatoid arthritis, atopic dermatitis, psoriatic arthritis, axial spondyloarthritis, Crohn's disease, ulcerative colitis, giant cell arteritis and Takayasu arteritis are ongoing.3-7,12-19 The use of upadacitinib in systemic lupus erythematosus is not approved and its safety and efficacy have not been evaluated by regulatory authorities.
US Indications and Important Safety Information about RINVOQ® (upadacitinib)3
USES
RINVOQ is a prescription medicine used to treat:
- Adults with moderate to severe rheumatoid arthritis (RA) when 1 or more medicines called tumor necrosis factor (TNF) blockers have been used and did not work well or could not be tolerated.
- Adults with active psoriatic arthritis (PsA) when 1 or more medicines called TNF blockers have been used and did not work well or could not be tolerated.
- Adults with moderate to severe ulcerative colitis (UC) when 1 or more medicines called TNF blockers have been used and did not work well or could not be tolerated.
- Adults with active ankylosing spondylitis (AS) when 1 or more medicines called TNF blockers have been used and did not work well or could not be tolerated.
- Adults with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation when a TNF blocker medicine has been used and did not work well or could not be tolerated.
It is not known if RINVOQ is safe and effective in children with juvenile idiopathic arthritis, psoriatic arthritis, ulcerative colitis, ankylosing spondylitis, or non-radiographic axial spondyloarthritis.
- Adults and children 12 years of age and older with moderate to severe eczema (atopic dermatitis [AD]) that did not respond to previous treatment and their eczema is not well controlled with other pills or injections, including biologic medicines, or the use of other pills or injections is not recommended.
RINVOQ is safe and effective in children 12 years of age and older weighing at least 88 pounds (40 kg) with atopic dermatitis.
It is not known if RINVOQ is safe and effective in children under 12 years of age with atopic dermatitis.
About AbbVie in Rheumatology
For more than 20 years, AbbVie has been dedicated to improving care for people living with rheumatic diseases. Anchored by a longstanding commitment to discovering and delivering transformative therapies, we pursue cutting-edge science that improves our understanding of promising new pathways and targets, ultimately helping more people living with rheumatic diseases reach their treatment goals. For more information, visit AbbVie in rheumatology.
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, virology, women's health and gastroenterology, in addition to products and services across our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook, LinkedIn or Instagram.
SOURCE AbbVie
AbbVie gains as Skyrizi succeeds in Phase 3 trial for ulcerative colitis
Mar. 23, 2023 9:02 AM ET
By: Dulan Lokuwithana, SA News Editor
AbbVie (NYSE:ABBV) added ~1% pre-market Thursday after announcing that its interleukin-23 inhibitor Skyrizi met the primary and all secondary endpoints in a Phase 3 trial for adults with ulcerative colitis, a disease in the large intestine.
https://seekingalpha.com/news/3950354-abbvie-gains-skyrizi-succeeds-ulcerative-colitis
Zynyz™ (Retifanlimab-Dlwr)
Incyte Announces FDA Approval Of Zynyz™ (Retifanlimab-Dlwr) For The Treatment Of Metastatic Or Recurrent Locally Advanced Merkel Cell Carcinoma (MCC)
March 22, 2023 at 1:14 PM EDTPDF Version
— First regulatory approval for Incyte PD-1 inhibitor based on the results of the POD1UM-201 trial
— Zynyz is also being studied in additional tumor types and in combination with other Incyte pipeline compounds
WILMINGTON, Del.--(BUSINESS WIRE)--Mar. 22, 2023-- Incyte (Nasdaq:INCY) today announced that the U.S. Food and Drug Administration (FDA) has approved Zynyz™ (retifanlimab-dlwr), a humanized monoclonal antibody targeting programmed death receptor-1 (PD-1), for the treatment of adults with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC). The Biologics License Application (BLA) for Zynyz for this indication has been approved under accelerated approval by the U.S. FDA based on tumor response rate and duration of response (DOR). Continued approval of Zynyz for this indication may be contingent on verification and description of clinical benefit in confirmatory trials.
MCC is a rare and aggressive type of skin cancer that frequently appears as a single, painless, reddish-purple skin nodule on the head, neck and arms in skin exposed to sunlight1. MCC tends to grow quickly and has a high rate of metastatic disease, leading to a poor prognosis2,3. The estimated five-year overall survival (OS) rate is 14% in patients with MCC who present with distant metastatic disease3. MCC impacts less than 1 per 100,000 people in the U.S., but incidence rates are rapidly rising, especially in adults over the age of 654,5.
“More than a third of patients with MCC present with regional or distant metastases, which are associated with high rates of mortality,” said Dr. Shailender Bhatia, University of Washington and Fred Hutchinson Cancer Center. “The approval of Zynyz offers healthcare providers another first-line treatment option against MCC that can result in durable responses in patients with metastatic disease, and I look forward to having Zynyz in our treatment portfolio for these difficult-to-treat patients.”
The FDA approval was based on data from the POD1UM-201 trial, an open-label, multiregional, single-arm study that evaluated Zynyz in adults with metastatic or recurrent locally advanced MCC who had not received prior systemic therapy for their advanced disease. Among chemotherapy-naïve patients (n=65), Zynyz monotherapy resulted in an objective response rate (ORR) of 52% (95% confidence interval [CI]: 40-65) as determined by independent central review (ICR) using RECIST v1.1. Complete response was seen in 12 patients (18%), and 22 patients (34%) showed partial response. Among the responding patients, the duration of response (DOR) ranged from 1.1 to 24.9+ months, and 76% (26/34) experienced a DOR of six months or longer, and 62% (21/34) experienced a DOR of 12 months or longer by landmark analysis.
Serious adverse reactions occurred in 22% of patients receiving Zynyz. The most frequent serious adverse reactions (≥ 2% of patients) were fatigue, arrhythmia and pneumonitis. Permanent discontinuation of Zynyz due to an adverse reaction occurred in 11% of patients. The most common (≥10%) adverse reactions that occurred in patients receiving Zynyz were fatigue, musculoskeletal pain, pruritus, diarrhea, rash, pyrexia and nausea.
“Zynyz offers patients and healthcare professionals an additional first-line anti-PD-1 option for patients with metastatic or recurrent locally advanced MCC, which can be a challenging and aggressive disease to treat,” said Hervé Hoppenot, Chief Executive Officer, Incyte. “Incyte is grateful to the investigators and patients around the world who participated in the POD1UM-201 trial. We continue to study the potential of Zynyz in additional tumor types and in combination with other Incyte pipeline compounds.”
Incyte is committed to supporting patients and removing barriers to access medicines. Eligible patients in the U.S. who are prescribed Zynyz have access to IncyteCARES (Connecting to Access, Reimbursement, Education and Support), a comprehensive program offering personalized patient support, including financial assistance and ongoing education and additional resources. More information about IncyteCARES is available by visiting www.incytecares.com or calling 1-855-452-5234.
About POD1UM
The POD1UM (PD1 Clinical Program in Multiple Malignancies) clinical trial program for retifanlimab includes POD1UM-201 and several other Phase 1, 2 and 3 studies for patients with solid tumors, including registration-directed POD1UM trials evaluating retifanlimab as a monotherapy for patients with microsatellite instability-high endometrial cancer and squamous cell carcinoma of the anal canal (SCAC); and in combination with platinum-based chemotherapy for patients with non-small cell lung cancer and SCAC.
About POD1UM-201
POD1UM-201 (NCT03599713) is an open label, multiregional, single arm study evaluating retifanlimab in patients with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC) who had not received prior systemic therapy for their advanced disease.
Patients received Zynyz 500 mg intravenously every four weeks until disease progression, unacceptable toxicity, for up to 24 months. Tumor response assessments were performed every eight weeks for the first year of therapy and 12 weeks thereafter.
The primary endpoint was objective response rate (ORR) as determined by independent central radiographic review using RECIST v1.1. Secondary endpoints included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS); safety and pharmacokinetics.
For more information about the study, please visit: https://clinicaltrials.gov/ct2/show/NCT03599713.
About Zynyz™ (retifanlimab-dlwr)
Zynyz (retifanlimab-dlwr), is an intravenous PD-1 inhibitor indicated in the U.S. for the treatment of adult patients with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Zynyz is marketed by Incyte in the U.S. In 2017, Incyte entered into an exclusive collaboration and license agreement with MacroGenics, Inc. for global rights to retifanlimab.
Zynyz is a trademark of Incyte.
Please see the full Prescribing Information for ZYNYZ for additional Important Safety Information.
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/20230322005618/en/
Source: Incyte
Incyte wins FDA nod for Zynyz to treat rare skin cancer
Mar. 22, 2023 2:09 PM ET
Incyte Corporation (INCY), MGNX
By: Dulan Lokuwithana, SA News Editor
- Incyte (NASDAQ:INCY) announced Wednesday that the FDA cleared its intravenous PD-1 inhibitor Zynyz under the agency’s accelerated approval program for patients with merkel cell carcinoma (MCC), a rare form of skin cancer.
- The decision is based on results about the tumor response rate and duration of response (DOR) linked to Zynyz from the company’s POD1UM-201 trial.
- https://seekingalpha.com/news/3950069-incyte-macrogenics-win-fda-nod-rare-skin-cancer-therapy
- Incyte Corporation (INCY), MGNX
- https://www.incyte.com/what-we-do/pharmaceutical-portfolio
XTANDI® (enzalutamide) plus Leuprolide
Phase 3 Study Shows XTANDI® (enzalutamide) plus Leuprolide Significantly Improves Metastasis-Free Survival in Men with Non-Metastatic Prostate Cancer
Thursday, March 16, 2023 - 07:30pmView pdf
Pfizer and Astellas announce positive topline results from Phase 3 EMBARK trial
NEW YORK and TOKYO, March 16, 2023 – Pfizer Inc. (NYSE: PFE) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., “Astellas”) today announced positive topline results from the Phase 3 EMBARK trial evaluating XTANDI® (enzalutamide) in men with non-metastatic hormone-sensitive prostate cancer (nmHSPC; also known as non-metastatic castration-sensitive prostate cancer or nmCSPC) with high-risk biochemical recurrence (BCR). Patients enrolled in the trial were randomized to one of three study arms: XTANDI plus leuprolide, placebo plus leuprolide, or XTANDI monotherapy. The study met its primary endpoint with a statistically significant and clinically meaningful improvement in metastasis-free survival (MFS) for patients treated with XTANDI plus leuprolide versus placebo plus leuprolide.
At the time of the analysis, a positive trend in the key secondary endpoint of overall survival (OS) was also observed, but these data were not yet mature. Patients in the trial will be followed for a subsequent final OS analysis. The study also met a key secondary endpoint with a statistically significant and clinically meaningful improvement in MFS for patients treated with XTANDI monotherapy versus placebo plus leuprolide. Additional key secondary endpoints reached statistical significance, including time to prostate-specific antigen (PSA) progression and time to first use of new antineoplastic therapy. Other secondary endpoints are being analyzed. No new safety signals have been observed to date in the preliminary safety analysis, which is consistent with the established safety profile of XTANDI.
“As the only novel hormone therapy approved for three disease states of prostate cancer in the U.S., XTANDI has impacted hundreds of thousands of men,” said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology and Rare Disease, Pfizer Global Product Development. “The topline findings from EMBARK are highly encouraging and we look forward to engaging with health authorities to potentially bring XTANDI to men with non-metastatic hormone-sensitive prostate cancer with high-risk biochemical recurrence.”
“While current treatment options for localized prostate cancer are intended to be curative, some men remain at higher risk for biochemical recurrence following primary treatment, which may result in metastases,” said Ahsan Arozullah, M.D., MPH, Senior Vice President and Head of Development Therapeutic Areas, Astellas. “The EMBARK trial is the first study to demonstrate a statistically significant improvement in MFS using the combination of XTANDI plus leuprolide in men with this stage of disease.”
Detailed results from EMBARK will be presented at a future medical meeting. These data will also be discussed with regulatory authorities, including the U.S. Food and Drug Administration (FDA), to support a potential regulatory submission for XTANDI in this indication.
About EMBARK
The Phase 3, randomized, double-blind, placebo-controlled, multi-national trial enrolled 1,068 patients with non-metastatic hormone-sensitive prostate cancer (nmHSPC; also known as non-metastatic castration-sensitive prostate cancer or nmCSPC) with high-risk biochemical recurrence (BCR) at sites in the United States, Canada, Europe, South America, and the Asia-Pacific region. Patients who were considered high-risk BCR had a prostate-specific antigen (PSA) doubling time ≤ 9 months, serum testosterone ≥ 150 ng/dL (5.2 nmol/L), and screening PSA by the central laboratory ≥ 1 ng/mL if they had a radical prostatectomy (with or without radiotherapy) as primary treatment for prostate cancer or at least 2 ng/mL above the nadir if they had radiotherapy only as primary treatment for prostate cancer. Patients in the EMBARK trial were randomized to receive enzalutamide 160 mg daily plus leuprolide, enzalutamide 160 mg as a monotherapy, or placebo plus leuprolide.
The primary endpoint of the trial was metastasis-free survival (MFS) for enzalutamide plus leuprolide and placebo plus leuprolide. MFS is defined as the duration of time in months between randomization and the earliest objective evidence of radiographic progression by central imaging or death. For more information on the EMBARK (NCT02319837) trial go to www.clinicaltrials.gov.
XTANDI has not been approved for the treatment of patients with nmHSPC with high-risk BCR.
About Non-Metastatic Hormone-Sensitive Prostate Cancer with High-Risk Biochemical Recurrence
Non-metastatic hormone- (or castration-) sensitive prostate cancer (nmHSPC or nmCSPC) means there is no detectable evidence of the cancer spreading to distant parts of the body (metastases) with conventional radiological methods (CT/MRI) and the cancer still responds to medical or surgical treatment to lower testosterone levels.1,2 Of men who have undergone definitive prostate cancer treatment, including radical prostatectomy, radiotherapy, or both, an estimated 20-40% will experience a biochemical recurrence (BCR) within 10 years.3 About 9 out of 10 men with high-risk BCR will develop metastatic disease, and 1 in 3 will die as a result of the recurrence.3 The EMBARK trial focused on men with high-risk BCR. Per the EMBARK protocol, patients with nmHSPC with high-risk BCR are those initially treated by radical prostatectomy or radiotherapy, or both, with a PSA doubling time ≤ 9 months. High-risk BCR patients with a PSA doubling time of ≤ 9 months have a higher risk of metastases and death.4
About XTANDI® (enzalutamide)
XTANDI (enzalutamide) is an androgen receptor signaling inhibitor. The recommended dosage of XTANDI is 160 mg (capsules or tablets) administered orally once daily with or without food. XTANDI is a standard of care that has received regulatory approvals for use in men with mHSPC, mCRPC, and nmCRPC in the United States and for one or more of these indications in more than 100 countries, including the European Union and Japan. More than 720,000 patients have been treated with XTANDI globally.5
Please see Full Prescribing Information for additional safety information.
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 that generated $12.1 billion in revenue in 2022, including the best-selling therapies for metastatic breast cancer and prostate cancer. Our in-line portfolio is focused on four broad, key areas where we have pioneered several breakthroughs: breast cancer, genitourinary cancer, hematology, and precision medicine, and we are advancing an extensive pipeline of 33 programs in clinical development.
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 the Pfizer/Astellas Collaboration
In October 2009, Medivation, Inc., which is now part of Pfizer (NYSE:PFE), and Astellas (TSE: 4503) entered into a commercial agreement to jointly develop and commercialize XTANDI® (enzalutamide) in the United States, while Astellas has responsibility for manufacturing and all additional regulatory filings globally, as well as commercializing the product outside the United States. Pfizer receives alliance revenues as a share of U.S. profits and receives royalties on sales outside the U.S.
Pfizer, Astellas' Xtandi meets main goal in phase 3 trial for prostate cancer subtype
Mar. 17, 2023 6:30 AM ET
Pfizer Inc. (PFE), ALPMF, ALPMY
By: Ravikash, SA News Editor
Pfizer (NYSE:PFE) and Astellas Pharma's (OTCPK:ALPMF) (OTCPK:ALPMY) Xtandi met the main goal of a phase 3 trial to treat men with non-metastatic hormone-sensitive prostate cancer (nmHSPC).
EVKEEZA® (EVINACUMAB-DGNB)
March 22, 2023 at 7:00 AM EDT Back
FDA APPROVES FIRST-IN-CLASS EVKEEZA® (EVINACUMAB-DGNB) FOR YOUNG CHILDREN WITH ULTRA-RARE FORM OF HIGH CHOLESTEROL
Approval extends Evkeeza to children aged 5 to 11 with homozygous familial hypercholesterolemia (HoFH), an inherited condition characterized by extremely high low-density lipoprotein cholesterol (LDL-C)
48% reduction in LDL-C from baseline at week 24 when Evkeeza was added to other lipid-lowering therapies in the pivotal trial
TARRYTOWN, N.Y., March 22, 2023 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced the U.S. Food and Drug Administration (FDA) has extended the approval of Evkeeza® (evinacumab-dgnb) as an adjunct to other lipid-lowering therapies to treat children aged 5 to 11 with homozygous familial hypercholesterolemia (HoFH). Evkeeza is the first angiopoietin-like 3 (ANGPTL3) inhibitor treatment indicated for children as young as 5 years old to control dangerously high levels of low-density lipoprotein cholesterol (LDL-C) caused by HoFH. Evkeeza was initially approved as an adjunct to other lipid-lowering therapies in those aged 12 years and older with HoFH in February 2021.
“At the Family Heart Foundation, we know that children with homozygous familial hypercholesterolemia, and those caring for them, often live in fear of what the future holds as they contend with the dangerously high levels of bad cholesterol, or LDL-C, caused by this genetic disorder,” said Mary McGowan, M.D., Chief Medical Officer of the Family Heart Foundation. “Only 5% of rare diseases actually have an FDA-approved treatment. With this FDA approval, the HoFH community now has a much-needed treatment for young children, potentially making it possible for many to achieve recommended LDL-C levels much earlier in the course of this rare disease. This is a hopeful development for those living with HoFH.”
HoFH is an ultra-rare inherited condition that affects approximately 1,300 people in the U.S. and is the most severe form of familial hypercholesterolemia (FH). HoFH occurs when two copies of the FH-causing genes are inherited, one from each parent, resulting in dangerously high levels (usually >400 mg/dL) of LDL-C. Those living with HoFH are at risk for premature atherosclerotic disease and cardiac events even in their teenage years. Many patients are not diagnosed or are only diagnosed later in life.
“Guidelines recommend screening all children at high risk for homozygous familial hypercholesterolemia starting at age 2. However, until now, a positive diagnosis was often met with the frustration of having limited treatment options to help these children,” said Carissa M. Baker-Smith, M.D., MPH, Co-Director of Nemours Cardiac Center Cardiovascular Research and Innovation Program, Director of Nemours Cardiac Center Pediatric Preventive Cardiology, pediatric cardiologist, and a trial investigator. “By adding Evkeeza to standard lipid-lowering therapies in this pivotal trial, children were able to reduce their LDL-C, with the vast majority able to achieve declines of nearly 50%. These are clinically meaningful results that physicians should consider when developing a treatment approach for these young patients.”
Despite treatment with other lipid-lowering therapies, children entered the Phase 3 trial with an average LDL-C level of 264 mg/dL, more than twice the target (<110 mg/dL) for pediatric patients with HoFH. With the addition of Evkeeza, children were able to reduce their LDL-C by 48% at week 24 on average, meeting the trial’s primary endpoint. Significant reductions were also observed in other key secondary endpoints including levels of apolipoprotein B (ApoB), non-high-density lipoprotein cholesterol (non-HDL-C) and total cholesterol.
The safety profile of Evkeeza observed in these patients (n=20) was consistent with the safety profile observed in adults and pediatric patients aged 12 years and older, with the additional adverse reaction of fatigue. Fatigue was reported in 3 (15%) patients. The most common adverse events (AEs) occurring in >15% of patients were COVID-19 (n=15), pyrexia (n=5), headache (n=4), throat pain (oropharyngeal pain, n=4) as well as upper abdominal pain, diarrhea, vomiting, fatigue, nasopharyngitis, rhinitis and cough (all n=3). Most reported AEs were mild or moderate, and none led to study discontinuation.
“Since it was first approved, Evkeeza has become the standard of care for homozygous familial hypercholesterolemia in those aged 12 years or older. We’re gratified that now children as young as 5 years old have the potential to benefit from this treatment,” said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer at Regeneron. “As a first-in-class medicine for this relentless disease, Evkeeza exemplifies the promise of genetics-based research to transform treatment paradigms. Evkeeza’s journey from target discovery to treatment innovation was only made possible due to our long-term investment in genetics research and monoclonal antibody technologies, and this remains a central tenet of our science-first approach to this day.”
Regeneron is committed to helping patients who have been prescribed Evkeeza access their medication. Regeneron's myRARE™ patient support program offers financial assistance to eligible patients who need help with the out-of-pocket cost of Evkeeza. Under the program, eligible patients with commercial insurance may pay as little as $0 in out-of-pocket costs for Evkeeza. In addition, myRARE™ offers resources to help patients and healthcare providers get started with Evkeeza including product information, insurance benefit verification, community resources and appointment reminders. For more information, call 1-833-EVKEEZA (833-385-3392) or visit www.EVKEEZA.com.
The FDA evaluated the supplemental biologics license for Evkeeza in this indication under Priority Review, which is reserved for medicines that represent potentially significant improvements in efficacy or safety in treating serious conditions.
The safety and effectiveness of Evkeeza have not been established in patients with other causes of hypercholesterolemia, including those with heterozygous familial hypercholesterolemia (HeFH). The effect of Evkeeza on cardiovascular morbidity and mortality has not been determined.
About the Pivotal Pediatric Trial
The three-part, single-arm, open-label trial evaluated Evkeeza added to other lipid-lowering therapies in pediatric patients with HoFH aged 5 to 11 years. Part A (n=6) was a Phase 1b trial designed to assess the pharmacokinetics (PK), safety and tolerability of Evkeeza. Part B (n=14) evaluated the efficacy of Evkeeza during a 24-week treatment period and enrolled patients with an average age of 9 years. Among them, 86% were on statins, 93% were on ezetimibe, 50% were on LDL apheresis and 14% were on lomitapide. Patients received Evkeeza 15 mg/kg every four weeks delivered intravenously alongside their lipid-lowering treatment regimen. The primary endpoint was change in LDL-C at week 24. Secondary endpoints included the effect of Evkeeza on other lipid parameters (i.e., apolipoprotein B, non-high-density lipoprotein cholesterol, lipoprotein[a] and total cholesterol), efficacy by mutation status, safety and tolerability, immunogenicity and PK.
Patients who completed Part A or B were allowed to continue treatment in Part C (n=20), an ongoing Phase 3 extension trial. Parts A, B and C were not designed to evaluate the effect of Evkeeza on cardiovascular events.
About Evkeeza® (evinacumab)
Evkeeza was invented using Regeneron’s VelocImmune® technology and is a fully human monoclonal antibody that binds to and blocks the function of angiopoietin-like 3 (ANGPTL3), a protein that inhibits lipoprotein lipase (LPL) and endothelial lipase (EL) and regulates circulating lipids, including LDL-C.
Regeneron scientists discovered the angiopoietin gene family more than two decades ago. Human genetics research published in New England Journal of Medicine in 2017 by scientists from the Regeneron Genetics Center® found that patients whose ANGPTL3 gene did not function properly (called a “loss-of function mutation”) have significantly lower levels of key blood lipids, including LDL-C, and that this is associated with a significantly lower risk of coronary artery disease.
The generic name for Evkeeza in its approved U.S. indications is evinacumab-dgnb, with dgnb the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. FDA.
Regeneron is responsible for the development and distribution of Evkeeza in the U.S. and is collaborating with Ultragenyx to clinically develop, commercialize and distribute Evkeeza outside of the U.S.
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® (alirocumab), Kevzara® (sarilumab) and Inmazeb® (atoltivimab, maftivimab and odesivimab-ebgn).
Please see 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, pain, 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 Twitter.
Regeneron gets FDA approval for expanded use of high cholesterol drug Evkeeza in kids
Mar. 22, 2023 7:54 AM ET
Regeneron Pharmaceuticals, Inc. (REGN), RARE
By: Ravikash, SA News Editor1 Comment
The U.S. Food and Drug Administration (FDA) approved the expanded use of Regeneron Pharmaceuticals' (NASDAQ:REGN) Evkeeza as an adjunct to other lipid-lowering therapies to treat children aged five to 11 years with homozygous familial hypercholesterolemia (HoFH).
NUBEQA® (darolutamide)
3/20/2023
Darolutamide approved for additional prostate cancer indication in China
Darolutamide approved for additional prostate cancer indication in China
ORION CORPORATION
PRESS RELEASE
20 March 2023 at 09:00 EET
Darolutamide approved for additional prostate cancer indication in China
- Darolutamide now approved for metastatic hormone-sensitive prostate cancer as well as non-metastatic castration-resistant prostate cancer
- Additional indication based on data from the pivotal Phase III ARASENS trial
The Chinese National Medical Products Administration (NMPA) has approved the oral androgen receptor inhibitor (ARi) darolutamide in combination with docetaxel for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC). Darolutamide is already approved in China for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC), who are at high risk of developing metastatic disease.
The approval is based on the positive results from the Phase III ARASENS trial, which demonstrated that darolutamide plus androgen deprivation therapy (ADT) in combination with docetaxel significantly reduced the risk of death by 32.5% compared to ADT with docetaxel, in patients with metastatic hormone-sensitive prostate cancer. Additionally, the darolutamide combination showed consistent benefits across clinically relevant secondary endpoints, with the overall incidence of treatment-emergent adverse events being similar between treatment arms. These results were published in The New England Journal of Medicine.1
Darolutamide is being investigated in a broad development program with three additional ongoing or planned large clinical studies, to evaluate its potential across prostate cancer patients from the early- to the late-stage of this disease. This includes the ARANOTE Phase III trial evaluating darolutamide plus androgen deprivation therapy (ADT) versus ADT alone for mHSPC.
Darolutamide is developed jointly by Orion and Bayer.
About the ARASENS Trial
The ARASENS trial is a randomized, Phase III, multi-center, double-blind, placebo-controlled trial which was prospectively designed to investigate the efficacy and safety of oral darolutamide, an androgen receptor inhibitor (ARi), plus androgen deprivation therapy (ADT) and the chemotherapy docetaxel in patients with metastatic hormone-sensitive prostate cancer (mHSPC). A total of 1,306 newly diagnosed patients were randomized in a 1:1 ratio to receive 600 mg of darolutamide twice a day or matching placebo, plus ADT and docetaxel.
The primary endpoint of this trial was overall survival (OS). Secondary endpoints included time to castration-resistant prostate cancer (CRPC), time to pain progression, time to first symptomatic skeletal event (SSE), time to initiation of subsequent anticancer therapy, all measured at 12‐week intervals, as well as adverse events (AEs) as a measure of safety and tolerability. Results from this trial were published in the New England Journal of Medicine.1 A plain language summary publication of these data was published in Future Oncology.2 The ARASENS trial demonstrated that darolutamide plus androgen deprivation therapy (ADT) and docetaxel significantly reduced the risk of death by 32.5% compared to ADT plus docetaxel.1 Improvements in the secondary endpoints supported the benefit observed in the primary endpoint, overall survival.1
About Metastatic Hormone-Sensitive Prostate Cancer
Prostate cancer is the second most commonly diagnosed malignancy in men worldwide. In 2020, an estimated 1.4 million men were diagnosed with prostate cancer, and about 375,000 died from the disease worldwide.3
At the time of diagnosis, most men have localized prostate cancer, meaning their cancer is confined to the prostate gland and can be treated with curative surgery or radiotherapy. Upon relapse, when the disease will metastasise or spread, or if the disease is newly diagnosed, but has already spread, the disease is hormone-sensitive and androgen deprivation therapy (ADT) is the cornerstone of treatment for this hormone-sensitive disease. Current treatment options for men with metastatic hormone-sensitive prostate cancer (mHSPC) include hormone therapy, such as ADT, androgen receptor pathway inhibitors plus ADT or a combination of docetaxel chemotherapy and ADT. Despite these treatments, a large proportion of men with mHSPC will eventually experience progression to metastatic castration-resistant prostate cancer (mCRPC), a condition with limited survival.
About darolutamide
Darolutamide is an oral androgen receptor inhibitor (ARi) with a distinct chemical structure that binds to the receptor with high affinity and exhibits strong antagonistic activity, thereby inhibiting the receptor function and the growth of prostate cancer cells. The low potential for blood-brain barrier penetration for darolutamide is supported by preclinical models and neuroimaging data in healthy humans. This is supported by the overall low incidence of central nervous system (CNS)-related adverse events (AEs) compared to placebo as seen in the ARAMIS Phase III trial4 and the maintained verbal learning and memory observed in the darolutamide arm of the Phase II ODENZA trial.5
The product is approved under the brand name Nubeqa® in more than 80 countries around the world for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC), who are at high risk of developing metastatic disease. It is also approved for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC) in a number of markets including the U.S., Japan, EU and China. Filings in other regions are underway or planned by Bayer. The compound is also being investigated in further studies across various stages of prostate cancer, including in the ARANOTE Phase III trial evaluating darolutamide plus androgen deprivation therapy (ADT) versus ADT alone for metastatic hormone-sensitive prostate cancer (mHSPC), as well as the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) led international Phase III co-operative group DASL-HiCaP (ANZUP1801) trial evaluating darolutamide as an adjuvant treatment for localised prostate cancer with very high risk of recurrence. Information about these trials can be found at www.clinicaltrials.gov. In addition, a study to explore the potential of darolutamide in the early setting for patients who have experienced a rise in their prostate specific antigen (PSA) levels following surgery or radiation, is also planned.
Bayer, Orion's Nubeqa gets approval in China for expanded use in prostate cancer
Mar. 21, 2023 4:55 AM ET
Bayer Aktiengesellschaft (BAYRY), BAYZF
By: Ravikash, SA News Editor
China's National Medical Products Administration (NMPA) approved Bayer (OTCPK:BAYRY) (OTCPK:BAYZF) and Orion Corporation's oral drug Nubeqa, in combination with docetaxel, to treat patients with metastatic hormone-sensitive prostate cancer (mHSPC).
PADCEV (enfortumab vedotin-ejfv)
Astellas and Seagen Announce China’s National Medical Products Administration Accepts Biologics License Application for Enfortumab Vedotin in Certain Patients with Locally Advanced or Metastatic Urothelial Cancer
03/09/2023
– Clinical data submitted are consistent with global data and support enfortumab vedotin as a platinum-free option in patients with locally advanced or metastatic urothelial cancer who received prior treatment with a PD-1/L1 inhibitor and platinum-based chemotherapy –
TOKYO & BOTHELL, Wash.--(BUSINESS WIRE)-- Astellas Pharma Inc. (TSE:4503, President and CEO: Kenji Yasukawa, Ph.D., “Astellas”) and Seagen Inc. (Nasdaq: SGEN) today announced that the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) has accepted the Biologics License Application (BLA) for enfortumab vedotin for the treatment of patients with locally advanced or metastatic urothelial cancer (la/mUC) who received prior treatment with a PD-1/L1 inhibitor and platinum-based chemotherapy.
“In China, there were nearly 86,000 new cases of bladder cancer in 2020, and we are working with the NMPA to seek approval for enfortumab vedotin for patients with advanced stage disease,” said Ahsan Arozullah, M.D., M.P.H., Senior Vice President and Head of Development Therapeutic Areas, Astellas. “Enfortumab vedotin has become a second- and third-line treatment option for many patients around the world with previously treated locally advanced or metastatic urothelial cancer, and an approval in China may bring this therapy to those patients.”
The BLA submission for enfortumab vedotin is based on data from the EV-203 study (NCT04995419), a single-arm, open-label, multicenter Phase 2 study of enfortumab vedotin in Chinese patients with la/mUC who previously received a PD-1/L1 inhibitor and platinum-based chemotherapy. Results showed that EV-203 met its primary endpoint, showing statistical significance in objective response rate (ORR) by independent review committee (IRC) for patients treated with enfortumab vedotin alone compared to historical controls. Efficacy and pharmacokinetic data from the study are in line with global data, and EV-203 is a bridging study to EV-301, a Phase 3 randomized study that has supported global registrations of enfortumab vedotin, and EV-201 Cohort 1.
Please see Important Safety Information, including BOXED WARNING, at the end of this press release for further safety information regarding enfortumab vedotin including serious skin reactions.
Enfortumab vedotin alone and in combination with other therapies is the subject of a robust clinical development program aimed at addressing unmet medical needs across the continuum of urothelial cancer and in other solid tumors.
About Bladder and Urothelial Cancer
Globally, approximately 573,000 new cases of bladder cancer and 212,000 deaths are reported annually.1 Urothelial cancer accounts for 90% of all bladder cancers and can also be found in the renal pelvis, ureter and urethra.2 Approximately 12% of cases are locally advanced or metastatic urothelial cancer at diagnosis.3
In China, the incidence rate of bladder cancer in 2020 ranked 12th among all cancers, with an estimated 85,649 new cases that year. The five-year prevalence of bladder cancer in China is estimated to be 16.26/100,000 cases, or 235,393 cases.4
About the EV-203 Trial
The EV-203 trial (NCT04995419) is a Phase 2, multicenter, single-arm bridging study in China designed to evaluate the efficacy, safety and pharmacokinetic performance of enfortumab vedotin as treatment for patients in China. A total of 40 patients were enrolled in the study.
About the EV-301 Trial
The EV-301 trial (NCT03474107) is a global, multicenter, open-label, randomized Phase 3 trial designed to evaluate enfortumab vedotin versus physician's choice of chemotherapy (docetaxel, paclitaxel or vinflunine) in 608 patients with locally advanced or metastatic urothelial cancer who were previously treated with a PD-1/L1 inhibitor and platinum-based chemotherapies. The primary endpoint is overall survival, and secondary endpoints include progression-free survival, overall response rate, duration of response and disease control rate, as well as assessment of safety/tolerability and quality-of-life parameters.
About the EV-201 Trial
The EV-201 trial (NCT03219333) is a single-arm, multi-cohort, multicenter, pivotal phase 2 clinical trial of enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1 or PD-L1 inhibitor, including those who have also been treated with a platinum-containing chemotherapy (Cohort 1) and those who have not received a platinum-containing chemotherapy in this setting and who are ineligible for cisplatin (Cohort 2). The trial enrolled 125 patients in Cohort 1 and 89 patients in Cohort 2 at multiple centers internationally. The primary endpoint is confirmed objective response rate per blinded independent central review. Secondary endpoints include assessments of duration of response, disease control rate, progression-free survival, overall survival, safety and tolerability.
Results of EV-301 and EV-201 Cohort 2 clinical trials supported the full and supplemental approval of PADCEV® (enfortumab vedotin-ejfv) by the U.S. Food and Drug Administration in July 2021. Additionally, results from EV-301 and EV-201 Cohort 1 serve as core data to support the Marketing Authorization Applications for enfortumab vedotin in the global market, including the European Union, Japan and Singapore.
About PADCEV
PADCEV (enfortumab vedotin-ejfv) is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.5 Nonclinical data suggest the anticancer activity of PADCEV is due to its binding to Nectin-4-expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).6
PADCEV (enfortumab vedotin-ejfv) U.S. Indication & Important Safety Information
BOXED WARNING: SERIOUS SKIN REACTIONS
- PADCEV can cause severe and fatal cutaneous adverse reactions including Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), which occurred predominantly during the first cycle of treatment, but may occur later.
- Closely monitor patients for skin reactions.
- Immediately withhold PADCEV and consider referral for specialized care for suspected SJS or TEN or severe skin reactions.
- Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions.
Indication
PADCEV® is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC) who:
- have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and platinum-containing chemotherapy, or
- are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of therapy.6
- https://www.padcev.com/hcp
For more information, please see the full Prescribing Information including BOXED WARNING for PADCEV here .
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 Seagen
Seagen Inc. is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people’s lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on the company’s marketed products and robust pipeline, visit www.seagen.com and follow @SeagenGlobal on Twitter.
About the Astellas and Seagen Collaboration
Astellas and Seagen are co-developing enfortumab vedotin under a 50:50 worldwide development and commercialization collaboration. In the United States, Astellas and Seagen co-promote enfortumab vedotin under the brand name PADCEV® (enfortumab vedotin-ejfv). In the Americas outside the US, Seagen holds responsibility for commercialization activities and regulatory filings. Outside of the Americas, Astellas holds responsibility for commercialization activities and regulatory filings.
Source: Seagen Inc.
Astellas, Seagen's bladder cancer therapy gets review in China
Mar. 10, 2023 6:21 AM ET
Seagen Inc. (SGEN), ALPMY, ALPMF
By: Ravikash, SA News Editor
- China's National Medical Products Administration (NMPA) accepted Astellas Pharma (OTCPK:ALPMF) (OTCPK:ALPMY) and Seagen's (NASDAQ:SGEN) application seeking approval of enfortumab vedotin to treat patients with locally advanced or metastatic urothelial cancer (la/mUC) who received prior therapy with a PD-1/L1 inhibitor and platinum-based chemotherapy.
- https://seekingalpha.com/news/3946367-astellas-seagens-bladder-cancer-therapy-gets-review-in-china
- Seagen Inc. (SGEN), ALPMY, ALPMF
- https://www.padcev.com/hcp
- https://www.seagen.com/
Tafinlar + Mekinist
Novartis Tafinlar + Mekinist approved by FDA for pediatric patients with BRAF V600E low-grade glioma, the most common pediatric brain cancer
Mar 17, 2023
- New approval based on TADPOLE trial showing overall response rate (ORR) of 47% and median progression-free survival (mPFS) of 20.1 months for Tafinlar + Mekinist compared to 11% ORR and 7.4 months mPFS for standard of care1,2
- Approval also received for liquid formulation options for ease of administration across multiple approved indications
- Tafinlar + Mekinist is now approved in six indications across multiple BRAF V600E solid tumors, including melanoma, thyroid cancer and lung cancer1,2
Basel, March 16, 2023 — Novartis today announced the U.S. Food and Drug Administration (FDA) granted approval for Tafinlar® (dabrafenib) + Mekinist® (trametinib) for the treatment of pediatric patients 1 year of age and older with low-grade glioma (LGG) with a BRAF V600E mutation who require systemic therapy. The FDA also approved liquid formulations of Tafinlar and Mekinist, marking the first time a BRAF/MEK inhibitor has been developed in a formulation suitable for patients as young as one year of age. These approvals make Tafinlar + Mekinist the first and only approved combination targeted therapy to treat pediatric patients with BRAF V600E LGG.
“Pediatric cancer research is vital to uncover new treatment methods for a population,” said Dr. Eric Bouffet, MD, FRCPC, Principal Investigator of the TADPOLE clinical trial and Associate Scientist Emeritus at The Hospital for Sick Children (SickKids). “Developing targeted therapies based on the unique genetic features of a patient’s tumor is the future of pediatric cancer care.”
This FDA approval of Tafinlar + Mekinist is based on results from the Phase II/III TADPOLE trial (NCT02684058) that showed patients randomized to receive Tafinlar + Mekinist experienced a statistically significant improvement in overall response rate (ORR) of 47% (CI: 35-59%) compared to 11% (CI: 3-25%) for those randomized to receive chemotherapy. At a median follow-up of 18.9 months, median progression-free survival (PFS) was 20.1 months with Tafinlar + Mekinist (CI: 12.8 months-not estimable) compared to 7.4 months with chemotherapy (CI: 3.6-11.8 months, hazard ratio=0.31 [CI: 0.17-0.55] [p<0.001]).
“It is more important than ever to test for genetic mutations in patients living with low-grade glioma. This FDA approval may offer new hope to pediatric patients living with BRAF V600E low-grade glioma,” said Dr. Roger Packer, senior vice president of the Center for Neurosciences and Behavioral Medicine at Children’s National Hospital. “This has the potential to change the way healthcare providers treat these pediatric patients, offering a significant advancement compared to chemotherapy.”
The safety profile of Tafinlar + Mekinist observed in this study was consistent with the known safety profile in other approved indications. The most common adverse reactions (>=15%) were pyrexia (68%), rash (51%), headache (47%), vomiting (34%), musculoskeletal pain (34%), fatigue (33%), diarrhea (29%), dry skin (26%), nausea (25%), hemorrhage (25%), abdominal pain (25%), dermatitis acneiform (22%), dizziness (15%), upper respiratory tract infection (15%) and weight increased (15%). These data were highlighted as part of an official press briefing and oral presentation at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.
“This new indication for Tafinlar + Mekinist is a potential new standard of care treatment option for young patients with this form of brain cancer with a BRAF V600E mutation, in formulations specifically designed for them,” said Reshema Kemps-Polanco, Executive Vice President, US Oncology at Novartis. “We are thankful for the families, including children and adolescents, that participated in the clinical trial that led to this approval and whose bravery has led to a new hope for children living with this serious brain cancer.”
LGG is the most common pediatric brain cancer. BRAF V600 mutations are present in 15-20% of pediatric LGGs and are associated with poor survival outcomes and less favorable response to chemotherapy4. BRAF mutations have been identified as drivers of cancer growth across a wide range of solid tumors, and often have limited treatment options4,5.
Full prescribing information for Tafinlar + Mekinist can be found at https://www.novartis.us/sites/www.novartis.us/files/tafinlar.pdf and https://www.novartis.us/sites/www.novartis.us/files/mekinist.pdf.
About Tafinlar + Mekinist
The combination of Tafinlar + Mekinist, the worldwide targeted therapy leader in BRAF/MEK-inhibition research and patients reached, may help to slow tumor growth by blocking signals associated with the BRAF and MEK kinases that are implicated in the growth of various types of cancer1,2,4,5. Tafinlar + Mekinist has been studied in more than 6,000 BRAF-positive patients in more than 20 ongoing and completed trials, including in pediatric patients 1 year of age and older, and has been prescribed to more than 200,000 patients worldwide6.
This FDA approval is the sixth for Tafinlar + Mekinist, which is indicated across multiple BRAF V600 solid tumors, including melanoma, thyroid cancer and lung cancer1,2.
https://www.us.tafinlarmekinist.com/
Indication and Important Safety Information
TAFINLAR and MEKINIST are prescription medicines that can be used in combination to treat people with a type of skin cancer called melanoma:
- that has spread to other parts of the body (metastatic) or cannot be removed by surgery (unresectable), and
- that has a certain type of abnormal “BRAF” (V600E or V600K mutation-positive) gene
TAFINLAR and MEKINIST are prescription medicines that can be used in combination to help prevent melanoma that has a certain type of abnormal “BRAF” gene from coming back after the cancer has been removed by surgery.
TAFINLAR and MEKINIST are prescription medicines that can be used in combination to treat a type of lung cancer called non-small cell lung cancer (NSCLC) that has spread to other parts of the body (metastatic NSCLC), and that has a certain type of abnormal “BRAF V600E” gene.
TAFINLAR and MEKINIST are prescription medicines that can be used in combination to treat a type of thyroid cancer called anaplastic thyroid cancer (ATC):
- that has spread to other parts of the body and you have no satisfactory treatment options and
- that has a certain type of abnormal “BRAF” gene
TAFINLAR and MEKINIST are prescription medicines that can be used in combination to treat solid tumors in adults and children 6 years of age and older:
- that cannot be removed by surgery or have spread to other parts of the body, and that have gotten worse (progressed) and you have no satisfactory treatment options and
- that have a certain type of abnormal “BRAF” gene
The effectiveness of TAFINLAR and MEKINIST in these patients is based on 2 adult studies and 1 pediatric study that measured 2 types of response to treatment (response rate and duration of response). No clinical information is available to show if these patients treated with TAFINLAR and MEKINIST live longer or if their symptoms improve. Ongoing studies exist to determine how TAFINLAR and MEKINIST works over a longer period.
TAFINLAR and MEKINIST are prescription medicines that can be used in combination to treat a type of brain tumor called glioma in children 1 year of age and older
- that is low-grade glioma (LGG), and
- that have a certain type of abnormal “BRAF” gene, and
- who require a medicine by mouth or injection (systemic therapy)
TAFINLAR, in combination with MEKINIST, is not for use in treating people with colorectal cancer or wild-type BRAF solid tumors. MEKINIST should not be used to treat people who already have received a BRAF inhibitor for treatment of their melanoma and it did not work or is no longer working.
Your health care provider will perform a test to make sure that TAFINLAR and MEKINIST, in combination, are right for you.
It is not known if TAFINLAR used in combination with MEKINIST is safe and effective in children younger than 6 years of age.
TAFINLAR and MEKINIST, in combination, may cause serious side effects such as the risk of new cancers, including both skin cancer and nonskin cancer. Patients should be advised to contact their health care provider immediately for any skin changes, including a new wart, skin sore, or bump that bleeds or does not heal, or a change in the size or color of a mole.
When TAFINLAR is used in combination with MEKINIST, it can cause serious bleeding problems, especially in the brain or stomach, that can lead to death. Patients should be advised to call their health care provider and get medical help right away if they have any signs of bleeding, including headaches, dizziness, or feeling weak, coughing up blood or blood clots, vomiting blood or their vomit looks like “coffee grounds,” or red or black stools that look like tar.
MEKINIST, alone or in combination with TAFINLAR, can cause inflammation of the intestines or tears in the stomach or intestines that can lead to death. Patients should report to their health care provider right away if they have any of the following symptoms: bleeding, diarrhea (loose stools) or more bowel movements than usual, stomach-area (abdomen) pain or tenderness, fever, or nausea.
TAFINLAR, in combination with MEKINIST, can cause blood clots in the arms or legs, which can travel to the lungs and can lead to death. Patients should be advised to get medical help right away if they have the following symptoms: chest pain, sudden shortness of breath or trouble breathing, pain in their legs with or without swelling, swelling in their arms or legs, or a cool or pale arm or leg.
The combination of TAFINLAR and MEKINIST can cause heart problems, including heart failure. A patient’s heart function should be checked before and during treatment. Patients should be advised to call their health care provider right away if they have any of the following signs and symptoms of a heart problem: feeling like their heart is pounding or racing, shortness of breath, swelling of their ankles and feet, or feeling lightheaded.
TAFINLAR, in combination with MEKINIST, can cause severe eye problems that can lead to blindness. Patients should be advised to call their health care provider right away if they get: blurred vision, loss of vision, or other vision changes, seeing color dots, halo (seeing blurred outline around objects), eye pain, swelling, or redness.
TAFINLAR, in combination with MEKINIST, can cause lung or breathing problems. Patients should be advised to tell their health care provider if they have new or worsening symptoms of lung or breathing problems, including shortness of breath or cough.
Fever is common during treatment with TAFINLAR in combination with MEKINIST but may also be serious. In some cases, chills or shaking chills, too much fluid loss (dehydration), low blood pressure, dizziness, or kidney problems may happen with the fever. Patients should be advised to call their health care provider right away if they get a fever.
Rash and other skin reactions are common side effects of TAFINLAR in combination with MEKINIST. In some cases, these rashes and other skin reactions can be severe or serious, may need to be treated in a hospital, or lead to death. Patients should be advised to call their health care provider if they get any of the following symptoms: blisters or peeling of skin, mouth sores, blisters on the lips or around the mouth or eyes, high fever or flu-like symptoms, and/or enlarged lymph nodes.
Some people may develop high blood sugar or worsening diabetes during treatment with TAFINLAR in combination with MEKINIST. For patients who are diabetic, their health care provider should check their blood sugar levels closely during treatment. Their diabetes medicine may need to be changed. Patients should be advised to tell their health care provider if they have increased thirst, urinate more often than normal, or produce an increased amount of urine.
TAFINLAR may cause healthy red blood cells to break down too early in people with glucose-6-phosphate dehydrogenase deficiency. This may lead to a type of anemia called hemolytic anemia, where the body does not have enough healthy red blood cells. Patients should be advised to tell their health care provider if they have yellow skin (jaundice), weakness or dizziness, or shortness of breath.
TAFINLAR, in combination with MEKINIST, can cause new or worsening high blood pressure (hypertension). A patient’s blood pressure should be checked during treatment. Patients should be advised to tell their health care provider if they develop high blood pressure, their blood pressure worsens, or if they have severe headache, lightheadedness, blurry vision, or dizziness.
For women of reproductive potential, TAFINLAR and MEKINIST, in combination, can harm your unborn baby. Your health care provider will do a test to see if you are pregnant before starting treatment with TAFINLAR and MEKINIST in combination. Use effective birth control (contraception) during treatment with TAFINLAR and MEKINIST in combination, and for 4 months after stopping treatment with TAFINLAR and MEKINIST.
Men (including those who have had a vasectomy) should use condoms during sexual intercourse during treatment with TAFINLAR and MEKINIST and for at least 4 months after the last dose of TAFINLAR and MEKINIST.
The most common side effects for patients with metastatic melanoma receiving the combination are pyrexia, nausea, rash, chills, diarrhea, headache, vomiting, hypertension, arthralgia, peripheral edema, and cough. The most common side effects for patients with stage III melanoma as adjuvant therapy receiving the combination are pyrexia, tiredness, nausea, headache, rash, chills, diarrhea, vomiting, arthralgia, and myalgia. The most common side effects for patients with NSCLC receiving the combination are pyrexia, tiredness, nausea, vomiting, diarrhea, dry skin, decreased appetite, edema, rash, chills, hemorrhage, cough, and dyspnea. The most common side effects for adults with solid tumors that cannot be removed by surgery or have spread to other parts of the body who are receiving the combination are fever, tiredness, nausea, rash, chills, headache, bleeding, cough, vomiting, constipation, diarrhea, muscle and or joint aches, and swelling of arms and legs. The most common side effects for children with solid tumors that cannot be removed by surgery or have spread to other parts of the body who are receiving the combination are fever, rash, vomiting, tiredness, dry skin, cough, diarrhea, acnearea, headache, stomach- (abdomen) pain, nausea, bleeding, constipation, and skin infection around fingernails or toenails. The most common side effects of in children 1 year of age and older with low-grade glioma receiving the combination include fever, rash, headache, vomiting, muscle and bone pain, tiredness, dry skin, diarrhea, nausea, bleeding, stomach area (abdomen) pain, and acne.
Please see full Prescribing Information for TAFINLAR and MEKINIST at https://www.novartis.us/sites/www.novartis.us/files/tafinlar.pdf and https://www.novartis.us/sites/www.novartis.us/files/mekinist.pdf.
About Novartis
Novartis is reimagining medicine to improve and extend people’s lives. We deliver high-value medicines that alleviate society’s greatest disease burdens through technology leadership in R&D and novel access approaches. In our quest to find new medicines, we consistently rank among the world’s top companies investing in research and development. About 106,000 people of more than 140 nationalities work together to bring Novartis products to nearly 800 million people around the world. Find out more at https://www.novartis.com
Novartis Tafinlar Mekinist combo gets FDA approval to treat brain cancer in children
Mar. 17, 2023 5:45 AM ET
By: Ravikash, SA News Editor
The U.S. Food and Drug Administration (FDA) approved the expanded use of Novartis' (NYSE:NVS) Tafinlar plus Mekinist to treat children one year of age and older with low-grade glioma (LGG) having a BRAF V600E mutation, requiring systemic therapy.
PAXLOVID™ (nirmatrelvir tablets and ritonavir tablets)
FDA Advisory Committee Votes in Support of Favorable Benefit-Risk Profile for Pfizer’s PAXLOVID™
Thursday, March 16, 2023 - 03:18pm View pdf
- The target Prescription Drug User Fee Act (PDUFA) action date for a decision by the FDA is May 2023
NEW YORK--(BUSINESS WIRE)-- Pfizer Inc. (NYSE: PFE) announced today that the U.S. Food and Drug Administration’s (FDA) Antimicrobial Drugs Advisory Committee (AMDAC) voted 16 to 1 that available data support the safety and effectiveness of PAXLOVID™ (nirmatrelvir tablets and ritonavir tablets) for the treatment of mild-to-moderate COVID-19 in adult patients who are at high risk for progression to severe illness. The AMDAC's vote, while not binding, will be considered by the FDA when making its decision regarding the potential approval of PAXLOVID.
“We believe it is critical for adults who are at high risk of progression to severe COVID-19 to have access to safe and effective treatment options, like PAXLOVID, to help prevent avoidable hospitalizations and deaths,” said James Rusnak, Senior Vice President and Chief Development Officer, Internal Medicine, Anti-infectives and Hospital, Pfizer. “We are encouraged by the AMDAC’s positive vote today. The outcome is well supported by the strong safety and efficacy data seen both in our clinical trials and in a growing base of real-world evidence, showing that PAXLOVID helps to reduce the risk of hospitalization or death for high-risk adult patients regardless of vaccination status.”
The AMDAC based its vote on the totality of scientific and real-world evidence shared by Pfizer, including safety and efficacy data from the EPIC (Evaluation of Protease Inhibition for COVID-19) clinical development program. This included results from the Phase 2/3 EPIC-HR study (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients), which enrolled unvaccinated, non-hospitalized adults, aged 18 years and older, with confirmed COVID-19 who are at increased risk of progressing to severe disease. The data showed an 86% reduction in risk of COVID-19-related hospitalization or death from any cause through Day 28 in patients treated with PAXLOVID within 5 days of symptoms onset, compared to placebo. The vote was further supported by results from a secondary endpoint of the Phase 2/3 EPIC-SR study (Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients) which showed the effectiveness of Paxlovid in a sub-group of non-hospitalized adults, aged 18 years and older, with confirmed COVID-19 who had at least one risk factor for progression to severe disease and who were fully vaccinated.
In addition, real-world evidence presented to the AMDAC showed that PAXLOVID’s clinical profile in the post-authorization setting is consistent with the safety and efficacy conclusions from the EPIC clinical program, including observations made when the Omicron variant and its lineages were the predominant forms of SARS-CoV-2 in circulation. This real-world evidence also shows the effectiveness of PAXLOVID among vaccinated patients and patients who developed natural immunity.1,2,3
COVID-19 continues to cause significant burden in the U.S. as case rates fluctuate and new variants and sub-variants emerge, regardless of virulence. Approximately 4,000‒5,000 hospital admissions and 500‒600 deaths are caused by the virus each day in the U.S., as of January 2023.4 With more than 200 million adults in the U.S. at high risk of severe COVID-19, there is a critical need for treatment options in this population.5 According to the U.S. Centers for Disease Control and Prevention (CDC), factors which could put someone at high risk of severe COVID-19 include any of the following: being aged 50 and older, obesity, diabetes (type 1 and type 2), heart conditions, smoking (current or former), physical inactivity, chronic kidney or liver disease, and cancer, among others.6
If approved by the FDA, PAXLOVID could be the first U.S. FDA-approved oral treatment for COVID-19. The target Prescription Drug User Fee Act (PDUFA) action date for a decision by the FDA is May 2023. Under the FDA emergency use authorization (EUA), PAXLOVID is currently authorized for use in, and remains available to, adults and pediatric patients (12 years of age and older weighing at least 40 kg) at high risk of progression to severe COVID-19. In the U.S., more than 10 million treatment courses of PAXLOVID have been prescribed to date.7
Pfizer continues to gather pediatric data from the ongoing clinical trial EPIC-Peds (Evaluation of Protease Inhibition for COVID-19 in Pediatric Patients) and intends to submit a supplemental New Drug Application (NDA) to support the FDA approval of PAXLOVID in children at a future date. In February 2023, the European Commission (EC) granted standard Marketing Authorization (MA) of PAXLOVID for the treatment of COVID-19 in adults who do not require supplemental oxygen and who are at increased risk of the disease becoming severe.
About PAXLOVID™ (nirmatrelvir tablets and ritonavir tablets)
PAXLOVID is a SARS-CoV-2 main protease (Mpro) inhibitor (also known as SARS-CoV-2 3CL protease inhibitor) therapy. It was developed to be administered orally so that it can be prescribed early after infection, potentially helping patients avoid severe illness (which can lead to hospitalization and death). Nirmatrelvir, which originated in Pfizer laboratories, is designed to block the activity of the Mpro, an enzyme that the coronavirus needs to replicate. Co-administration with a low dose of ritonavir helps slow the metabolism, or breakdown, of nirmatrelvir in order for it to remain active in the body for longer periods of time at higher concentrations to help combat the virus.
Nirmatrelvir is designed to inhibit viral replication at a stage known as proteolysis, which occurs before viral RNA replication. In preclinical studies, nirmatrelvir did not demonstrate evidence of mutagenic DNA interactions.
Current variants of concern can be resistant to treatments that work by binding to the spike protein found on the surface of the SARS-CoV-2 virus. PAXLOVID, however, works intracellularly by binding to the highly conserved Mpro (3CL protease) of the SARS-CoV-2 virus to inhibit viral replication. Nirmatrelvir has shown consistent in vitro antiviral activity against the variants Alpha, Beta, Delta, Gamma, Lambda, Mu, and Omicron BA.1, BA.2, BA.2.12.1, BA.4, BA.4.6, BA.5, BF.7, BQ.1.11, BQ.1 and XBB.1.5. Work is ongoing to evaluate activity against recently identified variants as they become available for testing.
PAXLOVID is generally administered at a standard dose of 300 mg (two 150 mg tablets) of nirmatrelvir with one 100 mg tablet of ritonavir, taken together twice-daily for five days. One carton contains five blister packs of PAXLOVID, as co-packaged nirmatrelvir tablets with ritonavir tablets, providing all required doses for a full five-day treatment course. The dose for patients with moderate renal impairment (eGFR ≥30 to <60 mL/min) should be reduced to 150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir (one 100 mg tablet), with both tablets taken together twice daily for five days (PAXLOVID is not recommended in patients with severe renal impairment [eGFR <30 mL/min]).
For more information, please visit www.PAXLOVID.com.
U.S. FDA Emergency Use Authorization Statement
PAXLOVID has not been approved, but has been authorized for emergency use by FDA under an EUA, for the treatment of adults and pediatric patients (12 years of age and older weighing at least 40 kg) with a current diagnosis of mild-to-moderate coronavirus disease 2019 (COVID-19) and who are at high risk for progression to severe COVID-19, including hospitalization or death.
The emergency use of PAXLOVID is only authorized for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of drugs and biological products during the COVID-19 pandemic under Section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless the declaration is terminated or authorization revoked sooner.
AUTHORIZED USE
The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for the emergency use of the unapproved product PAXLOVID for the treatment of adults and pediatric patients (12 years of age and older weighing at least 40 kg) with a current diagnosis of mild-to-moderate coronavirus disease 2019 (COVID-19) and who are at high risk for progression to severe COVID-19, including hospitalization or death.
Please see Fact Sheet for Healthcare Providers and Fact Sheet for Patients, Parents, and Caregivers.
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/20230316005635/en/
Source: Pfizer Inc.
Pfizer wins FDA panel vote for full approval of COVID pill
Mar. 16, 2023 3:30 PM ET
By: Dulan Lokuwithana, SA News Editor5 Comments
Update 3.30 PM EST: Adds remarks from Pfizer (NYSE:PFE)
- On Thursday, an independent advisory panel of the FDA endorsed Pfizer's (PFE) request to convert the emergency use authorization granted for its oral COVID therapy Paxlovid to a full approval.
- https://seekingalpha.com/news/3948279-pfizer-wins-fda-panel-vote-for-full-approval-of-covid-pill
- Pfizer Inc. (PFE)
- https://www.paxlovid.com/
- https://www.pfizer.com/
KEYTRUDA® (pembrolizumab) Plus Chemotherapy
KEYTRUDA® (pembrolizumab) Plus Chemotherapy Significantly Improved Overall Survival Versus Chemotherapy Alone as First-Line Treatment for Advanced Malignant Pleural Mesothelioma
March 10, 2023 6:45 am ET
RAHWAY, N.J. & KINGSTON, Ontario--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, and the Canadian Cancer Trials Group (CCTG) today announced that the Phase 2/3 CCTG IND.227/KEYNOTE-483 trial evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with chemotherapy met its primary endpoint of overall survival (OS) for the first-line treatment of patients with unresectable advanced or metastatic malignant pleural mesothelioma. IND.227 was sponsored by CCTG, in collaboration with investigators in Italy (co-sponsored by National Cancer Institute of Naples - NCIN), and France (co-sponsored by The French Cooperative Thoracic Intergroup - IFCT); Merck provided KEYTRUDA and support for the trial. At the final analysis of the study, KEYTRUDA plus chemotherapy showed a statistically significant and clinically meaningful improvement in OS compared to chemotherapy alone in these patients. The safety profile of KEYTRUDA in combination with chemotherapy in this study was consistent with previously reported studies. Results will be presented at an upcoming medical meeting and discussed with regulatory authorities worldwide.
“Malignant pleural mesothelioma is a rapidly progressing cancer that develops in the lining of the lungs and has a poor prognosis,” said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. “Patients are in need of new treatments that can improve survival outcomes, and these positive results support the potential of KEYTRUDA in combination with chemotherapy as a first-line treatment for patients with the most common form of malignant mesothelioma.”
“There have been few treatment advances for patients with malignant pleural mesothelioma, which can be challenging to treat through surgery and radiation alone,” said Dr. Quincy Chu, CCTG’s study chair of the IND.227 trial/KEYNOTE-483 trial. “The results from the trial have the potential to make a difference for patients with this disease who have had limited treatment options available to them.”
Merck has an extensive clinical development program in lung cancer and is advancing multiple registration-enabling studies, with research directed at earlier stages of disease and novel combinations.
About IND.227/KEYNOTE-483
IND.227/KEYNOTE-483 is a randomized, open-label, randomized Phase 2/3 trial (ClinicalTrials.gov, NCT02784171) sponsored and conducted by the Canadian Cancer Trials Group (CCTG) in collaboration with National Cancer Institute of Naples (NCIN) and Intergroupe Francophone de Cancérologie Thoracique (IFCT). Support for the trial was provided by Merck. The trial evaluated KEYTRUDA in combination with chemotherapy for the treatment of patients with unresected advanced malignant pleural mesothelioma. The primary endpoint of the study is OS, and secondary endpoints include progression-free survival (PFS) and objective response rate (ORR) as assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 modified for mesothelioma, safety and quality of life. The Phase 3 part of the trial enrolled 440 patients who were randomized to receive:
- KEYTRUDA (200 mg every three weeks for up to 35 cycles) in combination with pemetrexed (500 mg/m2 every three weeks for six cycles) and cisplatin (75 mg/m2 every three weeks for six cycles; carboplatin substitution was permitted), or
- Pemetrexed and cisplatin (carboplatin substitution was permitted) alone.
About malignant mesothelioma
Malignant mesothelioma is a type of cancer that starts in the linings of certain parts of the body, including the chest, abdomen, heart and testicles. Worldwide, it is estimated there were more than 30,000 new cases of malignant mesothelioma diagnosed and more than 26,000 deaths from the disease in 2020. Pleural mesothelioma, which develops in the lining of the lungs, is the most common form of malignant mesothelioma, accounting for about 75% of all cases. Malignant pleural mesothelioma often progresses rapidly, and the five-year survival rate is only 12%. Although incidence of malignant mesothelioma has gradually declined in the United States, continued use of and exposure to asbestos around the world has resulted in increasing global rates of this aggressive disease.
About the Canadian Cancer Trials Group
The Canadian Cancer Trials Group (CCTG) is a cancer clinical trials research cooperative that runs phase I-III trials to test anti-cancer and supportive therapies at over 85 hospitals and cancer centres across Canada. From their operations centre at Queen's University, CCTG has supported more than 600 trials enrolling 100,000 patients from 40 countries on 6 continents through a global network of 20,000 investigators and clinical trial staff. CCTG is a national program of the Canadian Cancer Society and their aim is to improve survival and quality of life for all people with cancer. CCTG IND.227 was supported by a grant from the Canadian Cancer Society (CCS) (707213). For further information, please visit the CCTG website: www.cctg.ca.
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, 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.
Additional Indications for KEYTRUDA 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.
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 Carcinoma
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC):
- 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.
Non-muscle Invasive Bladder Cancer
KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ 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.
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 MSI-H central nervous system cancers have not been established.
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 patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.
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.
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.
Merkel Cell Carcinoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). 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.
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
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 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’s Keytruda succeeds in pleural mesothelioma study with chemotherapy
Mar. 10, 2023 7:12 AM ET
By: Dulan Lokuwithana, SA News Editor1 Comment
- Merck’s (NYSE:MRK) anti-PD-1 therapy Keytruda with chemotherapy has reached the primary endpoint of overall survival in a Phase 2/3 trial against lung cancer pleural mesothelioma as a first-line option, the company and one of the trial’s partners announced Friday.
- https://seekingalpha.com/news/3946398-mercks-keytruda-pleural-mesothelioma-study-chemotherapy
- Merck & Co., Inc. (MRK)
- https://www.keytruda.com/
- https://www.merck.com/
ZAVZPRET™ (zavegepant)
Pfizer’s ZAVZPRET™ (zavegepant) Migraine Nasal Spray Receives FDA Approval
Friday, March 10, 2023 - 06:45am
ZAVZPRET is the first and only calcitonin gene-related peptide (CGRP) receptor antagonist nasal sprayfor the acute treatment of migraine in adults
Expands Pfizer’s migraine portfolio, which includes an oral therapy for both acute and preventive treatment, to further meet the needs of people living with this debilitating disease
NEW YORK--(BUSINESS WIRE)-- Pfizer Inc. (NYSE: PFE) today announced the U.S. Food and Drug Administration (FDA) has approved ZAVZPRET™ (zavegepant), the first and only calcitonin gene-related peptide (CGRP) receptor antagonist nasal spray for the acute treatment of migraine with or without aura in adults. In its pivotal Phase 3 study, ZAVZPRET was statistically superior to placebo on the co-primary endpoints of pain freedom and freedom from most bothersome symptom at two hours post-dose. The pivotal study also demonstrated pain relief as early as 15 minutes in a prespecified secondary endpoint versus placebo.
“The FDA approval of ZAVZPRET marks a significant breakthrough for people with migraine who need freedom from pain and prefer alternative options to oral medications,” said Angela Hwang, Chief Commercial Officer, President, Global Biopharmaceuticals Business, Pfizer. “ZAVZPRET underscores Pfizer’s commitment to delivering an additional treatment option to help people with migraine gain relief and get back to their daily lives. Pfizer will continue to build its migraine franchise to further support the billions of people worldwide impacted by this debilitating disease.”
The FDA approval is based on two pivotal randomized, double-blind, placebo-controlled studies that established the efficacy, tolerability and safety profiles of ZAVZPRET for the acute treatment of migraine. In these studies, ZAVZPRET was statistically superior to placebo on the co-primary endpoints of pain freedom (defined as a reduction of moderate or severe headache pain to no headache pain) and freedom from most bothersome symptom at two hours post-dose (defined as the absence of the self-identified most bothersome symptom). The pivotal Phase 3 study published in The Lancet Neurology found ZAVZPRET showed broad efficacy by also demonstrating statistically significant superiority to placebo across 13 of 17 prespecified secondary outcome measures, including early time point endpoints (e.g., 15 and 30-minute pain relief and return to normal function at 30 minutes), return to normal function at 2 hours, and durable efficacy endpoints (e.g., 2-24 and 2-48 hour sustained pain freedom and sustained pain relief). On the 14th endpoint, return to normal function at 15 minutes post-dose, the difference between ZAVZPRET and placebo was not significant. Consequently, in keeping with the trial’s statistical analysis plan, the remaining secondary endpoints were not formally tested.
“When a migraine hits, it has a significant negative impact on a person’s daily life,” said Kathleen Mullin, M.D., Associate Medical Director at New England Institute for Neurology & Headache. “Among my migraine patients, one of the most important attributes of an acute treatment option is how quickly it works. As a nasal spray with rapid drug absorption, ZAVZPRET offers an alternative treatment option for people who need pain relief or cannot take oral medications due to nausea or vomiting, so they can get back to normal function quickly.”
ZAVZPRET was well tolerated in clinical trials. The most common adverse reactions reported in at least 2% of patients treated with ZAVZPRET and at a frequency greater than placebo were taste disorders (includes dysgeusia and ageusia), nausea, nasal discomfort and vomiting. ZAVZPRET is contraindicated in patients with a history of hypersensitivity to zavegepant or to any of its components. Hypersensitivity reactions, including facial swelling and urticaria, have occurred with ZAVZPRET in clinical studies.
ZAVZPRET is anticipated to be available in pharmacies in July 2023.
About Migraine
Nearly 40 million people in the United States suffer from migraine1 and the World Health Organization classifies migraine as the second leading cause of disability in the world.2 Migraine is characterized by debilitating attacks lasting four to 72 hours with multiple symptoms, including pulsating headaches of moderate to severe pain intensity often associated with nausea or vomiting, and/or sensitivity to sound (phonophobia) and sensitivity to light (photophobia).3
About CGRP Receptor Antagonism
Small molecule CGRP receptor antagonists represent a novel class of drugs for the treatment of migraine. For acute treatment, this unique mode of action offers an alternative to other agents, including those patients who have contraindications to the use of triptans or who have a poor response to triptans or are intolerant to them. CGRP signal-blocking therapies have not been associated with medication overuse headache (MOH) or rebound headache, which can limit the clinical utility of other acute treatments.
About ZAVZPRET
Zavegepant is a third generation, high affinity, selective and structurally unique, small molecule CGRP receptor antagonist and the only CGRP receptor antagonist in clinical development with both intranasal and oral formulations.
INDICATION
ZAVZPRET™ (zavegepant) is indicated for the acute treatment of migraine with or without aura in adults.
Limitations of Use: ZAVZPRET is not indicated for the preventive treatment of migraine.
Please click here for full Prescribing Information.
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 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/20230309005795/en/
Source: Pfizer Inc.
Pfizer's nasal spray migraine therapy Zavzpret wins FDA approval
Mar. 10, 2023 7:01 AM ET
By: Ravikash, SA News Editor13 Comments
- The U.S. Food and Drug Administration (FDA) approved Pfizer's (NYSE:PFE) nasal spray Zavzpret (zavegepant) for the acute treatment of migraine with or without aura in adults.
- https://seekingalpha.com/news/3946390-pfizers-nasal-spray-migraine-therapy-zavzpret-wins-fda-approval
- Pfizer Inc. (PFE)
Polivy® (polatuzumab vedotin-piiq)
FDA Advisory Committee votes in favour of the clinical benefit of Roche’s Polivy combination for people with previously untreated diffuse large B-cell lymphoma
March 09, 2023
- U.S. FDA’s Oncologic Drugs Advisory Committee voted 11 to 2 in favour of the clinical benefit of the phase III POLARIX study of Polivy in combination with R-CHP for people with previously untreated diffuse large B-cell lymphoma (DLBCL)
- This is the first treatment in 20 years to show a significant and clinically meaningful improvement in progression-free survival over the standard of care for first-line DLBCL
- DLBCL is an aggressive, hard-to-treat disease and the most common form of non-Hodgkin lymphoma in the US
Basel, 10 March 2023 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the U.S. Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) voted 11 to 2 in favour of Polivy® (polatuzumab vedotin-piiq) in combination with Rituxan® (rituximab) plus cyclophosphamide, doxorubicin and prednisone (R-CHP) for the treatment of people with previously untreated diffuse large B-cell lymphoma (DLBCL). The ODAC provides the FDA with independent opinions and recommendations from outside medical experts though the recommendations are not binding. The FDA is expected to make a final decision on its review of the supplemental Biologics License Application (sBLA) for Polivy in this indication by 2 April 2023.
“Today’s committee decision to recognise the potential of this Polivy combination as a first-line treatment option is important since four in ten people with diffuse large B-cell lymphoma relapse or do not respond to initial treatment,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “We believe the clinical benefit demonstrated in the POLARIX study may improve outcomes for many people with newly diagnosed DLBCL and look forward to continued collaboration with the FDA to make this treatment option available in the US.”
More than 60 countries have approved this Polivy combination for the treatment of adult patients with previously untreated DLBCL, including in the EU, UK, Japan, Canada and China. Polivy in combination with R-CHP was recently added to the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines®) as a category 1, preferred regimen for first-line DLBCL.
DLBCL is an aggressive, hard-to-treat disease and is the most common form of non-Hodgkin lymphoma in the US. Limited progress has been made in improving patient outcomes in previously untreated DLBCL over the last two decades. Polivy in combination with R-CHP is the first treatment in 20 years to show a significant improvement in progression-free survival (PFS) over the standard of care, MabThera/Rituxan in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), in this setting.
The sBLA submission is based on pivotal data from the phase III POLARIX study, which demonstrated a statistically significant and clinically meaningful improvement in PFS with Polivy plus R-CHP compared to standard-of-care R-CHOP in first-line DLBCL. The risk of disease progression, relapse or death was reduced by 27% with Polivy plus R-CHP compared with R-CHOP (hazard ratio [HR] 0.73; 95% confidence interval [CI]: 0.57–0.95; p<0.02). Safety outcomes were consistent with those seen in previous clinical trials, and the safety profile was comparable for Polivy plus R-CHP versus R-CHOP, including rates of Grade 3-4 adverse events (AEs; 57.7% versus 57.5%), serious AEs (34.0% versus 30.6%), Grade 5 AEs (3.0% versus 2.3%), and AEs leading to dose reduction (9.2% versus 13.0%).
Polivy in combination with bendamustine and MabThera/Rituxan is currently approved in more than 80 countries worldwide for the treatment of adults with relapsed or refractory DLBCL after one or more prior therapies, including in the US under FDA accelerated approval, as a readily available, fixed-duration treatment option .
About the POLARIX study
POLARIX [NCT03274492] is an international phase III, randomised, double-blind, placebo-controlled study evaluating the efficacy, safety and pharmacokinetics of Polivy® (polatuzumab vedotin-piiq) plus MabThera®/Rituxan® (rituximab), cyclophosphamide, doxorubicin and prednisone (R-CHP) versus MabThera/Rituxan, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in people with previously untreated diffuse large B-cell lymphoma. Eight-hundred and seventy-nine patients were randomised 1:1 to receive either Polivy plus R-CHP plus a vincristine placebo for six cycles, followed by MabThera/Rituxan for two cycles; or R-CHOP plus a Polivy placebo for six cycles, followed by two cycles of MabThera/Rituxan. The primary outcome measure is progression-free survival as assessed by the investigator using the Lugano Response Criteria for malignant lymphoma. POLARIX is being conducted in collaboration with The Lymphoma Study Association and The Lymphoma Academic Research Organisation.
About diffuse large B-cell lymphoma
Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma (NHL), accounting for about one in three cases of NHL.1 DLBCL is an aggressive (fast-growing) type of NHL.1 While it is generally responsive to treatment in the frontline, as many as 40% of people will relapse or have refractory disease, at which time salvage therapy options are limited and survival is short.2,3 Approximately 160,000 people worldwide are estimated to be diagnosed with DLBCL each year.4
About Polivy® (polatuzumab vedotin-piiq)
Polivy is a first-in-class anti-CD79b antibody-drug conjugate (ADC). The CD79b protein is expressed specifically in the majority of B-cells, an immune cell impacted in some types of non-Hodgkin lymphoma (NHL), making it a promising target for the development of new therapies. Polivy binds to cancer cells such as CD79b and destroys these B-cells through the delivery of an anti-cancer agent, which is thought to minimise the effects on normal cells. Polivy is being developed by Roche using Seagen ADC technology and is currently being investigated for the treatment of several types of NHL.
https://www.polivy.com/
About Roche in haematology
Roche has been developing medicines for people with malignant and non-malignant blood diseases for more than 20 years; our experience and knowledge in this therapeutic area runs deep. Today, we are investing more than ever in our effort to bring innovative treatment options to patients across a wide range of haematologic diseases. Our approved medicines include MabThera®/Rituxan® (rituximab), Gazyva®/Gazyvaro® (obinutuzumab), Polivy® (polatuzumab vedotin-piiq), Venclexta®/Venclyxto® (venetoclax) in collaboration with AbbVie, Hemlibra® (emicizumab) and Lunsumio® (mosunetuzumab). Our pipeline of investigational haematology medicines includes T-cell engaging bispecific antibodies glofitamab, targeting both CD20 and CD3, and cevostamab, targeting both FcRH5 and CD3; Tecentriq® (atezolizumab), a monoclonal antibody designed to bind with PD-L1 and crovalimab, an anti-C5 antibody engineered to optimise complement inhibition. Our scientific expertise, combined with the breadth of our portfolio and pipeline, also provides a unique opportunity to develop combination regimens that aim to improve the lives of patients even further.
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 thirteenth 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.
NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibilities for their application or use in any way.
Roche gets FDA panel nod for Polivy as initial therapy for large B-cell lymphoma
Mar. 10, 2023 5:22 AM ET
Roche Holding AG (RHHBY), RHHBF
By: Ravikash, SA News Editor
Roche (OTCQX:RHHBY) (OTCQX:RHHBF) said a panel of the U.S. Food and Drug Administration (FDA) voted in favor of approval of a combination treatment consisting of its medicine Polivy to treat a type of blood cancer.
biotecMAX™ 2023 Insight
IMFINZI® (durvalumab) injection
Imfinzi significantly improved event-free survival in AEGEAN Phase III trial for patients with resectable non-small cell lung cancer
PUBLISHED9 March 2023 9 March 2023 07:00 GMT
Results showed that Imfinzi-based treatment before and after surgery significantly
increased the time patients live without recurrence or progression events
Positive high-level results from a planned interim analysis of the AEGEAN Phase III, placebo- controlled trial showed that treatment with AstraZeneca’s Imfinzi (durvalumab) in combination with neoadjuvant chemotherapy before surgery and as adjuvant monotherapy after surgery demonstrated a statistically significant and clinically meaningful improvement in event-free survival (EFS) versus neoadjuvant chemotherapy alone followed by surgery for patients with resectable early-stage (IIA-IIIB) non-small cell lung cancer (NSCLC).
Results from the final pathologic complete response (pCR) and major pathologic response (mPR) analyses were consistent with previously announced positive results. The trial will continue as planned to assess key secondary endpoints including disease-free survival (DFS) and overall survival (OS).
Each year there are an estimated 2.2 million people diagnosed with lung cancer globally with 80-85% of patients diagnosed with NSCLC, the most common form of lung cancer.1-3 Approximately 25-30% of all patients with NSCLC are diagnosed early enough to have surgery with curative intent.4-5 However, only around 56-65% of patients with Stage II disease will survive for five years.6 This decreases to 41% for patients with Stage IIIA and 24% for patients with Stage IIIB disease, reflecting a high unmet medical need.6
John V. Heymach, MD, PhD. Professor and Chair Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, said: “Treating patients early with durvalumab both before and after surgery delivers a significant and clinically meaningful benefit in resectable non-small cell lung cancer, where new options are urgently needed to offer patients the best chance of long-term survival. The AEGEAN results provide compelling evidence that this novel durvalumab regimen can drive improved outcomes in this curative-intent setting.”
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “Patients with resectable non-small cell lung cancer face unacceptably high rates of recurrence, despite treatment with chemotherapy and surgery. We have shown that adding Imfinzi both before and after surgery significantly increased the time patients live without recurrence or progression events. We will continue to follow patients for overall survival.”
Imfinzi was well tolerated and no new safety concerns were observed in the neoadjuvant and adjuvant settings. Further, adding Imfinzi to neoadjuvant chemotherapy was consistent with the known profile for this combination and did not increase complications or adverse events, or compromise patients' ability to undergo surgery versus chemotherapy alone.
These data will be presented at a forthcoming medical meeting and shared with global health authorities.
AstraZeneca has a comprehensive portfolio of approved and potential new medicines in development for patients with lung cancer. In addition to these results, the Company is also announcing today that Tagrisso (osimertinib) met a secondary endpoint of OS in the ADAURA Phase III trial in early-stage (IB, II and IIIA) epidermal growth factor receptor-mutated (EGFRm) NSCLC after complete tumour resection with curative intent.
Notes
Lung cancer
Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.1 Lung cancer is broadly split into NSCLC and small cell lung cancer (SCLC).2 The majority of NSCLC patients are diagnosed with advanced disease while approximately 25-30% present with resectable disease at diagnosis.4-5 Early-stage lung cancer diagnoses are often only made when the cancer is found on imaging for an unrelated condition.7-8
For patients with resectable tumours, the majority eventually develop recurrence despite complete tumour resection and adjuvant chemotherapy.9
AEGEAN
AEGEAN is a randomised, double-blind, multi-centre, placebo-controlled global Phase III trial evaluating Imfinzi as perioperative treatment for patients with resectable Stage IIA-IIIB (Eighth Edition AJCC Cancer Staging Manual) NSCLC, irrespective of PD-L1 expression. Perioperative therapy includes treatment before and after surgery, also known as neoadjuvant/adjuvant therapy. In the trial, 802 patients were randomised to receive a 1500mg fixed dose of Imfinzi plus chemotherapy or placebo plus chemotherapy every three weeks for four cycles prior to surgery, followed by Imfinzi or placebo every four weeks (for up to 12 cycles) after surgery. Patients with known EGFR or ALK genomic tumour aberrations were excluded from the primary efficacy analyses.
In the AEGEAN trial, the primary endpoints were pCR, defined as no viable tumour in the resection specimen (including lymph nodes) following neoadjuvant therapy, and EFS, defined as the time from randomisation to an event like tumour recurrence, progression precluding definitive surgery, or death. Key secondary endpoints were mPR, defined as residual viable tumour of less than or equal to 10% in the resected primary tumour following neoadjuvant therapy, DFS, OS, safety and quality of life. The final pathologic response analyses were performed after all patients had the opportunity for surgery and pathology assessment per the trial protocol. The trial enrolled participants in 264 centres in more than 25 countries including in the US, Canada, Europe, South America and Asia.
Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour's immune-evading tactics and releasing the inhibition of immune responses.
Imfinzi is the only approved immunotherapy and the global standard of care in the curative-intent setting of unresectable, Stage III NSCLC in patients whose disease has not progressed after chemoradiation therapy based on the PACIFIC Phase III trial.
Imfinzi is also approved in the US, EU, Japan, China and many other countries around the world for the treatment of extensive-stage SCLC based on the CASPIAN Phase III trial. In an exploratory analysis in 2021, updated results from the CASPIAN trial showed Imfinzi plus chemotherapy tripled patient survival at three years versus chemotherapy alone. Additionally, Imfinzi is approved in combination with a short course of Imjudo (tremelimumab) and chemotherapy for the treatment of metastatic NSCLC in the US, EU and Japan based on the POSEIDON Phase III trial.
In addition to its indications in lung cancer, Imfinzi is also approved in combination with chemotherapy in locally advanced or metastatic biliary tract cancer in the US, EU, Japan and several other countries; in combination with Imjudo in unresectable hepatocellular carcinoma in the US, EU and Japan; and in previously treated patients with advanced bladder cancer in several countries.
Since the first approval in May 2017, more than 150,000 patients have been treated with Imfinzi.
AstraZeneca has several ongoing registrational trials focused on testing Imfinzi in earlier stages of lung cancer, including in resectable NSCLC (ADJUVANT BR.31) and unresectable NSCLC (PACIFIC-2, 4, 5, 8 and 9), and in limited-stage SCLC (ADRIATIC).
As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, several gastrointestinal (GI) cancers, ovarian cancer, endometrial cancer and other solid tumours.
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 and Iressa (gefitinib); Imfinzi and Imjudo; 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 immuno-oncology (IO)
AstraZeneca is a pioneer in introducing the concept of immunotherapy into dedicated clinical areas of high unmet medical need. The Company has a comprehensive and diverse IO portfolio and pipeline anchored in immunotherapies designed to overcome evasion of the anti-tumour immune response and stimulate the body’s immune system to attack tumours.
AstraZeneca aims to reimagine cancer care and help transform outcomes for patients with Imfinzi as a single treatment and in combination with Imjudo as well as other novel immunotherapies and modalities. The Company is also exploring next-generation immunotherapies like bispecific antibodies and therapeutics that harness different aspects of immunity to target cancer.
AstraZeneca is boldly pursuing an innovative clinical strategy to bring IO-based therapies that deliver long-term survival to new settings across a wide range of cancer types. With an extensive clinical programme, the Company also champions the use of IO treatment in earlier disease stages, where there is the greatest potential for cure.
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 Twitter @AstraZeneca.
AstraZeneca's Imfinzi shows event-free survival benefit in lung cancer patients in trial
Mar. 09, 2023 4:46 AM ET
By: Ravikash, SA News Editor
AstraZeneca (NASDAQ:AZN) said data from a phase 3 trial showed that Imfinzi-based therapy before and after surgery significantly increased the time patients with lung cancer lived without the disease recurring or progressing.
The late stage study, dubbed AEGEAN, is evaluating Imfinzi (durvalumab) as a perioperative therapy for patients with resectable stage 2A-3B non-small cell lung cancer (NSCLC), irrespective of PD-L1 expression.
TAGRISSO® (osimertinib) tablets
Tagrisso demonstrated strong overall survival benefit in the ADAURA Phase III trial for adjuvant treatment of patients with early-stage EGFR-mutated lung cancer
PUBLISHED9 March 2023
9 March 2023 07:05 GMT
First Phase III trial to demonstrate survival benefit in this adjuvant setting
Positive high-level results from the ADAURA Phase III trial showed AstraZeneca’s Tagrisso (osimertinib) demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS), a key secondary endpoint, compared to placebo in the adjuvant treatment of patients with early-stage (IB, II and IIIA) epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) after complete tumour resection with curative intent.
In May 2020, AstraZeneca announced Tagrisso demonstrated a statistically significant and clinically meaningful improvement in disease-free survival (DFS) in this setting. In September 2022, updated results demonstrated a median DFS of nearly five and a half years.
Per the ADAURA trial protocol, patients on placebo that recurred with metastatic disease had the opportunity to receive open-label Tagrisso.
Roy S. Herbst, MD, PhD, Deputy Director and Chief of Medical Oncology at Yale Cancer Center and Smilow Cancer Hospital, New Haven, Connecticut, and principal investigator in the ADAURA Phase III trial, said: “These new survival data for osimertinib reinforce the unprecedented ADAURA disease-free survival results and confirm its potential to extend patients’ lives in early-stage disease. The ADAURA results provide powerful evidence that osimertinib offers the best possible care for patients with early-stage EGFR-mutated non-small cell lung cancer who historically faced high rates of recurrence and previously had no targeted options after surgery.”
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “The ADAURA trial brought the first targeted medicine to patients with early-stage EGFR-mutated non-small cell lung cancer. Today, these exciting overall survival results validate adjuvant Tagrisso as the standard of care in this setting and reinforce the importance of early diagnosis and testing for EGFR mutation in lung cancer.”
The safety and tolerability of Tagrisso in the ADAURA trial were consistent with its established profile and no new safety concerns were reported.
These new ADAURA OS results in the early-stage resectable setting add to the extensive body of evidence for Tagrisso in EGFRm NSCLC which has now shown a statistically significant and clinically meaningful OS benefit in both the early adjuvant and late-stage metastatic settings. The data will be presented at a forthcoming medical meeting.
Each year there are an estimated 2.2 million people diagnosed with lung cancer globally with 80-85% of patients diagnosed with NSCLC, the most common form of lung cancer.1-3 Approximately 25-30% of all patients with NSCLC are diagnosed early enough to have surgery with curative intent.4‑5 Further, 73% of patients with Stage IB and 56-65% of patients with Stage II disease will survive for five years.6 This decreases to 41% for patients with Stage IIIA and 24% for patients with Stage IIIB disease, reflecting a high unmet medical need.6
AstraZeneca has several ongoing registrational trials focused on testing Tagrisso in earlier stages of lung cancer, including in the neoadjuvant resectable setting (NeoADAURA), in the Stage IA2-IA3 adjuvant resectable setting (ADAURA2), and in the Stage III locally advanced unresectable setting (LAURA).
Tagrisso is approved to treat early-stage lung cancer in more than 90 countries, including in the US, EU, China and Japan, and additional global regulatory reviews are ongoing. Tagrisso is also approved for the 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC and for the treatment of locally advanced or metastatic EGFR T790M mutation-positive NSCLC in the US, EU, China, Japan and many other countries.
AstraZeneca has a comprehensive portfolio of approved and potential new medicines in development for patients with lung cancer. In addition to these results, the Company has also announced today positive results from the AEGEAN Phase III trial of Imfinzi (durvalumab) in combination with neoadjuvant chemotherapy before surgery and as adjuvant monotherapy after surgery in Stage IIA-IIIB resectable NSCLC.
Notes
Lung cancer
Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.1 Lung cancer is broadly split into NSCLC and small cell lung cancer.2 The majority of all NSCLC patients are diagnosed with advanced disease while approximately 25-30% present with resectable disease at diagnosis.4‑5 Early-stage lung cancer diagnoses are often only made when the cancer is found on imaging for an unrelated condition.7‑8
For patients with resectable tumours, the majority eventually develop recurrence despite complete tumour resection and adjuvant chemotherapy.9
Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.10-12 These patients are particularly sensitive to treatment with an EGFR-tyrosine kinase inhibitor (EGFR-TKI) which block the cell-signalling pathways that drive the growth of tumour cells.13
ADAURA
ADAURA was a randomised, double-blind, placebo-controlled, global Phase III trial in the adjuvant treatment of 682 patients with Stage IB, II, IIIA EGFRm NSCLC following complete tumour resection and, at physicians’ and patients’ discretion, adjuvant chemotherapy. Patients were treated with Tagrisso 80mg once-daily oral tablets or placebo for three years or until disease recurrence.
The trial was enrolled in more than 200 centres across more than 20 countries, including the US, Europe, South America, Asia and the Middle East. The primary endpoint was DFS in Stage II and IIIA patients and key secondary endpoints included DFS in Stage IB, II and IIIA patients, and OS in both the primary and overall populations.
Though the primary data readout was originally anticipated in 2022, data from the trial were reported early following a recommendation from an Independent Data Monitoring Committee (IDMC) based on its determination of overwhelming efficacy.
Tagrisso
Tagrisso (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system metastases. Tagrisso (40mg and 80mg once-daily oral tablets) has been used to treat nearly 700,000 patients across its indications worldwide and AstraZeneca continues to explore Tagrisso as a treatment for patients across multiple stages of EGFRm NSCLC.
In addition to investigating Tagrisso in early-stage disease, AstraZeneca is also studying the medicine in combination with chemotherapy in locally advanced and metastatic EGFRm NSCLC (FLAURA2). The Company is also researching ways to address tumour mechanisms of resistance through the SAVANNAH and ORCHARD Phase II trials, and the SAFFRON Phase III trial, which test Tagrisso given concomitantly with savolitinib, an oral, potent and highly selective MET TKI, as well as other potential new medicines.
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 Twitter @AstraZeneca.
AstraZeneca Tagrisso improves overall survival in lung cancer patients in phase 3 trial
Mar. 09, 2023 5:25 AM ET
By: Ravikash, SA News Editor1 Comment
AstraZeneca (NASDAQ:AZN) said Tagrisso showed survival benefit in patients with a type of lung cancer who had undergone surgery, in a phase 3 trial.
JARDIANCE® (empagliflozin tablets)
US FDA accepts supplemental New Drug Application for Jardiance® for children 10 years and older with type 2 diabetes
March 8, 2023Download PDF
- The application is based on phase III results from the DINAMO trial showing Jardiance® (empagliflozin) tablets significantly reduced A1c (a marker of average blood sugar) versus placebo in participants aged 10-17 living with type 2 diabetes
- If approved, Jardiance would be the first SGLT2 inhibitor indicated for this vulnerable population
RIDGEFIELD, Conn. and INDIANAPOLIS, March 8, 2023 /PRNewswire/ -- The U.S. Food and Drug Administration (FDA) accepted a supplemental New Drug Application (sNDA) for Jardiance® (empagliflozin) investigating a potential new indication to lower blood sugar along with diet and exercise in children 10 years and older with type 2 diabetes, Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY) announced.
"There are clear unmet needs for young people living with type 2 diabetes, which has nearly doubled in prevalence in people aged 10-19 over the past two decades," said Mohamed Eid, M.D., M.P.H., M.H.A., vice president, Clinical Development & Medical Affairs, Cardio-Renal-Metabolism & Respiratory Medicine, Boehringer Ingelheim Pharmaceuticals, Inc. "We look forward to working closely with the FDA during the review process and while we await a decision on our efforts to bring another potential treatment option to children 10 years and older with type 2 diabetes."
The sNDA is based on the results from the DINAMO phase III trial, in which Jardiance was associated with a statistically significant reduction in the primary endpoint of change from baseline in A1c at 26 weeks compared with placebo in participants aged 10-17 years with type 2 diabetes. When added to other baseline treatments (diet, exercise, metformin and/or insulin), Jardiance 10 mg and 25 mg pooled doses reduced A1c by 0.84% compared with placebo at week 26 (95% CI −1.50 to −0.19; P=0.012). Reduction in A1c in participants treated with Tradjenta® (linagliptin) was not statistically significant when compared with placebo. A numerical reduction of 0.34% (P=0.2935) was observed. Results were presented during the International Diabetes Federation World Diabetes Congress 2022.
Overall, the safety data in DINAMO was consistent with the previously known safety profile of Jardiance.
Initially approved in 2014, Jardiance is a once-daily tablet used along with diet and exercise to lower blood sugar in adults with type 2 diabetes; and to reduce the risk of cardiovascular death in adults with type 2 diabetes and known cardiovascular disease. Jardiance is also indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure. Jardiance is not for patients with type 1 diabetes, or to improve glycemic control in adults with type 2 diabetes with an eGFR <30 mL/min/1.73 m2. Jardiance is contraindicated in people with hypersensitivity to empagliflozin or any of the excipients in Jardiance, and in patients on dialysis. Please see additional Important Safety Information below.
"Impacting an estimated 39,000 people under the age of 20, type 2 diabetes is a growing health issue for young people in the U.S.," said Jeff Emmick, M.D., Ph.D., vice president, Product Development, Lilly. "If approved, Jardiance would be a new oral treatment option for type 2 diabetes in children 10 years and older in the U.S., making this application acceptance an important step forward as we add to the body of knowledge for this vulnerable patient population, for whom oral treatment options have been limited."
About DINAMO: DIabetes study of liNAgliptin and eMpagliflozin in children and adOlescents
DINAMO (NCT03429543) is a multicenter, randomized, double-blind, parallel group phase III trial that enrolled participants aged 10-17 years with type 2 diabetes (A1c 6.5% to 10.5%) previously treated with metformin or insulin. The primary endpoint was change from baseline in A1c at 26 weeks. Of the 262 participants screened, 158 were randomly assigned to treatment with Jardiance (10 mg) (n=52), Tradjenta (5 mg) (n=53) or placebo (n=53) once daily. Participants in the Jardiance group who did not have A1c below 7.0% by week 12 were re-randomized to either remain on 10 mg or increase to 25 mg. Participants in the placebo group were reassigned at week 26 to Tradjenta 5 mg or Jardiance 10 mg or 25 mg. All participants were treated with diet and exercise plus metformin and/or insulin (or no background if metformin intolerant). Safety was assessed until week 52.
What is JARDIANCE?
JARDIANCE is a prescription medicine used to:
- reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure, when the heart cannot pump enough blood to the rest of your body
- reduce the risk of cardiovascular death in adults with type 2 diabetes who also have known cardiovascular disease
- lower blood sugar along with diet and exercise in adults with type 2 diabetes
JARDIANCE is not for people with type 1 diabetes. It may increase their risk of diabetic ketoacidosis (increased ketones in the blood or urine).
JARDIANCE is not for use to lower blood sugar in adults with type 2 diabetes who have severe kidney problems, because it may not work.
IMPORTANT SAFETY INFORMATION
Do not take JARDIANCE if you are allergic to empagliflozin or any of the ingredients in JARDIANCE.
Do not take JARDIANCE if you are on dialysis.
For more information, please see Prescribing Information and Medication Guide.
Boehringer Ingelheim and Eli Lilly and Company
In January 2011, Boehringer Ingelheim and Eli Lilly and Company announced an Alliance that centers on compounds representing several of the largest diabetes treatment classes. Depending on geographies, the companies either co-promote or separately promote the respective molecules each contributing to the Alliance. The Alliance leverages the strengths of two of the world's leading pharmaceutical companies to focus on patient needs. By joining forces, the companies demonstrate their commitment, not only to the care of people with diabetes, but also to investigating the potential to address areas of unmet medical need.
About Boehringer Ingelheim
Boehringer Ingelheim is working on breakthrough therapies that improve the lives of humans and animals. As a leading research-driven biopharmaceutical company, the company creates value through innovation in areas of high unmet medical need. Founded in 1885 and family-owned ever since, Boehringer Ingelheim takes a long-term perspective. Around 52,000 employees serve more than 130 markets in the three business areas, Human Pharma, Animal Health, and Biopharmaceutical Contract Manufacturing. Learn more at www.boehringer-ingelheim.com/us.
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 47 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.
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SOURCE Eli Lilly and Company
Boehringer, Lilly get FDA review for expanded use of Jardiance in adolescents
Mar. 08, 2023 9:38 AM ET
By: Ravikash, SA News Editor
- The U.S. Food and Drug Administration (FDA) accepted to review Boehringer Ingelheim and Eli Lilly's (NYSE:LLY) application seeking expanded approval of Jardiance to lower blood sugar, along with diet and exercise, in children 10 years and older with type 2 diabetes.
- https://seekingalpha.com/news/3945363-boehringer-lilly-get-fda-review-for-expanded-use-of-jardiance-in-adolescents
- Eli Lilly and Company (LLY)
- https://www.lilly.com/
- https://www.jardiance.com/
Enhertu (trastuzumab deruxtecan)
Enhertu showed clinically meaningful and durable responses across multiple HER2-expressing tumour types in DESTINY-PanTumor02 Phase II trial
PUBLISHED6 March 2023 06 March 2023 07:00 GMT
AstraZeneca and Daiichi Sankyo’s Enhertu met prespecified criteria for objective
response rate and duration of response
Positive high-level results from an analysis of the ongoing DESTINY-PanTumor02 Phase II trial showed AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) met the prespecified target for objective response rate (ORR) and demonstrated durable response across multiple HER2-expressing advanced solid tumours in heavily pretreated patients.
Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.
The DESTINY-PanTumor02 Phase II trial is evaluating the efficacy and safety of Enhertu in patients with locally advanced, unresectable, or metastatic previously treated, HER2-expressing solid tumours not eligible for curative therapy, including biliary tract, bladder, cervical, endometrial, ovarian, pancreatic, and rare cancers. The primary endpoint of the trial is investigator-assessed confirmed ORR and investigator-assessed duration of response (DoR) is a key secondary endpoint.
The data will be presented at an upcoming medical meeting and shared with global regulatory authorities.
HER2 is a tyrosine kinase receptor protein expressed on the surface of various tissue cells throughout the body and is involved in normal cell growth.1,2 In some cancer cells, HER2 expression is amplified or the cells have activating mutations.1,3 While HER2-directed therapies have been used to treat breast, gastric and lung cancers, more research is needed evaluating their potential role in treating other HER2-expressing tumour types.2,4-6
Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said, “Enhertu has already demonstrated its potential to improve outcomes for patients with HER2-targetable breast, gastric and lung cancers, and these positive initial results in other tumour settings with significant unmet need are very encouraging. The DESTINY-PanTumor02 results mark an important step forward in our understanding of the potential role of Enhertu across multiple HER2-expressing tumour types.”
Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said, “The clinically meaningful responses seen in the DESTINY-PanTumor02 trial reaffirm our belief in the potential of Enhertu across multiple HER2-expressing cancers. The results seen so far across multiple cohorts of the trial will inform next steps of our broad development programme as we look to bring this important medicine to as many patients as quickly as possible.”
The safety profile observed in patients treated with Enhertu in the DESTINY-PanTumor02 trial was consistent with that seen in other trials of Enhertu with no new safety signals identified.
Notes
DESTINY-PanTumor02
DESTINY-PanTumor02 is a global, multicentre, multi-cohort, open-label Phase II trial evaluating the efficacy and safety of Enhertu (5.4mg/kg) for the treatment of HER2-expressing tumours, including biliary tract cancer, bladder cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer and rare tumours.
The primary efficacy endpoint of DESTINY-PanTumor02 is confirmed ORR as assessed by investigator. Secondary endpoints include DoR, disease control rate, progression-free survival, overall survival, safety, tolerability and pharmacokinetics.
DESTINY-PanTumor02 has enrolled 268 patients at multiple sites in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.
Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.
Enhertu (5.4mg/kg) is approved in more than 40 countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a (or one or more) prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.
Enhertu (5.4mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in-situ hybridisation [ISH]-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.
Enhertu (5.4mg/kg) is approved under accelerated approval in the US for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer whose tumours have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 trial. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Enhertu (6.4mg/kg) is approved in more than 30 countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial and/or DESTINY-Gastric02 trial.
Enhertu development programme
A comprehensive global development programme is underway evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.
Daiichi Sankyo collaboration
Daiichi Sankyo Company, Limited (TSE: 4568) [referred to as Daiichi Sankyo] and AstraZeneca entered into a global collaboration to jointly develop and commercialise Enhertu (a HER2-directed ADC) in March 2019, and datopotamab deruxtecan (DS-1062; a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and datopotamab deruxtecan.
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 Twitter @AstraZeneca.
AstraZeneca, Daiichi Sankyo's Enhertu shows promise in multiple cancer types in trial
Mar. 06, 2023 4:55 AM ET
AstraZeneca PLC (AZN), DSKYF, DSNKY
By: Ravikash, SA News Editor
AstraZeneca (NASDAQ:AZN) and Daiichi Sankyo (OTCPK:DSKYF) (OTCPK:DSNKY) said their drug Enhertu met the target for objective response rate (ORR) and showed durable response in multiple HER2-expressing advanced solid tumors in heavily pretreated patients in an ongoing phase 2 trial.
VOXZOGO® (vosoritide)
FDA Accepts BioMarin's Supplemental New Drug Application to Expand Use of VOXZOGO® (vosoritide) for Injection to Treat Children with Achondroplasia Under the Age of 5
Mar 7, 2023
The Supplemental New Drug Application is Based on Positive Results from Global Randomized Phase 2 Study in Infants and Young Children
FDA set PDUFA Target Action Date of October 21, 2023
SAN RAFAEL, Calif., March 7, 2023 /PRNewswire/ -- BioMarin Pharmaceutical Inc. (Nasdaq: BMRN), a global biotechnology company dedicated to transforming lives through genetic discovery, announced today that the U.S. Food and Drug Administration (FDA) has accepted the company's supplemental New Drug Application (sNDA) for VOXZOGO® (vosoritide) for injection to expand treatment in the United States to include children with achondroplasia under the age of 5. Achondroplasia is the most common form of disproportionate short stature.
The FDA has set a PDUFA target action date of October 21, 2023 for the sNDA.
"We are pleased that the FDA has accepted our sNDA and are working closely with the agency to facilitate completion of the review in a timely manner," said Hank Fuchs, M.D., president, Worldwide Research and Development at BioMarin. "There are currently no approved pharmacological treatments in the United States for children under 5 with achondroplasia and this approval could potentially extend access to all children with achondroplasia, whose growth plates are not closed."
The sNDA is supported by results from a Phase 2 randomized, double-blind, placebo-controlled clinical trial, which demonstrated similar safety and efficacy profiles in children under 5 years of age as compared to those ages 5 years and older.
In January, the European Medicines Agency (EMA) validated BioMarin's application for extension of indication for VOXZOGO to treat children with achondroplasia under the age of 2. Approval of the submissions would mean VOXZOGO could potentially be prescribed as early as birth for more than 1,000 additional children eligible for treatment for achondroplasia.
VOXZOGO is the first FDA and EMA approved treatment for children with achondroplasia with open epiphyses (bone growth plates).
About VOXZOGO® (vosoritide) for Injection
In patients 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.
VOXZOGO is also approved in the EU, Brazil, and Australia in children with achondroplasia who are 2 years of age and older with open growth plates. It is also approved in Japan in children from birth who have achondroplasia with open growth plates.
About Achondroplasia
Achondroplasia, the most common form of skeletal dysplasia leading to disproportionate short stature, 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 change in the gene. The worldwide incidence rate of achondroplasia is about one in 25,000 live births. VOXZOGO is being studied 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.
What are the most common side effects of VOXZOGO?
- The most common side effects of VOXZOGO include injection site reactions (including redness, itching, swelling, bruising, rash, hives, and injection site pain), vomiting, joint pain, decreased blood pressure, and stomachache. These are not all the possible side effects of VOXZOGO. Ask your healthcare provider for medical advice about side effects, and about any side effects that bother the patient or that do not go away.
How is VOXZOGO taken?
- VOXZOGO is taken daily as an injection given under the skin, administered by a caregiver after a healthcare provider determines the caregiver is able to administer VOXZOGO. Do not try to inject VOXZOGO until you have been shown the right way by your healthcare provider. VOXZOGO is supplied with Instructions for Use that describe the steps for preparing, injecting, and disposing VOXZOGO. Caregivers should review the Instructions for Use for guidance and any time they receive a refill of VOXZOGO in case any changes have been made.
- Inject VOXZOGO 1 time every day, at about the same time each day. If a dose of VOXZOGO is missed, it can be given within 12 hours from the missed dose. After 12 hours, skip the missed dose and administer the next daily dose as usual.
- The dose of VOXZOGO is based on body weight. Your healthcare provider will adjust the dose based on changes in weight following regular check-ups.
- Your healthcare provider will monitor the patient's growth and tell you when to stop taking VOXZOGO if they determine the patient is no longer able to grow. Stop administering VOXZOGO if instructed by your healthcare provider.
- 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 the 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.
BioMarin seeks FDA nod to expand use of its Voxzogo treatment in children under five
Mar. 07, 2023 5:58 PM ET
BioMarin Pharmaceutical Inc. (BMRN)
By: Anuron Mitra, SA News Editor
- BioMarin Pharmaceutical (NASDAQ:BMRN) on Tuesday said the U.S. Food and Drug Administration (FDA) had cleared expanding the use of its Voxzogo treatment in children with short stature under the age of five.
- https://seekingalpha.com/news/3945134-biomarin-seeks-fda-nod-to-expand-use-of-its-voxzogo-treatment-in-children-under-five
- BioMarin Pharmaceutical Inc. (BMRN)
- https://www.voxzogo.com/
- https://www.biomarin.com/
STELARA® (ustekinumab)
New STELARA® (ustekinumab) Long-Term Data Support its Established Safety Profile in Inflammatory Bowel Disease and Durable Efficacy in Ulcerative Colitis
Final cumulative pooled IBD safety data support the longstanding safety profile of STELARA across all IBD approved indications
Additional long term extension data demonstrate more than half of STELARA-treated patients with ulcerative colitis achieved clinical remission, clinical response, and/or demonstrated endoscopic improvement at four years
SPRING HOUSE, PENNSYLVANIA, March 4, 2023 – The Janssen Pharmaceutical Companies of Johnson & Johnson today announced final pooled long-term safety results for STELARA® (ustekinumab) through five years in adults with moderately to severely active Crohn’s disease (CD) and four years in adults with moderately to severely active ulcerative colitis (UC), as well as final four-year clinical and endoscopic outcomes from the UNIFI long-term extension (LTE) study evaluating the efficacy of STELARA for the treatment of adults with moderately to severely active UC.1,2 These data are a part of Janssen’s 22 oral and poster presentations at the 18th Congress of the European Crohn’s and Colitis Organization (ECCO), taking place in Copenhagen, Denmark, March 1-4.
“These data reinforce the known efficacy and safety profile of STELARA, and demonstrate it can be an effective long-term treatment option for patients living with moderately to severely active ulcerative colitis,” said UNIFI study author Waqqas Afif, M.D., Associate Professor, Department of Medicine, Division of Experimental Medicine and Division of Gastroenterology at McGill University Health Centre in Montreal, Canada.a “Importantly, clinical and endoscopic outcomes reinforce the durable efficacy of STELARA, as we remain committed to developing therapies that provide patients with lasting remission.”
Final STELARA long-term pooled safety analysis (Oral presentation OP39):1
A final pooled safety analysis of six Phase 2/3 IBD studies included 2,575 patients treated with STELARA and a total of 4,826 patient-years (PY) of follow-up.
- Overall safety profile: Data continue to support a well-established safety experience in adult patients with moderately to severely active ulcerative colitis (UC) through up to four years, and in adult patients with moderately to severely active Crohn’s disease (CD) through five years.
- Key safety events: Key safety event rates adjusted per 100 PYs for adverse events (AEs), serious AEs, infections, serious infections, major adverse cardiac events (MACE), and malignancies were similar between placebo and STELARA.
- Adverse events: The most frequently occurring adverse events (AEs) per 100 PY of follow-up (excluding disease related AEs under study) were headache (11.60 STELARA versus 16.66 placebo), arthralgia (11.23 STELARA versus 15.91 placebo), abdominal pain (9.86 STELARA versus 13.79 placebo), nausea (7.13 STELARA versus 11.35 placebo), and pyrexia (5.91 STELARA versus 11.35 placebo). The most frequently reported serious infections of anal abscess, pneumonia, cellulitis, and abdominal abscess were similar between STELARA and placebo, except gastroenteritis (0.25 STELARA versus 0.11 placebo). The most frequently reported infections were nasopharyngitis (19.10 STELARA versus 17.82 placebo) and upper respiratory tract infection (9.80 STELARA versus 11.78 placebo).
Final UNIFI LTE clinical and endoscopy outcomes through four years from STELARA treatment (Oral presentation OP15):2 Results from the UNIFI LTE study, among 205 adult patientsb with a history of moderate to severe UC who had achieved clinical response to treatment with intravenous (IV) STELARA, were randomized to STELARA 90 mg every eight weeks (q8w) or every 12 weeks (q12w)c at baseline of the maintenance study, and continued treatment in the LTE, showed that at week 200:d
- 58 percent (119/205) of patients were in clinical remissione
- 80 percent (164/205) of patients were in clinical responsef
- 79.5 percent (163/205) of patients were in modified Mayo score responseg
- 67 percent (138/205) of patients showed endoscopic improvementh
“These long-term studies underscore Janssen’s commitment to developing novel therapies addressing unmet medical need,” said Jan Wehkamp, M.D., Ph.D., Vice President, Gastroenterology Disease Area Leader, Janssen Research & Development, LLC. “Our findings reinforce our confidence in STELARA as a therapy of choice for patients seeking lasting relief from inflammatory bowel disease."
Editor’s Notes:
a. Dr. Afif received grant support from Janssen. He has not been compensated for any media work.
b. Patients were randomized to STELARA at maintenance baseline and continued treatment in the LTE, who either had Mayo score data (including endoscopy) at week 200 or had experienced treatment failure2
c. q12w dosing is not currently approved for STELARA in the U.S.; current approved dosing is a subcutaneous 90 mg dose eight weeks after initial intravenous dose, then every eight weeks thereafter3
d. Patients who had treatment failure (i.e., had ostomy or colectomy or discontinued STELARA due to lack of therapeutic effect or worsening UC) before week 200 were also included, and were imputed as nonresponders.2
e. Clinical remission is defined as a Mayo score ≤2 points and no individual subscore >12
f. Clinical response is defined as a decrease in Mayo score of ≥30% and ≥3 points from induction baseline with either a decrease in rectal bleeding subscore of ≥1 from induction baseline or a rectal bleeding subscore of 0 or 12
g. Modified Mayo score (without Physician’s Global Assessment subscore) response is defined as a decrease in modified Mayo score of ≥30% and ≥2 points from induction baseline with either a decrease in rectal bleeding subscore of ≥1 from induction baseline or a rectal bleeding subscore of 0 or 12
h. Endoscopic improvement, endoscopic healing, or mucosal healing is defined as an endoscopy subscore of 0 or 12
About UNIFI (NCT02407236)2,4
UNIFI was a Phase 3 protocol designed to evaluate the safety and efficacy of STELARA induction and maintenance dosing for the treatment of moderately to severely active ulcerative colitis in adults who demonstrated an inadequate response to or were unable to tolerate conventional (i.e., corticosteroids, immunomodulators) or biologic (i.e., one or more TNF blockers or vedolizumab) therapies. Both the induction and maintenance studies were randomized, double-blind, placebo-controlled, parallel group, multi-center studies.
The induction study was of at least 8 weeks duration for each participant. Participants achieving clinical response in the induction study were eligible for the maintenance study. The maintenance study was 44 weeks in duration. The primary endpoint of the induction study was clinical remission at week 8, and the primary endpoint for the maintenance study was clinical remission at week 44 among responders to a single intravenous (IV) STELARA infusion (130 mg or ~6 mg/kg). Overall, 523 IV STELARA induction responders were randomized to subcutaneous (SC) maintenance therapy (175 SC placebo; 172 STELARA 90 mg q12w; 176 STELARA 90 mg q8w). 284 STELARA patients who completed week 44 entered the LTE. Placebo patients were discontinued after week 44 unblinding. The long-term extension of UNIFI followed eligible participants for an additional three years upon completion of the maintenance study.
Starting at week 56, randomized patients with UC worsening could adjust to q8w dosing. Outcomes based on the Mayo score (including endoscopy assessed by a local reader) were evaluated in the final efficacy visit at week 200. Patients who had treatment failure (i.e., had ostomy or colectomy, or discontinued STELARA due to lack of therapeutic effect or worsening UC) before week 200 were also included, and were imputed as non-responders.
About Ulcerative Colitis
Ulcerative Colitis (UC) is a chronic disease of the large intestine, also known as the colon, in which the lining of the colon becomes inflamed and develops tiny open sores, or ulcers, that produce pus and mucus.5 It is the result of the immune system’s overactive response.5 Symptoms vary, but may include loose and more urgent bowel movements, persistent diarrhea, abdominal pain, bloody stool, loss of appetite, weight loss and fatigue.6
About Crohn’s Disease
CD is one of the two main forms of IBD, which affects an estimated three million Americans.7 CD is a chronic inflammatory condition of the gastrointestinal tract with no known cause, but the disease is associated with abnormalities of the immune system that could be triggered by a genetic predisposition, diet or other environmental factors.8
Symptoms of CD can vary, but often include abdominal pain and tenderness, frequent diarrhea, rectal bleeding, weight loss and fever.9
About STELARA® (ustekinumab)3
STELARA® (ustekinumab), a human interleukin (IL)-12 and IL-23 antagonist, is approved in the United States for the treatment of: 1) adults and children six years and older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy; 2) adults and children six years and older with active psoriatic arthritis; 3) adult patients (18 years and older) with moderately to severely active Crohn’s disease; 4) adult patients (18 years and older) with moderately to severely active ulcerative colitis.
The Janssen Pharmaceutical Companies of Johnson & Johnson maintain exclusive worldwide marketing rights to STELARA.
https://www.stelarainfo.com/ulcerative-colitis
Please click to read the full Prescribing Information and Medication Guide for STELARA® and discuss any questions you have with your doctor.
About the Janssen Pharmaceutical Companies of Johnson & Johnson
At Janssen, we’re creating a future where disease is a thing of the past. We’re the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular, Metabolism & Retina; Immunology; Infectious Diseases & Vaccines; Neuroscience; Oncology; and Pulmonary Hypertension.
Learn more at www.janssen.com.
Follow us at www.twitter.com/JanssenGlobal.
Janssen Research & Development, LLC is a part of the Janssen Pharmaceutical Companies of Johnson & Johnson.
Johnson & Johnson's Stelara demonstrates long-term efficacy in Crohn's disease
Mar. 04, 2023 12:21 PM ET
Johnson & Johnson (JNJ)By: Jonathan Block, SA News Editor3 Comments
- New data on Johnson & Johnson's Stelara (ustekinumab) showed that the IL-12 and IL-23 antagonist demonstrated long-term durable efficacy and safety in Crohn's disease.
- https://seekingalpha.com/news/3944195-pharma-research-developmeny-funding-soared-to-a-new-record-in-2022-as-oncology-candidates-dominate-pipelines
- Johnson & Johnson (JNJ)
- https://www.jnj.com/
- https://www.stelarainfo.com/ulcerative-colitis
DUPIXENT® (DUPILUMAB)
March 7, 2023 at 1:00 AM EST
DUPIXENT® (DUPILUMAB) APPLICATION FOR TREATMENT OF CHRONIC SPONTANEOUS URTICARIA (CSU) IN ADULTS AND ADOLESCENTS AGED 12 YEARS AND OLDER ACCEPTED FOR FDA REVIEW
More than 300,000 people in the U.S. suffer from CSU that is inadequately controlled by antihistamines
TARRYTOWN, N.Y. and PARIS, March 07, 2023 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) and Sanofi today announced that the U.S. Food and Drug Administration (FDA) has accepted for review the supplemental Biologics License Application (sBLA) for Dupixent® (dupilumab) to treat adults and adolescents aged 12 years and older with chronic spontaneous urticaria (CSU) that is not adequately controlled with the current standard of care, H1 antihistamine treatment. The target action date for the FDA decision is October 22, 2023.
CSU is an inflammatory skin condition driven in part by type 2 inflammation, which causes sudden and debilitating hives and swelling on the skin. Swelling, called angioedema, may occur most commonly on the face, hands and feet, but can also affect the throat and upper airways. CSU is typically treated with H1 antihistamines, medicines that target histamine-1 receptors on cells to control symptoms of urticaria. However, the disease remains uncontrolled in up to 50% of patients, who are left with limited alternative treatment options. These individuals continue to experience symptoms, including persistent itch or burning sensations that can be debilitating and significantly impact quality of life.
The sBLA is supported by data from two Phase 3 trials (LIBERTY-CUPID Studies A and B) evaluating Dupixent in two different patient populations with uncontrolled CSU. Study A was conducted in CSU patients who were uncontrolled on standard-of-care antihistamines with efficacy and safety data supporting the submission, while Study B was conducted in CSU patients who were uncontrolled on standard-of-care antihistamines and refractory to omalizumab with results providing additional supporting data.
The potential use of Dupixent in CSU is currently under clinical development, and the safety and efficacy have not been fully evaluated by any regulatory authority.
About the CSU Clinical Trial Program
The clinical trial program, known as LIBERTY-CUPID, includes Studies A and B, two Phase 3 randomized, double-blind, placebo-controlled trials evaluating the efficacy and safety of Dupixent in two different patient populations with uncontrolled CSU.
Study A evaluated Dupixent as an add-on therapy to standard-of-care H1 antihistamines compared to antihistamines alone in 138 patients with CSU aged 6 years and older who remained symptomatic despite antihistamine use and were not previously treated with omalizumab. Study B evaluated Dupixent in 108 patients with CSU aged 12 to 80 years who remained symptomatic despite standard-of-care treatment and were intolerant or incomplete responders to omalizumab.
In addition to CSU, Regeneron and Sanofi are also studying Dupixent in chronic inducible urticaria triggered by cold (LIBERTY-CINDU CUrIADS program) in an ongoing Phase 3 trial.
About Dupixent
Dupixent, which was invented using Regeneron's proprietary VelocImmune® technology, is a fully human monoclonal antibody that inhibits the signaling of the IL-4 and 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 eosinophilic esophagitis (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 or 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 500,000 patients have been 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 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 currently available. This includes Dupixent, REGEN-COV® (casirivimab and imdevimab), 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, atopic hand and foot dermatitis, chronic inducible urticaria-cold, CSU, chronic pruritus of unknown origin, chronic obstructive pulmonary disease with evidence of type 2 inflammation, chronic rhinosinusitis without nasal polyposis, allergic fungal rhinosinusitis, allergic bronchopulmonary aspergillosis 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 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, pain, 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 Twitter.
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.
FDA accepts for review Regeneron/Sanofi's Dupixent application for inflammatory skin condition
Mar. 07, 2023 6:39 AM ET
Regeneron Pharmaceuticals, Inc. (REGN), SNY
By: Mamta Mayani, SA News Editor
- Regeneron Pharmaceuticals (NASDAQ:REGN) and Sanofi (NASDAQ:SNY) announce that the FDA has accepted for review the supplemental Biologics License Application (sBLA) for Dupixent (dupilumab) to treat adults and adolescents aged 12 years and older with chronic spontaneous urticaria (CSU) that is not adequately controlled with the current standard of care, H1 antihistamine treatment.
- https://seekingalpha.com/news/3944785-fda-accepts-for-review-regeneronsanofis-dupixent-application-for-inflammatory-skin-condition
- Regeneron Pharmaceuticals, Inc. (REGN), SNY
- https://www.dupixent.com/
- https://www.regeneron.com/
Reblozyl® (luspatercept)
Bristol Myers Squibb Receives European Commission Approval of Reblozyl® (luspatercept) for Anemia in Adult Patients with Non-Transfusion-Dependent Beta Thalassemia
03/03/2023CATEGORY:
Third authorized indication in Europe for Reblozyl, a first-in-class treatment for patients with diseases impacted by anemia
PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced that the European Commission (EC) has granted full Marketing Authorization for Reblozyl® (luspatercept), a first-in-class therapeutic option, for treatment in adult patients of anemia associated with non-transfusion-dependent (NTD) beta thalassemia. Reblozyl is currently approved in the European Union (EU), United States and Canada to address anemia associated with transfusion-dependent beta thalassemia and transfusion-dependent lower-risk myelodysplastic syndromes. The centralized Marketing Authorization approves use of Reblozyl in all EU member states, as well as Norway, Iceland and Liechtenstein.*
“Beta thalassemia is an inherited blood disorder that puts patients at significant risk for long-term clinical complications due to anemia, leaving a substantial need for treatment options, regardless of a patient’s dependence on blood transfusions. This announcement is welcome news for patients with non-transfusion-dependent beta thalassemia associated anemia across the EU who are seeking newer treatment options to reduce these burdens,” said Noah Berkowitz, M.D., Ph.D., senior vice president, Hematology Development, Bristol Myers Squibb. “Today’s approval represents the third indication for Reblozyl in Europe, and we look forward to continuing to evaluate this first-in-class therapeutic option across multiple diseases impacted by the burden of anemia in a broad clinical development program.”
The EC approval of Reblozyl was based on results from the Phase 2 BEYOND study, evaluating the efficacy and safety of Reblozyl versus placebo in 145 adults with NTD beta thalassemia. Patients were eligible to receive best supportive care, including red blood cell transfusions and iron-chelating agents.
Reblozyl is being developed and commercialized through a global collaboration with Merck following Merck’s acquisition of Acceleron Pharma, Inc. in November 2021.
*Centralized Marketing Authorization does not include approval in Great Britain (England, Scotland and Wales).
About BEYOND
BEYOND (NCT03342404) is a Phase 2, double-blind, randomized, placebo-controlled, multicenter study to determine the efficacy and safety of luspatercept-aamt (ACE-536) versus placebo in adults with non-transfusion-dependent beta thalassemia. The study is divided into the Screening Period, Double-blind Treatment Period (DBTP) and Post-Treatment Follow-up Period (PTFP) and randomized 145 subjects at a 2:1 ratio of Reblozyl versus placebo. All patients were eligible to receive best supportive care, which included red blood cell transfusions; iron-chelating agents; use of antibiotic, antiviral, and antifungal therapy; and/or nutritional support, as needed. The primary endpoint of the study is the proportion of subjects who have an increase from baseline ≥1.0 g/dL in mean of hemoglobin values over a continuous 12-week interval from Week 13 to Week 24 of treatment in the absence of transfusions. Key secondary endpoints include mean change in non-transfusion-dependent beta thalassemia-patient reported outcome (NTDT-PRO) Tiredness and Weakness (TW) domain score and baseline hemoglobin (Hb).
Results demonstrated 74 of 96 (77.1%) patients in the Reblozyl treatment arm achieved the study’s primary endpoint, ≥1.0 g/dL mean Hb increase from baseline, versus 0 of 49 (0%) patients in the placebo arm (P<0.0001).
In a key secondary endpoint of the study, 47 of 96 patients (49.0%) treated with Reblozyl achieved mean Hb increase of ≥1.5 g/dL compared to baseline from Week 37-48 in the absence of transfusions versus 0 patients (0%) in the placebo arm (P<0.0001). In the Reblozyl arm, 89.6% of patients remained transfusion free at weeks 1-24 versus 67.3% of patients in the placebo arm (P=0.0013). Improvements in patient-reported QoL outcomes (tiredness and weakness) were also observed to correlate with Hb increases.
Serious adverse reactions occurred in 11.5% of patients (n=11) who received Reblozyl. The most common adverse reactions occurring in ≥10% of patients treated with Reblozyl were bone pain (36%), headache (30%), arthralgia (29%), back pain (28%), prehypertension (23%), hypertension (20%), cough (18%), diarrhea (17%), influenza-like illness (17%), asthenia (13%), influenza (13%), insomnia (11%) and nausea (10%).
About Beta Thalassemia
Beta thalassemia is an inherited blood disorder caused by a genetic defect in hemoglobin. It is one of the most common autosomal recessive disorders, and the total annual incidence of symptomatic individuals is estimated at 1 in 100,000 people globally.1 The disease is associated with ineffective erythropoiesis, which results in the production of fewer and less healthy red blood cells (RBCs), often leading to severe anemia—a condition that can be debilitating and can lead to other complications for patients—as well as other serious health issues.2 Treatment options for anemia associated with beta thalassemia are limited, consisting mainly of frequent RBC transfusions that have the potential to contribute to iron overload, which can cause serious complications such as organ damage.1 Non-transfusion-dependent beta thalassemia is a term used to describe patients who do not require lifelong regular transfusions for survival, although they may experience a range of clinical complications and require occasional or even frequent transfusions, usually for defined periods of time.
About Reblozyl®
Reblozyl, a first-in-class therapeutic option, promotes late-stage red blood cell (RBC) maturation in animal models.1 Reblozyl is being developed and commercialized through a global collaboration with Merck following Merck’s acquisition of Acceleron Pharma, Inc. in November 2021. Reblozyl is currently approved in the U.S. for the treatment of:
- anemia in adult patients with beta thalassemia who require regular red blood cell (RBC) transfusions
- anemia failing an erythropoiesis stimulating agent and requiring 2 or more red blood cell units over 8 weeks in adult patients with very low- to intermediate-risk myelodysplastic syndrome with ring sideroblasts (MDS-RS) or with myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T).
Reblozyl is not indicated for use as a substitute for RBC transfusions in patients who require immediate correction of anemia.
Please see full Prescribing Information for REBLOZYL.
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
EC approves Bristol Myers' Reblozyl for anemia due to beta thalassemia
Mar. 03, 2023 7:35 AM ET
Bristol-Myers Squibb Company (BMY)
By: Mamta Mayani, SA News Editor
- The European Commission (EC) has granted full Marketing Authorization for Bristol Myers Squibb's (NYSE:BMY) Reblozyl (luspatercept), a first-in-class therapeutic option, for treatment in adult patients of anemia associated with non-transfusion-dependent (NTD) beta thalassemia.
- https://seekingalpha.com/news/3943800-ec-approves-bristol-myers-reblozyl-for-anemia-due-to-beta-thalassemia
- Bristol-Myers Squibb Company (BMY)
- https://www.bms.com/
- https://www.reblozyl.com/
RINVOQ® (upadacitinib)
February 27, 2023
AbbVie Highlights Robust Gastroenterology Portfolio with New Analyses and Data in Inflammatory Bowel Diseases at the 18th Congress of European Crohn's and Colitis Organisation (ECCO)
- A total of 24 accepted abstracts, including six oral and digital oral presentations, reinforce AbbVie's commitment to research that helps advance standards of care for patients living with inflammatory bowel diseases
- Data from ADVANCE, MOTIVATE and FORTIFY studies highlighting efficacy outcomes and clinical response in patients receiving SKYRIZI for treatment of moderately to severely active Crohn's disease
- Oral presentations from sub-analyses of U-EXCEL, U-EXCEED and U-ENDURE address treatment of moderately to severely active Crohn's disease, including efficacy outcomes from the upadacitinib (RINVOQ® ) clinical trial program
NORTH CHICAGO, Ill., Feb. 27, 2023 /PRNewswire/ -- AbbVie (NYSE: ABBV) will present further analyses on SKYRIZI® (risankizumab) in Crohn's disease (CD) and RINVOQ® (upadacitinib) in ulcerative colitis (UC) as well as the investigational use of upadacitinib in CD at the 18th Congress of European Crohn's and Colitis Organisation (ECCO), to be held March 1-4 in Copenhagen, Denmark. AbbVie will present 24 abstracts, including four oral presentations, two digital oral presentations and 18 posters from a broad range of studies across its inflammatory bowel disease (IBD) portfolio.
"We are excited by the opportunity to present further analyses on the advancements of our expanding IBD portfolio at this year's 18th ECCO Congress," said Sofie Berg, Pharm.D, Ph.D., head of gastroenterology, global medical affairs, AbbVie. "Our data at ECCO underscore AbbVie's unwavering commitment to driving discoveries and delivering advancements for patients where expanded options are needed with the goal of positively impacting the treatment of those living with IBD."
Key data presentations will include:
- Sequencing in IBD - Scientific Session 2: Can we do better with current drugs? (2 Mar 2023, 14:30-16:00 CET)
- OP04 Efficacy of upadacitinib in ulcerative colitis: A Phase 3 post hoc analysis of biologic- and anti-TNF-inadequate response patients
- OP04 Efficacy of upadacitinib in ulcerative colitis: A Phase 3 post hoc analysis of biologic- and anti-TNF-inadequate response patients
- Sequencing in IBD - Scientific Session 5: Endoscopy as precision medicine approach to IBD - in collaboration with the European Society of Gastrointestinal Endoscopy (ESGE) (Plenary Hall, 3 Mar 2023, 11:00-12:30 CET)
- OP16 Endoscopic and clinical outcomes of upadacitinib in patients with moderately to severely active Crohn's disease by number and type of prior biologics
- OP17 Upadacitinib improves endoscopic outcomes in patients with moderate to severely active Crohn's disease irrespective of previous failure to respond to biologics or conventional therapies
- Sequencing in IBD - Scientific Session 6: Pain in IBD - in collaboration with the European Society of Neurogastroenterology and Motility (ESNM) (3 Mar 2023, 13:30-15:30 CET)
- OP20 The effects of upadacitinib on ulcerative colitis symptom resolution and fatigue normalization in patients with moderately to severely active ulcerative colitis: Phase 3 U-ACHIEVE and U-ACCOMPLISH results
"Despite continued advancements in the treatment of IBD, many patients are still negatively impacted by the burdens of living with their disease," said Silvio Danese, M.D. Ph.D. director of gastroenterology and endoscopy at IRCCS Ospedale San Raffaele and professor of gastroenterology at University Vita-Salute San Raffaele, Milan, Italy. "AbbVie's research at ECCO helps support their goal of providing a diverse portfolio of treatments and research that continues to advance the standard of care for IBD patients."
The full scientific program for the 18th ECCO Congress is available here.
SKYRIZI® (risankizumab) is part of a collaboration between Boehringer Ingelheim and AbbVie, with AbbVie leading development and commercialization globally.
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.1,2 The hallmark signs and symptoms of ulcerative colitis include rectal bleeding, abdominal pain, bloody diarrhea, tenesmus (a sense of pressure), urgency and fecal incontinence.1,3 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.2,4 The severity of symptoms and unpredictability of disease course can lead to substantial burden and often disability among those living with the disease.5
About Crohn's Disease
Crohn's disease is a chronic, systemic disease that manifests as inflammation within the gastrointestinal (or digestive) tract, causing persistent diarrhea, abdominal pain and rectal bleeding.2,6,7 It is a progressive disease, meaning it gets worse over time.2,7 Because the signs and symptoms of Crohn's disease are unpredictable, it causes a significant burden on people living with the disease—not only physically, but also emotionally and economically.5
About RINVOQ® (upadacitinib)
Discovered and developed by AbbVie scientists, RINVOQ is a selective JAK inhibitor that is being studied in several immune-mediated inflammatory diseases. Based on enzymatic and cellular assays, RINVOQ demonstrated greater inhibitory potency for JAK-1 vs JAK-2, JAK-3, and TYK-2.8 The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness and safety is not currently known.
In the U.S., RINVOQ 15 mg is approved for adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more TNF blockers; adults with active psoriatic arthritis who have had an inadequate response or intolerance to one or more TNF blockers; adults with active ankylosing spondylitis (AS) who have had an inadequate response or intolerance to one or more tumor necrosis factor (TNF) blockers and adults with active non-radiographic axial spondyloarthritis with objective signs of inflammation who have had an inadequate response or intolerance to TNF blocker therapy.8 RINVOQ 45 mg is approved for use in adult patients with moderately to severely active ulcerative colitis who have had an inadequate response or intolerance to one or more TNF blockers as an induction therapy once daily for 8 weeks. The recommended dose of RINVOQ for maintenance treatment is 15 mg once daily. A dosage of 30 mg once daily may be considered for patients with refractory, severe or extensive disease. Discontinue RINVOQ if an adequate response is not achieved with the 30 mg dose. Use the lowest effective dosage needed to maintain response. RINVOQ 15 mg once daily can also be initiated in adults and children 12 years of age and older weighing at least 40 kg with refractory, moderate to severe atopic dermatitis whose disease is not adequately controlled with other systemic drug products, including biologics or when use of those therapies is inadvisable. In these children and adults less than 65 years of age who do not achieve an adequate response, the dose may be increased to 30 mg once daily.
Phase 3 trials of RINVOQ in rheumatoid arthritis, atopic dermatitis, psoriatic arthritis, axial spondyloarthritis, Crohn's disease, ulcerative colitis, giant cell arteritis and Takayasu arteritis are ongoing.9-16
US Indications and Important Safety Information about RINVOQ® (upadacitinib)8
USES
RINVOQ is a prescription medicine used to treat:
- Adults with moderate to severe rheumatoid arthritis (RA) when 1 or more medicines called tumor necrosis factor (TNF) blockers have been used, and did not work well or could not be tolerated.
- Adults with active psoriatic arthritis (PsA) when 1 or more medicines called TNF blockers have been used, and did not work well or could not be tolerated.
- Adults with moderate to severe ulcerative colitis (UC) when 1 or more medicines called TNF blockers have been used, and did not work well or could not be tolerated.
- Adults with active ankylosing spondylitis (AS) when 1 or more medicines called TNF blockers have been used, and did not work well or could not be tolerated.
- Adults with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation when a TNF blocker medicine has been used, and did not work well or could not be tolerated.
It is not known if RINVOQ is safe and effective in children with juvenile idiopathic arthritis, psoriatic arthritis, ulcerative colitis, ankylosing spondylitis, or non-radiographic axial spondyloarthritis.
- Adults and children 12 years of age and older with moderate to severe eczema (atopic dermatitis [AD]) that did not respond to previous treatment and their eczema is not well controlled with other pills or injections, including biologic medicines, or the use of other pills or injections is not recommended.
RINVOQ is safe and effective in children 12 years of age and older weighing at least 88 pounds (40 kg) with atopic dermatitis.
It is not known if RINVOQ is safe and effective in children under 12 years of age with atopic dermatitis.
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, virology, women's health and gastroenterology, in addition to products and services across our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook, LinkedIn or Instagram.
AbbVie wins EU nod for Rinvoq in Crohn's disease
Feb. 27, 2023 5:48 AM ET
By: Dulan Lokuwithana, SA News Editor
- AbbVie (NYSE:ABBV) announced Monday that an expert medical panel in the EU recommended marketing authorization for its oral JAK inhibitor Rinvoq, known as upadacitinib in generic terms, for adults with the gastrointestinal disorder Crohn's disease.
- https://seekingalpha.com/news/3941008-abbvie-wins-eu-nod-rinvoq-crohns-disease
- AbbVie Inc. (ABBV)
- https://www.rinvoq.com/
- https://www.rinvoqhcp.com/
- https://www.abbvie.com/
Verzenio® (abemaciclib)
U.S. FDA Broadens Indication for Verzenio® (abemaciclib) in HR+, HER2-, Node-Positive, High Risk Early Breast Cancer
March 3, 2023Download PDF
High risk patients eligible for Verzenio can now be identified solely based on nodal status, tumor size, and tumor grade, regardless of Ki-67 score
Approval supported by four-year data from the monarchE trial; Verzenio added to adjuvant endocrine therapy (ET) reduced the risk of recurrence by 35% compared to adjuvant ET alone
Verzenio remains the first and only CDK4/6 inhibitor approved in the adjuvant setting
INDIANAPOLIS, March 3, 2023 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced that the U.S. Food and Drug Administration (FDA) approved an expanded indication for Verzenio® (abemaciclib), in combination with endocrine therapy (ET), for the adjuvant treatment of adult patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), node-positive, early breast cancer (EBC) at a high risk of recurrence. High risk patients eligible for Verzenio can now be identified solely based on nodal status, tumor size, and tumor grade (4+ positive nodes, or 1-3 positive nodes and at least one of the following: tumors that are ≥5 cm or Grade 3).1 This expanded adjuvant indication removes the Ki-67 score requirement for patient selection.
This label expansion is supported by four-year data from the Phase 3 monarchE trial of adjuvant Verzenio in combination with ET, which showed a deepened benefit in invasive disease-free survival (IDFS) beyond the two-year treatment course with adjuvant Verzenio. The absolute difference in IDFS between treatment groups increased over time. At four years, 85.5% of patients remained recurrence-free with Verzenio plus ET, compared to 78.6% with ET alone, an absolute difference in IDFS of 6.9%. At two years and at three years, the absolute differences between treatment groups were 3.1% and 5.0%, respectively; see Fig. 1 below. The addition of Verzenio to ET reduced the risk of recurrence by 35% compared to ET alone (HR=0.653 [95% CI: 0.567-0.753]). There were no new safety findings, and overall results are consistent with the well-established safety profile for Verzenio. These four-year monarchE data were presented at the 2022 San Antonio Breast Cancer Symposium and simultaneously published in The Lancet Oncology.2
The monarchE study enrolled 5,637 adults with high risk HR+, HER2-, node-positive EBC into two cohorts. Verzenio is now approved for use in the full Cohort 1 patient population, which comprised 91% of the study population. A statistically significant difference in IDFS was observed in the intent-to-treat (ITT) population, primarily due to patients in Cohort 1. As of the data cut-off date, while overall survival (OS) data remain immature across the entire study, an OS trend in favor of Verzenio was observed in the Cohort 1 population, but not the Cohort 2 population where more deaths were seen with Verzenio plus ET compared to ET alone (10/253 vs. 5/264). The "About the monarchE Study" section below provides more details on study design.
"Our goal in intensifying treatment for early breast cancer is to maintain remission and prevent the recurrence of cancer. The magnitude of benefit seen in the four-year data from the monarchE study reinforces my confidence in adjuvant Verzenio as the standard-of-care for high risk patients in this setting," said Erika P. Hamilton, M.D., medical oncologist, director of Breast and Gynecologic Cancer Research at Sarah Cannon Research Institute, and an investigator on the monarchE clinical trial. "The initial Verzenio FDA approval in early breast cancer was practice-changing and now, through this indication expansion, we have the potential to reduce the risk of breast cancer recurrence for many more patients, relying solely on commonly utilized clinicopathologic features to identify them."
More than 300,000 people are expected to be diagnosed with breast cancer in the U.S. in 2023.3 It is estimated that 90% of all breast cancers are detected at an early stage.4 Approximately 70% of all breast cancer cases are the HR+, HER2- subtype.5 Although the prognosis for HR+, HER2- EBC is generally favorable, high risk patients are three times more likely than those with low risk characteristics to experience recurrence – with the majority being incurable metastatic disease.6 These patients have an increased risk of recurrence during the first two years of endocrine therapy.
"This expanded approval will allow us to bring Verzenio to many more women and men with HR+, HER2-, high risk early breast cancer in the curative setting – before patients experience recurrence, potentially to incurable metastatic disease," said Jacob Van Naarden, chief executive officer of Loxo@Lilly. "The initial adjuvant approval for Verzenio changed the treatment paradigm, and the strength of the monarchE results supporting this approval underscores the role this differentiated CDK4/6 inhibitor can play in reducing the risk of recurrence in early breast cancer."
"This expanded approval for Verzenio is welcome news for our community," said Jean Sachs, chief executive officer of Living Beyond Breast Cancer. "A significant number of women and men have HR+, HER2- early breast cancer at high risk of returning. Making effective treatment options available is crucial to allowing people to make the best care decisions for themselves, together with their healthcare providers. We're pleased Verzenio will now be available to more people with this type of early breast cancer."
Concurrent with this expanded indication approval in EBC, the FDA has also broadened the indicated use of Verzenio in metastatic breast cancer (MBC) when used in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of people with HR+, HER2- advanced or MBC. This updated MBC indication now includes all adult patients, with the expanded indication including pre-/perimenopausal women when used in combination with ovarian suppression. See below "Indications for Verzenio" for full details on indicated uses in HR+, HER2- advanced or metastatic breast cancer. Verzenio is available in tablet strengths of 50 mg, 100 mg, 150 mg, and 200 mg.
The labeling for Verzenio contains warnings and precautions for diarrhea, neutropenia, interstitial lung disease (ILD/pneumonitis), hepatotoxicity, venous thromboembolism, and embryo-fetal toxicity. Instruct patients at the first sign of loose stools to initiate antidiarrheal therapy, increase oral fluids, and notify their healthcare provider. Perform complete blood counts and liver function tests prior to the start of Verzenio treatment, every two weeks for the first two months, monthly for the next two months and as clinically indicated. Based on results, Verzenio may require dose modification. Monitor patients for signs and symptoms of thrombosis and pulmonary embolism and treat as medically appropriate. Advise patients of potential risk to a fetus and to use effective contraception.
See Important Safety Information below and full Prescribing Information for additional information.
Click here to view the early breast cancer infographic.
About the monarchE Study
monarchE was a global, randomized, open-label, two cohort, multicenter Phase 3 clinical trial that enrolled 5,637 adults with HR+, HER2-, node-positive EBC at high risk of recurrence. To be enrolled in Cohort 1 (n=5,120), which is the FDA-approved population, patients had to have 4+ positive nodes or 1-3 positive nodes and at least one of the following: tumors that were ≥5 cm or Grade 3. Patients enrolled in Cohort 2 could not have met the eligibility criteria for Cohort 1. To be enrolled in Cohort 2 (n=517), patients had to have 1-3 positive nodes and Ki-67 score ≥20%. Patients in each cohort were randomized 1:1 to receive either Verzenio 150 mg twice daily plus standard-of-care adjuvant ET (Cohort 1, n=2,555; Cohort 2, n=253) or standard-of-care adjuvant ET alone (Cohort 1, n=2,565; Cohort 2, n=264) for 2 years. ET continued for at least 5 years if deemed medically appropriate. The primary endpoint was IDFS. Consistent with expert guidelines, IDFS was defined as the length of time before breast cancer comes back, any new cancer develops, or death.
About Early Breast Cancer and Risk of Recurrence
It is estimated that 90% of all breast cancers are detected at an early stage.4 Approximately 70% of all breast cancer cases are the HR+, HER2- subtype.5 Although the prognosis for HR+, HER2- EBC is generally favorable, high risk patients are three times more likely than those with low risk characteristics to experience recurrence – with the majority being incurable metastatic disease.6 These patients have an increased risk of recurrence during the first two years of endocrine therapy.
Factors associated with high risk of recurrence in HR+, HER2- early breast cancer include: positive nodal status, the number of positive nodes, large tumor size (≥5 cm), and high tumor grade (Grade 3). Node-positive means that cancer cells from the tumor in the breast have been found in the lymph nodes near the breast. Although breast cancer is removed through surgery, the presence of cancer cells in the lymph nodes signifies that there is a higher chance of developing recurrence and distant metastatic disease.
About Breast Cancer
Breast cancer has surpassed lung cancer as the most commonly diagnosed cancer worldwide, according to GLOBOCAN. The estimated 2.3 million new cases indicate that 1 in every 8 cancers diagnosed in 2020 is breast cancer. With approximately 685,000 deaths in 2020, breast cancer is the fifth-leading cause of cancer death worldwide.7 In the U.S., it is estimated that there will be more than 300,000 new cases of breast cancer diagnosed in 2023. Breast cancer is the second leading cause of cancer death in women in the U.S.3
About Verzenio® (abemaciclib)
Verzenio® (abemaciclib) is a targeted treatment known as a CDK4/6 inhibitor. Verzenio is a nonchemotherapy oral tablet.
Verzenio works inside the cell to block CDK4/6 activity and help stop the growth of cancer cells so that they may eventually die (based on preclinical studies). Cyclin-dependent kinases (CDK)4/6 are activated by binding to D-cyclins. In estrogen receptor-positive (ER+) breast cancer cell lines, cyclin D1 and CDK4/6 promote phosphorylation of the retinoblastoma protein (Rb), cell cycle progression and cell proliferation.
In vitro, continuous exposure to Verzenio inhibited Rb phosphorylation and blocked progression from G1 to S phase of the cell cycle, resulting in senescence and apoptosis (cell death). Preclinically, Verzenio dosed daily without interruption resulted in reduction of tumor size. Inhibiting CDK4/6 in healthy cells can result in side effects, some of which may be serious. Clinical evidence also suggests that Verzenio crosses the blood-brain barrier. In patients with advanced cancer, including breast cancer, concentrations of Verzenio and its active metabolites (M2 and M20) in cerebrospinal fluid are comparable to unbound plasma concentrations.
Verzenio is Lilly's first solid oral dosage form to be made using a faster, more efficient process known as continuous manufacturing. Continuous manufacturing is a new and advanced type of manufacturing within the pharmaceutical industry, and Lilly is one of the first companies to use this technology.
INDICATIONS FOR VERZENIO®
VERZENIO® is a kinase inhibitor indicated:
- in combination with endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer at high risk of recurrence.
- in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer.
- in combination with fulvestrant for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer with disease progression following endocrine therapy.
- as monotherapy for the treatment of adult patients with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting.
- Please see full Prescribing Information for Verzenio.
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 47 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
PP-AL-US-3657 © Lilly USA, LLC 2023. ALL RIGHTS RESERVED.
Verzenio® is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates.
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SOURCE Eli Lilly and Company
Eli Lilly wins additional breast cancer indication for Verzenio
Mar. 03, 2023 3:20 PM ET
By: Jonathan Block, SA News Editor1 Comment
- The US FDA has granted an additional indication for Eli Lilly's (NYSE:LLY) Verzenio (abemaciclib) in combination with endocrine therapy as an adjuvant treatment for HR+, HER2- node-positive, early breast cancer at high risk of occurrence.
- https://seekingalpha.com/news/3944114-eli-lilly-wins-additional-breast-cancer-indication-for-verzenio
- Eli Lilly and Company (LLY)
- https://www.lilly.com/
- https://www.verzenio.com/
KEYTRUDA® (pembrolizumab) in combination with chemotherapy
Merck Announces Phase 3 KEYNOTE-671 Trial Met Primary Endpoint of Event-Free Survival (EFS) in Patients With Resectable Stage II, IIIA or IIIB Non-Small Cell Lung Cancer
March 1, 2023 6:45 am ET
In pivotal study, KEYTRUDA® (pembrolizumab) in combination with chemotherapy before surgery and continuing as a single agent after surgery showed a statistically significant improvement in EFS versus pre-operative chemotherapy
KEYTRUDA-based regimen also showed statistically significant improvements in key secondary endpoints of pathological complete response and major pathological response
FDA accepted application based on these data and set PDUFA date of October 16, 2023
RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, announced today that the Phase 3 KEYNOTE-671 trial investigating KEYTRUDA, Merck’s anti-PD-1 therapy, met one of its dual primary endpoints, event-free survival (EFS), as a perioperative treatment regimen for patients with resectable stage II, IIIA or IIIB non-small cell lung cancer (NSCLC). A perioperative treatment regimen includes treatment before surgery (neoadjuvant) and continued after surgery (adjuvant). The trial will continue to evaluate the other dual primary endpoint of overall survival (OS).
At a prespecified interim analysis conducted by an independent Data Monitoring Committee, neoadjuvant KEYTRUDA plus chemotherapy followed by resection and adjuvant single-agent KEYTRUDA demonstrated a statistically significant and clinically meaningful improvement in EFS compared to neoadjuvant placebo plus chemotherapy followed by adjuvant placebo. Statistically significant improvements in the trial’s key secondary endpoints of pathological compete response (pCR) and major pathological response (mPR) were also demonstrated at this analysis. No new safety signals were observed.
Results will be presented at an upcoming medical meeting. The U.S. Food and Drug Administration (FDA) has accepted Merck’s new supplemental Biologics License Application (sBLA) based on these data for KEYTRUDA for the treatment of patients with resectable stage II, IIIA, or IIIB (T3-4N2) NSCLC in combination with platinum containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment. The FDA has set a Prescription Drug User Fee Act (PDUFA), or target action, date of October 16, 2023.
“Results from KEYNOTE-671 show that KEYTRUDA in combination with chemotherapy provided significant improvement in event-free survival, pathological complete response and major pathological response over chemotherapy alone as a perioperative treatment regimen for patients with resectable stage II, IIIA or IIIB non-small cell lung cancer,” said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. “By moving this KEYTRUDA-based regimen into earlier stages of non-small cell lung cancer, we may be able to significantly reduce the risk of recurrence for these patients. This study is an important milestone, and we look forward to sharing the detailed results with the medical community as soon as possible. We thank the patients and investigators for their important contributions to this study.”
Merck has an extensive clinical development program in lung cancer and is advancing multiple registration-enabling studies, with research directed at earlier stages of disease and novel combinations. Key studies in earlier stages of NSCLC include KEYNOTE-671, KEYNOTE-091, KEYNOTE-867, KEYLYNK-012 and KEYVIBE-006.
About KEYNOTE-671
KEYNOTE-671 is a randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT03425643) evaluating neoadjuvant KEYTRUDA plus chemotherapy, followed by adjuvant KEYTRUDA as a single agent versus placebo plus neoadjuvant chemotherapy followed by adjuvant placebo in patients with resectable stage II, IIIA or IIIB (T3-4N2) NSCLC. The trial’s dual primary endpoints are EFS and OS. Key secondary endpoints include pCR and mPR. The study enrolled 786 patients who were randomly assigned (1:1) to receive either:
- KEYTRUDA (200 mg intravenously [IV] every three weeks [Q3W] for up to four cycles) plus chemotherapy (cisplatin [75 mg/m^2, IV; given on Day 1 of each cycle] and either gemcitabine [1000 mg/m^2, IV; given on Days 1 and 8 of each cycle) or pemetrexed [500 mg/m^2, IV; given on Day 1 of each cycle]) as neoadjuvant therapy prior to surgery, followed by KEYTRUDA (200 mg IV Q3W for up to 13 cycles) as adjuvant therapy post-surgery, or;
- Placebo (saline IV Q3W for up to four cycles) plus chemotherapy (cisplatin [75 mg/m^2, IV; given on Day 1 of each cycle] and either gemcitabine [1000 mg/m^2, IV; given on Days 1 and 8 of each cycle] or pemetrexed [500 mg/m^2, IV; given on Day 1 of each cycle]) as neoadjuvant therapy prior to surgery, followed by placebo (saline IV Q3W for up to 13 cycles) as adjuvant therapy post-surgery.
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, accounting for about 81% of all cases. In the U.S., the overall five-year survival rate for patients diagnosed with lung cancer is 25%, which is a 21% 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 5.8% of people in the U.S. who are eligible were screened for lung cancer in 2021.
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 five 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’s early-stage cancer clinical program
Finding cancer at an earlier stage may give patients a greater chance of long-term survival. Many cancers are considered most treatable and potentially curable in their earliest stage of disease. Building on the strong understanding of the role of KEYTRUDA in later-stage cancers, Merck is studying KEYTRUDA in earlier disease states, with approximately 20 ongoing registrational studies across multiple types of cancer.
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, 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
Pediatric Use
In KEYNOTE-051, 161 pediatric patients (62 pediatric patients aged 6 months to younger than 12 years and 99 pediatric patients aged 12 years to 17 years) were administered KEYTRUDA 2 mg/kg every 3 weeks. The median duration of exposure was 2.1 months (range: 1 day to 24 months).
Adverse reactions that occurred at a ≥10% higher rate in pediatric patients when compared to adults were pyrexia (33%), vomiting (30%), leukopenia (30%), upper respiratory tract infection (29%), neutropenia (26%), headache (25%), and Grade 3 anemia (17%).
Additional Indications for KEYTRUDA 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.
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 Carcinoma
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC):
- 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.
Non-muscle Invasive Bladder Cancer
KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ 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.
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 MSI-H central nervous system cancers have not been established.
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 patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.
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.
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.
Merkel Cell Carcinoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). 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.
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.
About the Merck Access Program for KEYTRUDA
At Merck, we are committed to supporting accessibility to our cancer medicines. Merck provides multiple programs to help appropriate patients who are prescribed KEYTRUDA have access to our anti-PD-1 therapy. The Merck Access Program provides reimbursement support for patients receiving KEYTRUDA, including information to help with out-of-pocket costs and co-pay assistance for eligible patients. More information is available by calling 855-257-3932 or visiting https://www.merckaccessprogram-keytruda.com/.
About Merck’s Patient Support Program for KEYTRUDA
Merck is committed to helping provide patients and their caregivers support throughout their treatment with KEYTRUDA. The KEY+YOU Patient Support Program provides a range of resources and support. For further information and to sign up, eligible patients may call 85-KEYTRUDA (855- 398-7832) or visit www.keytruda.com.
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 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 says Keytruda trial met main goal as perioperative therapy in lung cancer
Mar. 01, 2023 7:26 AM ET
By: Dulan Lokuwithana, SA News Editor
Merck (NYSE:MRK) announced Wednesday that its blockbuster immunotherapy Keytruda reached one of the dual primary endpoints in a Phase 3 trial as perioperative therapy for certain lung cancer patients.
The trial named KEYNOTE-671 tested neoadjuvant KEYTRUDA (before surgery) plus chemotherapy, followed by adjuvant KEYTRUDA (after surgery) as a single agent against placebo plus neoadjuvant chemotherapy followed by adjuvant placebo.
Opdivo (nivolumab)
U.S. Food and Drug Administration Accepts Bristol Myers Squibb’s Supplemental Biologics License Application and European Medicines Agency Validates Application for Opdivo (nivolumab) ….
02/28/2023CATEGORY:
The applications are based on results from the Phase 3 CheckMate -76K trial, in which Opdivo demonstrated a statistically significant and clinically meaningful benefit in recurrence-free survival
The U.S. Food and Drug Administration has assigned a target action date of October 13, 2023
PRINCETON, N.J.--(BUSINESS WIRE)--
U.S. Food and Drug Administration Accepts Bristol Myers Squibb’s Supplemental Biologics License Application and European Medicines Agency Validates Application for Opdivo (nivolumab) as an Adjuvant Treatment for Patients with Completely Resected Stage IIB or IIC Melanoma
Bristol Myers Squibb (NYSE: BMY) today announced that the U.S. Food and Drug Administration (FDA) has accepted the supplemental Biologics License Application (sBLA) and the European Medicines Agency (EMA) has validated the Type II Variation Marketing Authorization Application (MAA) for Opdivo® (nivolumab) as monotherapy in the adjuvant setting for the treatment of patients with completely resected stage IIB or IIC melanoma. In the U.S., the FDA has assigned a Prescription Drug User Fee Act (PDUFA) date of October 13, 2023. In Europe, the EMA’s validation of the application confirms the submission is complete and begins the start of the EMA’s centralized review process.
“Melanoma can be a devastating diagnosis, and patients with stage IIB or IIC melanoma tend to be at high risk of disease recurrence. Approximately one third of stage IIB and half of stage IIC patients experience recurrence within five years after surgery,” said Gina Fusaro, PhD, vice president, development program lead, Bristol Myers Squibb. “The data from the CheckMate -76K trial demonstrate the benefit that Opdivo can have for patients with this earlier stage of cancer. We look forward to working with the U.S. Food and Drug Administration and the European Medicines Agency to potentially offer a treatment option to patients with stage IIB or IIC melanoma that could help prevent recurrence.”
The submissions were based on safety and efficacy results from the pivotal Phase 3 CheckMate -76K trial, in which Opdivo demonstrated a statistically significant and clinically meaningful benefit in recurrence-free survival (RFS) versus placebo in patients with completely resected stage IIB or IIC melanoma. The safety profile of Opdivo was consistent with previously reported studies.
Results from CheckMate -76K were presented as late-breaking data during a plenary session at the Society for Melanoma Research (SMR) Annual Meeting in October 2022.
CheckMate -76K is part of BMS’ development program studying Opdivo and Opdivo-based combinations in earlier stages of cancer (adjuvant, neoadjuvant, and peri-operative), which currently spans seven tumor types. To date, Opdivo-based therapies have shown improved efficacy in the neoadjuvant or adjuvant treatment of four tumor types: non-small cell lung cancer (NSCLC), bladder cancer, esophageal/gastroesophageal junction cancer, and melanoma.
Bristol Myers Squibb thanks the patients and investigators involved in the CheckMate -76K trial.
About CheckMate -76K
CheckMate -76K is a randomized Phase 3, double-blind study evaluating adjuvant Opdivo (nivolumab) 480 mg Q4W for up to 12 months versus placebo in patients with completely resected stage IIB/C melanoma.
The primary endpoint of the trial is recurrence-free survival (RFS). Secondary endpoints of the trial include overall survival (OS), distant metastases-free survival (DMFS), progression-free survival on next-line therapy (PFS2), and safety endpoints.
About Melanoma
Melanoma is a form of skin cancer characterized by the uncontrolled growth of pigment-producing cells (melanocytes) located in the skin. Metastatic melanoma is the deadliest form of the disease and occurs when cancer spreads beyond the surface of the skin to other organs. In the United States, approximately 97,610 new diagnoses of melanoma and about 7,990 related deaths are estimated for 2023. Globally, the World Health Organization estimates that by 2035, melanoma incidence will reach 424,102, with 94,308 related deaths. Melanomas can be mostly treatable when caught in very early stages; however, survival rates can decrease as the disease progresses.
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 scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at 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. Because 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 October 2015, the Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination 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 of age or 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 of age or older with unresectable or metastatic melanoma.
OPDIVO® (nivolumab) is indicated for the adjuvant treatment of adult and pediatric patients 12 years of age or older with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.
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), 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 US Full Prescribing Information for OPDIVO and YERVOY.
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, Twitter, YouTube, Facebook and Instagram.
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Bristol Myers Opdivo for skin cancer gets review in US, EU
Feb. 28, 2023 8:08 AM ET
Bristol-Myers Squibb Company (BMY)
By: Ravikash, SA News Editor
- The U.S. Food and Drug Administration (FDA) accepted to review Bristol Myers Squibb's (NYSE:BMY) supplemental biologics license application (sBLA) seeking approval of Opdivo (nivolumab) as monotherapy in the adjuvant setting to treat patients with completely resected stage 2B or 2C melanoma.
- https://seekingalpha.com/news/3941763-bristol-myers-opdivo-for-skin-cancer-gets-review-in-us-eu
- Bristol-Myers Squibb Company (BMY)
- https://www.opdivo.com/
- https://www.bms.com/
biotecMAX™ 2023 Insight
Imfinzi (durvalumab) and Imjudo (tremelimumab)
Imfinzi plus Imjudo approved in the EU for patients with advanced liver and non-small cell lung cancers
PUBLISHED22 February 2023
22 February 2023 07:00 GMT
Approvals based on significant survival benefits
in HIMALAYA and POSEIDON Phase III trials
AstraZeneca’s Imfinzi (durvalumab) and Imjudo (tremelimumab) immunotherapy combinations have been approved in the European Union (EU) for the treatment of advanced liver and lung cancers.
The approvals authorise Imfinzi in combination with Imjudo for the 1st-line treatment of adult patients with advanced or unresectable hepatocellular carcinoma (HCC) and Imfinzi in combination with Imjudo and platinum-based chemotherapy for the treatment of adult patients with metastatic (Stage IV) non-small cell lung cancer (NSCLC).
The two approvals by the European Commission follow positive recommendations by The Committee for Medicinal Products for Human Use of the European Medicines Agency in December 2022 and are based on positive results from the HIMALAYA Phase III trial, published in the New England Journal of Medicine Evidence and the POSEIDON Phase III trial, published in the Journal of Clinical Oncology.
Bruno Sangro, MD, PhD, Director of the Liver Unit and Professor of Internal Medicine at Clínica Universidad de Navarra, and a lead investigator in the HIMALAYA Phase III trial, said: “This approval in Europe is welcome news for eligible patients with advanced liver cancer, who face a poor prognosis and are in need of well-tolerated treatments that can meaningfully extend overall survival. In HIMALAYA, an estimated 31% of patients treated with this novel combination of tremelimumab with durvalumab were alive at three years, while only 20% of patients treated with sorafenib were still alive at the same duration of follow-up.”
Solange Peters, MD, PhD, Head of the Medical Oncology Service and Chair of Thoracic Oncology at Hospitalier Universitaire Vaudois, Lausanne, Switzerland, and principal investigator in the POSEIDON Phase III trial, said: “Patients with metastatic non-small cell lung cancer continue to need new therapies that can meaningfully extend survival, including for many patients whose disease does not respond to current therapies. The approval of tremelimumab added to durvalumab and chemotherapy means that patients in Europe with this devastating cancer now have a valuable new treatment approach with demonstrated long-term survival benefits.”
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “Lung cancer is one of the most prevalent and deadly cancers in Europe, and rates of liver cancer are rising steadily across the region. These approvals for Imfinzi and Imjudo bring critically needed, novel immunotherapy-based treatment regimens that will potentially deliver life-extending benefits for European patients with advanced liver and non-small cell lung cancers.”
Imjudo and Imfinzi approved in liver cancer
The approval for the treatment of HCC is based on results from the HIMALAYA Phase III trial, where the Single Tremelimumab Regular Interval Durvalumab (STRIDE) regimen, comprised of a single dose of the anti-CTLA-4 antibody Imjudo (300mg) combined with anti-PD-L1 antibody Imfinzi (1500mg dose) followed by Imfinzi every four weeks significantly reduced the risk of death by 22% versus sorafenib (hazard ratio [HR] 0.78; 95% confidence interval [CI], 0.66-0.92; p=0.0035). Median overall survival (OS) was 16.4 months versus 13.8 for sorafenib. An estimated 31% of patients treated with the combination were still alive after three years with 20% of patients treated with sorafenib still alive at the same duration of follow-up.
The safety profile of the combination of Imjudo added to Imfinzi were consistent with the known profiles of each medicine, and no new safety signals were identified.
Liver cancer is the third-leading cause of cancer death and the sixth most commonly diagnosed cancer worldwide.1,2 Approximately 87,000 Europeans were diagnosed with liver cancer in 2020, with 51% of patients at an advanced cancer stage at time of diagnosis. Rates of liver cancer continue to rise rapidly, with a 70% increase of liver cancer-related mortality in Europe from 1990-2019.3
Imfinzi and Imjudo approved in NSCLC
The approval for the treatment of metastatic NSCLC is based on results from the POSEIDON Phase III trial, which showed a limited course of five cycles of the anti-CTLA-4 antibody Imjudo added to Imfinzi plus four cycles of platinum-based chemotherapy significantly reduced the risk of death by 23% versus a range of chemotherapy options (HR 0.77; 95% CI, 0.65-0.92; p=0.00304). Median OS was 14.0 months versus 11.7 months for chemotherapy. An estimated 33% of patients were alive at two years versus 22% for chemotherapy. This treatment combination also reduced the risk of disease progression or death by 28% compared to chemotherapy alone (HR 0.72; 95% CI, 0.60-0.86; p=0.00031) with a median progression-free survival (PFS) of 6.2 months versus 4.8 months, respectively.
Updated results from the POSEIDON Phase III trial after approximately four years of follow-up presented at the European Society for Medical Oncology Congress 2022 demonstrated sustained survival benefit, reducing the risk of death by 25% compared to chemotherapy alone (HR 0.75; 95% CI, 0.63-0.88). Updated median OS was 14 months for the combination versus 11.7 months for chemotherapy alone. An estimated 25% of patients treated with the combination were alive at three years versus 13.6% for those treated with chemotherapy alone.
The safety profile for Imjudo plus Imfinzi and chemotherapy was consistent with the known profiles of each medicine, and no new safety signals were identified.
Metastatic lung cancer is the most advanced form of lung cancer.4,5 Approximately 40% of people with NSCLC have metastatic disease at the time of diagnosis.6 An estimated 5% of patients with metastatic NSCLC in Europe will survive five years after diagnosis.7-8
For the POSEIDON indication in the EU, Imjudo will be temporarily marketed under the name Tremelimumab AstraZeneca until the second half of 2023.
Notes
Liver cancer
About 75% of all primary liver cancers in adults are HCC.1 Between 80-90% of all patients with HCC also have cirrhosis.9 Chronic liver diseases are associated with inflammation that over time can lead to the development of HCC.9
More than half of patients are diagnosed at advanced stages of the disease, often when symptoms first appear.10 A critical unmet need exists for patients with HCC who face limited treatment options.10 The unique immune environment of liver cancer provides clear rationale for investigating medications that harness the power of the immune system to treat HCC.10
Stage IV NSCLC
Lung cancer is the leading cause of cancer-related death and is the second most common form of cancer globally, with more than two million patients diagnosed in 2020.11 Lung cancer is broadly split into NSCLC and small-cell lung cancer (SCLC), with 80-85% classified as NSCLC. Within NSCLC, patients are classified as squamous, representing 25-30% of patients, or non-squamous, in approximately 70-75% of patients.4, 12-13
HIMALAYA
HIMALAYA is a randomised, open-label, multicentre, global Phase III trial of Imfinzi monotherapy and a regimen comprising a single priming dose of Imjudo 300mg added to Imfinzi 1500mg followed by Imfinzi every four weeks versus sorafenib, a standard-of-care multi-kinase inhibitor.
The trial included a total of 1,324 randomised patients with unresectable, advanced HCC who had not been treated with prior systemic therapy and were not eligible for locoregional therapy (treatment localised to the liver and surrounding tissue).
The trial was conducted in 181 centres across 16 countries, including in the US, Canada, Europe, South America and Asia. The primary endpoint was OS for the combination versus sorafenib and key secondary endpoints included OS for Imfinzi versus sorafenib, objective response rate and PFS for the combination and for Imfinzi alone.
POSEIDON
POSEIDON is a randomised, open-label, multi-centre, global, Phase III trial of Imfinzi plus platinum-based chemotherapy or Imfinzi, tremelimumab and chemotherapy versus chemotherapy alone in the 1st-line treatment of 1,013 patients with metastatic NSCLC. The trial population included patients with either non-squamous or squamous disease and the full range of PD-L1 expression levels. POSEIDON excluded patients with certain epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) fusions.
In the experimental arms, patients were treated with a flat dose of either Imfinzi (1,500mg) or Imfinzi plus Imjudo (75mg) with up to four cycles of chemotherapy every three weeks before either Imfinzi maintenance once every four weeks or Imfinzi and a fifth dose of Imjudo given at week 16. In comparison, the control arm allowed up to six cycles of chemotherapy. Pemetrexed maintenance treatment was allowed in all arms in patients with non-squamous disease if given during the induction phase. Nearly all patients with non-squamous disease (95.5%) had pemetrexed and platinum, while the majority of patients with squamous disease receiving chemotherapy (88.3%) received gemcitabine and platinum.
Primary endpoints included PFS and OS for the Imfinzi plus chemotherapy arm. Key secondary endpoints included PFS and OS in the Imfinzi plus Imjudo and chemotherapy arm. As PFS endpoints were met for both experimental arms, the prespecified statistical analysis plan allowed for testing OS in the Imfinzi plus Imjudo and chemotherapy arm. The OS trend observed in the Imfinzi plus chemotherapy arm did not achieve statistical significance. The trial was conducted in more than 150 centres across 18 countries, including the US, Europe, South America, Asia and South Africa.
Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour's immune-evading tactics and releasing the inhibition of immune responses.
Imfinzi is the only approved immunotherapy in the curative-intent setting of unresectable, Stage III NSCLC in patients whose disease has not progressed after chemoradiotherapy and is the global standard of care in this setting based on the PACIFIC Phase III trial.
Imfinzi is also approved in the US, EU, Japan, China and many other countries around the world for the treatment of extensive-stage SCLC based on the CASPIAN Phase III trial. In an exploratory analysis in 2021, updated results from the CASPIAN trial showed Imfinzi plus chemotherapy tripled patient survival at three years versus chemotherapy alone.
Imfinzi is also approved in combination with Imjudo and chemotherapy in metastatic NSCLC in the US, EU and Japan; in combination with chemotherapy in locally advanced or metastatic biliary tract cancer (BTC) in the US, EU, Japan and several other countries; in combination with Imjudo in unresectable HCC in the US, EU and Japan; as monotherapy in unresectable HCC in Japan; and in previously treated patients with advanced bladder cancer in several countries.
Since the first approval in May 2017, more than 100,000 patients have been treated with Imfinzi.
As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, several gastrointestinal (GI) cancers, ovarian cancer, endometrial cancer and other solid tumours.
Imjudo
Imjudo (tremelimumab) is a human monoclonal antibody that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Imjudo blocks the activity of CTLA-4, contributing to T-cell activation, priming the immune response to cancer and fostering cancer cell death.
In addition to its approved indications in liver and lung cancers, Imjudo is being tested in combination with Imfinzi across multiple tumour types including locoregional HCC (EMERALD-3 trial), SCLC (ADRIATIC trial) and bladder cancer (VOLGA and NILE trials).
AstraZeneca in GI cancers
AstraZeneca has a broad development programme for the treatment of GI cancers across several medicines and a variety of tumour types and stages of disease. In 2020, GI cancers collectively represented approximately 5.1 million new cancer cases leading to approximately 3.6 million deaths.14
Within this programme, the Company is committed to improving outcomes in gastric, liver, biliary tract, oesophageal, pancreatic, and colorectal cancers.
In addition to its approved indications in biliary tract and liver cancers, Imfinzi is being assessed in combinations, including with Imjudo, in liver, oesophageal and gastric cancers in an extensive development programme spanning early to late-stage disease across settings.
Enhertu (trastuzumab deruxtecan), a HER2-directed antibody drug conjugate, is approved in the US, EU and several other countries for HER2-positive advanced gastric cancer and is being assessed in colorectal cancer. Enhertu is jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.
Lynparza (olaparib), a first-in-class PARP inhibitor, is approved in the US, EU and several other countries for the treatment of BRCA-mutated metastatic pancreatic cancer. Lynparza is developed and commercialised in collaboration with MSD (Merck & Co., Inc. inside the US and Canada).
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 immuno-oncology (IO)
AstraZeneca is a pioneer in introducing the concept of immunotherapy into dedicated clinical areas of high unmet medical need. The Company has a comprehensive and diverse IO portfolio and pipeline anchored in immunotherapies designed to overcome evasion of the anti-tumour immune response and stimulate the body’s immune system to attack tumours.
AstraZeneca aims to reimagine cancer care and help transform outcomes for patients with Imfinzi as a single treatment and in combination with Imjudo as well as other novel immunotherapies and modalities. The Company is also exploring next-generation immunotherapies like bispecific antibodies and therapeutics that harness different aspects of immunity to target cancer.
AstraZeneca is boldly pursuing an innovative clinical strategy to bring IO-based therapies that deliver long-term survival to new settings across a wide range of cancer types. With an extensive clinical programme, the Company also champions the use of IO treatment in earlier disease stages, where there is the greatest potential for cure.
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 Twitter @AstraZeneca.
AstraZeneca Imfinzi, Imjudo combo gets approval in EU to treat liver, lung cancers
Feb. 22, 2023 4:27 AM ET
By: Ravikash, SA News Editor
- The European Commission approved AstraZeneca's (NASDAQ:AZN) Imfinzi and Imjudo immunotherapy combinations to treat advanced liver and lung cancers.
- https://seekingalpha.com/news/3938875-astrazeneca-imfinzi-imjudo-combo-gets-approval-in-eu-to-treat-liver-lung-cancers
- AstraZeneca PLC (AZN)
- https://www.astrazeneca.com/
- https://www.imfinzi.com/
Ruxolitinib Cream (Opzelura™)
Incyte Announces Positive CHMP Opinion For Ruxolitinib Cream (Opzelura™) For The Treatment Of Non-Segmental Vitiligo In Adults And Adolescents
February 24, 2023 at 7:07 AM ESTPDF Version
- At approval, ruxolitinib cream will be the first treatment for repigmentation in non-segmental vitiligo available in the European Union (EU)
- In Europe, there are approximately 1.5 million patients diagnosed with vitiligo, a progressive and complex disease with a high unmet need
- The positive CHMP opinion is based on Phase 3 data showing treatment with ruxolitinib cream resulted in improvements in facial and total body repigmentation1
WILMINGTON, Del.--(BUSINESS WIRE)--Feb. 24, 2023-- Incyte (Nasdaq:INCY) today announced that the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending the approval of ruxolitinib cream (Opzelura™) for the treatment of non-segmental vitiligo with facial involvement in adults and adolescents from 12 years of age.
“The positive CHMP opinion brings us one step closer to bringing ruxolitinib cream, the first ever treatment for repigmentation in non-segmental vitiligo, to patients and healthcare professionals in the European Union (EU),” said Steven Stein, M.D., Chief Medical Officer, Chief Medical Officer, Incyte. “With no centrally approved treatment option currently available in the EU, this positive opinion marks a significant milestone for the vitiligo community.”
The CHMP opinion recommending the approval of ruxolitinib cream was based on data from two pivotal Phase 3 clinical trials (TRuE-V1 and TRuE-V2) evaluating the safety and efficacy of ruxolitinib cream versus vehicle (non-medicated cream) in more than 600 people with non-segmental vitiligo, age 12 and older1. Results from the TRuE-V program, recently published in The New England Journal of Medicine, showed that treatment with ruxolitinib cream resulted in significant improvements in facial and total body repigmentation versus vehicle as shown by the number of patients reaching the facial and total body Vitiligo Area Scoring Index (F-VASI-T-VASI) endpoints at Week 24 compared to vehicle, with a higher proportion of patients responding at Week 521. The most common adverse reactions (incidence ≥ 1%) were application site acne, application site pruritus, nasopharyngitis, headache, urinary tract infection, application site erythema, and pyrexia2.
The CHMP’s opinion is now being reviewed by the European Commission, which has the authority to grant centralized marketing authorizations for medicinal products in the EU. When approved, this will be the first approved vitiligo therapy available in the EU indicated for the treatment of non-segmental vitiligo with facial involvement in adults and adolescents from 12 years of age.
“Given its complex pathogenesis and unpredictable progression, vitiligo can be very challenging for dermatologists to treat,” said Thierry Passeron M.D., Ph.D., Professor and Chair, Department of Dermatology, Université Côte d'Azur in Nice, France and one of the lead investigators of the TRUE-V trials. “I welcome today’s news and look forward to the potential approval of an effective therapy that can address repigmentation, providing a much-needed option for those patients living with vitiligo who are actively seeking treatment, as well as the clinical community dedicated to its treatment.”
About Vitiligo
Vitiligo is a chronic autoimmune disease characterized by depigmentation of skin that results in patchy loss of skin color from the progressive destruction 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. In Europe, approximately 1.5 million patients are diagnosed with vitiligo (0.2 to 0.8% of the population3,4), and its overall prevalence is estimated to be less than 1%, with the majority of patients (approximately 8 in 10) suffering from non-segmental vitiligo5. Vitiligo can occur at any age, although many patients with vitiligo will experience initial onset before the age of 306. Vitiligo not only impacts physical health but also places a heavy burden on quality of life including employment and psychosocial health such as depression.
About TRuE-V
The TRuE-V clinical trial program includes two Phase 3 studies, TRuE-V1 (NCT04052425) and TRuE-V2 (NCT04057573), evaluating the safety and efficacy of ruxolitinib cream in patients with vitiligo. Each study enrolled approximately 300 patients (age ≥12 years) who have been diagnosed with non-segmental vitiligo.
About Ruxolitinib Cream (Opzelura™)
Ruxolitinib cream (Opzelura™), a novel cream formulation of Incyte’s selective JAK1/JAK2 inhibitor ruxolitinib, approved by the U.S. Food & Drug Administration for the topical treatment of nonsegmental vitiligo in patients 12 years of age and older, is the first and only treatment for repigmentation approved for use in the United States. Opzelura is also approved in the U.S. for the topical short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis (AD) in non-immunocompromised patients 12 years of age and older whose disease is not adequately controlled with topical prescription therapies, or when those therapies are not advisable. Use of Opzelura in combination with therapeutic biologics, other JAK inhibitors, or potent immunosuppressants, such as azathioprine or cyclosporine, is not recommended.
Incyte has worldwide rights for the development and commercialization of ruxolitinib cream, marketed in the United States as Opzelura. In April 2022, Incyte entered into a strategic alliance agreement with Maruho Co., Ltd. for the development, manufacturing and exclusive commercialization of ruxolitinib cream for treatment of autoimmune and inflammatory dermatology indications in Japan.
Opzelura is a trademark of Incyte.
About Incyte Dermatology
Incyte’s science-first approach and expertise in immunology has formed the foundation of the company. Today, we are building on this legacy as we discover and develop innovative dermatology treatments to bring solutions to patients in need.
Our research and development efforts in dermatology are initially focused on leveraging our knowledge of the JAK-STAT pathway. We are exploring the potential of JAK inhibition for a number of immune-mediated dermatologic conditions with a high unmet medical need, including atopic dermatitis, vitiligo and hidradenitis suppurativa.
To learn more, visit the Dermatology section of Incyte.com.
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/20230223006046/en/
Source: Incyte Corporation
Incyte wins EU nod for vitiligo cream Opzelura
Feb. 24, 2023 7:52 AM ETIncyte Corporation (INCY)
By: Dulan Lokuwithana, SA News Editor
Incyte (NASDAQ:INCY) announced Friday that a group of medical experts in the EU recommended the marketing authorization of ruxolitinib cream for non-segmental vitiligo with facial involvement in those aged 12 years and above.
https://seekingalpha.com/news/3940592-incyte-wins-eu-nod-vitiligo-cream-opzelura
EYLEA® (AFLIBERCEPT) INJECTION
February 8, 2023 at 6:45 PM EST
EYLEA® (AFLIBERCEPT) INJECTION APPROVED AS THE FIRST PHARMACOLOGIC TREATMENT FOR PRETERM INFANTS WITH RETINOPATHY OF PREMATURITY (ROP) BY THE FDA
ROP is a leading cause of childhood blindness worldwide
EYLEA now approved to treat five retinal conditions caused by ocular angiogenesis
TARRYTOWN, N.Y., Feb. 08, 2023 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced that the U.S. Food and Drug Administration (FDA) has approved EYLEA® (aflibercept) Injection to treat preterm infants with retinopathy of prematurity (ROP). Following this first pediatric approval, EYLEA is now indicated to treat five retinal conditions caused by ocular angiogenesis.
“Retinopathy of prematurity is a leading cause of childhood blindness worldwide. Until now, the only FDA-approved treatment in common use was laser photocoagulation, a complex and lengthy procedure that permanently ablates retina tissue and is stressful not only for infant patients but also the family navigating a delicate time after a preterm birth,” said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer of Regeneron, and a principal inventor of EYLEA. “For the first time, physicians will now have an FDA approved medication in EYLEA to treat this heartbreaking disease in these smallest of patients. We thank the investigators and the many families who participated in the clinical trials.”
Each year in the U.S., between 1,100 to 1,500 infants develop ROP that is severe enough to require medical treatment. This rare eye disease often impacts infants who are born before 31 weeks of pregnancy have been completed or who weigh less than 1,500 grams (3.3 lbs) pounds at birth. As retinal blood vessels are often only fully developed once an infant is full-term (~9 months of pregnancy), these infants are at risk of developing retinal blood vessels that are abnormal (retinal neovascularization) potentially leading to retinal detachment and irreversible vision loss. Mild cases of ROP may improve without treatment, but some cases require treatment to keep ROP from causing significant visual impairment and even blindness.
“With no existing FDA approved guidance for the treatment of retinopathy of prematurity with anti-VEGF therapies, there was a significant need for research to understand how best to treat the disease in a manner that puts patient safety first and preserves vision for a lifetime,” said Jeff Todd, Chief Executive Officer, Prevent Blindness. “Regeneron’s trials investigating EYLEA in retinopathy of prematurity have advanced our understanding of how to treat this disease and provided a needed evidence-based treatment option to potentially help preterm infants preserve their vision.”
About the Phase 3 Program in ROP
The FDA approval is supported by data from two randomized global Phase 3 trials – FIREFLEYE (N=113) and BUTTERFLEYE (N=120) – investigating EYLEA 0.4 mg versus laser photocoagulation (laser) in infants with ROP. In both trials, approximately 80% of EYLEA-treated infants achieved an absence of both active ROP and unfavorable structural outcomes at 52 weeks of age, which is better than would have been expected without treatment.
No new EYLEA safety signals were observed in either trial. Comparing EYLEA to laser, ocular adverse events (AEs) among patients occurred in 39% versus 37% in FIREFLEYE and 18% versus 26% in BUTTERFLEYE, with serious ocular AEs occurring in 8% for both groups in FIREFLEYE and 6.5% versus 11% in BUTTERFLEYE. AEs in both trials were consistent with infant prematurity or to the injection procedure, and with the AEs in similar ROP trials. The results of FIREFLEYE were published in Journal of the American Medical Association, and data from BUTTERFLEYE were presented at ROP Update 2022 meeting in the U.S.
Both trials were conducted pursuant to FDA Pediatric Written Request, and a Pediatric Exclusivity Determination was granted by FDA on October 12, 2022. This grant extends the period of U.S. market exclusivity for EYLEA by an additional six months through May 17, 2024.
EYLEA is being jointly developed by Regeneron and Bayer. The lead sponsors of the trials were Regeneron for BUTTERFLEYE and Bayer for FIREFLEYE. Bayer and Regeneron are collaborating on the global development of EYLEA. Regeneron maintains exclusive rights of EYLEA in the United States. Bayer has licensed the exclusive marketing rights outside the United States, where the companies share equally the profits from sales of EYLEA.
About EYLEA
EYLEA is a VEGF inhibitor formulated as an injection for the eye. It is designed to block the growth of new blood vessels and decrease the ability of fluid to pass through blood vessels (vascular permeability) in the eye by blocking VEGF-A and placental growth factor (PLGF), two growth factors involved in ocular angiogenesis. The EYLEA safety and efficacy profile is supported by a robust body of research that includes eight pivotal Phase 3 trials, more than 11 years of real-world experience and greater than 57 million EYLEA injections globally.
IMPORTANT SAFETY INFORMATION AND INDICATIONS FOR EYLEA
- EYLEA® (aflibercept) Injection is a prescription medicine administered by injection into the eye. You should not use EYLEA if you have an infection in or around the eye, eye pain or redness, or known allergies to any of the ingredients in EYLEA, including aflibercept.
- Injections into the eye with EYLEA can result in an infection in the eye and retinal detachment (separation of retina from back of the eye) can occur. Inflammation in the eye has been reported with the use of EYLEA.
- In some patients, injections with EYLEA may cause a temporary increase in eye pressure within 1 hour of the injection. Sustained increases in eye pressure have been reported with repeated injections, and your doctor may monitor this after each injection.
- In infants with Retinopathy of Prematurity (ROP), treatment with EYLEA will need extended periods of ROP monitoring.
- There is a potential but rare risk of serious and sometimes fatal side effects, related to blood clots, leading to heart attack or stroke in patients receiving EYLEA.
- The most common side effects reported in adult patients receiving EYLEA were increased redness in the eye, eye pain, cataract, vitreous (gel-like substance) detachment, vitreous floaters, moving spots in the field of vision, and increased pressure in the eye.
- The most common side effects reported in pre-term infants with ROP receiving EYLEA were separation of the retina from the back of the eye, increased redness in the eye, and increased pressure in the eye. Side effects that occurred in adults are considered applicable to pre-term infants with ROP, though not all were seen in clinical studies.
- You may experience temporary visual changes after an EYLEA injection and associated eye exams; do not drive or use machinery until your vision recovers sufficiently.
- Contact your doctor right away if you think you or your baby might be experiencing any side effects, including eye pain or redness, light sensitivity, or blurring of vision, after an injection.
- For additional safety information, please talk to your doctor and see the full Prescribing Information for EYLEA.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
INDICATIONS
EYLEA® (aflibercept) Injection 2 mg (0.05 mL) is a prescription medicine approved for the treatment of patients with Wet Age-related Macular Degeneration (AMD), Macular Edema following Retinal Vein Occlusion (RVO), Diabetic Macular Edema (DME), Diabetic Retinopathy (DR), and Retinopathy of Prematurity (ROP).
Please see the full Prescribing Information for EYLEA.
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, pain, 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 Twitter.
Source: Regeneron Pharmaceuticals, Inc.
Regeneron's high-dose Eylea application accepted for FDA priority review
Feb. 23, 2023 8:24 AM ET
Regeneron Pharmaceuticals, Inc. (REGN)BAYRY, BAYZF
By: Jonathan Block, SA News Editor
- The US FDA has accepted for priority review Regeneron Pharamceuticals' (NASDAQ:REGN) a high-dose version -- 8 mg -- of its best-selling macular degeneration and diabetic macular edema (DME) treatment Eylea (aflibercept).
- https://seekingalpha.com/news/3939903-regeneron-high-dose-eylea-application-accepted-for-fda-priority-review
- Regeneron Pharmaceuticals, Inc. (REGN)
- https://eylea.us/s/
Calquence (acalabrutinib)
Calquence tablet formulation approved in the EU for patients with chronic lymphocytic leukaemia
PUBLISHED22 February 2023
22 February 2023 07:05 GMT
Tablet formulation can be co-administered with gastric acid-reducing agents
allowing greater patient and physician choice
Approval based on ELEVATE-PLUS trials which showed
bioequivalence and consistent dosing vs. current capsule
AstraZeneca’s tablet formulation of Calquence (acalabrutinib) has been approved in the European Union (EU) for the treatment of adult patients with chronic lymphocytic leukaemia (CLL).
The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use and is based on results from the ELEVATE-PLUS trials published in the American Society of Haematology journal, Blood.1
In the trials, results showed the Calquence capsule and tablet formulations are bioequivalent, indicating the same efficacy and safety profile can be expected when prescribed with the same dosing strength and schedule.1 The tablet can be taken with gastric acid-reducing agents, including proton pump inhibitors (PPIs), antacids and H2-receptor antagonists (H2RAs).1 The majority of observed adverse events (AEs) in these studies were mild with no new safety concerns identified.1
Paolo Ghia, MD, Director, Strategic Research Program on CLL, Università Vita-Salute San Raffaele in Milan, said: “Many patients with chronic lymphocytic leukaemia face multiple medical conditions that require daily treatment, including the use of acid-reducing agents for conditions such as gastro-oesophageal reflux. The tablet formulation allows for co-administration with these drugs, allowing more patients with chronic lymphocytic leukaemia to assume Calquence.”
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “The Calquence tablet formulation underscores our commitment to understanding the needs of the chronic lymphocytic leukaemia community and providing patient-oriented treatment solutions. Today’s approval offers physicians and patients in the EU more flexibility to determine the right treatment plan and enables more patients to potentially benefit from this medicine.”
Calquence is approved as a capsule formulation for CLL in the EU. It is also approved in the US as a capsule and tablet formulation for patients with CLL, small lymphocytic lymphoma (SLL) and relapsed or refractory mantle cell lymphoma (MCL). Additionally, Calquence is approved as a capsule formulation in many other countries worldwide. Indications may vary by market.
Notes
CLL
CLL is the most prevalent type of leukaemia in adults, with over 100,000 new cases globally in 2019.2 Although some people with CLL may not experience any symptoms at diagnosis, others may experience symptoms, such as weakness, fatigue, weight loss, chills, fever, night sweats, swollen lymph nodes and abdominal pain.3
In CLL, there is an accumulation of abnormal lymphocytes within the bone marrow and in blood and lymph nodes. As the number of abnormal cells increases, there is less room within the marrow for the production of normal white blood cells, red blood cells and platelets. This could result in anaemia, infection and bleeding.4 B-cell receptor signalling through BTK is one of the essential growth pathways for CLL.
ELEVATE-PLUS
ELEVATE-PLUS is comprised of three Phase I, open-label, single-dose, cross-over studies conducted in 116 healthy subjects. The trials established bioequivalence between acalabrutinib tablets (100mg) and acalabrutinib (100mg) capsules, evaluated the PPI effect of acalabrutinib tablets administered in the presence versus absence of PPI rabeprazole and investigated the effect of food by comparing acalabrutinib tablets administered with a high-fat diet versus fasted.1
Calquence
Calquence (acalabrutinib) is a next-generation, selective inhibitor of Bruton’s tyrosine kinase (BTK). Calquence binds covalently to BTK, thereby inhibiting its activity.5,6 In B cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion.5
Calquence is available for prescribing in capsule and tablet formulations in the US and EU for the treatment of CLL. Capsules have restrictions in relation to use with gastric acid reducing agents.
Calquence capsules are approved for CLL in Japan, Canada, Australia and many other countries worldwide.
In the US and several other countries, Calquence capsules are also approved for the treatment of adult patients with MCL who have received at least one prior therapy. The US MCL 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. Calquence is not currently approved for the treatment of MCL in Europe or Japan.
As part of an extensive clinical development programme, AstraZeneca and Acerta Pharma are currently evaluating Calquence in more than 20 company-sponsored clinical trials. Calquence is being evaluated for the treatment of multiple B-cell blood cancers, including CLL, MCL, diffuse large B-cell lymphoma, Waldenström’s macroglobulinaemia, follicular lymphoma and marginal zone lymphoma.
AstraZeneca in haematology
AstraZeneca is pushing the boundaries of science to redefine care in haematology. We have expanded our commitment to patients with haematologic conditions, not only in oncology but also in rare diseases with the acquisition of Alexion, allowing us to reach more patients with high unmet needs. By applying our deep understanding of blood cancers, leveraging our strength in solid tumour oncology and delivering on Alexion’s pioneering legacy in complement science to provide innovative medicines for rare diseases, we are pursuing the end-to-end development of novel therapies designed to target underlying drivers of disease.
By targeting haematologic conditions with high unmet medical needs, we aim to deliver innovative medicines and approaches to improve patient outcomes. Our goal is to help transform the lives of patients living with malignant, rare and other related haematologic diseases, shaped by insights from patients, caregivers and physicians to have the most meaningful impact.
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 Twitter @AstraZeneca.
AstraZeneca's blood cancer drug Calquence's tablet form gets approval in EU
Feb. 22, 2023 4:44 AM ET
By: Ravikash, SA News Editor
- The European Commission (EC) approved AstraZeneca's (NASDAQ:AZN) tablet formulation of Calquence (acalabrutinib) to treat adult patients with chronic lymphocytic leukemia (CLL).
- https://seekingalpha.com/news/3938876-astrazenecas-blood-cancer-drug-calquences-tablet-form-gets-approval-in-eu
- AstraZeneca PLC (AZN)
- https://www.calquence.com/
- https://www.astrazeneca.com/
Trodelvy® (sacituzumab govitecan-hziy)
February 17, 2023
Trodelvy® Demonstrates Positive Efficacy Treating Both Platinum-Ineligible and Rapidly Progressing, Post-Platinum Metastatic Urothelial Cancer
– Oral Presentati on Highlights Trodelvy Efficacy of 13.5 Months Overall Survival in Pati ents with Platinum-Ineligible Metastatic UC After Checkpoint Inhibitor Therapy –
– Trodelvy Demonstrated 12.8 Months Overall Survival in Pa tients with Metastatic UC Whose Disease Progressed Rapidly Following Platinum-Based Chemotherapy –
FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced new and updated positive results from three cohorts of the Phase 2 TROPHY-U-01 study of Trodelvy® (sacituzumab govitecan-hziy) for the treatment of metastatic urothelial cancer (mUC). These data demonstrate that Trodelvy produced both rapid and durable responses for patients across a range of hard-to-treat types of mUC including platinum-ineligible and rapidly progressing, post-platinum mUC. These findings will be featured in both an oral session (abstract #520) and in poster presentations (abstract #518, #526) during the 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO-GU) Annual Meeting February 16-18.
“The TROPHY-U-01 data show consistent benefit of Trodelvy across multiple types of metastatic urothelial cancer, including the most difficult-to-treat and, often times, frail patients where treatment options are still scarce,” said Bill Grossman, MD, PhD, Senior Vice President, Therapeutic Area Head, Gilead Oncology. “Trodelvy has the potential to become a cornerstone treatment in metastatic urothelial cancer, and we are excited about the expected results from the ongoing Phase 3 TROPiCS-04 study that may serve to convert our U.S. accelerated approval to full approval for Trodelvy to treat patients with locally advanced or metastatic urothelial cancer following a platinum-containing chemotherapy and PD-1/PD-L1 inhibitor.”
Longer-term follow-up across Cohorts 1, 2, and 3 of TROPHY-U-01 provides an increasing body of evidence supporting the potential benefit of treating mUC with Trodelvy across clinically relevant, hard-to-treat patient populations.
In April 2021, the U.S. FDA granted accelerated approval of Trodelvy for use in adult patients with locally advanced or mUC who have previously received a platinum-containing chemotherapy and either a PD-1 or PD-L1 inhibitor. This approval is based on ORR and DOR established in Cohort 1.
Trodelvy has not been approved by any regulatory agency for the treatment of platinum-ineligible patients with mUC who progressed after prior CPI therapy, or in combination with pembrolizumab in patients with mUC who progressed after platinum-based therapy. Its safety and efficacy have not been established for these indications.
Trodelvy has a Boxed Warning for severe or life-threatening neutropenia and severe diarrhea; please see below for additional Important Safety Information.
About Metastatic Urothelial Cancer
Urothelial Cancer (UC) is the most common type of bladder cancer and occurs when the urothelial cells that line the inside of the bladder and other parts of the urinary tract grow unusually or uncontrollably. An estimated 83,000 Americans will be diagnosed with bladder cancer in 20231, and almost 90% of those diagnoses will be UC2. In total, 30% of cases are considered advanced or metastatic disease.3 Despite advancements in treating mUC, long-term survival remains low.
About the TROPHY U-01 Study
The Phase 2 TROPHY-U-01 trial is an ongoing, international, multi-center, open-label, multi-cohort, single-arm study evaluating Trodelvy monotherapy or combination therapy in patients with mUC after progression on a platinum-based regimen and anti-PD-1/PD-L1-based immunotherapy.
Cohort 1 is assessing Trodelvy after progression on platinum-based chemotherapy and checkpoint inhibitor (CPI) therapy. Cohorts 2, 3, 4 and 5 of the study are ongoing. Cohort 2 is assessing Trodelvy monotherapy in platinum-ineligible patients after progression on anti-PD-1/PD-L1-based immunotherapy. Cohort 3 is assessing Trodelvy in patients with rapidly progressing, mUC who progressed after platinum-based therapy. Cohorts 4 and 5 are assessing Trodelvy combination therapy in patients with treatment naive mUC, with those in Cohort 4 receiving cisplatin and those in Cohort 5 receiving cisplatin and avelumab, respectively, in addition to Trodelvy.
More information about TROPHY is available at https://clinicaltrials.gov/ct2/show/NCT03547973.
About Trodelvy
Trodelvy® (sacituzumab govitecan-hziy) is a first-in-class Trop-2 directed antibody-drug conjugate. Trop-2 is a cell surface antigen highly expressed in multiple tumor types, including in more than 90% of breast and bladder cancers. Trodelvy is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers potent activity to both Trop-2 expressing cells and the microenvironment.
Trodelvy is approved in more than 40 countries, with multiple additional regulatory reviews underway worldwide, for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease.
Trodelvy is also approved in the U.S. to treat certain patients with pre-treated HR+/HER2- metastatic breast cancer and has an accelerated approval for treatment of certain patients with second-line metastatic urothelial cancer; see below for full indication statements.
Trodelvy is also being developed for potential investigational use in other TNBC, HR+/HER2- and mUC populations, as well as a range of tumor types where Trop-2 is highly expressed, including metastatic non-small cell lung cancer (NSCLC), metastatic small cell lung cancer (SCLC), head and neck cancer, and endometrial cancer.
U.S. Indications for Trodelvy
In the United States, Trodelvy is indicated for the treatment of adult patients with:
- Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease.
- Unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting.
- Locally advanced or metastatic urothelial cancer (mUC) who have previously received a platinum-containing chemotherapy and either programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Please see full Prescribing Information , including BOXED WARNING.
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.
Source: Gilead Sciences, Inc.
Gilead updates Phase 2 data for bladder cancer therapy Trodelvy
Feb. 17, 2023 9:44 AM ET
Gilead Sciences, Inc. (GILD)MRK
By: Dulan Lokuwithana, SA News Editor
- Announcing updated data from its Phase 2 TROPHY-U-01 study, Gilead Sciences (NASDAQ:GILD) said Friday that its antibody-drug conjugate Trodelvy showed efficacy across new indications in bladder cancer.
- https://seekingalpha.com/news/3937727-gilead-updates-phase-2-data-for-bladder-cancer-therapy-trodelvy
- Gilead Sciences, Inc. (GILD)
- https://www.trodelvy.com/
- https://www.gilead.com/
vedolizumab (Entyvio®)
Takeda Presents Positive Results from Phase 3 Study of Vedolizumab for Prevention of Intestinal Acute Graft-Versus-Host Disease (aGvHD) in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT)
February 18, 2023
- The Phase 3 GRAPHITE Study Met Its Primary Efficacy Endpoint of Significant and Clinically Meaningful Intestinal aGvHD-Free Survival as Compared to Placebo by Day 180 after Allo-HSCT (p<0.001)
- No New Safety Signals Were Seen with Vedolizumab Compared with Placebo in Patients Who Received Allo-HSCT
- Data Were Presented as A Late-Breaking Abstract at The 2023 Tandem Meetings | Transplantation & Cellular Therapy Meetings of the American Society for Transplantation and Cellular Therapy (ASTCT) and the Center for International Blood & Marrow Transplant Research (CIBMTR)
OSAKA, Japan and CAMBRIDGE, Massachusetts,
February 18, 2023 – Takeda (TSE:4502/NYSE:TAK) today announced late-breaking data from the Phase 3 GRAPHITE study presented at the 2023 Tandem Meetings, demonstrating vedolizumab achieved a statistically significant and clinically meaningful improvement in lower gastrointestinal (GI) aGvHD-free survival by Day 180 after allo-HSCT with no relevant differences in safety profile versus placebo.1 Intestinal aGvHD is a serious complication characterized by inflammation of the GI tract which can affect patients undergoing allo-HSCT, a common treatment for blood cancers.
“Lower GI aGvHD represents a critical unmet need in patients undergoing allo-HSCT.” said Yi-Bin Chen, MD, Director, Hematopoietic Cell Transplant & Cell Therapy Program, Mass General Cancer Center. “I’m excited that this study can contribute to the understanding of this common and life-threatening complication in stem cell transplantation.”
Vedolizumab is not currently indicated for use in aGvHD.
The Phase 3, randomized, double-blind, placebo-controlled, multicenter GRAPHITE study evaluated the efficacy and safety of vedolizumab as prophylaxis for intestinal aGvHD in patients undergoing allo-HSCT from unrelated donors for the treatment of hematological malignancies. The study met its primary endpoint, with vedolizumab achieving a statistically significant improvement in intestinal aGvHD-free survival versus placebo by Day 180 after allo-HSCT (85.5% of patients in the vedolizumab arm versus 70.9% in the placebo arm [HR=0.45; 95% CI: 0.27, 0.73; p<0.001]).1 Statistically significant superiority of vedolizumab over placebo was also demonstrated for intestinal aGvHD-free and relapse-free survival by Day +180 (HR= 0.56, 95% CI: 0.37, 0.86; p = 0.0043), and for Grade C-D aGvHD-free (with any organ involvement) survival at Day +180 (HR: 0.59, 95% CI: 0.39, 0.91; p = 0.0204).1 In addition, no relevant differences in safety profile between the vedolizumab and placebo arms were observed, and no new safety signals were identified. Treatment-related adverse events were reported in 24.8% versus 28.4%, and treatment related serious adverse events in 8.5% versus 6.5% of patients treated with placebo versus vedolizumab, respectively. The most common adverse events of special interest were hypersensitivity reactions (placebo 82.4%, vedolizumab 79.3%), serious infections (placebo 67.3%, vedolizumab 74.0%), and liver injury (placebo 41.8%, vedolizumab 40.2%).1
“These results have advanced our understanding of vedolizumab, currently indicated for IBD, in another critical GI inflammatory condition.” said Chinwe Ukomadu, M.D., Ph.D., Head, Gastroenterology Therapeutic Area Unit at Takeda. “Our Phase 3 study in the prevention of lower GI aGvHD is the latest example of Takeda’s commitment to advancing the science of vedolizumab, furthering the understanding of its mechanism of action, and exploring new ways to help patients.”
Intestinal aGvHD can occur after stem cell transplantation when the immune cells of the donor (the graft) consider the recipient’s body (the host) as foreign and attack the organs and tissue.2 Intestinal aGvHD results in the majority of morbidity and mortality associated with GvHD. Effective prevention of aGvHD, especially with lower intestinal involvement, has been an important treatment goal for physicians when patients are undergoing allo-HSCT.3
About the GRAPHITE Study
GRAPHITE (vedolizumab-3035) is a randomized, double-blind, placebo controlled study designed to evaluate the use of vedolizumab as prophylaxis of intestinal aGvHD in participants who receive allo-HSCT as treatment for a hematologic malignancy or myeloproliferative disorder from an unrelated donor.1 The study enrolled 333 patients who were randomly assigned in a 1:1 ratio to one of two treatment groups receiving either an intravenous infusion of vedolizumab 300 mg or placebo on days -1 (before allo-HSCT), and on days +13, +41, +69, +97, +125, and +153 following allo-HSCT, alongside a background GvHD prophylaxis regimen. The overall time of participation in the study was 12 months.4
About vedolizumab (Entyvio®)
Vedolizumab is a gut-selective anti-lymphocyte therapy and is approved in both intravenous (IV) and subcutaneous (SC) formulations (approvals vary by market; vedolizumab is not currently approved in the SC formulation in the U.S.).5,6 It is a humanized monoclonal antibody designed to specifically antagonize the alpha4beta7 integrin, inhibiting the binding of alpha4beta7 integrin to intestinal mucosal addressin cell adhesion molecule 1 (MAdCAM-1), but not vascular cell adhesion molecule 1 (VCAM-1).7 MAdCAM-1 is preferentially expressed on blood vessels and lymph nodes of the gastrointestinal tract.8 The alpha4beta7 integrin is expressed on a subset of circulating white blood cells.7 These cells have been shown to play a role in mediating the inflammatory process in ulcerative colitis (UC) and Crohn’s disease (CD).7,9,10 By inhibiting alpha4beta7 integrin, vedolizumab may limit the ability of certain white blood cells to infiltrate gut tissues.7
Vedolizumab is approved for the treatment of adult patients with moderately to severely active UC and CD, who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumor necrosis factor-alpha (TNFα)-antagonist.5,6 Vedolizumab IV has been granted marketing authorization in over 70 countries, including the United States and European Union, with more than 1,000,000 patient years of exposure to date.11 Vedolizumab SC has been granted marketing authorization in the European Union and over 50 countries.
Therapeutic Indications for vedolizumab
Ulcerative Colitis
Vedolizumab is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumor necrosis factor-alpha (TNFα) antagonist.
Crohn’s Disease
Vedolizumab is indicated for the treatment of adult patients with moderately to severely active Crohn’s disease who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumor necrosis factor-alpha (TNFα) antagonist.
Pouchitis
Vedolizumab IV is indicated in the EU for the treatment of adult patients with moderately to severely active chronic pouchitis, who have undergone proctocolectomy and ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) and have had an inadequate response with or lost response to antibiotic therapy.
Please consult with your local regulatory agency for approved labeling in your country.
For EU audiences, please see the Summary of Product Characteristics (SmPC) for ENTYVIO®.
For U.S. audiences, please see the full Prescribing Information, including Medication Guide for ENTYVIO® IV.
About Takeda
Takeda is a global, values-based, RD-driven biopharmaceutical leader headquartered in Japan, committed to discover and deliver life-transforming treatments, guided by our commitment to patients, our people and the planet. Takeda focuses its RD efforts on four therapeutic areas: Oncology, Rare Genetics and Hematology, Neuroscience, and Gastroenterology (GI), with expertise in immune and inflammatory diseases. We also make targeted RD investments in Plasma-Derived Therapies and Vaccines. We are focusing on developing highly innovative medicines that contribute to making a difference in people’s lives by advancing the frontier of new treatment options and leveraging our enhanced collaborative RD engine and capabilities to create a robust, modality-diverse pipeline. Our employees are committed to improving quality of life for patients and to working with our partners in health care in approximately 80 countries and regions. For more information, visit .
Takeda Entyvio meets main goal in phase 3 trial to prevent intestinal acute graft-versus-host disease
Feb. 20, 2023 5:18 AM ET
Takeda Pharmaceutical Company Limited (TAK)
By: Ravikash, SA News Editor
Takeda Pharmaceutical's (NYSE:TAK) drug vedolizumab met the main goal of a phase 3 trial to prevent intestinal acute graft-versus-host disease (aGvHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Opdivo (nivolumab)
Adjuvant Opdivo (nivolumab) Continues to Provide Significant, Durable Clinical Benefits for Patients with Radically Resected, High-Risk Muscle-Invasive Urothelial Carcinoma After Three Years in CheckMate -274 Trial
02/17/2023 CATEGORY:
Three-year median follow-up data demonstrate significantly improved disease-free survival, non-urothelial tract recurrence-free survival, distant metastasis-free survival and second progression-free survival with adjuvant Opdivo compared to placebo
Randomized patients who received Opdivo after radical surgery remained disease-free more than twice as long vs. placebo; patients whose tumor cells express PD-L1 ≥1% remained disease-free more than six times as long vs. placebo
Updated results from the Phase 3 CheckMate -274 trial will be presented in a late-breaking oral presentation at ASCO GU 2023
PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced three-year follow-up results from the Phase 3 CheckMate -274 trial, demonstrating significant sustained clinical benefits with Opdivo (nivolumab) for the adjuvant treatment of patients with surgically resected, high-risk muscle-invasive urothelial carcinoma. With a median follow-up of 36.1 months (31.6 months minimum), adjuvant Opdivo continued to show improved disease-free survival (DFS), non-urothelial tract recurrence-free survival (NUTRFS), distant metastasis-free survival (DMFS) and second progression-free survival (PFS2) compared to placebo across all-randomized patients and in patients whose tumor cells express PD-L1 ≥1%. These updated results will be featured in a late-breaking oral presentation at the American Society of Clinical Oncology (ASCO) 2023 Genitourinary Cancers Symposium from February 16-18, 2023.
“Patients with muscle-invasive urothelial carcinoma face a high chance of recurrence due to micrometastatic disease, especially within the first three years after surgical removal of the bladder or kidney. The three-year results from CheckMate -274 show a stable decrease in the risk of disease with adjuvant nivolumab with longer follow-up,” said Matthew D. Galsky,* M.D., Professor of Medicine, Director of Genitourinary Medical Oncology, Associate Director for Translational Research, and Co-Director of the Center of Excellence for Bladder Cancer at The Tisch Cancer Institute and the Icahn School of Medicine at Mount Sinai. “Nivolumab remains the only immunotherapy, as well as the only medical treatment in general, to decrease the risk of urothelial cancer recurrence after radical surgery in patients who received chemotherapy prior to surgery or who are ineligible for chemotherapy. The results of this trial have changed the way that urothelial cancer is treated.”
With three years of follow-up in the CheckMate -274 trial:
- DFS (primary endpoint): Across all randomized patients, Opdivo more than doubled the average length of time patients lived without disease recurrence, demonstrating a median disease-free survival of 22.0 months compared to 10.9 months with placebo, a risk reduction of 29% (Hazard Ratio [HR] 0.71, 95% Confidence Interval [CI]: 0.58 to 0.86). The risk reduction remained consistent with that observed at the primary analysis, with only a 1% change with an additional 25.7 months of minimum follow-up (a risk reduction of 30% was observed with 5.9 months minimum follow-up at the primary analysis; HR 0.70). In patients whose tumor cells express PD-L1 ≥1%, Opdivo extended the average length of time patients lived without disease recurrence more than six times compared to placebo, with median DFS of 52.6 months vs. 8.4 months with placebo (HR 0.52, 95% CI: 0.37 to 0.72), a 48% reduction in the risk of disease recurrence or death.
- NUTRFS (secondary endpoint): In all randomized patients, those treated with Opdivo showed a median NUTRFS, defined as the time that patients lived without disease recurrence outside of the bladder, ureters or renal pelvis, of 25.9 months compared to 13.7 months for placebo (HR 0.72, 95% CI: 0.59 to 0.88). In patients whose tumor cells express PD-L1 ≥1%, median NUTRFS was 52.6 months with Opdivo vs. 8.4 months with placebo (HR 0.53, 95% CI: 0.38 to 0.74).
- DMFS (exploratory endpoint): Across all randomized patients, median DMFS, defined as the time that patients live without cancer spreading from the primary tumor to distant organs or lymph nodes, was 47.1 months with Opdivo vs. 28.7 months with placebo (HR 0.74, 95% CI: 0.60 to 0.92). Among patients whose tumor cells express PD-L1 ≥1%, median DMFS was not reached with Opdivo, compared to 20.7 months with placebo (HR 0.58, 95% CI: 0.40 to 0.84).
- PFS2 (exploratory endpoint): Median PFS2, defined as the time from randomization to disease progression after subsequent next-line systemic therapy, start of second subsequent next-line systemic therapy, or death, was 61.2 months for all-randomized patients treated with Opdivo compared to 47.1 months with placebo (HR 0.79, 95% CI: 0.63 to 0.98). In patients whose tumor cells express PD-L1 ≥1%, median PFS2 was not reached with Opdivo vs. 39.4 months with placebo (HR 0.54, 95% CI: 0.37 to 0.79).
- Safety: Grade 3-4 treatment-related adverse events occurred in 18.2% and 7.2% of patients in the Opdivo and placebo arms, respectively, consistent with the primary analysis.
“We strive to provide hope for patients by offering safe and effective options that may help prevent recurrence and improve long-term outcomes. This is why earlier stages of cancer is an important research area for Bristol Myers Squibb across multiple tumor types, including hard-to-treat cancers with high unmet needs like urothelial carcinoma,” said Dana Walker, M.D., M.S.C.E., vice president, development program lead, genitourinary cancers, Bristol Myers Squibb. “The durable follow-up results from CheckMate -274 continue to fuel our excitement toward our ongoing research in earlier stages and its potential to change outcomes for patients. We look forward to closely following the CheckMate -274 trial, which is ongoing to assess additional key secondary endpoints, including overall survival to which we currently remain blinded.”
Bristol Myers Squibb thanks the patients and investigators involved in the CheckMate -274 clinical trial.
About CheckMate -274
CheckMate -274 is a Phase 3 randomized, double-blind, multi-center study evaluating Opdivo compared to placebo in patients with muscle-invasive urothelial carcinoma at a high risk of recurrence after radical resection. A total of 709 patients were randomized 1:1 to receive Opdivo 240 mg or placebo every two weeks for up to one year. The primary endpoints of the trial are disease-free survival (DFS) in all randomized patients (i.e., the intention-to-treat population) and in the subset of patients whose tumor cells express PD-L1 ≥1%. Key secondary endpoints include overall survival (OS), non-urothelial tract recurrence-free survival (NUTRFS) and disease-specific survival (DSS). Key exploratory endpoints include distant metastasis-free survival (DMFS), quality of life (QoL) and second progression-free survival (PFS2).
About Urothelial Carcinoma
Bladder cancer is the 10th most common cancer in the world, with more than 573,000 new cases diagnosed annually. Urothelial carcinoma, which most frequently begins in the cells that line the inside of the bladder, accounts for approximately 90% of bladder cancer cases. In addition to the bladder, urothelial carcinoma can occur in other parts of the urinary tract, including the ureters and renal pelvis. The majority of urothelial carcinomas are diagnosed at an early stage, but rates of recurrence and disease progression are high. Approximately 50% of patients who undergo radical surgery will experience disease recurrence, especially within the first three years after surgical removal of the bladder or kidney. For patients whose disease recurs as metastatic cancer, the prognosis is poor, with a median overall survival of approximately 12 to 14 months when treated with systemic therapy.
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 scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at 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. Because 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 combination 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 (12 years and older) patients with unresectable or metastatic melanoma.
OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adult and pediatric (12 years and older) patients with unresectable or metastatic melanoma.
OPDIVO® (nivolumab) is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.
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), 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 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 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 US Full Prescribing Information for OPDIVO and YERVOY.
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.
For more information, please see U.S. Full Prescribing Information and Medication Guide for OPDIVO,
and U.S. Full Prescribing Information and Medication Guide for YERVOY, or talk to your healthcare team.
Information provided on this website is not a substitute for talking with your healthcare professional.
Your healthcare professional is the best source of information about your disease.
All individuals depicted are models used for illustrative purposes only.
Bristol's Opdivo improves disease-free survival in urothelial carcinoma over long term
Feb. 17, 2023 11:01 AM ET
Bristol-Myers Squibb Company (BMY)
By: Jonathan Block, SA News Editor
- Three-year follow-up data examining Bristol-Myers Squibb's (NYSE:BMY) Opdivo (nivolumab) as an adjunct therapy for urothelial carcinoma showed several durable benefits compared to placebo in a phase 3 trial.
- https://seekingalpha.com/news/3937750-bristol-opdivo-improves-disease-free-survival-in-urothelial-carcinoma-over-long-term
- Bristol-Myers Squibb Company (BMY)
ONPATTRO® (patisiran)
Alnylam Announces U.S. Food and Drug Administration (FDA) Acceptance of Supplemental New Drug Application for ONPATTRO® (patisiran) for the Treatment of the Cardiomyopathy of ATTR Amyloidosis
Feb 21, 2023
– PDUFA Date Set for October 8, 2023 –
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Feb. 21, 2023-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today announced that the U.S. Food and Drug Administration (FDA) has accepted for filing the Company’s supplemental New Drug Application (sNDA) for patisiran, an investigational RNAi therapeutic in development for the treatment of the cardiomyopathy of transthyretin-mediated (ATTR) amyloidosis. The FDA has set an action date of October 8, 2023 under the Prescription Drug User Fee Act (PDUFA). In their file acceptance letter, the FDA stated that they have not identified any review issues. The Agency also noted that they are planning to hold an advisory committee meeting to discuss the application. Patisiran is the established name for ONPATTRO®, which is currently approved by the U.S. FDA for the treatment of the polyneuropathy of hereditary ATTR amyloidosis in adults.
“ATTR amyloidosis with cardiomyopathy is an increasingly recognized cause of heart failure for which there are limited treatment options. The FDA’s acceptance of our sNDA for patisiran is a positive step forward as we work to bring patients with ATTR amyloidosis with cardiomyopathy a new treatment option that addresses the underlying cause of disease and has the potential to meaningfully improve functional capacity and quality of life,” said Rena N. Denoncourt, Vice President, TTR Franchise Lead. “The acceptance also marks another important milestone as we continue to build an industry-leading franchise for the treatment of ATTR amyloidosis.”
The application to the FDA was based on positive results from APOLLO-B, a randomized, double-blind, placebo-controlled, multicenter, global Phase 3 study that demonstrated favorable effects of patisiran on both functional capacity and quality of life in patients with ATTR amyloidosis with cardiomyopathy relative to placebo at 12 months. The majority of adverse events were mild or moderate in severity, and the overall safety profile in APOLLO-B was consistent with prior clinical trials and post-marketing experience with ONPATTRO. The 12-month results from the study were presented at the 18th International Symposium on Amyloidosis (ISA) on September 8, 2022 and at the Heart Failure Society of America’s Annual Scientific Meeting on September 30, 2022.
ONPATTRO Indication and Important Safety Information
Indication
ONPATTRO is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.
About ONPATTRO® (patisiran)
ONPATTRO (patisiran) is an RNAi therapeutic that is approved in the United States and Canada for the treatment of the polyneuropathy of hATTR amyloidosis in adults. ONPATTRO is also approved in the European Union, Switzerland and Brazil for the treatment of hATTR amyloidosis in adults with Stage 1 or Stage 2 polyneuropathy, and in Japan for the treatment of hATTR amyloidosis with polyneuropathy. ONPATTRO is an intravenously administered RNAi therapeutic targeting transthyretin (TTR). It is designed to target and silence TTR messenger RNA, thereby reducing the production of TTR protein before it is made. Reducing the pathogenic protein leads to a reduction in amyloid deposits in tissues.
About ATTR Amyloidosis
Transthyretin-mediated (ATTR) amyloidosis is a rare, rapidly progressive, debilitating disease caused by misfolded transthyretin (TTR) proteins which accumulate as amyloid fibrils in multiple tissues including the nerves, heart, and gastrointestinal (GI) tract. There are two different types of ATTR amyloidosis – Hereditary ATTR (hATTR) amyloidosis, caused by a TTR gene variant, and Wild-type ATTR (wtATTR) amyloidosis, which occurs without a TTR gene variant. hATTR amyloidosis affects approximately 50,000 people worldwide, while wtATTR amyloidosis is estimated to impact 200,000 – 300,000 people worldwide.
About LNP Technology
Alnylam has licenses to Arbutus Biopharma LNP intellectual property for use in RNAi therapeutic products using LNP technology.
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 20 years ago, Alnylam