Moorestown, New Jersey, United States
biotecHOPE™ 2022
biotecHOPE™ 2022
ACI-24.060 Anti-Amyloid Beta Vaccine
aypirca™ (pirtobrutinib)
aypirca™ (pirtobrutinib)
ACI-24.060 Anti-Amyloid Beta Vaccine
aypirca™ (pirtobrutinib)
U.S. FDA Approves Jaypirca™ (pirtobrutinib), the First and Only Non-Covalent (Reversible) BTK Inhibitor, for Adult Patients with Relapsed or Refractory Mantle Cell Lymphoma After at Least Two Lines of Systemic Therapy, Including a BTK Inhibitor
January 27, 2023
Jaypirca is the first BTK inhibitor of any kind specifically approved for patients with mantle cell lymphoma previously treated with a covalent BTK inhibitor
In the BRUIN Phase 1/2 trial, covalent BTK inhibitor pre-treated patients with relapsed or refractory MCL achieved an overall response rate of 50%, with 13% of patients achieving a complete response
INDIANAPOLIS, Jan. 27, 2023 /PRNewswire/ -- Loxo@Lilly, the oncology unit of Eli Lilly and Company (NYSE: LLY), today announced that the U.S. Food and Drug Administration (FDA) approved Jaypirca™ (pirtobrutinib, 100 mg & 50 mg tablets) for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a Bruton's tyrosine kinase (BTK) inhibitor. Jaypirca was approved under the FDA's Accelerated Approval pathway based on response rate from the open-label, single-arm, international, Phase 1/2 study, called the BRUIN trial.1 Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Jaypirca, a highly selective kinase inhibitor, utilizes a novel binding mechanism and is the first and only FDA approved non-covalent (reversible) BTK inhibitor. Jaypirca can reestablish BTK inhibition in MCL patients previously treated with a covalent BTK inhibitor (ibrutinib, acalabrutinib, or zanubrutinib) and extend the benefit of targeting the BTK pathway.
"The approval of Jaypirca represents an important advance for patients with relapsed or refractory MCL, who currently have limited options and historically have had a poor prognosis following discontinuation of treatment with a covalent BTK inhibitor," said Michael Wang, M.D., Puddin Clarke Endowed Professor of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center. "These data indicate that Jaypirca can provide efficacy in patients previously treated with a covalent BTK inhibitor, potentially extending the time patients may benefit from BTK inhibition therapy. Jaypirca offers a new approach to targeting the BTK pathway following treatment with a covalent BTK inhibitor and has the potential to meaningfully impact the treatment paradigm for relapsed and refractory MCL patients."
The labeling for Jaypirca contains warnings and precautions for infections, hemorrhage, cytopenias, atrial fibrillation and flutter, second primary malignancies, and embryo-fetal toxicity. See Important Safety Information below and full Prescribing Information for additional information, including dosing modifications.
"We are pleased to bring a meaningful new therapeutic option to patients with MCL that can reestablish the benefit of targeting the BTK pathway after receiving multiple prior therapies, including a covalent BTK inhibitor," said Jacob Van Naarden, chief executive officer, Loxo@Lilly. "We are grateful to the patients, investigators, and other members of the clinical care teams for their contributions. Our team has been committed to rapidly advancing the development of Jaypirca for patients with MCL, and we look forward to building on this milestone by continuing to bring forward important new treatments for people with hematologic malignancies."
The FDA approval is based on data from a subset of patients in the BRUIN Phase 1/2 trial. The assessment of efficacy was based on 120 patients with MCL treated with Jaypirca 200 mg once daily until disease progression or unacceptable toxicity. Patients with active central nervous system lymphoma or allogeneic hematopoietic stem cell transplantation or CAR T-cell therapy within 60 days were excluded. Patients had received a median of three prior lines of therapy (range: 1 to 9), with 93% having two or more prior lines; all patients received one or more prior lines of therapy containing a covalent BTK inhibitor. Eighty-three percent (83%) of patients discontinued their last BTK inhibitor due to refractory or progressive disease. Efficacy was based on overall response rate (ORR) and duration of response (DOR) as assessed by an independent review committee (IRC) using 2014 Lugano criteria.
Jaypirca is expected to be available in the United States in the coming weeks.
The confirmatory Phase 3 trial (NCT04662255; BRUIN MCL-321) is currently enrolling patients.
See Important Safety Information below and full Prescribing Information for additional information.
Click here to view the mantle cell lymphoma infographic.
Click to view the Jaypirca product photos: 100 mg and 50 mg.
Click here to view the Jaypirca logo.
About the BRUIN Phase 1/2 Trial
The BRUIN Phase 1/2 clinical trial is the ongoing first-in-human, global, multi-center evaluation of Jaypirca in patients with hematologic malignancies, including mantle cell lymphoma (MCL).
The trial includes a Phase 1 dose-escalation phase, a Phase 1b combination arm, and a Phase 2 dose-expansion phase. The primary endpoint of the Phase 1 study is maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D). Secondary endpoints include safety, pharmacokinetics (PK), and preliminary efficacy measured by overall response rate (ORR) for monotherapy. The primary endpoint of the Phase 1b study is safety of the drug combinations. The secondary endpoints are PK and preliminary efficacy measured by ORR for the drug combinations. The primary endpoint for the Phase 2 study is ORR as determined by an independent review committee (IRC). Secondary endpoints include ORR as determined by investigator, best overall response (BOR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety, and PK.
About Jaypirca™ (pirtobrutinib)
Jaypirca (pirtobrutinib, formerly known as LOXO-305) (pronounced jay-pihr-kaa) is a highly selective (300 times more selective for BTK versus 98% of other kinases tested in preclinical studies), non-covalent (reversible) inhibitor of the enzyme BTK.2 BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including mantle cell lymphoma.3,4 Jaypirca is a U.S. FDA-approved oral prescription medicine, 100 mg or 50 mg tablets taken as a once-daily 200 mg dose with or without food until disease progression or unacceptable toxicity.
About Mantle Cell Lymphoma
MCL is a rare blood cancer and a form of non-Hodgkin lymphoma (NHL). Annually, about one in 200,000 people worldwide develop MCL.5
MCL arises in B lymphocytes, a type of white blood cell and part of the immune system. MCL frequently begins in B cells located in the mantle zone of the outer edge of lymph nodes. As the cancer progresses, it can spread to bone marrow, the spleen, the liver, or the digestive tract.5
INDICATIONS FOR JAYPIRCA
Jaypirca is a kinase inhibitor indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Please see Prescribing Information and Patient Information for Jaypirca.
About Lilly
Lilly unites caring with discovery to create medicines that make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help more than 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
Jaypirca™ is a trademark owned by or licensed to Eli Lilly and Company, its subsidiaries, or affiliates.
View original content to download multimedia:https://www.prnewswire.com/news-releases/us-fda-approves-jaypirca-pirtobrutinib-the-first-and-only-non-covalent-reversible-btk-inhibitor-for-adult-patients-with-relapsed-or-refractory-mantle-cell-lymphoma-after-at-least-two-lines-of-systemic-therapy-including-a-301732669.html
SOURCE Eli Lilly and Company
Eli Lilly wins FDA accelerated approval for lymphoma therapy
Jan. 27, 2023 2:42 PM ET
By: Dulan Lokuwithana, SA News Editor1 Comment
The oncology division of Eli Lilly (NYSE:LLY) announced Friday that the FDA greenlighted its Bruton's tyrosine kinase (BTK) inhibitor Jaypirca as a late-line option for certain patients with mantle cell lymphoma (MCL), a rare blood cancer.
https://seekingalpha.com/news/3929112-lly-stock-wins-fda-accelerated-approval-lymphoma-therapy
ACI-24.060 Anti-Amyloid Beta Vaccine
ACI-24.060 Anti-Amyloid Beta Vaccine
ACI-24.060 Anti-Amyloid Beta Vaccine
AC Immune’s ACI-24.060 Anti-Amyloid Beta Vaccine For Alzheimer’s Shows Positive Initial Interim Safety And Immunogenicity In Phase 1b/2 ABATE Trial
Jan 26, 2023
AC Immune’s ACI-24.060 Anti-Amyloid Beta Vaccine for Alzheimer’s Shows Positive Initial Interim Safety and Immunogenicity in Phase 1b/2 ABATE Trial
- ACI-24.060 elicited an anti-Abeta antibody response in ABATE’s first, low dose cohort
- ACI-24.060 was generally well tolerated with no safety concerns observed
- With these findings, dosing in the second, higher dose Alzheimer’s cohort has begun
- Screening of cohort of study participants with Down syndrome also cleared to begin
- Further safety and immunogenicity findings from ABATE cohorts expected in H2 2023
- Initial data on amyloid plaque reduction measured via PET imaging anticipated in 2024
Lausanne, Switzerland, January 26, 2023 – AC Immune SA (NASDAQ: ACIU), a clinical-stage biopharmaceutical company pioneering precision medicine for neurodegenerative diseases, today announced the first interim safety, tolerability and immunogenicity findings from the Phase 1b/2 ABATE trial of its anti-amyloid-beta (Abeta) vaccine ACI-24.060 in patients with prodromal Alzheimer’s disease (AD). ABATE will now be expanded, as planned, to include individuals with Down syndrome (DS) and to evaluate higher doses in Alzheimer’s patients.
Targeting Abeta using antibodies has recently been validated with FDA approvals of new monoclonal antibody treatments for patients with AD. By eliciting polyclonal anti-Abeta antibodies, the ACI-24.060 anti-Abeta vaccine development program aims to ultimately deliver significant benefits to patients, their caregivers, and healthcare systems in terms of potential safety and tolerability, low frequency dosing, low overall costs and durable responses.
Early results from the first cohort of AD patients in ABATE showed that low dose ACI-24.060 could elicit an anti-Abeta antibody response as soon as week 6 (2 weeks after the second injection). The data show that ACI-24.060 vaccination has been safe and well tolerated to date. As a result, dosing in ABATE’s second, higher dose AD cohort has now begun and the trial is cleared to begin screening individuals with DS for part 2 of the study.
Dr. Andrea Pfeifer, CEO of AC Immune SA, commented: “We are delighted with the encouraging initial safety and immunogenicity findings for ACI-24.060 in ABATE reported today. We believe ACI-24.060’s successful development could provide patients with a novel therapeutic option offering numerous potential advantages in treatment, maintenance, and prevention settings. These early findings from ABATE represent an important step towards this goal, and we look forward to reporting more detailed data at a future conference.”
Dr. Johannes Streffer, CMO of AC Immune SA, commented: “ABATE’s innovative design includes interim Abeta PET imaging analyses that can be benchmarked against the levels of plaque clearance achieved with clinically-validated monoclonal antibodies. This will provide an opportunity for early de-risking of ACI-24.060 and potentially a rapid transition to a pivotal program. Moreover, the inclusion of cohorts of participants with DS in the trial positions us to potentially address the needs of a vastly underserved vulnerable population, virtually all of whom will develop amyloid plaques and AD. While looking forward to the trial’s continued advancement and upcoming data readouts, I want to thank the participants and investigators for their participation and support.”
About the Phase 1b/2 ABATE Study (ClinicalTrials.gov Identifier: NCT05462106)
The ABATE study is a Phase 1b/2, multicenter, adaptive, double-blind, randomized, placebo-controlled study to assess the safety, tolerability, immunogenicity, and pharmacodynamic effects of ACI-24.060 in subjects with prodromal Alzheimer’s disease and in adults with Down syndrome. All participants in the trial must have brain Abeta pathology confirmed by a positron emission tomography (PET) scan. The trial begins with a dose escalation phase in AD patients, during which various doses/dosing regimens may be evaluated, and also includes individuals with DS.
About ACI-24.060
ACI-24.060, derived from AC Immune’s SupraAntigen® platform, has been shown in preclinical studies to induce a strong polyclonal antibody response that matures and is maintained against both oligomeric and pyroglutamate-Abeta species, key pathological forms of Abeta believed to drive Abeta plaque formation and disease progression. ACI-24.060 is designed to enhance the formation of broad-spectrum protective antibodies with the same safety and tolerability previously demonstrated in the ACI-24 program in Phase 1 and 2 trials. This investigational candidate has the potential to efficiently inhibit plaque formation and increase plaque clearance, and thereby may reduce or prevent disease progression.
About AC Immune SA
AC Immune SA is a clinical-stage biopharmaceutical company that aims to become a global leader in precision medicine for neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and NeuroOrphan indications driven by misfolded proteins. The Company’s two clinically validated technology platforms, SupraAntigen® and Morphomer®, fuel its broad and diversified pipeline of first- and best-in-class assets, which currently features ten therapeutic and three diagnostic candidates, five of which are currently in Phase 2 clinical trials and one of which is in Phase 3. AC Immune has a strong track record of securing strategic partnerships with leading global pharmaceutical companies including Genentech, a member of the Roche Group, Eli Lilly and Company, and others, resulting in substantial non-dilutive funding to advance its proprietary programs and >$3 billion in potential milestone payments.
SupraAntigen® is a registered trademark of AC Immune SA in the following territories: AU, EU, CH, GB, JP, RU, SG and USA. Morphomer® is a registered trademark of AC Immune SA in CN, CH, GB, JP, KR, NO and RU.
The information on our website and any other websites referenced herein is expressly not incorporated by reference into, and does not constitute a part of, this press release.
Source: AC Immune SA
AC Immune rises ~10% as Alzheimer’s vaccine shows promise in early-stage trial
Jan. 26, 2023 7:51 AM ET
By: Ravikash, SA News Editor
- AC Immune (NASDAQ:ACIU) said its ACI-24.060 anti-amyloid beta (Abeta) vaccine for Alzheimer's disease (AD) showed positive initial interim safety and immunogenicity in a phase 1b/2 trial called ABATE.
- https://seekingalpha.com/news/3928320-ac-immune-rises-10-as-alzheimers-vaccine-shows-promise-in-early-stage-trial
- AC Immune SA (ACIU)
- https://www.acimmune.com/pipeline/
Breyanzi® (lisocabtagene maraleucel)
BXCL701 in combination with KEYTRUDA® (pembrolizumab)
ACI-24.060 Anti-Amyloid Beta Vaccine
Bristol Myers Squibb Announces TRANSCEND CLL 004 Trial of Breyanzi® (lisocabtagene maraleucel) Met Primary Endpoint of Complete Response Rate in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia
01/26/2023
CATEGORY:
PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced topline results from TRANSCEND CLL 004, a Phase 1/2, open-label, single-arm, multicenter study evaluating Breyanzi (lisocabtagene maraleucel) in adults with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Results from TRANSCEND CLL 004 showed the study met the primary endpoint of complete response rate compared to historical controlin the prespecified subset of patients with R/R CLL that was refractory to a BTK inhibitor and pretreated with a BCL-2 inhibitor. No new safety signals were reported for Breyanzi in this study.
“CLL is an incurable disease with complex biology and immune dysregulation that has made the development of T cell-based therapies that provide deep remission very challenging,” said Anne Kerber, senior vice president, head of Cell Therapy Development, Bristol Myers Squibb. “In a population that has limited options, the TRANSCEND CLL 004 study represents the first multicenter trial evaluating a CAR T cell therapy in heavily pre-treated patients with relapsed or refractory CLL or SLL, with results showing the potential of Breyanzi as a personalized one-time treatment approach for patients with this difficult-to-treat disease.”
Bristol Myers Squibb will complete a full evaluation of the TRANSCEND CLL 004 data and work with investigators to present detailed results at an upcoming medical meeting, as well as discuss these results with health authorities. Bristol Myers Squibb thanks the patients and investigators who are participating in the TRANSCEND CLL 004 clinical trial.
About TRANSCEND CLL 004
TRANSCEND CLL 004 (NCT03331198) is a Phase 1/2 open-label, single-arm, multicenter study evaluating Breyanzi in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma. The Phase 1 dose escalation portion of the study assessed the safety and recommended dose for the subsequent Phase 2 expansion cohort. The Phase 2 portion of the study is evaluating Breyanzi at the recommended dose from the Phase 1 monotherapy arm. The primary endpoint of the Phase 2 portion of the study was complete response rate, including complete remission with incomplete bone marrow recovery, based on independent review committee according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines.
About CLL and SLL
Chronic lymphocytic leukemia (CLL) is one of the most common types of leukemia in adults. In CLL, too many blood stem cells in the bone marrow become abnormal lymphocytes, and these abnormal cells have difficulty fighting infections. As the number of abnormal cells grows, there is less room for healthy white blood cells, red blood cells and platelets. Small lymphocytic lymphoma (SLL) also affects the lymphocytes, with cancer cells found mostly in the lymph nodes. While there are several treatments available for CLL and SLL, there is a need for additional effective therapies as there is no standard of care for relapsed or refractory CLL or SLL after prior therapy with targeted agents. Patients with relapsed or refractory disease have limited treatment options and generally experience shorter periods of response with each subsequent treatment.
About Breyanzi
Breyanzi is a CD19-directed CAR T cell therapy with a 4-1BB costimulatory domain, which enhances the expansion and persistence of the CAR T cells. Breyanzi is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal LBCL, and follicular lymphoma grade 3B who have refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy, or refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplant due to comorbidities or age, or relapsed or refractory disease after two or more lines of systemic therapy. Breyanzi is not indicated for the treatment of patients with primary central nervous system lymphoma. Please see the Important Safety Information section below, including Boxed WARNINGS for Breyanzi regarding cytokine release syndrome and neurotoxicity.
Breyanzi is also approved in Europe, Switzerland, Canada and Japan for relapsed and refractory LBCL after two or more lines of systemic therapy. Bristol Myers Squibb’s clinical development program for Breyanzi includes clinical studies in earlier lines of treatment for patients with relapsed or refractory LBCL and other types of lymphoma and leukemias. For more information, visit clinicaltrials.gov.
BREYANZI REMS
Because of the risk of CRS and neurologic toxicities, BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS. The required components of the BREYANZI REMS are:
- Healthcare facilities that dispense and administer BREYANZI must be enrolled and comply with the REMS requirements.
- Certified healthcare facilities must have on-site, immediate access to tocilizumab.
- Ensure that a minimum of 2 doses of tocilizumab are available for each patient for infusion within 2 hours after BREYANZI infusion, if needed for treatment of CRS.
- Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer BREYANZI are trained on the management of CRS and neurologic toxicities.
Further information is available at www.BreyanziREMS.com, or contact Bristol Myers Squibb at 1-888-423-5436.
Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide.
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.
Learn more about the science behind cell therapy and ongoing research at Bristol Myers Squibb here.
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
Bristol Myers says trial for CAR T therapy met main goal in leukemia
Jan. 26, 2023 7:22 AM ET
Bristol-Myers Squibb Company (BMY)
By: Dulan Lokuwithana, SA News Editor
- Bristol Myers Squibb (NYSE:BMY) announced Thursday that a Phase 1/2 trial for its CAR T cell therapy Breyanzi reached the primary endpoint in adults with relapsed or refractory chronic lymphocytic leukemia (CLL).
- https://seekingalpha.com/news/3928300-bristol-myers-says-trial-car-t-therapy-met-main-goal-leukemia
- Bristol-Myers Squibb Company (BMY)
- https://www.breyanzi.com/
MRTX1133
BXCL701 in combination with KEYTRUDA® (pembrolizumab)
BXCL701 in combination with KEYTRUDA® (pembrolizumab)
Mirati Announces IND Clearance by U.S. FDA Enabling Phase 1 Initiation for First-in-Class Oral KRASG12D Selective Inhibitor, MRTX1133
01/19/2023
IND demonstrates Mirati's leadership in KRAS, representing the Company's third KRAS or KRAS-signaling program to enter clinical development
SAN DIEGO, Jan. 19, 2023 /PRNewswire/ -- Mirati Therapeutics, Inc. (NASDAQ: MRTX), announced today the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application of MRTX1133, a potential first-in-class oral KRASG12D selective inhibitor for clinical evaluation. KRASG12D mutations impact approximately 180,000 patients in the US and Europe, representing approximately a 2.5-fold increase in prevalence compared to KRASG12C mutations. No targeted oncology treatment options currently exist for these patients.
MRTX1133 is a highly potent investigational inhibitor of the KRASG12D driver mutation and demonstrated selective and reversible inhibition of KRASG12D in both its active and inactive states. In addition, MRTX1133 administration resulted in marked tumor response in preclinical KRASG12D mutated pancreatic cancer models as well as lung and colorectal cancer models. MRTX1133 has demonstrated favorable properties including a low risk for off-target activity and drug interactions and a predicted human half-life of greater than 50 hours.
"The clearance by the FDA to initiate clinical evaluation of MRTX1133, the third program in our KRAS franchise to enter clinical development, is illustrative of the innovative approach to drug discovery and demonstrates the best-in-class capabilities of the Mirati team. This particular mutation has been difficult to target, and we are confident in our novel oral formulation strategy, which we believe will enable near-complete target inhibition over the full dosing interval," said James Christensen, Ph.D. chief scientific officer, Mirati Therapeutics, Inc. "We are thrilled to advance MRTX1133 into clinical development and the potential to positively impact people living with KRASG12D-mutated cancers."
The Phase 1/2 clinical trial will launch in early 2023 with plans for multiple expansion cohorts in pancreatic, colorectal, lung and other KRASG12D tumor types.
About Mirati Therapeutics, Inc.
Mirati Therapeutics, Inc. is a biotechnology company whose mission is to discover, design and deliver breakthrough therapies to transform the lives of patients with cancer and their loved ones. The company is relentlessly focused on bringing forward therapies that address areas of high unmet need, including lung cancer, and advancing a pipeline of novel therapeutics targeting the genetic and immunological drivers of cancer. Unified for patients, Mirati's vision is to unlock the science behind the promise of a life beyond cancer.
For more information about Mirati, visit us at Mirati.com or follow us on Twitter, LinkedIn and Facebook.
About MRTX1133
MRTX1133 is an investigational, highly potent, selective and reversible small molecule inhibitor of KRASG12D that is optimized to sustain near complete target inhibition with the potential to be both a first and best-in-class treatment option. MRTX1133 is entering Phase 1 clinical evaluation in 2023 investigating the drug's impact on KRASG12D-driven cancers. For more information visit Mirati.com/science.
View original content to download multimedia:https://www.prnewswire.com/news-releases/mirati-announces-ind-clearance-by-us-fda-enabling-phase-1-initiation-for-first-in-class-oral-krasg12d-selective-inhibitor-mrtx1133-301726331.html
SOURCE Mirati Therapeutics, Inc.
FDA clears Mirati's investigational new drug application for its inhibitor MRTX1133
Jan. 19, 2023 5:15 PM ET
Mirati Therapeutics, Inc. (MRTX)
By: Anuron Mitra, SA News Editor
- Mirati Therapeutics (NASDAQ:MRTX) on Thursday said the U.S. Food and Drug Administration had cleared its investigational new drug (IND) application for its inhibitor MRTX1133.
- https://seekingalpha.com/news/3926159-fda-clears-miratis-investigational-new-drug-application-for-its-inhibitor-mrtx1133
- Mirati Therapeutics, Inc. (MRTX)
- https://www.mirati.com/science/programs/kras-inhibitors/kras-g12d-inhibitor/
- https://www.mirati.com/
BXCL701 in combination with KEYTRUDA® (pembrolizumab)
BXCL701 in combination with KEYTRUDA® (pembrolizumab)
BXCL701 in combination with KEYTRUDA® (pembrolizumab)
BioXcel Therapeutics Announces Promising Top-Line Results from Phase 2 Trial of BXCL701 in Aggressive Form of Rare Prostate Cancer
Jan 11, 2023
Results demonstrate encouraging response rate of BXCL701 plus KEYTRUDA® (pembrolizumab) in patients with SCNC
Full data will be presented at the 2023 ASCO Genitourinary Cancers Symposium in February
NEW HAVEN, Conn., Jan. 11, 2023 (GLOBE NEWSWIRE) --
BioXcel Therapeutics, Inc. (Nasdaq: BTAI), a biopharmaceutical company utilizing artificial intelligence approaches to develop transformative medicines in neuroscience and immuno-oncology, today announced promising top-line data from its Phase 2 trial of BXCL701, the Company's investigational, oral innate immune activator, in combination with KEYTRUDA® (pembrolizumab) in small cell neuroendocrine metastatic castration-resistant prostate cancer (SCNC) patients. Full data have been submitted to the 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU).
“We are pleased that BXCL701 in combination with pembrolizumab has demonstrated an encouraging response rate in this difficult-to-treat cancer with no currently approved FDA therapies,” said Vincent J. O’Neill, M.D., Chief R&D Officer, OnkosXcel Therapeutics, a wholly owned subsidiary of BioXcel Therapeutics. “BXCL701’s promising profile as an oral innate immune activator with a large safety dataset and novel mechanism of action further supports OnkosXcel’s pipeline and use of BioXcel’s AI platform, and reinforces our confidence in BXCL701’s potential to enable checkpoint inhibitor therapy in traditionally cold cancers.”
SCNC represents a rare, underserved, growing patient population, with SCNC cases increasing due to earlier and more widespread use of androgen receptor inhibitors. In 2022, there were an estimated 268,5001 new prostate cancer patients, with approximately 10,740 patients progressing to SCNC.
The Phase 2a trial is an open-label, multicenter study to evaluate the safety and efficacy of BXCL701 in combination with pembrolizumab in men with SCNC. Eligibility criteria include histologically confirmed de novo or treatment-emergent SCNC, progression as defined by PCWG3 criteria, and at least 1 prior line of chemotherapy for locally advanced or metastatic prostate cancer. 28 evaluable SCNC patients received 0.3 mg of BXCL701 twice daily (BID) on days 1 through 14 of a 21-day cycle (0.2 mg BID the first week of Cycle 1) plus 200 mg of pembrolizumab administered intravenously on day 1 and every subsequent 21 days. The primary endpoint of the trial is a composite response rate defined as RECIST 1.1 and/or PSA50 and/or CTC count conversion. Secondary endpoints include duration of response, progression-free survival, overall survival, and biomarker evaluation as measured by changes in circulating cytokines and correlation of outcome with baseline tumor characteristics.
About BXCL701
BXCL701 is an investigational, oral innate immune activator designed to initiate inflammation in the tumor microenvironment. Approved and experimental immunotherapies often struggle to address cancers that appear “cold” or uninflamed. Therefore, BXCL701 may render “cold” tumors “hot,” making them more detectable by the adaptive immune system and thereby facilitating the development of a strong anti-cancer immune response. BioXcel Therapeutics’ preclinical data supports BXCL701’s synergy with both current checkpoint inhibitor-based therapies and emerging immunotherapies directed to activate T-cells. BXCL701 is currently being developed as a potential therapy for the treatment of aggressive forms of prostate cancer and advanced solid tumors that are refractory or treatment naïve to checkpoint inhibitors. BXCL701 has received Orphan Drug Designation from the U.S. Food & Drug Administration in four indications: acute myelogenous leukemia, pancreatic cancer, stage IIb to IV melanoma, and soft tissue sarcoma.
About OnkosXcel Therapeutics, LLC
OnkosXcel Therapeutics, LLC is a wholly owned subsidiary of BioXcel Therapeutics, Inc., focused on developing transformative medicines in oncology utilizing artificial intelligence approaches. The subsidiary was formed in 2022 to develop BXCL701, a Phase 2, investigational, oral innate immune activator for the treatment of aggressive forms of prostate cancer and advanced solid tumors that are refractory or treatment naïve to checkpoint inhibitors, as well as other immuno-oncology focused assets.
About BioXcel Therapeutics, Inc.
BioXcel Therapeutics, Inc., is a biopharmaceutical company utilizing artificial intelligence approaches to develop transformative medicines in neuroscience and immuno-oncology. The Company’s drug re-innovation approach leverages existing approved drugs and/or clinically validated product candidates together with big data and proprietary machine learning algorithms to identify new therapeutic indications. The Company’s commercial product, IGALMI™ (developed as BXCL501), is a proprietary, sublingual film formulation of dexmedetomidine approved for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults. The safety and effectiveness of IGALMI have not been established beyond 24 hours from the first dose. For more information, please visit IGALMIhcp.com and also see the IGALMI full Prescribing Information. BXCL501 is under evaluation for at-home use for the acute treatment of agitation in bipolar and schizophrenia patients, for acute treatment of Alzheimer’s-related agitation, and as an adjunctive treatment for major depressive disorder. The safety and efficacy of BXCL501 for these uses have not been established. The Company is also developing BXCL502 as a potential therapy for chronic agitation in dementia. Under its subsidiary, OnkosXcel Therapeutics LLC, the Company is developing BXCL701, an investigational, oral innate immune activator for the treatment of aggressive forms of prostate cancer and advanced solid tumors that are refractory or treatment naïve to checkpoint inhibitors. The safety and efficacy of BXCL502 and BXCL701 have not been established. For more information, please visit bioxceltherapeutics.com.
Source: BioXcel Therapeutics, Inc.
BioXcel's BXCL701, Keytruda combo shows promise in mid-stage trial for prostate cancer
Jan. 11, 2023 7:33 AM ET
BioXcel Therapeutics, Inc. (BTAI), MRK
By: Ravikash, SA News Editor
- BioXcel Therapeutics (NASDAQ:BTAI) said its oral medicine BXCL701 in combination with Merck's (NYSE:MRK) Keytruda showed encouraging response rate in patients with a type of prostate cancer in a phase 2a trial.
- The study evaluated BXCL701 in combination with Keytruda (pembrolizumab) in men with small cell neuroendocrine metastatic castration-resistant prostate cancer (SCNC).
- In the trial, 28 evaluable patients received the drug combination. The main goal of the study is a composite response rate, while secondary goals include duration of response, progression-free survival, overall survival, and biomarker evaluation.
- https://seekingalpha.com/news/3923614-bioxcels-bxcl701-keytruda-combo-shows-promise-in-mid-stage-trial-for-prostate-cancer
- BioXcel Therapeutics, Inc. (BTAI), MRK
- https://www.bioxceltherapeutics.com/our-pipeline/
LP-284
IBI351 (KRASG12C Inhibitor)
LP-284
FDA Grants Lantern Pharma Orphan Drug Designation for Drug Candidate LP-284 in Mantle Cell Lymphoma
January 05, 2023 8:59am EST
- The Orphan Drug Designation strengthens LP-284’s clinical development path and provides the opportunity for additional market exclusivity and commercial protection.
- Lantern is anticipating filing the IND with the FDA and initiating a first-in-human Phase 1 trial for LP-284 in B-cell non-Hodgkin’s lymphomas (NHL), including mantle cell lymphoma (MCL), by mid 2023.
- In the US, MCL is diagnosed in approximately 4,500 patients each year and has an estimated annual market potential of $600 million.
DALLAS--(BUSINESS WIRE)-- Lantern Pharma Inc. (NASDAQ: LTRN), a clinical stage biopharmaceutical company using its proprietary RADR® artificial intelligence ("A.I.") and machine learning (“M.L.”) platform to transform the cost, pace, and timeline of oncology drug discovery and development, today announced that the U.S. Food and Drug Administration (FDA) has granted LP-284 Orphan Drug Designation (ODD) for the treatment of mantle cell lymphoma (MCL). MCL is a rare and aggressive form of B-cell non-Hodgkin's lymphoma (NHL) that is typically diagnosed at advanced stages in elderly patients. As nearly all MCL patients acquire resistance and relapse from treatment with standard-of-care (SOC) agents, there is an urgent and unmet clinical need for new and effective therapies to treat MCL.
LP-284 is a novel small molecule agent that preferentially damages DNA in cancer cells harboring mutations in DNA damage repair pathways. Lantern is developing LP-284 for several aggressive B-cell NHL’s, including MCL and double hit lymphoma (DHL), where LP-284 has shown potent anti-tumor activity in preclinical models. Lantern has been able to advance LP-284 from initial RADR® A.I. insights regarding anti-cancer activity and potential mechanisms of action in hematological cancers, to selection of specific subtypes of lymphomas with superior response, to late stage IND enabling studies and initial design of first in human clinical trials in less than 2 years.
"Receiving Orphan Drug Designation is an important milestone for our latest drug candidate, LP-284, and further validates our data-driven approach to oncology drug discovery and development” stated Panna Sharma, President & CEO of Lantern Pharma. "At ASH, we recently reported positive preclinical data demonstrating LP-284’s potent anti-tumor activity in new MCL tumors and also against tumors that had grown resistant to the MCL standard-of-care agents Ibrutinib and Bortezomib. These findings are critically pertinent due to the high relapse rate, and poor prognosis of the majority of MCL patients,” continued Sharma.
“This orphan designation is the fourth overall designation granted to Lantern, with the other three granted for our drug candidate LP-184. Acquiring these orphan designations is a key element of our business model as they provide a number of benefits including seven years of market exclusivity and eligibility for expedited drug development programs. Looking forward, these designations further position Lantern to advance our discussions with biopharma companies for partnering and collaborative development opportunities.”
The FDA's Office of Orphan Products Development grants orphan status to drugs intended for the safe and effective treatment, diagnosis or prevention of rare diseases or conditions affecting fewer than 200,000 people in the United States. ODD is designed to provide drug developers with various benefits to support the development of novel drugs, including market exclusivity for seven years upon FDA approval, eligibility for tax credits for qualified clinical trials, waiver of marketing registration application fees, reduced annual product fees, clinical protocol assistance and qualification for expedited development programs.
In addition to the ODD granted for LP-284 in MCL, Lantern was previously granted ODD’s by the FDA for its drug candidate LP-184 for the treatment of malignant gliomas, atypical teratoid rhabdoid tumors (ATRT), and pancreatic cancer. Lantern has also been granted a Rare Pediatric Disease Designation for LP-184 in ATRT.
About Lantern Pharma:
Lantern Pharma (NASDAQ: LTRN) is a clinical-stage oncology-focused biopharmaceutical company leveraging its proprietary RADR® A.I. and machine learning platform to discover biomarker signatures that identify patients most likely to respond to its pipeline of genomically-targeted therapeutics. Lantern is currently developing four drug candidates and an ADC program across 12 disclosed tumor targets, including two phase 2 programs. By targeting drugs to patients whose genomic profile identifies them as having the highest probability of benefiting from the drug, Lantern's approach represents the potential to deliver best-in-class outcomes.
FDA grants orphan drug designation to Lantern Pharma's lymphoma treatment candidate
Jan. 05, 2023 9:51 AM ET
By: Anuron Mitra, SA News Editor
- Lantern Pharma (NASDAQ:LTRN) on Thursday said the U.S. Food and Drug Administration (FDA) had granted an orphan drug designation to its LP-284 candidate for the treatment of mantle cell lymphoma (MCL).
- https://seekingalpha.com/news/3922371-fda-grants-orphan-drug-designation-to-lantern-pharmas-lymphoma-treatment-candidate
- Lantern Pharma Inc. (LTRN)
- https://www.lanternpharma.com/pipeline#lp284
VAX-24
IBI351 (KRASG12C Inhibitor)
LP-284
Vaxcyte’s VAX-24 Granted FDA Breakthrough Therapy Designation for the Prevention of Invasive Pneumococcal Disease in Adults
January 5, 2023PDF Version
-- Breakthrough Therapy Designation for 24-Valent Investigational Pneumococcal Conjugate Vaccine Candidate Based on Positive Topline Proof-of-Concept Data Results in Adults Aged 18-64 That Suggest Potential Best-in-Class Profile --
-- Topline Safety, Tolerability and Immunogenicity Data from VAX-24 Phase 2 Study in Adults 65 and Older Expected in Q2 2023 --
-- Company Continues to Advance PCV Franchise, Including VAX-24 and VAX-31, While Progressing Early-Stage Vaccine Programs --
SAN CARLOS, Calif., Jan. 05, 2023 (GLOBE NEWSWIRE) -- Vaxcyte, Inc. (Nasdaq: PCVX), a clinical-stage vaccine innovation company engineering high-fidelity vaccines to protect humankind from the consequences of bacterial diseases, announced today that the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation for VAX-24, the Company’s investigational 24-valent pneumococcal conjugate vaccine (PCV) candidate for the prevention of invasive pneumococcal disease (IPD), in adults. The FDA’s decision was based on positive topline results from the Phase 1/2 proof-of-concept study, which evaluated the safety, tolerability and immunogenicity of VAX-24 in adults 18-64 years of age.
In the Phase 1/2 clinical study, VAX-24 met the primary safety and tolerability objectives, demonstrating a safety profile similar to Prevnar 20™ (PCV20) for all doses studied. The study also demonstrated that VAX-24 met or exceeded the established regulatory immunogenicity standards for all 24 serotypes at the conventional 2.2mcg dose, which the Company intends to move forward into a pivotal Phase 3 program. At this dose, VAX-24 met the standard opsonophagocytic activity response non-inferiority criteria for all 20 serotypes common with PCV20, of which 16 achieved higher immune responses.
“The FDA’s Breakthrough Therapy designation supports further acceleration of the VAX-24 development program in adults, while also providing validation of the potential of VAX-24 to deliver broader coverage and better immune responses relative to the standard of care,” said Grant Pickering, Chief Executive Officer and Co-Founder of Vaxcyte. “Our focus remains on advancing our VAX-24 clinical programs in both adults and infants and we anticipate announcing the topline data from the Phase 2 study in adults 65 and older in the second quarter of 2023.”
The FDA’s Breakthrough Therapy process is designed to expedite the development and review of drugs that are intended to treat a serious or life-threatening condition. The designation is based upon preliminary clinical evidence indicating that the drug or vaccine may demonstrate substantial improvement over available therapies on one or more clinically significant endpoints. With Breakthrough Therapy designation, Vaxcyte will have access to all of the elements of the FDA’s Fast Track program, as well as the ability to receive guidance and support from the FDA on an efficient drug development program and an organizational commitment from senior managers within the FDA.
“We are pleased to have received this important designation for VAX-24, which we believe underscores the public health need for broader protection from IPD, as well as the importance of innovative technology platforms in vaccine development, such as our cell-free, carrier-sparing approach,” said Jim Wassil, Executive Vice President and Chief Operating Officer of Vaxcyte. “In addition to our PCV franchise, comprising VAX-24 and VAX-31, our PCV candidate with 31 strains (formerly VAX-XP), we are also leveraging the XpressCF™ cell-free platform to develop earlier-stage vaccines, including VAX-A1 and VAX-PG, that are designed to prevent or treat bacterial infectious diseases and further demonstrate the full potential of our platform.”
Anticipated Key Milestones
Vaxcyte is advancing the clinical development of its PCV and early-stage programs with several anticipated key milestones, including:
VAX-24 Adult Program
- Topline safety, tolerability and immunogenicity data from the Phase 2 study in adults 65 and older are anticipated in the second quarter of 2023.
- Final results with the 6-month safety data from the two Phase 2 adult studies are anticipated in the first half of 2023.
- Following the receipt of the final safety reports from the two adult Phase 2 studies, regulatory interactions to inform the Phase 3 program are anticipated in the second half of 2023.
- Topline safety, tolerability and immunogenicity data from the pivotal Phase 3 non-inferiority study in adults are expected in 2025.
VAX-24 Pediatric Program
- The infant Investigational New Drug (IND) application submission and the Phase 2 study initiation are both anticipated in first half of 2023.
- Topline safety, tolerability and immunogenicity data from the infant Phase 2 study following the primary 3-dose immunization series are expected by 2025. The study design will include a primary immunization series consisting of three doses followed by a subsequent booster dose.
VAX-31 (Formerly VAX-XP) Adult Program
- The IND application submission for VAX-31 is anticipated in the second half of 2023.
- Topline safety, tolerability and immunogenicity data from a Phase 1/2 study in adults 18 years of age and older are expected in 2024.
VAX-A1
- Vaxcyte continues to advance the development of VAX-A1, a novel conjugate vaccine designed to prevent infections caused by Group A Strep bacteria, and further information about the anticipated timing of an IND application will be provided as the program progresses.
VAX-PG
- Vaxcyte nominated a final vaccine candidate for VAX-PG, its novel therapeutic vaccine designed to treat periodontal disease, in the fourth quarter of 2022 and continues to progress the program.
About VAX-24
VAX-24 is an investigational 24-valent PCV candidate designed to prevent IPD, which can be most serious for infants, young children, older adults and those with immune deficiencies or certain chronic health conditions. The public health community continues to affirm the need for vaccines that offer broader protection to prevent IPD. VAX-24 is intended to improve upon the standard-of-care PCVs for both children and adults by covering the serotypes that are responsible for most of the pneumococcal disease currently in circulation. Vaxcyte aims to efficiently create and deliver high-fidelity, broad-spectrum vaccines, such as VAX-24, by using modern synthetic techniques, including advanced chemistry and the XpressCF™ cell-free protein synthesis platform. Vaxcyte is deploying this approach with VAX-24 in order to add more pneumococcal strains without compromising the overall immune response.
About Vaxcyte
Vaxcyte is a vaccine innovation company engineering high-fidelity vaccines to protect humankind from the consequences of bacterial diseases. The Company is developing broad-spectrum conjugate and novel protein vaccines to prevent or treat bacterial infectious diseases. Vaxcyte’s lead candidate, VAX-24, is a 24-valent, broad-spectrum, carrier-sparing PCV being developed for the prevention of IPD. Vaxcyte is re-engineering the way highly complex vaccines are made through modern synthetic techniques, including advanced chemistry and the XpressCF™ cell-free protein synthesis platform, exclusively licensed from Sutro Biopharma, Inc. Unlike conventional cell-based approaches, the Company’s system for producing difficult-to-make proteins and antigens is intended to accelerate its ability to efficiently create and deliver high-fidelity vaccines with enhanced immunological benefits. Vaxcyte’s pipeline also includes VAX-31, a PCV with coverage of 31 strains; VAX-A1, a prophylactic vaccine candidate designed to prevent Group A Strep infections; and VAX-PG, a therapeutic vaccine candidate designed to slow or stop the progression of periodontal disease. Vaxcyte is driven to eradicate or treat invasive bacterial infections, which have serious and costly health consequences when left unchecked.
FDA grants breakthrough therapy designation to Vaxcyte's pneumococcal conjugate vaccine
Jan. 05, 2023 9:35 AM ETVaxcyte, Inc. (PCVX)By: Anuron Mitra, SA News Editor
- Vaxcyte (NASDAQ:PCVX) on Thursday said the U.S. Food and Drug Administration (FDA) had granted a breakthrough therapy designation to its pneumococcal conjugate vaccine (PCV) candidate VAX-24.
- https://seekingalpha.com/news/3922358-fda-grants-breakthrough-therapy-designation-to-vaxcytes-pneumococcal-conjugate-vaccine
- V Vaxcyte, Inc. (PCVX) Vaxcyte, Inc. (PCVX)
- https://vaxcyte.com/
- https://vaxcyte.com/pipeline/
IBI351 (KRASG12C Inhibitor)
IBI351 (KRASG12C Inhibitor)
IBI351 (KRASG12C Inhibitor)
- Innovent Announces NMPA’s Breakthrough Therapy Designation for IBI351 (KRASG12C Inhibitor) as Monotherapy for Previous Treated Advanced Non-small Cell Lung CancerPublished on: Jan 5th, 2023Back
- ROCKVILLE, U.S. and SUZHOU, China, January 5, 2023 - Innovent Biologics, Inc. (“Innovent”) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, autoimmune, metabolic, ophthalmology and other major diseases, announced that the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has granted Breakthrough Therapy Designation (BTD) for IBI351 (GFH925) for the treatment of advanced non-small cell lung cancer patients with KRASG12C mutation that have received at least one prior line of systemic therapy.
- The NMPA BTD for IBI351 was based on the results from a phase I/II trial (CDE Registration No. CTR20211933). This study aims to evaluate the safety, tolerability and efficacy of IBI351 monotherapy in patients with advanced solid tumors who failed or intolerant to standard of care treatment.
- The latest results of IBI351 from the phase I study were presented at the 2022 Chinese Society of Clinical Oncology (CSCO) Annual Meeting. As data cutoff (29 July 2022), of 55 evaluable NSCLC patients, the investigator assessed objective response rate (ORR) was 50.9% and disease control rate (DCR) was 92.7%. Of 21 patients with NSCLC treated at 600mg BID (the recommended phase 2 dose), better efficacy signal was observed, with investigator assessed ORR 61.9% and DCR 100%. Median duration of response (DOR) and median progression free survival (PFS) were not reached yet.
As data cutoff date, IBI351 was well tolerated. No DLT was reported and MTD was not reached. Treatment-related adverse events (TRAEs) occurred in 92.5% (62/67) patients and the most common TRAEs were anemia, transferase increased, bilirubin increased, pruritus and fatigue. The majority of the TRAEs were grade 1-2 with 19.4% (13/67) of patients reporting grade 3 or higher TRAEs. There were no grade 5 TRAEs or TRAEs led to treatment discontinuation.
Favorable safety and tolerability and promising antitumor activity of IBI351 monotherapy were observed. The single-arm registrational trial of IBI351 monotherapy in previously-treated advanced non-small cell lung cancer patients with KRASG12C mutation is ongoing. Relevant updated study results will be published at an upcoming medical conference in 2023.
“We are glad to see the NMPA grants Breakthrough Therapy Designation based on the results of Phase I data of IBI351,” said Dr. Hui Zhou, Senior Vice President of Innovent. “KRASG12C mutated NSCLC patients have limited treatment options. IBI351 demonstrated encouraging efficacy and safety data in Phase I study. A single arm registrational trial of IBI351 monotherapy in previously-treated advanced NSCLC is ongoing. We are working to advance into late stage clinical development to explore the potential of IBI351 as monotherapy and in combo-therapy.”
NMPA Breakthrough Therapy Designation is intended to facilitate and expedite the development and review of an investigational drug to treat a serious disease or condition when preliminary clinical evidence indicates that the drug has demonstrated substantial improvement over current therapies. The BTD will not only qualify a drug candidate to receive status for rapid review by the CDE, but it will also allow the sponsor to obtain timely advice and communication from the CDE to accelerate the approval and launch to address the unmet clinical need of patients at an accelerated pace. Click here for the published list of drugs which have been granted BTD by NMPA.
About Non-small Cell Lung Cancer
Lung cancer is one of the malignancies with the highest incidence and mortality worldwide, among which non-small cell lung cancer (NSCLC) is the most common pathological type, accounting for about 85% of all lung cancers. KRAS mutations are common driver gene mutations in NSCLC, most of which occur in lung adenocarcinoma. KRAS mutations rarely co-exist with driver mutations such as EGFR and ALK, and patients with advanced NSCLC with KRASG12C mutations are often unable to benefit from the multiple drugs already on the market that target these mutations or rearrangements. After the progress of first-line standard treatment in this population, there are limited second-line treatment options with low effective rate and poor prognosis.
About IBI351/GFH925(KRASG12C Inhibitor)
Discovered by GenFleet Therapeutics, GFH925 (Innovent R&D code: IBI351) is a novel, orally active, potent KRASG12C inhibitor designed to effectively target the GTP/GDP exchange, an essential step in pathway activation, by modifying the cysteine residue of KRASG12C protein covalently and irreversibly. Preclinical cysteine selectivity studies demonstrated high selectivity of IBI351 towards KRASG12C. Subsequently, IBI351 effectively inhibits the downstream signal pathway to induce tumor cells’ apoptosis and cell cycle arrest.
In September 2021, Innovent and GenFleet Therapeutics entered into an exclusive license agreement for the development and commercialization of IBI351 in China (including mainland China, Hong Kong, Macau and Taiwan) with additional option-in rights for global development and commercialization.
About Innovent
Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to developing, manufacturing and commercializing high-quality innovative medicines for the treatment of cancer, autoimmune disease, metabolic disorder and other major diseases. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code: 01801.HK.
Since its inception, Innovent has developed a fully integrated multi-functional platform which includes R&D, CMC (Chemistry, Manufacturing, and Controls), clinical development and commercialization capabilities. Leveraging the platform, the company has built a robust pipeline of 36 valuable assets in the fields of cancer, metabolic disorder, autoimmune disease and other major therapeutic areas, with 8 approved products on the market. These include: TYVYT® (sintilimab injection), BYVASDA® (bevacizumab biosimilar injection), SULINNO® (adalimumab biosimilar injection), HALPRYZA® (rituximab biosimilar injection) , Pemazyre® (pemigatinib oral inhibitor), olverembatinib (BCR-ABL TKI) , Cyramza® (ramucirumab) and Retsevmo® (selpercatinib). An additional 2 assets are under NMPA NDA review, 6 assets are in Phase 3 or pivotal clinical trials, and 20 more molecules are in clinical studies.
Innovent has built an international team with advanced talent in high-end biological drug development and commercialization, including many global experts. The company has also entered into strategic collaborations with Eli Lilly and Company, Sanofi, Adimab, Incyte, MD Anderson Cancer Center and other international partners. Innovent strives to work with many collaborators to help advance China's biopharmaceutical industry, improve drug availability and enhance the quality of the patients' lives. For more information, please visit: www.innoventbio.com. and www.linkedin.com/company/innovent-biologics/.
Innovent wins China’s breakthrough therapy status for KRASG12C Inhibitor
Jan. 05, 2023 6:48 AM ET
Innovent Biologics, Inc. (IVBIY), IVBXF
By: Dulan Lokuwithana, SA News Editor
- Innovent Biologics (OTCPK:IVBIY) (OTCPK:IVBXF) announced that China's Center for Drug Evaluation (CDE) issued Breakthrough Therapy Designation (BTD) for its KRASG12C inhibitor IBI351 (GFH925) as a treatment for advanced non-small-cell-lung cancer (NSCLC).
- https://seekingalpha.com/news/3922252-innovent-wins-chinas-breakthrough-therapy-status-for-krasg12c-inhibitor
- Innovent Biologics, Inc. (IVBIY), IVBXF
- https://www.innoventbio.com/
- https://www.innoventbio.com/ScienceAndProducts/Pipeline
biotecHOPE™ 2022
BT8009
fidanacogene elaparvovec
fidanacogene elaparvovec
CAMBRIDGE, England & BOSTON--(BUSINESS WIRE)--Jan. 4, 2023--
Bicycle Therapeutics plc (NASDAQ:BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle®) technology, today announced that the United States Food and Drug Administration (FDA) has granted Fast Track Designation (FTD) to Bicycle’s BT8009 monotherapy for the treatment of adult patients with previously treated locally advanced or metastatic urothelial cancer. BT8009 is a potential first in class Bicycle Toxin Conjugate (BTC®) targeting Nectin-4, a protein that is highly expressed in urothelial cancer (UC) and other solid tumors.
“FTD represents another positive step in the development of BT8009 and reflects the pressing need for a clinically meaningful, differentiated therapy compared to what is available for patients,” said Kevin Lee, Ph.D., Chief Executive Officer. “We believe this designation is a valuable component of our future clinical and regulatory strategy as we work to align with the FDA to address the pressing unmet needs of people living with urothelial cancer.”
FTD is intended to facilitate and expedite development and review of new drugs to address unmet medical need in the treatment of a serious or life-threatening condition. This unmet medical need is defined as providing a therapy where either none exists or providing a therapy which may prove superior to existing therapy. A clinical program that receives FTD may benefit from more frequent meetings and communications with the FDA to discuss development plans and ensure the collection of appropriate data needed to support approval. Clinical programs conducted under FTD may be eligible for Accelerated Approval and Priority Review if relevant criteria are met. More information on the Fast Track process is available here.
About Bicycle Therapeutics
Bicycle Therapeutics (NASDAQ: BCYC) is a clinical-stage biopharmaceutical company developing a novel class of medicines, referred to as Bicycles, for diseases that are underserved by existing therapeutics. Bicycles are fully synthetic short peptides constrained with small molecule scaffolds to form two loops that stabilize their structural geometry. This constraint facilitates target binding with high affinity and selectivity, making Bicycles attractive candidates for drug development. Bicycle is evaluating BT5528, a second-generation Bicycle Toxin Conjugate (BTC®) targeting EphA2; BT8009, a second-generation BTC targeting Nectin-4, a well-validated tumor antigen; and BT7480, a Bicycle TICA® targeting Nectin-4 and agonizing CD137, in company-sponsored Phase I/II trials. In addition, BT1718, a BTC that targets MT1-MMP, is being investigated in an ongoing Phase I/IIa clinical trial sponsored by the Cancer Research UK Centre for Drug Development. Bicycle is headquartered in Cambridge, UK, with many key functions and members of its leadership team located in Lexington, MA. For more information, visit bicycletherapeutics.com.
View source version on businesswire.com: https://www.businesswire.com/news/home/20230104005096/en/
Source: Bicycle Therapeutics plc
Bicycle Therapeutics adds 10% on FDA’s fast track tag for bladder cancer therapy
Jan. 04, 2023 7:52 AM ET
Bicycle Therapeutics plc (BCYC)
By: Dulan Lokuwithana, SA News Editor
- Clinical-stage biotech Bicycle Therapeutics (NASDAQ:BCYC) jumped ~10% pre-market Wednesday after announcing that the FDA granted Fast Track Designation for its experimental bladder cancer therapy BT8009.
- hhttps://www.bicycletherapeutics.com/ttps://seekingalpha.com/news/3921890-bcyc-stock-gains-fdas-fast-track-tag-for-bladder-cancer-therapy
- Bicycle Therapeutics plc (BCYC)
- https://www.bicycletherapeutics.com/programs/bicycle-conjugates/
fidanacogene elaparvovec
fidanacogene elaparvovec
fidanacogene elaparvovec
Pfizer Announces Positive Top-Line Results from Phase 3 Study of Hemophilia B Gene Therapy Candidate
Thursday, December 29, 2022 - 06:45amOpen in tab
NEW YORK--(BUSINESS WIRE)-- Pfizer Inc. (NYSE: PFE) today announced positive top-line results from the Phase 3 BENEGENE-2 study (NCT03861273) evaluating fidanacogene elaparvovec, an investigational gene therapy, for the treatment of adult males with moderately severe to severe hemophilia B.
The BENEGENE-2 study met its primary endpoint of non-inferiority and superiority in the annualized bleeding rate (ABR) of total bleeds post-fidanacogene elaparvovec infusion versus prophylaxis regimen with Factor IX (FIX), administered as part of usual care. The results demonstrated superiority with a mean ABR for all bleeds of 1.3 for the 12 months from week 12 to month 15 compared to an ABR of 4.43 during the lead-in pre-treatment period of at least six months, resulting in a 71% reduction in ABR (p<0.0001) after a single dose of 5e11 vg/kg of fidanacogene elaparvovec. Key secondary endpoints demonstrated a 78% reduction in treated ABR (p=0.0001) and a 92% reduction in annualized infusion rate (p<0.0001). Mean FIX activity was 27% at 15 months by one-stage SynthASil assay and 25% at 24 months. The mean steady-state FIX:C was significantly higher than the pre-specified threshold of 5% (p<0.0001).
Fidanacogene elaparvovec was generally well-tolerated, with a safety profile consistent with Phase 1/2 results. Fourteen serious adverse events (SAEs) were reported in seven (16%) patients, with two assessed as related to treatment, a duodenal ulcer hemorrhage occurring in the setting of corticosteroid use, and an immune-mediated elevation of liver aminotransferase levels. No deaths, SAEs associated with infusion reactions, thrombotic events, or FIX inhibitors were reported.
Fidanacogene elaparvovec is a novel, investigational vector that contains a bio-engineered adeno-associated virus (AAV) capsid (protein shell) and a high-activity human coagulation FIX gene. The goal of this gene therapy for people living with hemophilia B, once treated, is that they will be able to produce FIX via this one-time treatment rather than having to regularly receive exogenous FIX. In this Phase 3 trial, eligible study participants (n=45) completed a minimum six months of routine exogeneous FIX prophylaxis therapy during the lead-in study (NCT03587116) and then received one intravenous dose of fidanacogene elaparvovec at a dose of 5e11 vg/kg. Participants in the BENEGENE-2 study were screened with a validated assay designed to identify individuals who test negative for neutralizing antibodies to the gene therapy vector. Clinical trial participants will be evaluated as part of a long-term study over the course of 15 years.
“Pfizer has more than 30 years of experience in developing and commercializing therapies for hematological disorders, and a deep understanding of the significant challenges that people living with hemophilia continually face. We are proud to advance the latest innovation for people living with hemophilia B and are encouraged by the potential of this investigational gene therapy,” said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology and Rare Disease, Pfizer Global Product Development. “We are extremely appreciative of those who are participating in the trial and to the investigators contributing to this innovative research as we work to unlock the full potential of gene therapies for people living with hemophilia.”
Pfizer currently has three Phase 3 programs investigating gene therapy in populations where there is a high unmet need: hemophilia B, hemophilia A, and Duchenne muscular dystrophy. A Phase 3 trial is also ongoing investigating marstacimab, a potential novel subcutaneous therapy option being studied for the treatment of people with hemophilia A and B with and without inhibitors.
“The burden people living with hemophilia B face is significant, with many receiving routine infusions or injections which can interfere with their ability to take part in day-to-day activities that many take for granted,” said Adam Cuker, M.D., M.S., Director, Penn Comprehensive and Hemophilia Thrombosis Program. “The BENEGENE-2 data demonstrate the promise of this gene therapy candidate as a potential one-time option for people living with hemophilia B as a means of reducing the clinical and treatment burden over the long term.”
Fidanacogene elaparvovec has been granted breakthrough, regenerative medicines advance therapy (RMAT), and orphan drug designations from the US Food and Drug Administration, as well as PRIority MEdicines (PRIME) and orphan drug designation from the European Medicines Agency. Pfizer will discuss these data with regulatory authorities in early 2023.
Additional key data will be presented at a scientific conference in early 2023 as well.
About fidanacogene elaparvovec
Fidanacogene elaparvovec is a novel, investigational gene therapy that contains a bio-engineered AAV capsid and a high-activity human coagulation FIX gene. The goal of this investigational treatment for people living with hemophilia B, once treated, is that they will be able to produce FIX themselves via this one-time treatment rather than having to receive exogenous FIX.
Pfizer licensed SPK-9001 (fidanacogene elaparvovec), from Spark Therapeutics pursuant to a December 2014 agreement under which Spark Therapeutics was responsible for conducting all Phase 1/2 studies for the investigational gene therapy while Pfizer assumed responsibility for pivotal studies, any regulatory activities, and potential global commercialization.
View source version on businesswire.com: https://www.businesswire.com/news/home/20221229005024/en/
Pfizer:
Source: Pfizer Inc.
Pfizer says hemophilia B gene therapy met key goal in Phase 3 trial
Dec. 29, 2022 7:08 AM ET
Pfizer Inc. (PFE), RHHBY, RHHBF
By: Dulan Lokuwithana, SA News Editor1 Comment
Pfizer (NYSE:PFE) announced Thursday that the company’s investigational gene therapy for hemophilia B, fidanacogene elaparvovec, met the primary endpoint in a Phase 3 trial called BENEGENE-2 involving adults males with a moderately severe to severe form of the disease.
Pfizer Inc. (PFE), RHHBY, RHHBF
https://www.pfizer.com/science/drug-product-pipeline
GTX-102
fidanacogene elaparvovec
Renazorb (lanthanum dioxycarbonate)
Acasti Announces Preliminary Topline Results Met All Outcome Measures in the Pharmacokinetic Bridging Study for GTX-102, the Company’s Drug Candidate for the Treatment of Ataxia Telangiectasia
December 28, 2022
LAVAL, Québec, Dec. 28, 2022 (GLOBE NEWSWIRE) -- Acasti Pharma Inc. (“Acasti” or the “Company”) (Nasdaq: ACST and TSX-V: ACST), a late-stage, specialty pharma company advancing three clinical stage drug candidates addressing rare and orphan diseases, announces that the preliminary topline results of the pharmacokinetic (PK) bridging study for GTX-102 met all outcome measures. The objectives of the study were to evaluate the bioavailability, pharmacokinetics, and safety of GTX-102, a novel, concentrated oral-mucosal metered spray of betamethasone in healthy volunteers. This new formulation is intended to improve the neurological symptoms of Ataxia Telangiectasia (A-T) in a pediatric population for which there are currently no FDA-approved therapies. GTX-102 can be sprayed conveniently over the tongue of A-T patients, who often have difficulties swallowing. This PK study was the next step in the proposed 505(b)(2) regulatory pathway for GTX-102.
Jan D’Alvise, Chief Executive Officer of Acasti, stated, “The completion of this PK bridging study is an important milestone in the advancement of our GTX-102 program designed to provide a new and convenient therapy for treating the chronic symptoms of A-T in children with this rare genetic disorder. We are very pleased to report the results of this study, which we expect will now support the advancement of the program directly into Phase 3. Currently there are no drugs approved for A-T, and we are pleased to report the topline findings of this pivotal study as we remain committed to bring this exciting and proprietary treatment to children who suffer from A-T.”
This PK bridging study is a Phase 1, randomized, open-label, crossover study in healthy adult subjects to evaluate the comparative bioavailability, PK, and safety of GTX-102 administered as an oral spray compared to intramuscular (IM) betamethasone (which is expected to be the reference product for bridging purposes), and to an oral solution (OS) of betamethasone, which is available in Europe but not approved in the US. The betamethasone OS was shown to reduce neurological symptoms in children with A-T in a published multicenter, double-blind, randomized, placebo-controlled crossover trial conducted in Italy (Zannolli et al, 2012).
The primary objective of this PK bridging study was to evaluate and characterize the PK profile of GTX-102 as an oral spray. Details of the study design can be found on ClinicalTrials.gov (Identifier: NCT05531890).
A total of 48 healthy adult subjects (27 males and 21 females) were enrolled in this single center, 5-treatment, 8-sequence, 2-period cross-over study. The 5 treatments assessed in the study were:
- GTX-102: low dose at 0.0125 mg/kg, medium dose at 0.05 mg/kg, and high dose at 0.1 mg/kg
- OS betamethasone at 0.1 mg/kg
- IM betamethasone at 0.1 mg/kg
Each subject received a single dose of 2 treatments in a cross-over fashion, in a randomized sequence over 2 treatment periods separated by 15 days. The dosing started on September 13, 2022 and ended on November 24, 2022. Betamethasone blood levels were compared between all treatment groups.
GTX-102 PK study outcome measures definitions and preliminary topline findings are as follows:
- Primary outcome measures and their definitions include:
- AUC0-72 is the area under the concentration time curve up to 72 hours post-dose
- AUC∞ is the area under the concentration time curve extrapolated to infinity
- Cmax is the maximum concentration occurring between 0 hour to 72 hours after study drug administration.
- GTX-102 given at doses of 0.0125 (low), 0.5 (medium) or 0.1 (high) mg/kg, showed betamethasone blood concentrations that were highly predictable and consistent based on AUC and Cmax, indicating good linearity and dose-proportionality.
- Following the high dose of GTX-102 (0.1 mg/kg), betamethasone blood concentrations were within the same range of exposure as IM betamethasone (0.1 mg/kg), based on AUC. The IM formulation of betamethasone will serve as a bridge for GTX-102 in the context of the proposed 505(b)(2) regulatory pathway.
- In addition, Betamethasone blood concentrations following the high dose of GTX-102 (0.1 mg/kg) were within the same range of exposure as OS betamethasone (0.1 mg/kg), based on AUC. This OS formulation was the same one that was used by Zannolli et al and may serve as a clinical comparator for further clinical development of GTX-102.
- There was statistically no significant difference (p>0.05) between GTX-102 (0.05 mg/kg) when comparing a fast rate of administration (each spray immediately following the preceding one) to a slow rate (1 spray/minute), as indicated by Cmax and AUC. This is important because being able to use the fast or the slow rate of administration may provide greater flexibility for patients and caregivers.
- The Cmax of GTX-102 was within the same range of exposure as the OS, but the Cmax for the IM formulation was lower than both GTX-102 and the OS, as well as what has been reported previously for the IM in the literature. It is important to note that achieving bioequivalence with the IM was not an objective of this study, nor was it expected.
- No serious adverse events (AE) were reported during the study. AEs leading to study discontinuation consisted of cough/fever/body pain/stuffy nose (1 case), Covid-19 (1 case) and elevated creatinine kinase (1 case), and all events occurred prior to receiving the second treatment. None were judged as being related to the study drugs by the investigator. The most frequent drug-related AE was mild headache (4 cases).
- Based on this data, Acasti will work with our clinical experts and FDA to determine the best final dosing regimen for GTX-102 to incorporate into our Phase 3 study design.
D’Alvise concluded, “With the completion of this important comparative PK bridging study, we are confident that the expected final development step for GTX-102 will be to conduct a Phase 3 safety and efficacy trial in A-T patients using a treatment regimen similar to the one already proved effective by Zannolli, et al. We plan to request a Type B meeting with the FDA following the receipt of the full PK study dataset sometime in calendar H1 2023 to confirm the proposed Phase 3 study design. If all proceeds as planned, the Phase 3 study is expected to be initiated in the second half of calendar 2023. If the Phase 3 program meets the primary endpoints, an NDA filing for GTX-102 under Section 505(b)(2) is expected to follow.”
About A-T
A-T is a progressive, genetic, neurodegenerative disorder that primarily effects young children, causing severe disability, impairment of the immune system and an increasing susceptibility to infections and cancer. The hallmark symptoms of A-T are cerebellar ataxia and other motor dysfunction, and dilated blood vessels (telangiectasia) that occur in the sclera of the eyes and on the skin. Children begin to experience balance and coordination problems when they begin to walk (toddler age), and ultimately become wheelchair bound in their second decade of life. In pre-adolescence (age 5-8 years), patients experience oculomotor apraxia, dysarthria, and dysphagia. They often develop compromised immune systems and are at increased risk of developing respiratory tract infections and cancer (typically lymphomas and leukemia). Patients typically die by age 25 years from complications of lung disease or cancer.
A-T is diagnosed through a combination of clinical assessments, laboratory analysis, and genetic testing. There is no known treatment to slow disease progression, and treatments that are used are strictly aimed at symptoms (e.g., physical, occupational or speech therapy for neurologic issues), or conditions secondary to the disease (e.g., antibiotics for lung infections, chemotherapy for cancer, etc.).
A market research study commissioned by Acasti found that A-T affects approximately 4,300 patients per year in the United States and has a potential total addressable market of $150 million, based on the number of treatable patients (as disclosed in Acasti’s most recently filed quarterly report on Form 10-Q).
About Acasti
Acasti is a late-stage specialty pharma company with drug delivery technologies and drug candidates addressing rare and orphan diseases. Acasti’s novel drug delivery technologies have the potential to improve the performance of currently marketed drugs by achieving faster onset of action, enhanced efficacy, reduced side effects, and more convenient drug delivery—all which could help to increase treatment compliance and improve patient outcomes. Acasti’s three lead clinical assets have each been granted Orphan Drug Designation by the FDA, which provide the assets with seven years of marketing exclusivity post-launch in the United States, and additional intellectual property protection with over 40 granted and pending patents. Acasti’s lead clinical assets target underserved orphan diseases: (i) GTX-104, an intravenous infusion targeting Subarachnoid Hemorrhage (SAH), a rare and life threatening medical emergency in which bleeding occurs over the surface of the brain in the subarachnoid space between the brain and skull; (ii) GTX-102, an oral mucosal spray targeting Ataxia-telangiectasia (A-T), a progressive, neurodegenerative genetic disease that primarily affects children, causing severe disability, and for which no treatment currently exists; and (iii) GTX-101, a topical spray targeting Postherpetic Neuralgia (PHN), a persistent and often debilitating neuropathic pain caused by nerve damage from the varicella zoster virus (shingles), which may persist for months and even years.
For more information, please visit: https://www.acasti.com/en.
Source: Acasti Pharma, Inc.
Released December 28, 2022
Acasti soars ~15% as phase 1 bridging study of neurodegenerative disorder drug shows promise
Dec. 28, 2022 9:07 AM ET
Acasti Pharma Inc. (ACST), ACST:CA
By: Ravikash, SA News Editor
Acasti Pharma (NASDAQ:ACST) said results from a pharmacokinetic (PK) phase 1 bridging study of GTX-102 met all outcome measures.
Renazorb (lanthanum dioxycarbonate)
Renazorb (lanthanum dioxycarbonate)
Renazorb (lanthanum dioxycarbonate)
Unicycive Achieves Primary Endpoint in Pivotal Bioequivalence Study of Renazorb
December 28, 2022 8:30am EST Download as PDF
Renazorb demonstrates pharmacodynamic bioequivalence to Fosrenol
Renazorb’s enhanced product profile features reduced pill burden and small, swallowable tablets, which may improve patient compliance
On track to file New Drug Application mid-2023
LOS ALTOS, Calif., Dec. 28, 2022 (GLOBE NEWSWIRE) -- Unicycive Therapeutics, Inc. (Nasdaq: UNCY), a clinical-stage biotechnology company developing therapies for patients with kidney disease, today announced that the primary endpoint was met in the Company’s pivotal bioequivalence (BE) study comparing Renazorb to Fosrenol®. Based on the topline results, pharmacodynamic (PD) BE of Renazorb to Fosrenol was established and met the regulatory criteria for PD BE in the healthy volunteer BE study.
Renazorb is an investigational phosphate binding agent utilizing proprietary nanoparticle technology that is being developed to treat hyperphosphatemia in chronic kidney disease (CKD) patients on dialysis. If approved, Renazorb may dramatically reduce the pill burden that patients endure with currently available medications. The global market opportunity for treating hyperphosphatemia is projected to be in excess of $2.5 billion in 2022, with the United States accounting for more than $1 billion of that total. Despite the availability of several U.S. Food and Drug Administration (FDA)-cleared medications, 75 percent of U.S. dialysis patients fail to achieve the target phosphorus levels recommended by published medical guidelines. Market research indicates that the top reason for this significant unmet medical need is related to the high pill burden, which leads to poor patient compliance.
Unicycive previously received confirmatory guidance from the FDA that this single BE study in healthy volunteers would satisfy all clinical regulatory requirements and that no other clinical studies would be required for a New Drug Application (NDA) filing through the 505(b)(2) pathway.
Today's positive results are from a randomized, open-label, two-way crossover BE study to establish PD BE between Renazorb and Fosrenol. The study enrolled 40 subjects per treatment arm. The study design, including the dose, primary endpoint, and sample size, was reviewed, and aligned by the FDA before the initiation of the study.
"We are delighted with the successful outcome of our registrational BE study of Renazorb. This is a major milestone for Unicycive that brings us one step closer to obtaining market approval for Renazorb to treat hyperphosphatemia,” said Shalabh Gupta, M.D., Chief Executive Officer of Unicycive. “Our R&D team has extensive experience filing NDA submissions and a demonstrated track record of multiple product approvals from the FDA. We look forward to filing the NDA for Renazorb in mid-2023 and for its potential approval in order to benefit the multitude of hyperphosphatemia patients who are not well served by current treatment options.”
The primary outcome measure of the BE study was Least Square (LS) mean change in urinary phosphate excretion (in mg/day) from baseline to the evaluation period (PD variable). Based on the mixed-effect linear model, the 90% Confidence Interval (CI) was constructed for the difference in PD variable for Renazorb and Fosrenol. In addition, the acceptable range was defined as ± 20% of the LS mean of the PD variability for Fosrenol. PD BE was achieved because the 90% CI was completely contained within the acceptable range.
About Renazorb (lanthanum dioxycarbonate)
Renazorb is an investigational next-generation lanthanum-based phosphate binding agent utilizing proprietary nanoparticle technology being developed for the treatment of hyperphosphatemia in patients with chronic kidney disease (CKD). Its potential best-in-class profile has meaningful patient adherence benefits over currently available treatment options as it requires smaller and fewer number of pills per dose and is swallowed instead of chewed.
https://unicycive.com/focus/renazorb/
About Unicycive Therapeutics
Unicycive Therapeutics is a biotechnology company developing novel treatments for kidney diseases. Unicycive’s lead drug, Renazorb, is a novel phosphate binding agent being developed for the treatment of hyperphosphatemia. UNI-494 is a patent-protected new chemical entity in late preclinical development for the treatment of acute kidney injury. For more information, please visit www.unicycive.com.
Source: Unicycive Therapeutics, Inc.
Released December 28, 2022
Unicycive jumps 25% as kidney disease drug meets main goal in key trial
Dec. 28, 2022 8:57 AM ET
Unicycive Therapeutics, Inc. (UNCY)TAK
By: Dulan Lokuwithana, SA News Editor
- Nano-cap biotech Unicycive Therapeutics (NASDAQ:UNCY) added ~25% pre-market Wednesday after announcing that its pivotal bioequivalence (BE) study for kidney disease therapy Renazorb met the primary goal.
- https://seekingalpha.com/news/3920905-uncy-stock-jumps-as-kidney-disease-drug-meets-main-goal-in-key-trial
- Unicycive Therapeutics, Inc. (UNCY)
- https://unicycive.com/focus/renazorb/
GS-1811 (formerly JTX-1811)
Renazorb (lanthanum dioxycarbonate)
Olpruva (sodium phenylbutyrate)
Gilead To Acquire All Remaining Rights To Potential First-In-Class Immunotherapy GS-1811 From Jounce Therapeutics
-- Agreement Covers Buyout of Remaining Financial Obligations for Anti-CCR8 Antibody in Development as a Potential Treatment for Solid Tumors --
FOSTER CITY, Calif. and CAMBRIDGE, Mass., Dec. 27, 2022 (GLOBE NEWSWIRE) -- Gilead Sciences, Inc. (Nasdaq: GILD) and Jounce Therapeutics, Inc. (Nasdaq: JNCE) amended their existing license agreement for GS-1811 (formerly JTX-1811), enabling Gilead to buyout remaining contingent payments potentially due under the license agreement executed in August 2020. As part of the transaction, certain operational obligations of the parties related to GS-1811, an anti-CCR8 antibody, set forth in the license agreement have also been terminated. Gilead will acquire certain related intellectual property, including all outstanding rights of Jounce to GS-1811, pursuant to the transaction agreement. GS-1811, a potentially first-in-class immunotherapy, is designed to selectively deplete immunosuppressive tumor-infiltrating T regulatory cells in the tumor microenvironment and is currently in Phase 1 clinical development as a possible treatment for patients with solid tumors.
“We are pleased to announce the signing of this transaction with Gilead who have a strong track record of developing and successfully commercializing leading brands in biotechnology,” said Richard Murray, Ph.D., chief executive officer and president of Jounce. “This transaction allows us to extend our runway and remain focused on delivering meaningful and long-lasting benefits to cancer patients. It was important for Jounce at this time to bolster our cash resources given challenges in capital markets for biotech companies.”
Jounce will receive proceeds of $67 million for this transaction and Gilead will be solely responsible for all further research, development, and commercialization of GS-1811 globally.
“Today’s news about GS-1811 further demonstrates our commitment to our rapidly evolving oncology franchise and mission of pioneering next-generation medicines for people with cancer,” said Bill Grossman, M.D., Ph.D., Senior Vice President, Therapeutic Area Head, Gilead Oncology. “GS-1811, with its potential new pathway of activating the immune system, gives us the opportunity to potentially change the standard of care with a treatment that works from inside cancerous cells to shrink solid tumors.”
Beginning in the first quarter of 2022, consistent with recent industry communications from the U.S. Securities and Exchange Commission (SEC), Gilead no longer excludes acquired IPR&D expenses from its non-GAAP financial measures. We expect the transaction with Jounce to reduce Gilead’s GAAP and non-GAAP 2022 EPS by approximately $0.04.
Jounce will no longer be entitled to receive the remaining contingent payments of up to $645 million in milestones and high single digit to mid-teens royalties based upon worldwide sales under the original license agreement. Additional details of the transaction, including related agreements and matters, will be contained in a Current Report on Form 8-K to be filed by Jounce.
About Jounce Therapeutics
Jounce Therapeutics, Inc. is a clinical-stage immunotherapy company dedicated to transforming the treatment of cancer by developing therapies that enable the immune system to attack tumors and provide long-lasting benefits to patients through a biomarker-driven approach. Jounce currently has multiple development stage programs ongoing while simultaneously advancing additional early-stage assets from its robust discovery engine based on its Translational Science Platform. Jounce’s highest priority program, JTX-8064, is a LILRB2 (ILT4) receptor antagonist shown to reprogram immune-suppressive tumor associated macrophages to an anti-tumor state in preclinical studies. JTX-8064 is being investigated alone and in combination with pimivalimab (formerly JTX-4014), Jounce’s internal PD-1 inhibitor, in one monotherapy and seven indication-specific combination therapy cohorts in the Phase 1/2 INNATE trial and is currently enrolling patients with advanced solid tumors in the Phase 2 portion of the study. Jounce’s most advanced product candidate, vopratelimab, is a monoclonal antibody that binds to and activates ICOS, and is currently being studied in the SELECT Phase 2 trial. Pimivalimab is a PD-1 inhibitor intended for combination use with Jounce’s broader pipeline. For more information, please visit www.jouncetx.com.
About Gilead Sciences
Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California.
Jounce soars 59% after Gilead will acquire remaining rights to cancer immunotherapy
Dec. 27, 2022 5:12 PM ET
Jounce Therapeutics, Inc. (JNCE), GILD
By: Jonathan Block, SA News Editor1 Comment
- Jounce Therapeutics (NASDAQ:JNCE) is receiving $67M from Gilead Sciences (NASDAQ:GILD) in exchange for giving up rights to its phase 1 cancer immunotherapy GS-1811 (formerly JTX-1811).
- https://seekingalpha.com/news/3920812-jounce-therapeutics-soars-59-after-gilead-will-acquire-remaining-rights-to-cancer-immunotherapy
- Jounce Therapeutics, Inc. (JNCE), GILD
- https://jouncetx.com/our-pipeline/
- https://jouncetx.com/
Olpruva (sodium phenylbutyrate)
Renazorb (lanthanum dioxycarbonate)
Olpruva (sodium phenylbutyrate)
NDA 214860 NDA APPROVAL Acer Therapeutics Inc. Attention: Renée M. Carroll, MS, RAC Vice President, Head of Regulatory Affairs One Gateway Center, Suite 356 300 Washington Street Newton, MA 02458 Dear Ms. Carroll:
Please refer to your new drug application (NDA) dated and received August 5, 2021, and your amendments, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act (FDCA) for Olpruva (sodium phenylbutyrate) for oral suspension. We acknowledge receipt of your amendment dated July 15, 2022, which constituted a complete response to our June 15, 2022, action letter. This NDA provides for the use of Olpruva (sodium phenylbutyrate) for oral suspension as adjunctive therapy to standard of care, which includes dietary management, for the chronic management of adult and pediatric patients weighing 20 kg or greater and with a body surface area (BSA) of 1.2 m2 or greater, with urea cycle disorders (UCDs) involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase (AS). APPROVAL & LABELING We have completed our review of this application, as amended. It is approved, effective on the date of this letter, for use as recommended in the enclosed agreed-upon labeling. CONTENT OF LABELING As soon as possible, but no later than 14 days from the date of this letter, submit the content of labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA automated drug registration and listing system (eLIST), as described at FDA.gov.1 Content of labeling must be identical to the enclosed labeling (text for the Prescribing Information, Patient Package Insert, and Instructions for Use) as well as annual reportable changes not included in the enclosed labeling. Information on 1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm Reference ID: 5100040 NDA 214860 Page 2 U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov submitting SPL files using eLIST may be found in the guidance for industry SPL Standard for Content of Labeling Technical Qs and As. 2 The SPL will be accessible via publicly available labeling repositories. CARTON AND CONTAINER LABELING Submit final printed carton and container labeling that are identical to the enclosed carton and container labeling as soon as they are available, but no more than 30 days after they are printed. Please submit these labeling electronically according to the guidance for industry SPL Standard for Content of Labeling Technical Qs & As. For administrative purposes, designate this submission “Final Printed Carton and Container Labeling for approved NDA 214860.” Approval of this submission by FDA is not required before the labeling is used. DATING PERIOD Based on the stability data submitted to date, the expiry dating period for Olpruva (sodium phenylbutyrate) for oral suspension shall be 36 months from the date of manufacture when stored at 20º to 25ºC (68º to 77ºF) and excursions permitted to 15º to 30ºC (59º to 86ºF) [see USP Controlled Room Temperature] in the proposed container closure system. REQUIRED PEDIATRIC ASSESSMENTS Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for new active ingredients (which includes new salts and new fixed combinations), new indications, new dosage forms, new dosing regimens, or new routes of administration are required to contain an assessment of the safety and effectiveness of the product for the claimed indication in pediatric patients unless this requirement is waived, deferred, or inapplicable. We are deferring submission of your pediatric study for patients who weigh <20 kg and patients who weigh ≥20 kg with a BSA <1.2 m2 for this application because this product is ready for approval for use in adult and pediatric patients weighing 20 kg or greater and with a BSA of 1.2 m2 or greater. Pediatric studies in patients who weigh <20 kg and patients who weigh ≥20 kg with a BSA <1.2 m2 have not been completed. Studies to develop appropriate dosage strength(s) for dosing patients who weigh <20 kg and patients who weigh ≥20 kg with a BSA <1.2 m2 are necessary to ensure appropriate dosing of Olpruva in these patients, and the development of such dosage strength(s) will depend upon the feasibility of manufacturing and demonstration of stability of lower strength(s). 2 We update guidances periodically. For the most recent version of a guidance, check the FDA Guidance Documents Database https://www.fda.gov/RegulatoryInformation/Guidances/default.htm. Reference ID: 5100040 NDA 214860 Page 3 U.S. Food and Drug Administration Silver Spring, MD 20993 www.fda.gov Your deferred pediatric study required by section 505B(a) of the FDCA is a required postmarketing study. The status of this postmarketing study must be reported annually according to 21 CFR 314.81 and section 505B(a)(4)(C) of the FDCA. This required study is listed below. 4380-1 Develop dosage strength(s) to accommodate the recommended dosing for pediatric patients who weigh <20 kg and patients who weigh ≥20 kg with a body surface area <1.2 m2. The timetable you submitted on December 12, 2022, states that you will conduct this trial according to the following schedule: Draft Protocol Submission: 03/2023 Final Protocol Submission: 05/2023 Study Completion: 09/2023 Final Report Submission: 10/2023 FDA considers the term final to mean that the applicant has submitted a protocol, the FDA review team has sent comments to the applicant, and the protocol has been revised as needed to meet the goal of the study or clinical trial.3 Submit the protocol(s) to your IND 143822, with a cross-reference letter to this NDA. Reports of this required pediatric postmarketing study must be submitted as an NDA or as a supplement to your approved NDA with the proposed labeling changes you believe are warranted based on the data derived from this study. When submitting the reports, please clearly mark your submission "SUBMISSION OF REQUIRED PEDIATRIC ASSESSMENTS" in large font, bolded type at the beginning of the cover letter of the submission. This product is appropriately labeled for use in pediatric patients weighing 20 kg or greater and with a BSA of 1.2 m2 or greater for this indication. Therefore, no additional studies are needed in this pediatric group.
Acer wins FDA OK for Olpruva to treat urea cycle disorders
Dec. 23, 2022 2:30 PM ET
Acer Therapeutics Inc. (ACER), RLFTF, RLFTY
By: Dulan Lokuwithana, SA News Editor
The U.S. Food and Drug Administration (FDA) has greenlighted Olpruva, being developed by Acer Therapeutics (NASDAQ:ACER) and Swiss biotech Relief Therapeutics (OTCQB:RLFTF) (OTCQB:RLFTY) as a treatment for patients with urea cycle disorders (UCD).
Acer Therapeutics Inc. (ACER), RLFTF, RLFTY
https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2022/214860Orig1s000ltr.pdf
Eftilagimod Alpha (Efti)
VLA1553 a live-attenuated, single dose investigational vaccine candidate targeting chikungunya virus
VLA1553 a live-attenuated, single dose investigational vaccine candidate targeting chikungunya virus
ASX/Media Release Immutep Announces Successful Meeting with the FDA on Eftilagimod Alpha plus Chemotherapy for the Treatment of Metastatic Breast Cancer • Agreement with FDA on Phase II/III trial design positions the Company to exploit eftilagimod alpha’s potential to address high unmet need for metastatic breast cancer patients • Patient population expanded to include patients with triple-negative breast cancer • Late-stage clinical development efforts remain focused on frontline non-small cell lung cancer (NSCLC) in combination with anti-PD-1 therapy • Immutep’s cash runway extended to the end of the 1st half of calendar year 2024 SYDNEY, AUSTRALIA – 23 December 2022 – Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep” or “the Company”), a clinical-stage biotechnology company developing novel LAG-3 immunotherapiesfor cancer and autoimmune disease, today announces the results of a positive follow-up Type C meeting with the US Food and Drug Administration (FDA) regarding late-stage clinical development plans for its first-in-class soluble LAG-3 protein, eftilagimod alpha (“efti”), in conjunction with standard-of-care chemotherapy for the treatment of metastatic breast cancer (MBC). The Company and the FDA have agreed to an integrated Phase II/III trial design that will help inform a Biologics License Application (BLA). Based on the encouraging efficacy, favourable safety, and learnings from the randomised AIPAC Phase IIb trial, which administered efti and chemotherapy on different days and ceased chemotherapy at six months, patients will receive efti and paclitaxel on the same day and treatment will continue until disease progression. The patient population has also been expanded to include triple-negative breast cancer (TNBC), an aggressive form of breast cancer with limited treatment options. Immutep CEO, Marc Voigt, commented: “As recently announced, our late-stage clinical development efforts for efti are now focused on frontline NSCLC in combination with anti-PD-1 therapy, given the large market opportunity and need for more durable and tolerable options. With this said, progress reported to date with the FDA and EMA provides Immutep and its potential partners flexibility for late-stage clinical development of efti plus standard-of-care chemotherapy to address the high unmet need for metastatic breast cancer patients, while maintaining their quality of life as was shown in the AIPAC trial.” Immutep CSO & CMO, Dr. Frédéric Triebel, stated: “We are excited about efti’s promise to stimulate the immune system and improve standard-of-care chemotherapy by activating dendritic cells to present antigens from chemo-induced cancer cell death to cytotoxic T cells. Our engagement with regulatory agencies to establish the optimal design of a registrational trial has steadily progressed during the year and we are pleased with the FDA’s positive feedback during this follow up meeting. The chosen trial design provides us with a very risk-balanced approach before potentially embarking on the Phase 3 part of this study.” Subject to regulatory and ethic committee feedback, the Phase II portion of the MBC trial is expected to begin during the first quarter of 2023. In addition to the biologically active 30mg dosing for efti, the Company and FDA have agreed to test 90mg efti dosing in combination with paclitaxel driven predominantly by the excellent safety profile of the AIPAC Phase IIb trial, along with the FDA’s Project Optimus initiative in oncology. The trial design has a safety lead in of 6 to 12 patients, given the higher 90mg dosing of efti, followed by 58 patients for the randomised Phase II portion of the trial. Depending on Phase II results and resources, the Phase III portion will follow and be directed to MBC patients most likely to benefit from treatment, taking into consideration the strong overall survival results in pre-specified and post-hoc subgroups from the AIPAC trial. The Phase II portion of the MBC trial and the initiation of the registrational trial in 1st line NSCLC are included in the budget of the Company and have no impact on its expected cash runway to the end of the 1st half of calendar year 2024. About Eftilagimod Alpha (Efti) Efti is Immutep’s proprietary soluble LAG-3 clinical stage candidate that is a first-in-class antigen presenting cell (APC) activator for the treatment of cancer, capitalising on LAG-3’s unique characteristics to stimulate both innate and adaptive immunity. Efti binds to and activates antigen presenting cells via MHC II molecules leading to expansion and proliferation of CD8+ (cytotoxic) T cells, CD4+ (helper) T cells, dendritic cells, NK cells, and monocytes. It also upregulates the expression of key biological molecules like CXCL10 that further boost the immune system’s ability to fight cancer. Efti is under evaluation for a variety of solid tumours including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and HER2–/HR+ metastatic breast cancer. Its favourable safety profile enables various combinations, including with anti-PD-[L]1 immunotherapy and/or chemotherapy. Efti has received Fast Track Designation in 1st line HNSCC and in 1st line NSCLC from the United States Food and Drug Administration (FDA). About Immutep Immutep is a clinical stage biotechnology company leading the development of LAG-3 related immunotherapy products for the treatment of cancer and autoimmune disease. The Company is dedicated to leveraging its technology and expertise to bring innovative treatment options to market for patients and to maximise value to shareholders. Immutep’s lead product candidate is eftilagimod alpha (“efti” or “IMP321”), a soluble LAG-3 fusion protein (LAG-3Ig), which is a first-in-class antigen presenting cell (APC) activator being explored in cancer in multiple clinical trials. The Company is also developing an agonist of LAG-3 (IMP761) for autoimmune disease. Additional LAG-3 product candidates, including antibodies for immune response modulation, are being developed under license by Immutep’s large pharmaceutical partners. Further information can be found on the Company’s website www.immutep.com or by contacting:
Immutep surges 25% after 'positive' FDA meeting for eftilagimod's trial in breast cancer
Dec. 23, 2022 9:01 AM ET
By: Ravikash, SA News Editor1 Comment
Immutep (NASDAQ:IMMP) (OTCPK:PRRUF) said it had a positive follow-up Type C meeting with the U.S. Food and Drug Administration (FDA) regarding late-stage clinical development plans for eftilagimod alpha (efti), with standard-of-care chemotherapy, to treat metastatic breast cancer (MBC).
VLA1553 a live-attenuated, single dose investigational vaccine candidate targeting chikungunya virus
VLA1553 a live-attenuated, single dose investigational vaccine candidate targeting chikungunya virus
VLA1553 a live-attenuated, single dose investigational vaccine candidate targeting chikungunya virus
Valneva Completes BLA Submission to U.S. FDA for its Single-Shot Chikungunya Vaccine Candidate
December 23, 2022
Saint-Herblain (France), December 23, 2022 – Valneva SE (Nasdaq: VALN; Euronext Paris: VLA), a specialty vaccine company, today announces that it has completed rolling submission of the Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for its single-shot chikungunya vaccine candidate, VLA1553. Valneva is seeking approval of its investigational chikungunya vaccine in persons aged 18 years and above.
This BLA application follows final pivotal Phase 3 data reported in March 2022[1] and final lot-to-lot consistency results reported in May 2022[2]. A clinical study of VLA1553 in adolescents is ongoing in Brazil[3], which may support future regulatory submissions in this group if VLA1553 is initially approved in adults. The Company also recently reported positive antibody persistence data with a 99% seroresponse rate 12 months after a single-dose vaccination[4].
Juan Carlos Jaramillo, MD, Chief Medical Officer of Valneva, commented, “The completion of our BLA submission is extremely important as it takes us a step closer to potentially bringing a preventative solution to fight this debilitating disease. Chikungunya is a major public health threat transmitted to humans by infected mosquitoes, and no vaccine or specific treatments for the disease are currently available. If the FDA approves the submission, our goal is to provide a tool to help curtail this growing, unmet medical need.”
The FDA will now review the filing for acceptance, determine priority review eligibility and the action date which it targets to complete its evaluation. The program received FDA Fast Track and Breakthrough Therapy designations in 2018 and 2021, respectively. VLA1553 was also granted PRIority MEdicine (PRIME) designation by the European Medicines Agency (EMA) in 2020, and Valneva plans to make regulatory submissions for VLA1553 in Europe in the second half of 2023.
About Chikungunya
Chikungunya is a mosquito-borne viral disease caused by the chikungunya virus (CHIKV), a Togaviridae virus, transmitted by Aedes mosquitoes. Infection leads to symptomatic disease in 72-92% of humans after four to seven days following the mosquito bite. While mortality with CHIKV is low, morbidity is high, and the global market for vaccines against chikungunya is estimated to exceed $500 million annually by 2032[5]. Clinical symptoms include acute onset of fever, debilitating joint and muscle pain, headache, nausea, rash and chronic arthralgia. Chikungunya virus often causes sudden large outbreaks with high attack rates, affecting one-third to three-quarters of the population in areas where the virus is circulating. The high-risk areas of infection for travelers are places where chikungunya virus-carrying mosquitos are endemic, including the Americas, parts of Africa, and Southeast Asia, and the virus has spread to more than 100 countries. As of July 2022, more than three million cases have been reported in the Americas[6] and the economic impact is considered to be significant. The medical and economic burden is expected to grow as the CHIKV primary mosquito vectors continue to spread geographically. There are no preventive vaccines or effective treatments available and, as such, chikungunya is considered to be a major public health threat.
About VLA1553
VLA1553 is a live-attenuated, single dose investigational vaccine candidate targeting the chikungunya virus, which has spread to over 100 countries. It has been designed by deleting a part of the chikungunya virus genome.
Valneva reported final data from the pivotal Phase 3 trial of VLA1553 in March 2022[7] and final lot-to-lot consistency results in May 2022[8].
If approved, VLA1553 would expand Valneva’s existing commercial vaccines portfolio and as such, Valneva intends to commercialize this vaccine, leveraging its existing manufacturing and commercial operations.
To make VLA1553 more accessible to Low- and Middle-Income Countries (LMIC), Valneva and Instituto Butantan in Brazil signed an agreement in January 2021 for the development, manufacturing and marketing of VLA1553[9]. The collaboration falls within the framework of the agreement signed between CEPI and Valneva in July 2019[10], which provides funding of up to $23.4 million with support from the European Union’s Horizon 2020 program.
About Valneva SE
Valneva is a specialty vaccine company focused on the development and commercialization of prophylactic vaccines for infectious diseases with significant unmet medical need. The Company takes a highly specialized and targeted approach to vaccine development and then applies its deep understanding of vaccine science to develop prophylactic vaccines addressing these diseases. Valneva has leveraged its expertise and capabilities both to successfully commercialize two vaccines and to rapidly advance a broad range of vaccine candidates into and through the clinic, including candidates against Lyme disease, the chikungunya virus and COVID-19.
Valneva stock rises as it seeks FDA approval of single-shot chikungunya vaccine
Dec. 23, 2022 5:03 AM ET
By: Ravikash, SA News Editor
- Valneva (NASDAQ:VALN) (OTCPK:INRLF) said it completed a rolling submission of an application to the U.S. Food and Drug Administration (FDA) seeking approval of its single-shot chikungunya vaccine VLA1553 in people aged 18 years and above.
- https://seekingalpha.com/news/3920173-valneva-stock-rises-as-it-seeks-fda-approval-of-single-shot-chikungunya-vaccine
- Valneva SE (VALN), INRLF
- https://valneva.com/research-development/chikungunya/
BNT163
VLA1553 a live-attenuated, single dose investigational vaccine candidate targeting chikungunya virus
ABI-H3733 and ABI-4334
BioNTech Starts Phase 1 Clinical Trial for Prophylactic Herpes Simplex Virus-2 Vaccine Candidate BNT163
- First-in-human study aims to evaluate the safety and immunogenicity of prophylactic herpes virus vaccine candidate BNT163
- BNT163 is the first candidate from BioNTech’s infectious disease mRNA vaccine collaboration with the University of Pennsylvania to enter the clinic
- The program is part of BioNTech’s strategy to address diseases with high unmet medical need, as no vaccine has been approved for prevention of genital lesions caused by HSV
MAINZ, Germany, December 21, 2022 – BioNTech SE
(Nasdaq: BNTX, “BioNTech” or the "Company”) today announced that the first subject was dosed in a first-in-human Phase 1 clinical research study with BNT163, a herpes simplex virus (HSV) vaccine candidate for the prevention of genital lesions caused by HSV-2 and potentially HSV-1. The trial (NCT05432583) will evaluate the safety, tolerability, and immunogenicity of BNT163. The mRNA vaccine encodes three HSV-2 glycoproteins with the aim of helping to prevent HSV cellular entry and spread, as well as counteract the immunosuppressive properties of HSVs.
According to the World Health Organization (“WHO”), approximately 500 million people globally are estimated to be affected by genital infections caused by HSV-2,1 with painful genital lesions, an increased risk for meningitis and high levels of emotional distress. Once acquired, HSV persists lifelong in the body with reoccurring symptomatic outbreaks. Moreover, HSV-2 infection increases the risk of acquiring HIV infections by approximately three-fold, and co-infections with both HIV and HSV-2 increase the likelihood of transmitting HIV to others according to the WHO.2 No vaccine has been approved for prevention of genital lesions caused by HSV to date. Currently available HSV therapies only reduce the severity and frequency of symptoms.
BioNTech’s placebo-controlled, observer blinded, dose-escalation Phase 1 trial is expected to enroll around 100 healthy volunteers aged 18 to 55 years without current or history of symptomatic genital herpes infections in the U.S. The study consists of a first dose escalation part that will focus on safety evaluations and assess the optimal dose-response in various dose levels. The second part of the trial is designed to expand the safety characterization for the selected dosing of BNT163 for a more comprehensive assessment of the impact of pre-existing immunity to HSV-1 and -2 on the safety and BNT163-induced immune responses.
“This program is part of our strategy to help address diseases with a high unmet medical need and of global health relevance by combining our new technologies such as mRNA and our expertise in immune engineering,” said Prof. Özlem Türeci, M.D., Chief Medical Officer and Co-Founder of BioNTech. “BNT163 is based on three non-infectious mRNA-encoded HSV-2 glycoproteins. We aim to induce a broad immune response which is directed against multiple antigens of the virus and mobilizes various immune effectors to support virus neutralization and clearance.”
“HSV-2 is a very challenging and life-altering disease which can only be partially prevented. My colleagues and I are proud to have contributed to the early development and preclinical testing of this exciting new mRNA vaccine candidate that may have the potential to prevent people from contracting the virus,” said Prof. Harvey M. Friedman, M.D., Professor of Infectious Diseases at the University of Pennsylvania’s Perelman School of Medicine, who conducted preclinical and discovery science work on HSV and is the University of Pennsylvania’s principal investigator for the preclinical discovery and IND-enabling studies.
In 2018, Penn and BioNTech entered a research collaboration and license agreement to develop novel mRNA vaccine candidates for the prevention and treatment of various infectious diseases. Under the terms of the agreement, BioNTech can obtain an exclusive worldwide license to further develop and commercialize product candidates arising from the research collaboration. After completion of all IND-enabling studies, BNT163 is the first candidate from this collaboration to enter the clinic.
Editor’s Note: The University of Pennsylvania has licensed some intellectual property related to the BNT163 vaccine candidate to BioNTech. The University of Pennsylvania receives sponsored research funding from BioNTech related to preclinical development of the BNT163 vaccine candidate. As inventors of certain intellectual property related to the BNT163 vaccine candidate, some of the scientists involved in the preclinical development of the candidate along with Penn, may receive additional financial benefits under the BioNTech license in the future.
About BioNTech
Biopharmaceutical New Technologies is a next generation immunotherapy company pioneering novel therapies for cancer and other serious diseases. The Company exploits a wide array of computational discovery and therapeutic drug platforms for the rapid development of novel biopharmaceuticals. Its broad portfolio of oncology product candidates includes individualized and off-the-shelf mRNA-based therapies, innovative chimeric antigen receptor T cells, bispecific immune checkpoint modulators, targeted cancer antibodies and small molecules. Based on its deep expertise in mRNA vaccine development and in-house manufacturing capabilities, BioNTech and its collaborators are developing multiple mRNA vaccine candidates for a range of infectious diseases alongside its diverse oncology pipeline. BioNTech has established a broad set of relationships with multiple global pharmaceutical collaborators, including Genmab, Sanofi, Genentech, a member of the Roche Group, Regeneron, Genevant, Fosun Pharma, and Pfizer. For more information, please visit www.BioNTech.com.
BioNTech starts phase 1 trial of mRNA herpes vaccine
Dec. 21, 2022 7:46 AM ET
By: Ravikash, SA News Editor
- BioNTech (NASDAQ:BNTX) said the first person was dosed in a phase 1 trial of its mRNA herpes simplex virus (HSV) vaccine candidate BNT163 to prevent genital lesions caused by HSV-2 and potentially HSV-1.
- https://seekingalpha.com/news/3919346-biontech-starts-phase-1-trial-of-mrna-herpes-vaccine
- BioNTech SE (BNTX)
- https://www.biontech.com/int/en/home/pipeline-and-products/pipeline.html
- https://www.biontech.com/int/en/home.html
ABI-H3733 and ABI-4334
ABI-H3733 and ABI-4334
ABI-H3733 and ABI-4334
Assembly Biosciences Announces Promising Interim Results from Two Clinical Trials Evaluating Highly Potent Next-Generation Core Inhibitor Candidates ABI-H3733 and ABI-4334
December 19, 2022 at 8:01 AM EST
- In initial ABI-H3733 cohort of 50 mg in 28-day Phase 1b study, six of eight HBV patients on treatment reached lower limit of quantification for HBV DNA by day 21 and patients showed a mean reduction of 3.1 logs in plasma HBV DNA
- Initial ABI-4334 Phase 1a single-dose 30 mg cohort demonstrated pharmacokinetic profile supportive of once-daily oral dosing and provides early indication that ABI-4334's very high potency seen preclinically can be accessed clinically
- No serious adverse events or significant laboratory abnormalities including alanine aminotransferase (ALT) elevation were observed in either study
- Given potent antiviral activity in the initial 50 mg cohort, second 25 mg cohort ongoing in Phase 1b trial of ABI-H3733 to explore dose-response curve; 100 mg cohorts ongoing for both studies with further data expected in Q1 2023
SOUTH SAN FRANCISCO, Calif., Dec. 19, 2022 (GLOBE NEWSWIRE) -- Assembly Biosciences, Inc. (Nasdaq: ASMB), a clinical-stage biotechnology company developing innovative, investigational therapeutics targeting hepatitis B virus (HBV) and other viral diseases, today announced promising interim efficacy, safety and pharmacokinetic (PK) results from two ongoing clinical studies of its investigational next-generation HBV core inhibitors, a Phase 1b clinical study of ABI-H3733 (3733) and a Phase 1a clinical study of ABI-4334 (4334).
“We are excited to see that these interim results from ongoing Phase 1 studies of our next-generation core inhibitors 3733 and 4334 are exceeding our expectations for key elements of the clinical profile we’re looking for to impact chronic HBV infection,” said John McHutchison, AO, MD, chief executive officer of Assembly Bio.
Assembly Bio specifically designed 3733 and 4334 to optimize potency against both new virus production (first mechanism) and formation of covalently closed circular DNA (cccDNA), the viral reservoir (second mechanism). Both compounds have demonstrated significantly increased potency preclinically against both mechanisms compared to first-generation core inhibitors. This increased potency, particularly against cccDNA formation, is critical to Assembly Bio’s HBV strategy to bring finite therapies and cures for those living with chronic HBV (cHBV) infection.
“In this first look at antiviral activity for 3733 in the Phase 1b study, we are seeing steep declines in HBV DNA at the low starting dose of 50 mg,” continued Dr. McHutchison. “The antiviral activity from this cohort against the first mechanism surpasses both what we demonstrated preclinically for 3733 as well as what we saw clinically in similar time frames with our first-generation core inhibitors at much higher doses. We are also highly encouraged by the initial pharmacokinetic data from our first-in-human clinical study of our most potent core inhibitor, 4334, which show the potential to reach high levels of activity against both mechanisms clinically at a low dose.”
Jason Okazaki, president and chief operating officer and CEO-elect of Assembly Bio, concluded, “With 100 mg cohorts of both 3733 (28-day dosing) and 4334 (single dose) underway, we are eager to see and share data in early 2023 that we anticipate will drive the optimal dose selection to maximize activity against both mechanisms of action. While early, we believe the interim results in both studies are an encouraging indication that the preclinical potency documented for our next-generation core inhibitors against the second mechanism of cccDNA formation will translate into the clinic with longer-term dosing.”
Complete results of these clinical trials, when available, together with ongoing nonclinical and chronic toxicity studies, will inform future clinical development planning for Assembly Bio’s next-generation core inhibitor programs.
Phase 1b Study for 3733 – Study ABI-H3733-102
The ongoing Phase 1b clinical trial is a randomized, multi-center, double-blind and placebo-controlled study evaluating the safety, PK and antiviral activity of 3733, including changes in HBV DNA and other viral parameters associated with 3733 treatment in adults with cHBV infection who are treatment naïve or off treatment. Patients were randomized 8:2 between the new tablet formulation of 3733 and placebo for a period of 28 days. The patient population for the data included here consists primarily of e-antigen negative patients. The study remains externally blinded, so individual patient data are not provided.
The dose selected for the first cohort was 50 mg. Given the potent antiviral activity observed at 50 mg, a 25 mg dose was selected for the second cohort to further explore the dose response curve of 3733. A dose of 100 mg has been selected for the third cohort, for which dosing is ongoing with initial data anticipated in the first quarter of 2023.
50 mg Cohort Efficacy (Viral Nucleic Acids):
As of the data cutoff date of December 18, 2022, dosing in the 3733 Phase 1b trial has been completed for all 10 patients in the first cohort of 50 mg. Nine of 10 patients enrolled were HBeAg negative, so efficacy data are provided for these patients. Interim efficacy results from this cohort at the data cutoff date include HBV DNA, HBV RNA and antigen measurements for all patients for the full 28-day dosing period.
In the 50 mg cohort, six of eight patients receiving 3733 achieved HBV DNA less than the lower limit of quantification (<LLOQ) within 21 days, with a mean decline in HBV DNA over the treatment period of approximately 3.1 logs. Data on HBV RNA declines were limited due to low baseline levels in predominantly e-antigen negative patients.
25 mg Cohort Efficacy (Viral Nucleic Acids):
The second cohort, evaluating a dose of 25 mg, is fully enrolled. Nine of 10 patients enrolled were HBeAg negative, so efficacy data are provided for these patients. In the five patients that have so far completed 28 days of treatment, the mean reduction in HBV DNA was approximately 1.9 logs. Data on HBV RNA levels were not available as of the data cutoff date.
50 and 25 mg Cohorts (Safety, PK and Viral Antigens):
Safety data reported here reflect data received for both cohorts through the data cutoff date. In these initial cohorts, all treatment-emergent adverse events (AEs) and laboratory abnormalities reported were Grade 1 or Grade 2. Further, no AEs led to treatment discontinuation, and no clinically significant ECG abnormalities or patterns of AEs or lab abnormalities were noted.
The observed PK for the new tablet formulation of 3733 was consistent with predictions from preclinical studies, providing exposure equivalent to the liquid formulation evaluated in the Phase 1a study for 3733. Clinical PK exposures exhibited dose-proportional increases from 25 mg to 50 mg, as measured by maximum concentration (Cmax) and area-under-curve (AUC).
As expected given the 28-day dosing period, limited changes in viral antigens were observed in both the 50 mg and 25 mg cohorts.
Phase 1a Study for 4334 – Study ABI-4334-101
The Phase 1a clinical trial is a randomized, blinded and placebo-controlled study evaluating the safety, tolerability and PK of 4334 following single ascending dose and multiple ascending dose administration in healthy subjects. The objectives of the study include assessment of the proportion of subjects with AEs, premature treatment discontinuation due to AEs and abnormal laboratory results.
Dosing has completed for all eight subjects in the initial 30 mg single dose cohort. In this cohort, 4334 had a mean half-life of 24 hours, supporting once-a-day (QD) dosing. Based on the PK data from this initial cohort and preclinical studies, daily minimum plasma trough concentrations (Cmin) are projected to achieve double-digit multiples of the protein-adjusted EC50 for both antiviral activity and against cccDNA formation at a low dose of 4334.
In this initial cohort, treatment-emergent AEs and laboratory abnormalities were mild to moderate and all were considered not related to study treatment. There were no clinically significant ECG abnormalities or patterns of AEs or laboratory abnormalities noted.
A dose of 100 mg has been selected for the second single-dose cohort. Dosing for the second cohort is complete and initial data from this cohort are anticipated in the first quarter of 2023.
About Assembly Biosciences
Assembly Bio is a clinical-stage biotechnology company pioneering the development of novel therapeutics for serious viral diseases. Assembly Bio is advancing a leading portfolio of more potent, next-generation core inhibitor drug candidates that aim to break the complex viral replication cycle of hepatitis B virus (HBV) to achieve finite and potentially curative therapies for the 296 million people living with HBV worldwide. The company’s research pipeline includes differentiated antiviral approaches against HBV/hepatitis delta virus and herpesviruses. For more information, visit assemblybio.com.
Assembly Biosciences surges 19% on positive data from two trials to treat hepatitis B virus
Dec. 19, 2022 9:07 AM ET
Assembly Biosciences, Inc. (ASMB)
By: Dania Nadeem, SA News Editor
- Assembly Biosciences (NASDAQ:ASMB) is trading ~19% higher premarket after it announced positive data from two ongoing studies of its investigational hepatitis B virus (HBV) inhibitors, a Phase 1b clinical study of ABI-H3733 and a Phase 1a clinical study of ABI-4334.
- https://seekingalpha.com/news/3918396-assembly-biosciences-surges-19-on-positive-data-from-two-trials-to-treat-hepatitis-b-virus
- Assembly Biosciences, Inc. (ASMB)
- https://www.assemblybio.com/
- https://www.assemblybio.com/pipeline/
resmetirom
ABI-H3733 and ABI-4334
Zolbetuximab
Madrigal Announces Positive Topline Results from the Pivotal Phase 3 MAESTRO-NASH Clinical Trial of Resmetirom for the Treatment of NASH and Liver Fibrosis
- In MAESTRO-NASH, a 52-week serial liver biopsy Phase 3 study in more than 950 patients, resmetirom achieved both primary endpoints and potentially clinically meaningful effects with both daily oral doses, 80 mg and 100 mg, relative to placebo
- NASH resolution (ballooning of 0, inflammation of 0-1) and ≥2-point NAS reduction with no worsening of fibrosis (p<0.0001 at both doses)
- Fibrosis improvement by at least one stage with no worsening of NAS (p=0.0002 and <0.0001 at 80 and 100 mg, respectively)
- Potentially clinically meaningful LDL-lowering, a key secondary endpoint (p<0.0001)
- Multiple positive effects on NASH biomarkers and imaging
- Resmetirom was safe and well-tolerated in the MAESTRO-NASH study, consistent with the overall safety in Phase 3 MAESTRO trials, expanding the large safety database
- Madrigal intends to file a new drug application seeking accelerated approval of resmetirom for the treatment of non-cirrhotic NASH with liver fibrosis
Madrigal to host conference call at 8:00 am ET to review the results
CONSHOHOCKEN, Pa., Dec. 19, 2022 (GLOBE NEWSWIRE) -- Madrigal Pharmaceuticals, Inc. (NASDAQ:MDGL), a clinical-stage biopharmaceutical company pursuing novel therapeutics for nonalcoholic steatohepatitis (NASH), today announced positive topline results from the pivotal Phase 3 MAESTRO-NASH biopsy clinical trial of resmetirom, a liver-directed selective thyroid hormone receptor agonist. MAESTRO-NASH, a registrational Phase 3 trial, has achieved both liver histological improvement endpoints that FDA proposed as reasonably likely to predict clinical benefit to support accelerated approval for the treatment NASH with liver fibrosis.
Becky Taub, M.D., Chief Medical Officer and President of Research & Development of Madrigal, stated, “These pivotal Phase 3 results demonstrate the potential for resmetirom to help patients achieve improvement in both the underlying steatohepatitis that drives this disease and the resulting fibrosis that is associated with progression to cirrhosis and its complications. The topline data also reinforce our confidence in the safety and tolerability profile of resmetirom. We believe the Phase 3 MAESTRO clinical development program, including the MAESTRO-NAFLD-1 and MAESTRO-NAFLD-OLE safety clinical trials and the recently initiated MAESTRO-NASH-OUTCOMES clinical trial, provides a strong foundation for our new drug application (NDA) and the potential accelerated approval of resmetirom for the treatment of non-cirrhotic NASH with liver fibrosis.”
Dr. Taub added, “I want to thank the MAESTRO-NASH investigators and study sites participating in the study, my colleagues on the R&D team at Madrigal, and, most of all, the patients who made achievement of this important milestone possible.”
Stephen Harrison, M.D., Chairman for both Pinnacle Clinical Research and Summit Clinical Research, San Antonio, Texas, Visiting Professor of Hepatology, Oxford University, and lead Principal Investigator of the MAESTRO studies, commented, “NASH with liver fibrosis puts patients at risk of progressing to liver failure, liver cancer, need for liver transplant, and premature mortality; with no approved treatment, this disease represents one of the most urgent unmet needs in healthcare today. These unprecedented results from the MAESTRO-NASH clinical trial signal a major turning point for the field.”
Paul Friedman, M.D., Chief Executive Officer of Madrigal, stated, “MAESTRO-NASH achieved both primary endpoints proposed by the FDA as reasonably likely to predict clinical benefit and we have established a large safety database, supported by a second Phase 3 clinical trial (MAESTRO-NAFLD-1) and MAESTRO-NAFLD-OLE, to inform benefit-risk assessment. With these unequivocally positive Phase 3 data in hand, our path forward is clear. In the first half of 2023, we intend to file a new drug application seeking accelerated approval of resmetirom. I want to thank my colleagues for their sustained efforts and strong execution; our team is committed to delivering resmetirom to patients in need.”
MAESTRO-NASH Week 52 Results
MAESTRO-NASH is an ongoing blinded Phase 3 clinical trial, and enrolled patients continue on therapy after the Week 52 liver biopsy for up to a total of 54 months to accrue hepatic clinical outcome events including histologic conversion to cirrhosis and hepatic decompensation events.
Efficacy Results
Patients meeting eligibility requirements for MAESTRO-NASH were randomized 1:1:1 to receive resmetirom 80 mg, resmetirom 100 mg, or placebo taken orally once daily. Baseline characteristics in the 966 randomized patients in the primary analysis NASH population (ITT, safety population) were balanced across treatment arms and include age 57 (10) (mean (SD)), female 56%, white 89%, Hispanic 21%, BMI 36 (7) kg/m2, type 2 diabetes 67%, hypertension 78%, dyslipidemia 71%, hypothyroidism 13%, FibroScan, kilopascals (kPa) 13 (7), CAP 348 (38), MRI-PDFF 18% (7), FIB-4 1.4 (0.7), ALT 55 (32) IU, AST 41 (23) IU, LDL 99 (40) mg/dL, triglycerides 188 (132) mg/dL, hemoglobin A1C 6.6 (1) %, ELF 9.8 (0.9). Medications included 49% on statins, 14% on GLP-1 agonists, 14% on SGLT2 inhibitors. Baseline liver biopsy fibrosis scores included F3 (~60%), F2 (~35%), F1B (~5%) (primary analysis population) with 84% with NAS ≥5 based on independent primary glass slide reads of the entire study by two central pathologists.
A second biopsy was conducted after 52 weeks of treatment for assessment of the dual primary endpoints. The primary efficacy analysis assessed histological response at 52 weeks in 955 patients with biopsy-confirmed NASH with fibrosis (modified intent-to-treat (mITT) population) that excluded 11 ITT patients who had their Week 52 biopsy after Week 60 due to COVID-related reasons per regulatory guidelines. Patients without a second biopsy due to early study discontinuation or missing liver biopsy (~17% across treatment arms) were included and considered as non-responders in the primary efficacy analyses (mITT). The compliance to treatment was high and minimally impacted by COVID pandemic restrictions.
All biopsies were read independently by two central pathologists. Each pathologist's scores showed a similar statistically significant magnitude of response at both doses for both liver biopsy endpoints. Biopsy endpoints were achieved independent of baseline fibrosis stage or diabetes status, including similar statistical significance and magnitude of effect at both doses in subgroups of F2, F3, and F2/F3 patients. Other secondary liver biopsy endpoints that were achieved at both doses include ≥2 point reduction in NAS with no worsening of fibrosis, ≥2 point reduction in NAS with ≥1-stage improvement in fibrosis, NASH resolution (with ≥2 point reduction in NAS) with ≥1-stage improvement in fibrosis, and a 2-stage reduction in fibrosis without worsening of NAS.
Multiple secondary endpoints were achieved, including statistically significant reduction from baseline in liver enzymes (ALT, AST and GGT). Reductions in atherogenic lipids and lipoproteins, fibrosis biomarkers and imaging tests (MRI-PDFF, CAP and liver stiffness measures) were observed in resmetirom treatment arms as compared with placebo.
MAESTRO-NASH included many biomarker and imaging assessments that may be used in real world clinical practice to identify appropriate patients for treatment and monitor response to resmetirom, if approved.
Madrigal intends to submit primary results for publication in a peer-reviewed journal and present study results at a future scientific congress.
Safety Results
Resmetirom was safe and well-tolerated at both the 80 mg and 100 mg doses. The frequency of serious adverse events (SAEs) was similar across treatment arms: 11.8%, 12.7% and 12.1% for the 80 mg, 100 mg, and placebo groups, respectively. The rate of study discontinuation for adverse events was low: 2.8%, 7.7% and 3.7% for the 80 mg, 100 mg and placebo groups, respectively. SAEs occurred at expected rates based on the patient population.
Consistent with previous Phase 2 and Phase 3 data, the most common adverse events reported with greater frequency in the resmetirom groups vs placebo were an excess of generally mild and transient diarrhea at the beginning of therapy, in 28%, 34%, 16% in the 80 mg, 100 mg and placebo groups, respectively, and generally mild nausea that occurred at rates of 22%, 19% and 13% in the 80 mg, 100 mg and placebo arms, respectively.
About the Resmetirom Phase 3 Registration Program for the Treatment of NASH
Madrigal is currently conducting four Phase 3 clinical trials to demonstrate the safety and efficacy of resmetirom for the treatment of NASH: MAESTRO-NASH, MAESTRO-NAFLD-1, MAESTRO-NAFLD-OLE, and MAESTRO-NASH-OUTCOMES.
MAESTRO-NASH is a multicenter, randomized, double-blind, placebo-controlled Phase 3 study of resmetirom in patients with liver biopsy-confirmed NASH and was initiated in March 2019. The subpart H portion of the study enrolled more than 1,000 patients with biopsy-proven NASH (at least half with F3 (advanced) fibrosis, the remainder F2 or F1B (moderate fibrosis) with a few earlier F1 patients), randomized 1:1:1 to receive once-daily resmetirom 80 mg, resmetirom 100 mg, or placebo. After 52 weeks of treatment, a second liver biopsy is performed. The dual primary surrogate endpoints on biopsy are NASH resolution with ≥2-point reduction in NAS (NAFLD Activity Score), and with no worsening of fibrosis OR a 1-point decrease in fibrosis with no worsening of NAS. Achievement of either primary endpoint is considered a successful trial outcome. A key secondary endpoint is lowering of LDL-C.
All patients enrolled in the MAESTRO-NASH study (up to 2,000 in total) continue on therapy after the initial 52-week treatment period for up to 54 months to accrue and measure hepatic clinical outcome events including progression to cirrhosis on biopsy (52 weeks and 54 months) and hepatic decompensation events, as well as all-cause mortality.
MAESTRO-NAFLD-1 was initiated in December 2019 and the 52-week multicenter, randomized, placebo-controlled Phase 3 study of resmetirom in over 1,200 patients with NAFLD, presumed NASH, has completed the double-blind arms and an open-label 100 mg arm. An additional open-label active treatment arm in patients with early (well-compensated) NASH cirrhosis is ongoing. The primary endpoint was to evaluate the safety and tolerability of resmetirom. A separate 52 week Phase 3 clinical trial, an open-label extension study of MAESTRO-NAFLD-1 (MAESTRO-NAFLD-OLE), is ongoing.
Patients in the 52-week Phase 3 MAESTRO-NAFLD-1 study were randomized 1:1:1:1 to receive once-daily resmetirom 80 mg, resmetirom 100 mg, placebo in double-blind arms or resmetirom 100 mg in an open-label arm. MAESTRO-NAFLD-1 (unlike MAESTRO-NASH), did not include a liver biopsy and represents a “real-life” NASH study. Patients with 3 metabolic risk factors were documented with NASH or NAFLD by historical liver biopsy or noninvasive techniques. Using noninvasive measures, MAESTRO-NAFLD-1 was designed to provide incremental safety information to support the NASH indication as well as provide additional data regarding clinically relevant key secondary efficacy endpoints to better characterize the potential clinical benefits of resmetirom on cardiovascular- and liver-related endpoints. The primary safety endpoint and several key secondary endpoints were met, including LDL-C, apolipoprotein B, and triglyceride lowering and reduction of liver fat as determined by MRI-PDFF. Additional secondary and exploratory endpoints were assessed including reduction in liver enzymes, FibroScan, and MRE scores, and other NASH biomarkers.
Data from the 52-week first 1,000 patient portion of MAESTRO-NASH, together with data from MAESTRO-NAFLD-1, MAESTRO-NAFLD-OLE, Phase 2 and Phase 1 data, including safety parameters, will form the basis for a potential subpart H submission to FDA for accelerated approval of resmetirom for treatment of NASH.
In August 2022, Madrigal initiated MAESTRO-NASH-OUTCOMES, a randomized double-blind placebo-controlled study in approximately 700 patients with early NASH cirrhosis to allow for noninvasive monitoring of progression to liver decompensation events. A positive outcome is expected to support the full approval of resmetirom for noncirrhotic NASH, potentially accelerating the timeline to full approval. In addition, this study has the potential to support an additional indication for resmetirom in patients with well-compensated NASH cirrhosis.
About NASH
Nonalcoholic steatohepatitis (NASH) is a more advanced form of nonalcoholic fatty liver disease (NAFLD). NAFLD is estimated to afflict more than 20% of adults globally, about 30% in the United States. Of that population, 20% may have NASH.
NASH is a leading cause of liver related mortality and an increasing burden on healthcare systems globally. Additionally, patients with NASH, especially those with more advanced metabolic risk factors (hypertension, concomitant type 2 diabetes), are at increased risk for adverse cardiovascular events and increased morbidity and mortality.
Once NASH progresses to significant liver fibrosis (stages F2 and F3) the risk of adverse liver outcomes increases dramatically. NASH is rapidly becoming the leading cause of liver transplantation in the U.S. There are currently no FDA-approved therapies available for the treatment of NASH.
About Madrigal Pharmaceuticals
Madrigal Pharmaceuticals, Inc. (Nasdaq: MDGL) is a clinical-stage biopharmaceutical company pursuing novel therapeutics for nonalcoholic steatohepatitis (NASH), a liver disease with high unmet medical need. Madrigal’s lead candidate, resmetirom, is a once daily, oral, thyroid hormone receptor (THR)-β selective agonist designed to target key underlying causes of NASH in the liver. For more information, visit www.madrigalpharma.com.
Source: Madrigal Pharmaceuticals, Inc.
Madrigal up 210% on positive late-stage results for NASH candidate resmetirom
Dec. 19, 2022 8:48 AM ET
Madrigal Pharmaceuticals, Inc. (MDGL)VKTX
By: Jonathan Block, SA News Editor5 Comments
- Madrigal Pharmaceuticals (NASDAQ:MDGL) is up 210% in premarket trading after releasing late-stage results on resmetirom for nonalcoholic steatohepatitis (NASH) and liver fibrosis.
- https://seekingalpha.com/news/3918385-madrigal-up-210-on-positive-late-stage-results-for-nash-liver-candidate-resmetirom
- Madrigal Pharmaceuticals, Inc. (MDGL)
- https://www.madrigalpharma.com/our-programs/resmetirom/
- https://www.madrigalpharma.com/
Zolbetuximab
ABI-H3733 and ABI-4334
Zolbetuximab
Astellas Announces Zolbetuximab Meets Primary Endpoint in Phase 3 GLOW Trial as First-Line Treatment in Claudin 18.2 Positive, HER2-negative Locally Advanced Unresectable or Metastatic Gastric and Gastroesophageal Junction (GEJ) Cancers
Astellas' GLOW trial, the second Phase 3 trial in CLDN18.2 positive, HER2-negative locally advanced unresectable or metastatic gastric and GEJ cancers, meets primary endpoint for progression-free survival (PFS) and key secondary endpoint for overall survival (OS)
GLOW results, along with SPOTLIGHT topline results, mark progress in Astellas' gastric cancer development program
TOKYO, Dec. 15, 2022 /PRNewswire/ -- Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") today announced positive topline results from the Phase 3 GLOW clinical trial evaluating the efficacy and safety of zolbetuximab in combination with CAPOX (a combination chemotherapy regimen that includes capecitabine and oxaliplatin). Zolbetuximab is an investigational first-in-class Claudin-18.2 (CLDN18.2) targeted monoclonal antibody, for the first-line treatment of patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.
The GLOW study met its primary endpoint showing statistical significance in progression-free survival (PFS) for patients treated with zolbetuximab plus CAPOX compared to placebo plus CAPOX. In addition, the study met a key secondary endpoint, overall survival (OS), showing statistical significance for patients treated with zolbetuximab plus CAPOX compared to placebo plus CAPOX. The most frequent treatment-emergent adverse events (TEAEs) were nausea and vomiting. Detailed results will be presented at a future scientific congress and submitted for publication.
"Zolbetuximab has the potential to be an innovative therapeutic option for patients with locally advanced unresectable or metastatic gastric or GEJ cancer, a difficult disease for which treatment options are still limited," said Ruihua Xu, MD, PhD, Primary Investigator for the GLOW study and Professor in the Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China. "I am so pleased with the topline results from GLOW that establish progression-free survival and overall survival in patients treated with zolbetuximab plus CAPOX."
"We are extremely pleased to share positive topline results from GLOW following the positive SPOTLIGHT readout last month. This further confirms the potential role of zolbetuximab in gastric cancer treatment, an important milestone in our gastric cancer development program," said Ahsan Arozullah, MD, MPH, Senior Vice President and Head of Development Therapeutic Areas, Astellas. "We intend to discuss these results with regulatory authorities as we continue to develop zolbetuximab for the first-line treatment of patients with locally advanced unresectable or metastatic gastric and GEJ cancer."
Zolbetuximab acts by binding to CLDN18.2 on the cancer cell surface of gastric epithelial cells. In pre-clinical studies, this binding interaction then induces cancer cell death by activating two distinct immune system pathways – antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).1 CLDN18.2 is a type of transmembrane protein found in normal gastric cells and is a major component of epithelial tight junctions controlling the flow of molecules between cells.2 Pre-clinical studies have shown that CLDN18.2, which is frequently present in gastric tumors, may become more exposed and accessible to targeted antibodies as gastric tumors develop.3,4,5 Based on the SPOTLIGHT and GLOW studies, approximately 38% of these patients have CLDN18.2-positive tumors, meeting the qualification of CLDN18.2 expression in ≥75% of tumor cells with strong to moderate staining intensity based on a validated immunohistochemistry assay.6
The Phase 3 GLOW trial (n=507) is a global, multi-center, double-blind, randomized study assessing the efficacy and safety of zolbetuximab plus CAPOX compared to placebo plus CAPOX. This study, and the Phase 3 SPOTLIGHT trial (n=565), which evaluated the efficacy and safety of zolbetuximab plus a combination regimen of oxaliplatin, leucovorin and fluorouracil (mFOLFOX6) compared to placebo plus mFOLFOX6, were conducted to provide foundational data for regulatory submissions in the U.S., Europe, Asia and other countries globally. These studies are part of Astellas' gastric cancer development program to investigate new treatment options such as zolbetuximab and address patient needs in locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma.
Gastric cancer is often diagnosed in the advanced or metastatic stage, or once it has spread from the tumor's origin to other body tissues or organs.7 The five-year relative survival rate for patients at the metastatic stage is approximately six percent.8,9
About Zolbetuximab
Zolbetuximab is an investigational, first-in-class chimeric IgG1 monoclonal antibody (mAb) that targets and binds to CLDN18.2, a transmembrane protein. Zolbetuximab acts by binding to CLDN18.2 on the cancer cell surface of gastric epithelial cells. In pre-clinical studies, this binding interaction then induces cancer cell death by activating two distinct immune system pathways — antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).1 The safety and efficacy of zolbetuximab are under investigation in gastric, gastroesophageal and pancreatic cancers and have not been established. There is no guarantee the agent will receive regulatory approval or become commercially available for the uses being investigated.
About GLOW Phase 3 Clinical Trial
GLOW is a Phase 3, global, multi-center, double-blind, randomized study, assessing the efficacy and safety of zolbetuximab (IMAB362) plus CAPOX (a combination chemotherapy regimen which includes capecitabine and oxaliplatin) compared to placebo plus CAPOX as a first-line treatment of patients with CLDN18.2 positive, HER2- negative, locally advanced unresectable or metastatic gastric or GEJ cancer. The study enrolled 507 patients at 165 study locations in the U.S., Canada, United Kingdom, Europe, South America and Asia. The primary endpoint is progression-free survival of participants treated with combination of zolbetuximab plus CAPOX compared to those treated with placebo plus CAPOX. Secondary endpoints include overall survival, objective response rate, duration of response, safety and tolerability and quality-of-life parameters.
For more information, please visit clinicaltrials.gov under Identifier NCT03653507.
About SPOTLIGHT Phase 3 Clinical Trial
SPOTLIGHT is a Phase 3, global, multi-center, double-blind, randomized study, assessing the efficacy and safety of zolbetuximab (IMAB362) plus mFOLFOX6 (combination regimen of oxaliplatin, leucovorin and fluorouracil) compared to placebo plus mFOLFOX6 as a first-line treatment of patients with CLDN18.2-positive, HER2- negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction cancer. The study enrolled 565 patients at 220 study locations in the U.S., United Kingdom, Australia, Europe, South America and Asia. The primary endpoint is progression-free survival of participants treated with combination of zolbetuximab plus mFOLFOX6 compared to those treated with placebo plus mFOLFOX6. Secondary endpoints include overall survival, objective response rate, duration of response, safety and tolerability and quality-of-life parameters.
For more information, please visit clinicaltrials.gov under Identifier NCT03504397
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.
Astellas zolbetuximab shows survival benefit, meets main goal in 2nd gastric cancer trial
Dec. 16, 2022 6:29 AM ET
Astellas Pharma Inc. (ALPMY), ALPMF
By: Ravikash, SA News Editor
Astellas Pharma (OTCPK:ALPMF) (OTCPK:ALPMY) said its drug zolbetuximab, in combination with CAPOX, met the main goal of progression-free survival (PFS) in patients with gastric cancer in a phase 3 trial.
Astellas Pharma Inc. (ALPMY), ALPMF
https://www.astellas.com/en/system/files/2q2022_pip_en_1.pdf
biotecHOPE™ 2022
MVP-S, in combination with pembrolizumab
MVP-S, in combination with pembrolizumab
MVP-S, in combination with pembrolizumab
IMV Inc. Announces Initial Data from the Ongoing Phase 2B VITALIZE Trial in Patients with r/r DLBCL
DECEMBER 15, 2022 7:05AM EST
Complete responses were observed in patients who received at least three previous lines of treatment (including CAR-T's)
Recent clinical data add to the growing enthusiasm for the therapeutic potential of cancer vaccines in combination with checkpoint inhibitors
Oral presentation of the clinical data at the Immuno-Oncology 360° conference in February 2023
DARTMOUTH, Nova Scotia, & CAMBRIDGE, Mass.--(BUSINESS WIRE)-- IMV Inc. (Nasdaq: IMV; TSX: IMV) (“IMV” or the “Company”), a clinical-stage biopharmaceutical company developing a portfolio of immune-educating therapies based on its novel DPX® platform to treat solid and hematologic cancers, today announced positive initial patient data from the VITALIZE Phase 2B trial evaluating its lead DPX product, MVP-S, in combination with pembrolizumab in patients with relapsed, refractory Diffuse Large B Cell Lymphoma (“r/r DLBCL”) who received at least three previous lines of treatment. Detailed results will be presented in a podium presentation at the Immuno-Oncology 360° conference to be held in New York City on February 7-10, 2023.
“The initial clinical data from the VITALIZE trial are encouraging and the accelerating recruitment in this study reflects a growing interest for this therapeutic combination in DLBCL,” said Dr. Matthew Matasar, Chief of Blood Disorders at Rutgers Cancer Institute of New Jersey and RWJBarnabas Health, and primary investigator of the VITALIZE trial. He added: “We find it remarkable that we have seen complete responses in this trial in patients that were refractory to prior cellular therapy and other advanced therapies.”
“Positive initial results for the VITALIZE trial are an important development milestone for MVP-S” said Andrew Hall, CEO of IMV “Alongside other compelling cancer vaccine data announced this week, these data on MVP-S highlight renewed interest in the potential for cancer vaccines as a therapeutic class.”
Andrew Hall added “A well-tolerated, easy-to-administer therapy, such as MVP-S, that provides durable clinical benefit is meaningful for patients who have already been subject to aggressive, toxic treatment regimens. Clinical activity in a highly refractory patient population may represent a path to registration in DLBCL.”
About the VITALIZE Study
The VITALIZE Phase 2B trial is a randomized, parallel group, Simon two-stage study designed to assess IMV’s lead candidate, MVP-S, in combination with pembrolizumab with or without cyclophosphamide. Across the arms of this study, the combination will be evaluated in up to 102 subjects with r/r DLBCL who have received at least two prior lines of systemic therapy and who are ineligible or have failed autologous stem cell transplant (ASCT) or CAR-T therapy.
The primary endpoint is Objective Response Rate (ORR), centrally evaluated per Lugano (2014) and measured by the number of subjects per arm achieving a best clinical response of Partial or Complete Response (PR+CR) during the 2-year treatment period. All subjects will be evaluated for their baseline PD-L1 expression. Exploratory endpoints include evaluation of cell-mediated immune response, tumor immune cell infiltration, and other biomarker analyses.
About IMV
IMV Inc. is a clinical-stage immuno-oncology company advancing a portfolio of therapies based on the Company’s immune-educating platform, DPX®. Through a differentiated mechanism of action, the DPX platform delivers instruction to the immune system to generate a specific, robust, and persistent immune response. IMV’s lead candidate, maveropepimut-S (MVP-S), delivers antigenic peptides from survivin, a well-recognized cancer antigen commonly overexpressed in advanced cancers. MVP-S also delivers an innate immune activator and a universal CD4 T cell helper peptide. These elements foster maturation of antigen presenting cells as well as robust activation of CD8 T cell effector and memory function. MVP-S treatment has been well tolerated and has demonstrated defined clinical benefit in multiple cancer indications as well as the activation of a targeted and sustained, survivin-specific anti-tumor immune response. MVP-S is currently being evaluated in clinical trials for hematologic and solid cancers, including Diffuse Large B Cell Lymphoma (DLBCL) as well as ovarian, bladder and breast cancers. IMV is also developing a second immunotherapy leveraging the DPX immune delivery platform, DPX-SurMAGE. This dual-targeted immunotherapy combines antigenic peptides for both the survivin and MAGE-A9 cancer proteins to elicit immune responses to these two distinct cancer antigens simultaneously. A Phase 1 clinical trial in bladder cancer, using MVP-S or DPX-SurMAGE, was initiated in early 2022. For more information, visit www.imv-inc.com and connect with us on Twitter and LinkedIn.
View source version on businesswire.com: https://www.businesswire.com/news/home/20221215005319/en/
Source: IMV Inc.
Released December 15, 2022
IMV surges 40% on positive initial data from trial to treat Diffuse Large B Cell Lymphoma
Dec. 15, 2022 8:57 AM ET
By: Dania Nadeem, SA News Editor
- IMV (NASDAQ:IMV) is trading ~40% higher premarket after a mid-stage trial testing its lead DPX product, MVP-S, in combination with Merck's drug Keytruda (pembrolizumab) to treat relapsed, refractory Diffuse Large B Cell Lymphoma showed complete response in patients who received at least three previous lines of treatment.
- https://seekingalpha.com/news/3917557-imv-surges-40-on-positive-initial-data-from-trial-to-treat-diffuse-large-b-cell-lymphoma
- IMV Inc. (IMV), IMV:CA
- https://www.imv-inc.com/product-pipeline/maveropepimut-S
KT-474 (IRAK4)
MVP-S, in combination with pembrolizumab
MVP-S, in combination with pembrolizumab
Kymera Announces Positive Results from Phase 1 Clinical Trial Evaluating KT-474 in Patients with HS and AD and Sanofi’s Decision to Advance KT-474 into Phase 2 Clinical Trials
Dec 14, 2022
KT-474 Phase 1 clinical data in HS and AD patients demonstrate robust IRAK4 knockdown in blood and active skin lesions and systemic suppression of proinflammatory cytokines and chemokines with a favorable safety profile
Clinical endpoints addressing disease burden and symptoms demonstrate a highly competitive profile after four weeks of dosing, with substantial responses in majority of both HS and AD patients
Modest, non-adverse QTc prolongation spontaneously resolves back to baseline during the 4-week dosing period
Sanofi has committed to advance KT-474 (SAR444656) into Phase 2 clinical trials
Oncology programs KT-413 and KT-333 demonstrate substantial target knockdown in ongoing Phase 1a dose escalation clinical trials, with no dose limiting toxicities observed
MDM2 (KT-253) IND cleared by FDA; Phase 1 to start in early 2023
Kymera to host webcast today at 8:00 a.m. EST; webcast link available here.
WATERTOWN, Mass., Dec. 14, 2022 (GLOBE NEWSWIRE) -- Kymera Therapeutics, Inc. (NASDAQ: KYMR), a clinical-stage biopharmaceutical company advancing targeted protein degradation (TPD) to deliver novel small molecule protein degrader medicines, today announced positive clinical results from the patient cohort portion of its KT-474 (IRAK4) Phase 1 clinical trial, as well as updates on its three oncology programs: KT-413 (IRAKIMiD), KT-333 (STAT3) and KT-253 (MDM2).
“This is a pivotal moment for Kymera and for the field of protein degradation,” said Nello Mainolfi, PhD, Founder, President and CEO. “Kymera was founded to harness the enormous potential of targeted protein degradation and bring more effective therapies to patients. We believe that, for the first time, we have demonstrated clinical impact of a degrader, KT-474, outside of oncology and in complex inflammatory diseases such as HS and AD. We have also demonstrated the superior clinical potential of an IRAK4 degrader over a small molecule inhibitor, validating our platform and target selection strategy. In addition, we are excited that programs from our oncology pipeline continue to show fidelity of translation of PK, PD and safety from preclinical to human patients, validating our proprietary molecular design and translational quantitative system pharmacology modelling. We are on track to achieve our ambitious objectives of building a disease- and technology-agnostic, fully integrated global biopharmaceutical company that will continue to advance degrader drugs with potentially best-in-class, differentiated profiles across multiple indications.”
IRAK4 Degrader (KT-474)
Part C of Kymera’s KT-474 Phase 1 clinical trial was designed to confirm that the PK/PD and safety data previously demonstrated in healthy volunteers would translate into patients with hidradenitis suppurativa (HS) and atopic dermatitis (AD). Data was also collected on the change in circulating inflammatory biomarkers and proinflammatory gene transcripts in the patients’ skin, as well as on multiple clinical endpoints.
“The patient cohort results exceeded our expectations for a trial with only 4 weeks of dosing, demonstrating not only robust IRAK4 degradation in blood and skin with a favorable safety profile comparable to what was observed in healthy volunteers, but also a systemic anti-inflammatory response associated with improvement in skin lesions and symptoms in both HS and AD patients,” said Jared Gollob, MD, Chief Medical Officer. “We believe these results provide the first clinical validation for targeting the IRAK4 pathway with a degrader in TLR/IL-1R-driven inflammatory diseases, with KT-474 exhibiting activity that is clearly differentiated from IRAK4 small molecule kinase inhibitors and that has the potential to improve the lives of patients with HS and AD.”
Sanofi, which is collaborating with Kymera on the development of KT-474 (SAR444656) outside of the oncology and immune-oncology fields, has notified Kymera of its commitment to advance KT-474 into Phase 2 clinical studies. Initial Phase 2 clinical trial of KT-474 will investigate its potential in HS and AD with the first study initiating in 2023.
“The HS and AD patient data are encouraging as they highlight the broad potential of KT-474 and continue to validate Sanofi’s commitment to the target and to TPD’s unique ability to unlock this critical pathway,” said Naimish Patel, MD, Head of Global Development, Immunology and Inflammation at Sanofi. “We look forward to advancing the program into Phase 2 studies, and the potential that KT-474 offers to patients with a variety of immunological conditions.”
Study Design: Part C patients were dosed for 28 days and subsequently followed for an additional 2 weeks out to Day 42. Patients received 75 mg of KT-474 once daily in the fed state. That dose was selected to achieve similar exposures to healthy volunteers in the multiple ascending dose (MAD) portion of the Phase 1 clinical trial who received 100 mg in the fasted state (MAD3).
Baseline Characteristics and Disposition: A total of 21 patients were enrolled in the trial, including 13 HS and 8 AD patients, with median age 31-40 years (13 female, 8 male). Disease severity for HS was moderate (10), severe (1) and very severe (2) and for AD was mild (1), moderate (5) and severe (2). One HS and 1 AD patient withdrew from treatment early due to personal reasons, resulting in 12 HS and 7 AD patients evaluable for PD and clinical efficacy.
Pharmacokinetics/IRAK4 Pharmacodynamics: In patients with HS and AD, KT-474 demonstrated plasma PK in Part C that was comparable to healthy volunteers in MAD3. Baseline IRAK4 level in skin lesions of HS and AD patients was approximately two-fold higher compared to healthy volunteers. KT-474 demonstrated IRAK4 knockdown in both blood and skin that was comparable to MAD3, with maximum degradation exceeding 90%. Target degradation was similar across HS and AD patients in both blood and skin.
Activity Against Biomarkers of Inflammation: In ex vivo cytokine stimulation assays, KT-474 demonstrated broad and deep inhibition of multiple disease-relevant cytokines, including inhibition of up to 84% in HS and up to 98% in AD. Cytokine reductions across both patient groups in Part C were comparable or superior to what was observed in MAD3. KT-474 also reduced several circulating cytokines and acute phase reactants in vivo such as IL-6, CRP, IL-1b and serum amyloid A (SAA). In serial biopsies of skin lesions, proinflammatory gene transcripts that were strongly downregulated in at least 50% of evaluable patients included but not limited to: IL-5, NLRP3, CXCL1 and IL-2RB in AD and IL-1b, IL-36A, IL-17A, IFN-g, IL-8, granzyme B, IL-2RA and CSF3 in HS.
Safety: KT-474 was generally safe and well-tolerated, with no serious adverse events, no drug-related infections, and no dose interruptions or discontinuations due to adverse events. Adverse events, which included headache, fatigue and diarrhea, were predominantly mild, and all fully resolved. Previously seen modest, non-adverse QTcF prolongation was observed at Days 7-14, the mean of which was slightly below the mean levels at similar timepoints in HV MAD3. The QTcF prolongation declined spontaneously with continued dosing, with resolution to baseline by Day 28, and remained in the same normal range after cessation of dosing.
“I am pleased to see the positive clinical activity signals in both HS and AD in this patient cohort, with the internal consistency between effects on inflammatory biomarkers and impact on clinical endpoints increasing confidence in results from a single-arm trial,” said Afsaneh Alavi, MD, Professor of Dermatology at Mayo Clinic. “I believe these promising early efficacy and safety data in patients support the further development and exciting potential of orally-administered KT-474 in HS and AD.”
Oncology Degraders: KT-333, KT-413, KT-253
Kymera’s oncology programs include two molecules in Phase 1 clinical trials, KT-333 and KT-413, and KT-253, a program that is scheduled to enter the clinic in early 2023.
“We believe the initial data from the dose escalation phase of our ongoing KT-333 and KT-413 trials are very encouraging, as they are demonstrating fidelity of PK/PD translation from preclinical models to patients, and showing that, even at low doses, we are seeing target degradation in blood and tumor without any dose limiting toxicities observed,” said Dr. Gollob. “We view this as important proof of mechanism and a critical first step in our plans to escalate dosing to levels which we expect will demonstrate clinical impact in our target patient populations and look forward to sharing additional data in 2023.”
STAT3 degrader program (KT-333)
KT-333 is a potent degrader of STAT3, a transcriptional regulator that has been linked to numerous cancers and other inflammatory and autoimmune diseases. KT-333 is being developed for the treatment of STAT3-dependent hematological malignancies and solid tumors. The Phase 1 clinical trial of KT-333 is designed to evaluate the safety, tolerability, PK/PD and clinical activity of KT-333 dosed weekly on Days 1, 8 and 15 of 28-day cycles in adult patients with relapsed and/or refractory lymphomas, leukemias and solid tumors.
The Phase 1a dose escalation portion of the trial is ongoing; dose level 1 (DL1, 0.05 mg/kg) has been completed with a total of four patients enrolled. All patients were heavily pretreated with multiple prior lines of therapy and included three patients with solid tumors and one patient with cutaneous T-cell lymphoma. Plasma PK and PD translated as expected in humans with mean maximum STAT3 degradation in PBMC following the first 2 doses averaging 66%, with maximum STAT3 knockdown of up to 86% as measured by mass spectrometry. There were no DLTs or treatment-related SAEs observed in DL1. DL2 [0.10 mg/kg] is currently enrolling.
Kymera plans to share additional STAT3 clinical data in 2023.
IRAKIMiD degrader program (KT-413)
KT-413 is a novel heterobifunctional degrader targeting both IRAK4 and the IMiD substrates Ikaros and Aiolos. Designed to address both the IL-1R/TLR and Type 1 IFN pathways synergistically with a single molecule, KT-413 is in development for the treatment of MYD88-mutant B cell malignancies. The Phase 1 clinical trial of KT-413 is designed to evaluate the safety, tolerability, PK/PD and clinical activity of KT-413 administered as an IV infusion once every 3 weeks to adult patients with relapsed and/or refractory B-cell non-Hodgkin's lymphomas.
The Phase 1a dose escalation portion of the trial is ongoing; dose level 1 (DL1, 0.16 mg/kg) and dose level 2 (DL2, 0.32 mg/kg) have been completed. Patients in both dose cohorts were heavily pretreated, having received multiple prior lines of therapy, and included follicular lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma, which were both wild-type for MYD88. Plasma PK and PD also translated as expected in humans with DL1 and DL2 showing dose-dependent degradation of IRAK4, Ikaros and Aiolos in PBMC, with up to 95/100% knockdown of Ikaros/Aiolos and 40% knockdown of IRAK4 in DL2. Serial tumor biopsies at Cycle 3/Day 4 in the patient treated at DL1 showed comparable knockdown of Ikaros/Aiolos and IRAK4 as in plasma. There were no DLTs or treatment-related SAEs and no neutropenia observed in DL1 and DL2 patient cohorts. Phase 1a dose escalation is ongoing and DL3 (0.51 mg/kg) is currently enrolling.
Kymera plans to share additional IRAKIMiD clinical data in 2023.
MDM2 degrader program (KT-253)
The FDA has cleared the IND for KT-253, a degrader that targets MDM2, the crucial regulator of the most common tumor suppressor, p53, which remains intact (WT) in more than 50% of cancers. Unlike small molecule inhibitors, KT-253 has been shown preclinically to have the ability to suppress the MDM2 feedback loop and rapidly induce apoptosis, even with brief exposures. Kymera is currently preparing to initiate a Phase 1 clinical trial evaluating the safety, tolerability, PK/PD and clinical activity of KT-253 in adult patients with liquid and solid tumors in 2023. Kymera plans to share more details around the trial design and timelines in early 2023.
About Kymera Therapeutics
Kymera is a biopharmaceutical company pioneering the field of targeted protein degradation, a transformative approach to address disease targets and pathways inaccessible with conventional therapeutics. Kymera’s Pegasus platform is a powerful drug discovery engine, advancing novel small molecule programs designed to harness the body’s innate protein recycling machinery to degrade dysregulated, disease-causing proteins. With a focus on undrugged nodes in validated pathways, Kymera is advancing a pipeline of novel therapeutic candidates designed to address the most promising targets and provide patients with more effective treatments. Kymera’s initial programs target IRAK4, IRAKIMiD, and STAT3 within the IL-1R/TLR or JAK/STAT pathways, and the MDM2 oncoprotein, providing the opportunity to treat patients with a broad range of immune-inflammatory diseases, hematologic malignancies, and solid tumors. For more information, visit www.kymeratx.com.
Founded in 2016, Kymera is headquartered in Watertown, Mass. Kymera has been named a “Fierce 15” company by Fierce Biotech and has been recognized by both the Boston Globe and the Boston Business Journal as one of Boston’s top workplaces. For more information about our people, science, and pipeline, please visit www.kymeratx.com or follow us on Twitter or LinkedIn.
Kymera surges 30% as Sanofi plans to advance drug after promising data in skin disorders
Dec. 14, 2022 7:54 AM ET
Kymera Therapeutics, Inc. (KYMR), SNY
By: Ravikash, SA News Editor
Kymera Therapeutics (NASDAQ:KYMR) reported data from a patient group portion of its drug KT-474 (IRAK4) from a phase 1 trial, and updates on its three oncology programs: KT-413 (IRAKIMiD), KT-333 (STAT3) and KT-253 (MDM2).
KT-474:
The company said Part C of its KT-474 phase 1 trial was designed to confirm that the Pharmacokinetics/Pharmacodynamics ((PK/PD)) and safety data previously shown in healthy people would translate into patients with hidradenitis suppurativa (HS) and atopic dermatitis (AD), also known as eczema.
Kymera Therapeutics, Inc. (KYMR), SNY
https://www.kymeratx.com/pipeline/
upifitamab rilsodotin (UpRi)
MVP-S, in combination with pembrolizumab
upifitamab rilsodotin (UpRi)
European Commission Designates UpRi as an Orphan Medicinal Product for the Treatment of Ovarian Cancer
December 14, 2022
CAMBRIDGE, Mass., Dec. 14, 2022 (GLOBE NEWSWIRE) -- Mersana Therapeutics, Inc. (NASDAQ: MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, today announced that the European Commission (EC) has designated upifitamab rilsodotin (UpRi) as an orphan medicinal product for the treatment of ovarian cancer. UpRi is Mersana’s first-in-class NaPi2b-targeting ADC with a novel scaffold-linker-payload that is designed to enable a high drug-to-antibody ratio and controlled bystander effect.
“Receiving this orphan designation in the European Union is an important regulatory milestone for Mersana as we seek to expedite UpRi’s global development,” said Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics. “This designation reinforces the unmet needs that patients with ovarian cancer continue to face today. We look forward to advancing our ongoing clinical trials, which aim to establish UpRi as a foundational medicine in ovarian cancer.”
The European Commission designates drugs as orphan medicinal products based on positive opinions adopted by the European Medicines Agency (EMA) Committee for Orphan Medicinal Products (COMP). Orphan designations are granted for potential treatments for rare diseases that are life-threatening or chronically debilitating that affect fewer than five in 10,000 people across the European Union. Medicines designated as orphan medicinal products by the EMA may qualify for financial and regulatory incentives, including protocol assistance at reduced fees during product development, access to centralized marketing authorization and 10 years of marketing exclusivity in the European Union after product approval.
About Mersana Therapeutics
Mersana Therapeutics is a clinical-stage biopharmaceutical company using its differentiated and proprietary ADC platforms to rapidly develop novel ADCs with optimal efficacy, safety and tolerability to meaningfully improve the lives of people fighting cancer. Mersana’s lead product candidate, upifitamab rilsodotin (UpRi), is a Dolaflexin ADC targeting NaPi2b that is being studied in UPLIFT, a single-arm registrational trial in patients with platinum-resistant ovarian cancer; UPGRADE-A, a Phase 1/2 clinical trial evaluating UpRi in combination with carboplatin; and UP-NEXT, a Phase 3 clinical trial of UpRi as monotherapy maintenance following treatment with platinum doublets in recurrent platinum-sensitive ovarian cancer. Mersana is also advancing XMT-1660, a Dolasynthen ADC targeting B7-H4, and XMT-2056, an Immunosynthen ADC targeting a novel epitope of human epidermal growth factor receptor 2 (HER2), in addition to other earlier-stage assets. In addition, multiple partners are using Mersana’s platforms to advance their ADC pipelines. Mersana routinely posts information that may be useful to investors on the “Investors & Media” section of its website at www.mersana.com.
Mersana Therapeutics gets European orphan drug designation for ovarian cancer treatment
Dec. 14, 2022 9:05 AM ET
Mersana Therapeutics, Inc. (MRSN)
By: Anuron Mitra, SA News Editor
- Mersana Therapeutics (NASDAQ:MRSN) on Wednesday said the European Commission had granted an orphan drug designation to its antibody drug conjugate for the treatment of ovarian cancer.
- https://seekingalpha.com/news/3916921-mersana-gets-european-orphan-drug-designation-for-ovarian-cancer-treatment
- Mersana Therapeutics, Inc. (MRSN)
- https://www.mersana.com/pipeline/xmt-1536/
KRAZATI™ (adagrasib)
AYVAKIT® (avapritinib)
upifitamab rilsodotin (UpRi)
Mirati Therapeutics Announces U.S. FDA Accelerated Approval of KRAZATI™ (adagrasib) as a Targeted Treatment Option for Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) with a KRASG12C Mutation
12/12/2022
SAN DIEGO, Dec. 12, 2022 /PRNewswire/ -- Mirati Therapeutics, Inc. (NASDAQ: MRTX), a targeted oncology company, today announced that the U.S. Food and Drug Administration (FDA) has granted accelerated approval for KRAZATI™ (adagrasib), a targeted treatment option for adult patients with KRASG12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy.
Experience the full interactive Multichannel News Release here: https://www.multivu.com/players/English/8999051-mirati-therapeutics-fda-accelerated-approval-of-krazati-adagrasib/
This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial(s).
To view the multimedia assets associated with this release, please visit: Mirati.com/approval
"The FDA approval of KRAZATI is a positive development for thousands of patients with KRASG12C mutations, including the approximately 14% of patients with NSCLC adenocarcinomas histology that harbor a KRASG12C mutation.1 Mirati is thrilled to make KRAZATI available in a tablet formulation to patients in the U.S. with advanced NSCLC who have progressed beyond a first-line treatment for the historically difficult-to-treat KRAS mutation," David Meek, chief executive officer, Mirati Therapeutics, Inc., continued, "We look forward to continuing to advance our KRAZATI development program including several monotherapy and combination studies in KRASG12C-mutated solid tumors."
KRAZATI has demonstrated a positive benefit-risk profile with accelerated approval based on the Phase 2 registration-enabling cohort of the KRYSTAL-1 study, evaluating KRAZATI 600 mg capsules administered orally twice daily in 116 patients with KRASG12C-mutated advanced NSCLC who previously received treatment with a platinum-based regimen and an immune checkpoint inhibitor. The primary efficacy endpoints were confirmed ORR and DOR as evaluated by blinded independent central review (BICR) according to response evaluation criteria in solid tumors (RECIST v1.1).
The trial demonstrated an ORR of 43% (95% CI: 34-53) with 80% (95% CI: 71-87) of patients achieving disease control. The median DOR was 8.5 months (95% CI: 6.2-13.8).
In a pooled efficacy analysis (n=132) including Phase 1/1b NSCLC and registrational Phase 2 NSCLC cohorts from the KRYSTAL-1 study evaluating adagrasib as a single agent at 600 mg capsules orally twice daily, adagrasib showed an ORR of 44% and a disease control rate of 81% based on BICR, a median DOR of 12.5 months (95% CI, 7.3-NE) and median overall survival of 14.1 months (94% CI, 9.2-19.2).
The safety profile of KRAZATI was evaluated in a pooled patient population with NSCLC and other solid tumors as a single agent at 600 mg orally twice daily in 366 patients enrolled in KRYSTAL-1 and KRYSTAL-12. The most common (≥ 25%) adverse reactions were nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, renal impairment, edema, dyspnea and decreased appetite. Permanent discontinuation of KRAZATI due to an adverse reaction occurred in 13% of patients.
Although KRASG12C is the most common KRAS mutation in NSCLC, patients have had limited options for the treatment of this debilitating and difficult-to-treat condition.2,3
"The approval of KRAZATI offers an effective therapy for patients with advanced NSCLC harboring the KRASG12C mutation. The positive ORR and DOR results, as observed in previously treated patients with NSCLC harboring the KRASG12C mutation, demonstrate the effectiveness of KRAZATI as an option for these difficult-to-treat patients," said Shirish M. Gadgeel, MD, chief of the Division of Hematology and Oncology, Department of Internal Medicine, Henry Ford Cancer Institute/Henry Ford Health System.
"KRASG12C in NSCLC is an area of high unmet need and new treatment options offer patients and our community new hope for survivorship," said Bonnie J. Addario, co-founder and board chair of the GO2 Foundation for Lung Cancer. "I'm pleased that patients have options, there's more awareness of this disease and we are all focused on improving the journeys of people living with KRASG12C-mutated NSCLC."
The Company partnered with Agilent and QIAGEN to develop blood- and tissue-based companion diagnostics (CDx), respectively, for KRAZATI that are now available. With tissue and blood modalities for companion diagnostics, patients have more flexibility, and clinicians have greater options for biomarker testing. These solutions help to personalize a patient's treatment path.
Mirati Therapeutics is launching Mirati & Me, a comprehensive program dedicated to supporting patients, caregivers and the oncology community including coverage and access, financial, educational and emotional support services. Learn more by visiting the Mirati & Me website or 1-844-647-2842.
For more information, visit KRAZATI.com.
About KRAZATI (adagrasib)
Mirati has risen to meet one of the most challenging mutations in cancer research by developing KRAZATI, a highly selective and potent oral small-molecule inhibitor of KRASG12C.
Intentionally designed to meet the challenge of KRASG12C, adagrasib is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12C-mutated cancers, as the KRASG12C protein regenerates every 24−48 hours.4 Adagrasib has shown clinically to be a CNS penetrant, which may be important given that CNS metastases frequently occur in NSCLC and lead to poor prognosis.5,6,7
In the U.S., KRAZATI was reviewed by the FDA for Accelerated Approval (Subpart H), which allows for the approval of drugs that treat serious conditions, and that fill an unmet medical need based on surrogate endpoints. KRAZATI was reviewed under the FDA Real-Time Oncology Review (RTOR) pilot program, which aims to explore a more efficient review process that ensures safe and effective treatments are made available to patients as early as possible. Mirati submitted a Marketing Authorization Application (MAA) in the EU in May 2022. In 2021, adagrasib achieved Breakthrough Therapy Designation in the U.S. as a potential treatment for patients with NSCLC harboring the KRASG12C mutation who have received at least one prior systemic therapy.
Adagrasib continues to be evaluated as monotherapy and in combination with other anti-cancer therapies in patients with advanced KRASG12C-mutated solid tumors, including NSCLC, colorectal cancer, and pancreatic cancer. For more information, visit Mirati.com/science.
Mirati has an Expanded Access Program (EAP) for adagrasib for the treatment of eligible patients with KRASG12C-mutated cancers, regardless of tumor type, including patients with treated or untreated CNS metastases, in the U.S. Learn more about the EAP at Mirati.com/expanded-access-policy.
KRAZATI (adagrasib) U.S. Indication
KRAZATI is indicated for the treatment of adult patients with KRASG12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy.
This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial(s).
Please see Full Prescribing Information .
About Mirati Therapeutics, Inc.
Mirati Therapeutics, Inc. is a commercial-stage biotechnology company whose mission is to discover, design and deliver breakthrough therapies to transform the lives of patients with cancer and their loved ones. The company is relentlessly focused on bringing forward therapies that address areas of high unmet need, including lung cancer, and advancing a pipeline of novel therapeutics targeting the genetic and immunological drivers of cancer. Unified for patients, Mirati's vision is to unlock the science behind the promise of a life beyond cancer.
For more information about Mirati, visit us at Mirati.com or follow us on Twitter, LinkedIn and Facebook.
SOURCE Mirati Therapeutics, Inc.
Mirati non-small cell lung cancer treatment adagrasib gains FDA approval - Bloomberg
Dec. 12, 2022 5:28 PM ET
Mirati Therapeutics, Inc. (MRTX)AMGN
By: Jonathan Block, SA News Editor3 Comments
- The US FDA has approved Mirati Therapeutics' (NASDAQ:MRTX) Krazati (adagrasib) a second-line treatment for non-small cell lung cancer, Bloomberg reported.
- https://seekingalpha.com/news/3916337-mirati-non-small-cell-lung-cancer-treatment-adagrasib-gains-fda-approval-bloomberg
- Mirati Therapeutics, Inc. (MRTX)
- https://www.mirati.com/science/pipeline/
- https://www.statnews.com/2022/12/12/lung-cancer-mirati-krazati-fda-approval-kras/
VX-522
AYVAKIT® (avapritinib)
AYVAKIT® (avapritinib)
Dec 12, 2022
Vertex Announces Investigational New Drug (IND) Application for VX-522, mRNA Therapy for People With Cystic Fibrosis, Cleared by FDA
- Novel, inhaled mRNA therapy intended for the ~5,000 people with CF who cannot benefit from CFTR modulators -
- VX-522 clinical trial in people with CF to initiate in coming weeks -
BOSTON--(BUSINESS WIRE)--Dec. 12, 2022-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that the U.S. Food and Drug Administration has cleared its Investigational New Drug (IND) application for VX-522, a messenger ribonucleic acid (mRNA) therapy targeted at treating the underlying cause of cystic fibrosis (CF) lung disease for the approximately 5,000 people with CF who cannot benefit from a cystic fibrosis transmembrane conductance regulator (CFTR) modulator. Vertex plans to initiate a single ascending dose clinical trial for VX-522 in people with CF in the coming weeks.
This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20221208005977/en/
VX-522 is delivered to the lung through inhalation of a CFTR mRNA encapsulated by a lipid nanoparticle. Once delivered to the target lung cells, the mRNA is designed to produce functional copies of the CFTR protein. VX-522 is the result of an exclusive research collaboration established with Moderna in 2016.
“It has been our longstanding goal to bring highly effective therapies to all people with CF. Clearance of the IND represents a pivotal turning point in reaching the remaining ~5,000 people with CF who are still waiting for a medicine to treat the underlying cause of their disease,” said Reshma Kewalramani, M.D., FASN, Chief Executive Officer and President, Vertex. “The partnership with Moderna that began more than five years ago has been instrumental in achieving this milestone, and we look forward to continuing our work together.”
“This partnership brings together Vertex’s scientific expertise and decades of experience in developing cystic fibrosis medicines with Moderna’s proven leadership in mRNA technologies,” said Moderna Chief Executive Officer Stéphane Bancel. “Moderna’s development of a proprietary inhalable lipid nanoparticle to deliver a functional cystic fibrosis treatment to the lungs could lead to a transformational medical achievement. We are excited by the progress that has been made with the upcoming advancement of VX-522 to the clinic and look forward to our ongoing collaboration to develop treatments for the underlying cause of cystic fibrosis.”
About VX-522
This investigational messenger ribonucleic acid (mRNA) therapy aims to address the underlying cause of cystic fibrosis (CF). It is being evaluated by Vertex to treat lung disease for people living with CF who cannot benefit from cystic fibrosis transmembrane conductance regulator (CFTR) modulator treatments because they do not make any CFTR protein that responds to a CFTR modulator therapy. Globally, this represents a population of approximately 5,000 people living with this very rare form of the disease. The therapy is designed to deliver full length CFTR mRNA encapsulated in a lipid nanoparticle via inhalation directly to the lungs. Once delivered to target airway cells, the mRNA enables the production of functional CFTR protein. Improvements in CFTR quantity and function can lead to transformative benefits for people living with CF.
About the VX-522 Clinical Trial
Vertex plans to initiate a single dose escalation study in the coming weeks evaluating the safety and tolerability of VX-522 in people 18 years of age and older with cystic fibrosis and a CFTR genotype not responsive to CFTR modulator therapy.
About the Vertex and Moderna Collaboration
VX-522 is the result of an exclusive research collaboration Vertex established with Moderna in 2016 to discover and develop mRNA therapeutics for CF. Under the terms of the collaboration, Moderna leads asset identification efforts, combining its leading mRNA platform technology and mRNA delivery expertise together with Vertex's scientific experience in CF biology, functional understanding of CFTR, and Vertex’s proprietary assay platform that utilizes human bronchial epithelial (HBE) cells of multiple different CF gene mutations from people with CF. Vertex leads preclinical and clinical development, regulatory and commercialization activities associated with the advancement of mRNA therapeutics that result from this collaboration and will fund all expenses related to the collaboration. Moderna is responsible for mRNA and lipid nanoparticle (LNP) process development and manufacturing. Per Vertex's agreement with Moderna, Moderna will receive certain milestone payments, as well as royalty payments from this collaboration.
About Vertex
Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has multiple approved medicines that treat the underlying cause of cystic fibrosis (CF) — a rare, life-threatening genetic disease — and has several ongoing clinical and research programs in CF. Beyond CF, Vertex has a robust clinical pipeline of investigational small molecule, cell and genetic therapies in other serious diseases where it has deep insight into causal human biology, including sickle cell disease, beta thalassemia, APOL1-mediated kidney disease, pain, type 1 diabetes and alpha-1 antitrypsin deficiency.
Founded in 1989 in Cambridge, Mass., Vertex's global headquarters is now located in Boston's Innovation District and its international headquarters is in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia and Latin America. Vertex is consistently recognized as one of the industry's top places to work, including 13 consecutive years on Science magazine's Top Employers list and one of Fortune’s Best Workplaces in Biotechnology and Pharmaceuticals and Best Workplaces for Women. For company updates and to learn more about Vertex's history of innovation, visit www.vrtx.com or follow us on Facebook, Twitter, LinkedIn, YouTube and Instagram.
View source version on businesswire.com: https://www.businesswire.com/news/home/20221208005977/en/
Source: Vertex Pharmaceuticals Incorporated
Vertex receives IND clearance for mRNA cystic fibrosis therapy
Dec. 12, 2022 10:54 AM ET
Vertex Pharmaceuticals Incorporated (VRTX)
By: Jonathan Block, SA News Editor1 Comment
- The US FDA has cleared an IND application from Vertex Pharmaceuticals (NASDAQ:VRTX) for VX-522, an mRNA candidate for cystic fibrosis ("CF").
- https://seekingalpha.com/news/3916164-vertex-receives-ind-clearance-for-mrna-cystic-fibrosis-therapy
- Vertex Pharmaceuticals Incorporated (VRTX)
- https://www.vrtx.com/our-science/pipeline/
AYVAKIT® (avapritinib)
AYVAKIT® (avapritinib)
AYVAKIT® (avapritinib)
Blueprint Medicines Reports Clinical Data Highlighting Leadership in Developing Targeted Treatment Options for Patients with Systemic Mastocytosis
December 11, 2022 at 5:45 PM EST
-- 95 percent confirmed overall response rate and 37 percent confirmed complete remission rate in treatment-naïve patients with SM-AHN, the most common subtype of advanced SM, in PATHFINDER trial of AYVAKIT® (avapritinib) --
-- Ongoing survival benefits, with up to six years of follow-up, in patients with advanced SM from EXPLORER trial of AYVAKIT --
-- Top-line, 12-week Part 1 data from HARBOR trial show elenestinib (BLU-263) improved measures of mast cell burden and patient-reported symptoms in indolent SM --
CAMBRIDGE, Mass., Dec. 11, 2022 /PRNewswire/ -- Blueprint Medicines Corporation (NASDAQ: BPMC) today announced AYVAKIT® (avapritinib) data showing high, durable response rates and prolonged overall survival (OS) in patients with advanced systemic mastocytosis (Advanced SM), including SM with an associated hematological neoplasm (SM-AHN). The findings are being reported in two presentations, including an oral presentation featuring updated follow-up from treatment-naïve patients in the PATHFINDER trial, at the 64th American Society of Hematology (ASH) Annual Meeting and Exposition in New Orleans. AYVAKIT is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults with Advanced SM.
SM is a rare hematologic disorder driven by the KIT D816V mutation in approximately 95 percent of cases. In advanced SM, the median OS has ranged from less than six months to approximately 3.5 years, depending on the subtype.1 AYVAKIT was designed to potently and selectively inhibit D816V mutant KIT.
"AYVAKIT has demonstrated significant clinical benefits in patients with advanced systemic mastocytosis, including complete remissions and durable responses that have translated into a highly meaningful impact on overall survival," said Deepti Radia, M.D., a hematologist and an investigator on the PATHFINDER and EXPLORER trials. "As a physician specializing in SM and other myeloproliferative neoplasms, I am encouraged that treatment-naïve patients with SM-AHN had a 95 percent response rate and an estimated two-year survival rate of 86 percent in the PATHFINDER trial. Before the introduction of KIT D816V-targeted therapy, physicians often focused on treating the AHN component of SM-AHN. AYVAKIT represents a practice-changing advancement for this patient population, and updated PATHFINDER data highlight the importance of treating the SM for early therapeutic intervention in SM-AHN patients with measurable 'C' findings, excluding those with aggressive AHNs."
"AYVAKIT has become the standard of care treatment for advanced systemic mastocytosis in the U.S., with a growing number of patients receiving the therapy early in the course of their disease. This position is further reinforced by updated AYVAKIT results in the treatment-naïve setting, which include overall response, complete remission and survival rates that establish a new benchmark for patients with advanced SM," said Becker Hewes, M.D., Chief Medical Officer at Blueprint Medicines. "Through our long-term partnership with the SM community, we have amassed datasets reflecting hundreds of patient years of clinical experience across advanced and non-advanced forms of the disease. This breadth of data highlights strong clinical execution and reflects our leadership in developing a portfolio of targeted treatment options designed to address the medical needs of patients with SM."
AYVAKIT – Updated data from the PATHFINDER and EXPLORER trials in advanced SM
Long-term follow-up of 38 treatment-naïve patients from the PATHFINDER trial and 69 patients from the EXPLORER trial – regardless of line of therapy – further validate the clinical efficacy and safety profile of AYVAKIT in advanced SM. Based on modified IWG-MRT-ECNM criteria, the overall response rate (ORR) was defined as complete remission with full or partial recovery of peripheral blood counts (CR/CRh), partial remission or clinical improvement. All responses were confirmed.
In the PATHFINDER trial, AYVAKIT showed broad clinical activity in treatment-naïve patients evaluable for response (n=25), including those with SM-AHN (n=19), as of a data cutoff date of April 20, 2021.
For treatment-naïve patients across advanced SM subtypes:
- ORR was 84 percent and CR/CRh rate was 32 percent.
- Median time to response was two months and median time to CR/CRh was six months.
- Median duration of response (DOR) has not been reached.
- Estimated 24-month OS rate was 88 percent.
For treatment-naïve patients with SM-AHN:
- ORR was 95 percent and CR/CRh rate was 37 percent.
- Estimated 24-month OS rate was 86 percent.
In addition, improvements were observed across hematologic parameters, such as monocytes and eosinophils in the peripheral blood, suggesting multi-lineage involvement of the KIT D816V mutation.
In the EXPLORER trial, 57 patients across lines of therapy were evaluable for response as of a data cutoff date of April 5, 2022. The ORR was 77 percent, with median DOR and OS not reached in patients followed for up for six years.
Safety data from the PATHFINDER and EXPLORER trials were consistent with previously reported results and the FDA approved labeling for AYVAKIT, and reinforce the favorable benefit-risk profile of AYVAKIT at the 200 mg once-daily (QD) recommended dose. The most common treatment-related adverse events (AEs) included periorbital edema, thrombocytopenia, peripheral edema, anemia and nausea. Discontinuations due to treatment-related AEs occurred in four treatment-naïve patients (11 percent) since the initiation of the PATHFINDER trial in 2018, and seven patients across lines of therapy (10 percent) since the initiation of the EXPLORER trial in 2016.
Copies of Blueprint Medicines data presentations from the ASH annual meeting are available in the "Science—Publications and Presentations" section of the company's website at www.BlueprintMedicines.com.
Elenestinib (BLU-263) – Top-line results from Part 1 of HARBOR trial in indolent SM
In addition, Blueprint Medicines today announced top-line, 12-week results from the dose-finding Part 1 of the HARBOR trial of elenestinib, a next-generation KIT D816V inhibitor, reflecting the company's long-term commitment to SM. HARBOR Part 1 was designed to assess concurrent dose cohorts of elenestinib plus best available therapy (elenestinib group) versus placebo plus best available therapy (placebo group) in patients with indolent SM. The trial included 29 patients in the elenestinib group (n=10 at 25 mg QD; n=10 at 50 mg QD; n=9 at 100 mg QD), and 10 patients in the placebo group.
Elenestinib showed evidence of clinical activity and safety consistent with its preclinical profile and a completed Phase 1 healthy volunteer trial. Elenestinib treatment led to rapid improvements in objective measures of mast cell burden, including serum tryptase and KIT D816V allele fraction, and total symptom score (TSS) as measured by the Indolent SM Symptom Assessment Form (ISM-SAF). At 12 weeks, elenestinib demonstrated similar reductions in TSS across dose cohorts. In addition, consistent with previously reported data from the PIONEER trial of AYVAKIT in indolent SM, change in serum tryptase was not correlated with change in TSS. Safety results show that elenestinib was generally well-tolerated, and there were no discontinuations due to AEs. Blueprint Medicines plans to present data from Part 1 of the HARBOR trial at a medical congress in 2023.
About AYVAKIT (avapritinib)
AYVAKIT (avapritinib) is a kinase inhibitor approved by the FDA for the treatment of adults with Advanced SM, including aggressive SM (ASM), SM with an associated hematological neoplasm (SM-AHN) and mast cell leukemia (MCL), and adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a PDGFRA exon 18 mutation, including PDGFRA D842V mutations. For more information, visit AYVAKIT.com. This medicine is approved in Europe (AYVAKYT®) for the treatment of adults with ASM, SM-AHN or MCL, after at least one systemic therapy, and adults with unresectable or metastatic GIST harboring the PDGFRA D842V mutation. Please click here to see the full U.S. Prescribing Information for AYVAKIT, and click here to see the European Summary of Product Characteristics for AYVAKYT. AYVAKIT/AYVAKYT is not approved for the treatment of any other indication in the U.S. or Europe.
To learn about ongoing or planned clinical trials, contact Blueprint Medicines at medinfo@blueprintmedicines.com or 1-888-BLU-PRNT (1-888-258-7768). Additional information is available at blueprintclinicaltrials.com or clinicaltrials.gov.
Please click here to see the full Prescribing Information for AYVAKIT.
About Blueprint Medicines
Blueprint Medicines is a global precision therapy company that invents life-changing therapies for people with cancer and blood disorders. Applying an approach that is both precise and agile, we create medicines that selectively target genetic drivers, with the goal of staying one step ahead across stages of disease. Since 2011, we have leveraged our research platform, including expertise in molecular targeting and world-class drug design capabilities, to rapidly and reproducibly translate our scientific innovation into a broad pipeline of important approved and investigational precision therapies aimed at addressing difficult-to-treat cancers and blood disorders. Today, we are delivering our approved medicines to patients in the United States, Europe, and in other geographies ourselves or through our partners. In addition, we are globally advancing multiple programs for systemic mastocytosis, lung cancer, breast cancer, and other genomically defined cancers, and cancer immunotherapy. For more information, visit www.BlueprintMedicines.com and follow us on Twitter (@BlueprintMeds) and LinkedIn.
Trademarks
Blueprint Medicines, AYVAKIT, AYVAKYT, GAVRETO and associated logos are trademarks of Blueprint Medicines Corporation.
SOURCE Blueprint Medicines Corporation
Blueprint reports long term data for Ayvakit; elenestinib shows promise in phase 1 trial
Dec. 12, 2022 5:34 AM ET
Blueprint Medicines Corporation (BPMC)
By: Ravikash, SA News Editor
Blueprint Medicines (NASDAQ:BPMC) reported long term updated of Ayvakit from the PATHFINDER and EXPLORER trials in patients with advanced systemic mastocytosis (SM) and part of 1 of the HARBOR study of elenestinib.
Blueprint Medicines Corporation (BPMC)
IBI110 (anti-LAG-3 mAb) in combination with Sintilimab (anti-PD-1 mAb)
IBI110 (anti-LAG-3 mAb) in combination with Sintilimab (anti-PD-1 mAb)
IBI110 (anti-LAG-3 mAb) in combination with Sintilimab (anti-PD-1 mAb)
Innovent Presents Phase Ib Clinical Data Update of IBI110 (Anti-LAG-3 Monoclonal Antibody) at the 2022 European Society For Medical Oncology Immuno-Oncology Congress
Published on: Dec 9th, 2022Back
ROCKVILLE, M.D. and SUZHOU, China, Dec 9, 2022 — Innovent Biologics, Inc. (“Innovent”) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, autoimmune, metabolic, ophthalmology and other major diseases, today announced that updated clinical data of IBI110 (anti-LAG-3 monoclonal antibody) in advanced squamous non-small cell lung cancer (sqNSCLC) is presented at the 2022 European Society for Medical Oncology Immuno-Oncology Congress (ESMO-IO), held Dec 7-9, 2022.
Efficacy and safety of IBI110 (anti-LAG-3 mAb) in combination with Sintilimab (anti-PD-1 mAb) in Advanced Squamous Non-small Cell Lung Cancer (sqNSCLC): Updated Results from a Phase Ib Study
Poster #: 86P
IBI110 is an IgG4κ recombinant human anti-LAG-3 monoclonal antibody developed by Innovent Biologics. The Phase Ib study aims to evaluate the efficacy and safety of IBI110 in combination with sintilimab and chemotherapy (paclitaxel plus carboplatin) as first-line therapy for advanced sqNSCLC.
• 20 treatment naïve sqNSCLC patients received IBI110 (200 mg, Q3W) combined with sintilimab and chemotherapy and received at least 1 post-baseline tumor assessment. As of the data cutoff date of Oct 25, 2022, median follow-up time was 12.0 (95% CI, 11.9 -13.1) months, 16 patients achieved partial response (PR), the objective response rate (ORR) was 80%; the 12-month progression free survival (PFS) rate was 60.0% (95% CI, 35.7-77.6), the median PFS was not reached; the 12-month overall survival (OS) rate was 85.0% (95% CI, 60.4-94.9) .
• For safety results, the most common treatment related adverse events (TRAEs) ≥ grade 3 were decreased neutrophil count (30.0%) and decreased white blood cell count (20.0%). Immune-related AEs (irAEs) occurred in 14 patients, in which only 4 patients experienced irAE ≥ grade 3. No treatment-related deaths occurred.
• IBI110 combined with sintilimab and chemotherapy in advanced sqNSCLC continues to show robust anti-tumor activity and favorable safety. The study is ongoing with the clinical data in squamous NSCLC continuing to mature and will be disclosed in the future academic conference/journals.
Professor Caicun Zhou, Shanghai Pulmonary Hospital, stated: “Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death worldwide, of which non-small cell lung cancer accounts for about 80% . In recent years, PD-1/PD-L1 inhibitors have shown promising efficacy in non-small cell lung cancer . However, persistent response to immune checkpoint inhibitor monotherapy remains a challenge in clinical practice. IBI110 plus sintilimab indicate promising antitumor activity and a manageable safety profile in untreated squamous non-small cell lung cancer patients. In the current 20 patients, the ORR reached 80% and the 12-month PFS rate was 60%, which warrants further investigation into the safety and efficacy of IBI110 combination therapy in this indication.”
Dr. Hui Zhou, Senior Vice President of Innovent, stated: “We are pleased to present our clinical development updates at the 2022 ESMO-IO Meeting. IBI110 in combination with sintilimab demonstrated encouraging efficacy and safety data in sqNSCLC. We will continue to provide updates on the PoC data for IBI110 and plan to initiate pivotal clinical studies. As immunotherapy moves into the next era, we are actively advancing the development of next-generation immune checkpoint inhibitors, among which IBI110 represents a high-potential LAG-3 asset, which we hope will benefit patients in need soon.”
To learn more about Innovent’s R&D updates and activities, please visit https://investor.innoventbio.com/cn/investors/webcasts-and-presentations/.
About IBI110
IBI110 is an IgG4κ recombinant human anti-LAG-3 monoclonal antibody independently developed by Innovent Biologics. Based on the mechanism of action and preclinical data of IBI110, it is assumed that IBI110 can inhibit the immune checkpoint signaling to achieve anti-tumor effect, which may further improve the efficacy of immunotherapy, overcome the primary drug resistance, and overcome the drug resistance after anti-PD-1 /PD-L1 monoclonal antibody treatment . Based on the urgent clinical needs, Innovent has carried out clinical studies to explore PK/PD characteristics of IBI110 single agent and combined with sintilimab in humans as well as its efficacy and safety in various advanced tumors. This clinical trial (NCT04085185) is the first in human clinical study of IBI110.
About Innovent
Inspired by the spirit of "Start with Integrity, Succeed through Action," Innovent's mission is to develop, manufacture and commercialize high-quality biopharmaceutical products that are affordable to ordinary people. Established in 2011, Innovent is committed to developing, manufacturing and commercializing high-quality innovative medicines for the treatment of cancer, autoimmune disease, metabolic disorder and other major diseases. On October 31, 2018, Innovent was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code: 01801.HK.
Since its inception, Innovent has developed a fully integrated multi-functional platform which includes R&D, CMC (Chemistry, Manufacturing, and Controls), clinical development and commercialization capabilities. Leveraging the platform, the company has built a robust pipeline of 35 valuable assets in the fields of cancer, metabolic disorder, autoimmune disease and other major therapeutic areas, with 8 approved products on the market. These include: TYVYT® (sintilimab injection), BYVASDA®(bevacizumab biosimilar injection), SULINNO® (adalimumab biosimilar injection), HALPRYZA®(rituximab biosimilar injection), Pemazyre®(pemigatinib oral inhibitor), olverembatinib (BCR ABL TKI), Cyramza® (ramucirumab) and selpercatinib. An additional 2 assets are under NMPA NDA review, 5 assets are in Phase 3 or pivotal clinical trials, and 20 more molecules are in clinical studies.
Innovent has built an international team with advanced talent in high-end biological drug development and commercialization, including many global experts. The company has also entered into strategic collaborations with Eli Lilly and Company, Sanofi, Adimab, Incyte, MD Anderson Cancer Center and other international partners. Innovent strives to work with many collaborators to help advance China's biopharmaceutical industry, improve drug availability and enhance the quality of the patients' lives. For more information, please visit: www.innoventbio.com. and www.linkedin.com/company/innovent-biologics/.
Note:
TYVYT® (sintilimab injection) is not an approved product in the United States.
BYVASDA® (bevacizumab biosimilar injection), SULINNO®, and HALPRYZA® (rituximab biosimilar injection) are not approved products in the United States.
TYVYT® (sintilimab injection, Innovent)
BYVASDA® (bevacizumab biosimilar injection, Innovent)
HALPRYZA® (rituximab biosimilar injection, Innovent)
SULINNO® (adalimumab biosimilar injection, Innovent)
Pemazyre® (pemigatinib oral inhibitor, Incyte Corporation). Pemazyre® was discovered by Incyte Corporation and licensed to Innovent for development and commercialization in Mainland China, Hong Kong, Macau and Taiwan.
CYRAMZA® (ramucirumab, Eli Lilly). CYRAMZA® was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China.
Selpercatinib (Eli Lilly). Selpercatinib was discovered by Eli Lilly and licensed to Innovent for commercialization in Mainland China.
Disclaimer:
1. The indications are still under clinical study, which haven’t been approved in China.
2. Innovent does not recommend any off-label usage.
Innovent's drug shows promise in advanced lung cancer patients in early-stage trial
Dec. 09, 2022 5:27 AM ET
Innovent Biologics, Inc. (IVBIY), LLY, IVBXF
By: Ravikash, SA News Editor
Innovent Biologics (OTCPK:IVBIY) (OTCPK:IVBXF) reported data from a phase 1b trial of IBI939 in combination with the company and Eli Lilly's (NYSE:LLY) Tyvyt (sintilimab) in patients with previously untreated, locally advanced unresectable or metastatic PD-L1 TPS≥50% non-small cell lung cancer (NSCLC) without sensitizing mutations.
Innovent Biologics, Inc. (IVBIY), LLY, IVBXF
https://www.innoventbio.com/Collaborations/Partners
Datopotamab deruxtecan (Dato-DXd)
IBI110 (anti-LAG-3 mAb) in combination with Sintilimab (anti-PD-1 mAb)
IBI110 (anti-LAG-3 mAb) in combination with Sintilimab (anti-PD-1 mAb)
Datopotamab deruxtecan showed encouraging and durable efficacy in patients with heavily pretreated HR-positive, HER2-low or negative metastatic breast cancer
PUBLISHED8 December 2022
8 December 2022 23:00 GMT
First results for AstraZeneca and Daiichi Sankyo’s TROP2-directed ADC in this setting reported from TROPION-PanTumor01 Phase I trial
Pivotal TROPION-Breast01 Phase III trial is ongoing, evaluating datopotamab deruxtecan in these patients in earlier lines of treatment
Initial results from the TROPION-PanTumor01 Phase I trial of datopotamab deruxtecan (Dato-DXd) showed encouraging and durable efficacy in patients with heavily pretreated hormone receptor (HR)-positive, HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in-situ hybridisation [ISH] negative) or HER2-negative (IHC 0) unresectable or metastatic breast cancer. Safety results were consistent with previous trials of datopotamab deruxtecan. Results were presented today at the 2022 San Antonio Breast Cancer Symposium (abstract #PD13-08).
Datopotamab deruxtecan is a specifically engineered TROP2-directed DXd antibody drug conjugate (ADC) being jointly developed by Daiichi Sankyo and AstraZeneca.
In this cohort of TROPION-PanTumor01 (n=41), datopotamab deruxtecan demonstrated an objective response rate (ORR) of 27% as assessed by blinded independent central review (BICR). All responses were partial (n=11) and 56% of patients achieved stable disease (n=23). The disease control rate (DCR) was 85% and median progression-free survival (PFS) was 8.3 months (95% confidence interval [CI], 5.5-11.1). With median follow-up of 13.7 months, the median duration of response (DoR) and the median overall survival (OS) had not been reached with 59% of patients alive for more than one year.
Approximately 70% of breast cancer tumours are considered HR-positive and HER2-low or negative.1 For patients with HR-positive, HER2-low or negative metastatic breast cancer that progress on or are not suitable candidates for endocrine therapy, the current standard of care is single-agent chemotherapy.2
Funda Meric-Bernstam, Chair, Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, and investigator in the TROPION-PanTumor01 trial, said: “Patients with HR-positive, HER2-low or negative metastatic breast cancer who are not eligible for endocrine therapy or have exhausted treatment options have a poor prognosis. These preliminary results with datopotamab deruxtecan in patients with heavily pretreated HR-positive, HER2-low or negative metastatic breast cancer are encouraging and warrant further evaluation in this setting.”
Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said: “Many of these patients with metastatic breast cancer in TROPION-PanTumor01 had exhausted most of their available treatment options, having received a striking median of five prior regimens including a CDK4/6 inhibitor for nearly all patients. These promising results with datopotamab deruxtecan in such a heavily pretreated patient population support our strong belief that this TROP2-directed antibody drug conjugate has the potential to improve outcomes for patients with HR-positive, HER2-low or negative breast cancer in this, and possibly earlier settings.”
Mark Rutstein, Global Head, Oncology Clinical Development, Daiichi Sankyo, said: “These results add to the growing body of data demonstrating the potential of datopotamab deruxtecan to treat certain types of metastatic breast cancer. We look forward to the continued evaluation of our TROP2-directed antibody drug conjugate, including comparisons to standard therapy in earlier lines of treatment for HR-positive, HER2-low or negative metastatic breast cancer through our ongoing TROPION-Breast01 Phase III trial.”
Patients in the TROPION-PanTumor01 trial were heavily pretreated, receiving a median of five lines of prior regimens in the metastatic setting (range 3-10). Prior treatments included CDK4/6 inhibitors (95%), capecitabine (83%), taxanes (59%), anthracyclines (54%), neoadjuvant chemotherapy (37%), mTOR inhibitors (29%) and PI3KCA inhibitors (20%). As of data cut-off on 22 July 2022, five patients remained on study treatment.
The safety profile of datopotamab deruxtecan was consistent with previous data with no new safety signals identified. The most common Grade 3 or higher treatment-emergent adverse events (TEAEs) were decreased lymphocyte count (15%), stomatitis (10%), anaemia (7%), dyspnoea (2%) and fatigue (2%). Serious TEAEs were observed in six patients (15%), including one death due to dyspnoea that was not considered treatment-related. Treatment discontinuations due to an adverse event occurred in five patients (12%). No cases of Grade 3 or higher diarrhoea or febrile neutropenia were observed. One case of Grade 3 interstitial lung disease was adjudicated as treatment-related.
AstraZeneca and Daiichi Sankyo have a broad clinical development programme for datopotamab deruxtecan in breast cancer, including the ongoing pivotal TROPION-Breast01 Phase III trial evaluating datopotamab deruxtecan in patients with HR-positive, HER2-low or negative, inoperable or metastatic breast cancer previously treated with chemotherapy.
Notes
HR-positive breast cancer
Breast cancer is the most common cancer and one of the leading causes of cancer-related deaths worldwide.3 More than two million breast cancer cases were diagnosed in 2020, with nearly 685,000 deaths globally.3
HR-positive breast cancer (expressing estrogen or progesterone receptors, or both) is the most common subtype of breast cancer with approximately 70% of breast cancer tumours considered HR-positive and HER2-low or negative.1
The growth of HR-positive breast cancer cells is often driven by estrogen receptors (ER), and endocrine therapies that target ER-driven disease are widely used as 1st-line treatment in the advanced setting, and often paired with cyclin-dependent kinase (CDK) 4/6 inhibitors.4-6 However, resistance to CDK4/6 inhibitors and current endocrine therapies develops in many patients with advanced disease.6 Once this occurs, the treatment options are limited – with chemotherapy being the current standard of care – and survival rates are low with 30% of patients anticipated to live beyond five years after diagnosis.1,2,6
Optimising endocrine therapy and overcoming resistance for patients with ER-driven disease at all stages of treatment as well as identifying new therapies for those who no longer have ER-driven disease are active areas of focus for breast cancer research.
TROP2 (trophoblast cell-surface antigen 2) is a transmembrane glycoprotein that is broadly expressed in several types of solid tumours, including HR-positive, HER2-low or negative breast cancer.7-8 TROP2 expression is an unfavourable prognostic factor for overall survival in all types of breast cancer.7
TROPION-PanTumor01
TROPION-PanTumor01 is a first-in-human, open-label, two-part, multicentre Phase I trial evaluating the safety and preliminary efficacy of datopotamab deruxtecan in patients with advanced solid tumours that have relapsed or are refractory to standard treatment or for which no standard treatment is available. The dose escalation portion of the trial enrolled patients with non-small cell lung cancer (NSCLC) to assess the safety and efficacy of datopotamab deruxtecan to determine the recommended dose for expansion (6mg/kg). The dose expansion part of TROPION-PanTumor01 is enrolling several different cohorts including patients with NSCLC, triple-negative breast cancer (TNBC), HR-positive, HER2-low or negative breast cancer, small cell lung cancer, urothelial, gastric, pancreatic, castration-resistant prostrate and esophageal cancer.
Safety endpoints include dose-limiting toxicities and serious adverse events. Efficacy endpoints include ORR, DoR, time to response, PFS and OS. Pharmacokinetic, biomarker and immunogenicity endpoints also are being evaluated.
Datopotamab deruxtecan (Dato-DXd)
Datopotamab deruxtecan (Dato-DXd) is an investigational TROP2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, datopotamab deruxtecan is one of three leading ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programmes in AstraZeneca’s ADC scientific platform. Datopotamab deruxtecan is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads, an exatecan derivative, via tetrapeptide-based cleavable linkers.
A comprehensive development programme called TROPION is underway globally with more than 10 trials evaluating the efficacy and safety of datopotamab deruxtecan across multiple TROP2-targetable tumours, including TNBC, HR-positive, HER2-low or negative breast cancer and NSCLC. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.
AstraZeneca and Daiichi Sankyo collaboration
AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise datopotamab deruxtecan in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for the manufacturing and supply of datopotamab deruxtecan.
AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge, and redefine, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.
AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment.
With Enhertu (trastuzumab deruxtecan), a HER2-directed ADC, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive and HER2-low metastatic breast cancer and are exploring its potential in earlier lines of treatment and in new breast cancer settings.
In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and aims to reshape the HR-positive space with next-generation oral selective estrogen receptor degrader (ngSERD) and potential new medicine camizestrant as well as a potential first-in-class AKT kinase inhibitor, capivasertib. AstraZeneca is also collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan, in this setting.
PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in early and metastatic breast cancer with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in these settings and to explore its potential in earlier disease.
To bring much-needed treatment options to patients with TNBC, an aggressive form of breast cancer, AstraZeneca is evaluating the potential of datopotamab deruxtecan alone and in combination with immunotherapy Imfinzi (durvalumab), capivasertib in combination with chemotherapy, and Imfinzi in combination with other oncology medicines, including Lynparza and Enhertu.
AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.
The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.
AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.
AstraZeneca, Daiichi Sankyo's drug shows promise in heavily pretreated breast cancer patients in trial
Dec. 09, 2022 4:52 AM ET
AstraZeneca PLC (AZN), DSKYF, DSNKY
By: Ravikash, SA News Editor
AstraZeneca (NASDAQ:AZN) and Daiichi Sankyo (OTCPK:DSKYF) (OTCPK:DSNKY) said on Thursday that their medicine datopotamab deruxtecan (Dato-DXd) showed durable efficacy in patients with a type of breast cancer in an early stage study.
AstraZeneca PLC (AZN), DSKYF, DSNKY
December 09, 2022
R&D
Capivasertib Plus FASLODEX® (fulvestrant)
IBI110 (anti-LAG-3 mAb) in combination with Sintilimab (anti-PD-1 mAb)
Capivasertib Plus FASLODEX® (fulvestrant)
Capivasertib plus Faslodex reduced the risk of disease progression or death by 40% versus Faslodex in advanced HR-positive breast cancer
PUBLISHED 8 December 2022
8 December 2022 13:30 GMT
CAPItello-291 Phase III trial results presented at SABCS 2022
show potential of capivasertib as first-in-class AKT inhibitor
Detailed results from the CAPItello-291 Phase III trial showed AstraZeneca’s capivasertib in combination with Faslodex (fulvestrant) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) versus placebo plus Faslodex in patients with hormone receptor (HR)-positive, HER2-low or negative, locally advanced or metastatic breast cancer, following recurrence or progression on, or after, endocrine therapy (with or without a CDK4/6 inhibitor).1 Results will be presented today in an oral presentation at the 2022 San Antonio Breast Cancer Symposium (SABCS).
Results showed capivasertib in combination with Faslodex demonstrated a 40% reduction in the risk of disease progression or death versus placebo plus Faslodex in the overall trial population (based on a hazard ratio [HR] of 0.60, 95% confidence interval [CI] 0.51-0.71; p=<0.001; median 7.2 versus 3.6 months).1 In the AKT pathway biomarker-altered population, capivasertib plus Faslodex reduced the risk of disease progression or death by 50% versus placebo plus Faslodex (HR of 0.50, 95% CI 0.38-0.65; p=<0.001; median 7.3 versus 3.1 months).1 Alterations within the AKT pathway (PI3K/AKT/PTEN) occur frequently in breast cancer, affecting up to 50% of patients with advanced HR-positive breast cancer.2-4
Nicholas Turner, MD, PhD, Professor of Molecular Oncology at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, London, UK, and principal investigator in the CAPItello-291 Phase III trial, said: “These data demonstrate the practice-changing potential of capivasertib as a new treatment option for patients with advanced HR-positive breast cancer. Critically, this potentially first-in-class treatment has shown it delays disease progression for those who have progressed on, or become resistant to, endocrine therapies and CDK4/6 inhibitors.”
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “Capivasertib brings important progress to an area with persistent treatment gaps as the first therapy of its kind shown to be effective in a Phase III trial in patients with advanced HR-positive, HER2-low or negative breast cancer. We believe these results which showed benefit in all-comers and biomarker positive populations can reshape HR-positive breast cancer treatment, and that capivasertib can become an important new option for patients.”
Summary of results: CAPItello-2911
Capivasertib plus Faslodex
n=355
Placebo plus Faslodex
n=353
Median PFS in overall population (months)
7.2
3.6
HR (95% CI)
0.60 (0.51-0.71)
p-value
p=<0.001
Median PFS in the biomarker-altered population (months)
7.3
3.1
HR (95% CI)
0.50 (0.38-0.65)
p-value
p=<0.001
ORR in overall population
22.9%
12.2%
ORR in biomarker-altered population
28.8%
9.7%
HR, hazard ratio; CI, confidence interval; PFS, progression-free survival; ORR, objective response rate
Confirmed objective response rate (ORR) was 22.9% for the capivasertib plus Faslodex arm versus 12.2% for the placebo plus Faslodex arm in the overall trial population, and 28.8% versus 9.7%, respectively, in the biomarker-altered population.1 Although the overall survival (OS) data were immature at the time of the analysis, early data are encouraging.1 The trial will continue to assess OS as a key secondary endpoint.
The safety profile of capivasertib plus Faslodex was similar to that observed in previous trials evaluating this combination.1 In the overall trial population, the most frequent any grade adverse events (AEs) with capivasertib plus Faslodex occurring in 20% or more of patients were diarrhoea (72.4%), nausea (34.6%), rash (group term including rash, rash macular, maculo-papular rash, rash papular and rash pruritic; 38%) fatigue (20.8%) and vomiting (20.6%).1 The most frequent Grade 3 or higher AEs occurring in 5% or more of patients were diarrhoea (9.3%) and rash (12.1%).1
Notes
HR-positive breast cancer
Breast cancer is the most common cancer and is one of the leading causes of cancer-related deaths worldwide.5 More than two million patients were diagnosed with breast cancer in 2020, with nearly 685,000 deaths globally.5
HR-positive breast cancer (expressing estrogen or progesterone receptors, or both), is the most common subtype of breast cancer with approximately 70% of breast cancer tumours considered HR-positive and HER2-low or negative.6
The growth of HR-positive breast cancer cells is often driven by estrogen receptors (ER),7 and endocrine therapies that target ER-driven disease are widely used as 1st-line treatment in the advanced setting, and often paired with cyclin-dependent kinase (CDK) 4/6 inhibitors.8,9 However, resistance to CDK4/6 inhibitors and current endocrine therapies develops in many patients with advanced disease.9 Once this occurs, treatment options are limited9 – with chemotherapy being the current standard of care10 – and survival rates are low with 30% of patients anticipated to live beyond five years after diagnosis.6
Optimising endocrine therapy and overcoming resistance for patients with ER-driven disease at all stages of treatment as well as identifying new therapies for those who no longer have ER-driven disease are active areas of focus for breast cancer research.
CAPItello-291
CAPItello-291 is a Phase III, double-blind, randomised trial that is part of a larger clinical programme focused on capivasertib, an investigational AKT (serine/threonine kinase) inhibitor. CAPItello-291 is evaluating the efficacy of capivasertib in combination with Faslodex versus placebo plus Faslodex for the treatment of locally advanced (inoperable) or metastatic HR-positive, HER2-low or negative breast cancer.
The global trial enrolled 708 adult patients with histologically confirmed HR-positive, HER2-low or negative breast cancer whose disease has recurred or progressed during or after aromatase inhibitor therapy, with or without a CDK4/6 inhibitor, and up to one line of chemotherapy for advanced disease. The trial has dual primary endpoints of PFS in the overall patient population and in a population of patients whose tumours have qualifying alterations in the AKT pathway (PIK3CA, AKT1 or PTEN genes). In the trial, approximately 40% of tumours had these alterations.
Capivasertib
Capivasertib is an investigational oral treatment currently in Phase III trials for the treatment of multiple subtypes of breast cancer, prostate cancer and a Phase II trial for haematologic malignancies. A potent, selective adenosine triphosphate (ATP)-competitive inhibitor of all three AKT isoforms (AKT1/2/3), capivasertib is being evaluated as a monotherapy and in combination with existing therapies in tumours harbouring alterations in the AKT pathway (PI3K/AKT/PTEN), and in tumours reliant on signalling via this pathway for survival. Capivasertib 400 mg is administered twice daily according to an intermittent dosing schedule of four days on and three days off. This was chosen in early phase trials based on tolerability and the degree of target inhibition.
The capivasertib clinical research programme is investigating the safety and efficacy of capivasertib when used alone and in combination with established treatment regimens.
Capivasertib was discovered by AstraZeneca subsequent to a collaboration with Astex Therapeutics (and its collaboration with the Institute of Cancer Research and Cancer Research Technology Limited).
AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge, and redefine, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.
AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment.
With Enhertu (trastuzumab deruxtecan), a HER2-directed ADC, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive and HER2-low metastatic breast cancer and are exploring its potential in earlier lines of treatment and in new breast cancer settings.
In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and aims to reshape the HR-positive space with next-generation SERD and potential new medicine camizestrant as well as a potential first-in-class AKT kinase inhibitor, capivasertib. AstraZeneca is also collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan, in this setting.
PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in early and metastatic breast cancer with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in these settings and to explore its potential in earlier disease.
To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is evaluating the potential of datopotamab deruxtecan alone and in combination with immunotherapy Imfinzi (durvalumab), capivasertib in combination with chemotherapy, and Imfinzi in combination with other oncology medicines, including Lynparza and Enhertu.
AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.
The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.
AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.
AstraZeneca says adding to capivasertib to Faslodex reduces breast cancer progression
Dec. 08, 2022 3:18 PM ET
By: Jonathan Block, SA News Editor
- Adding AstraZeneca's (NASDAQ:AZN) experimental cancer drug capivasertib to Faslodex (fulvestrant) led to a 40% reduction in the risk of disease progression or death compared to Faslodex alone.
- https://seekingalpha.com/news/3915462-astrazeneca-says-adding-to-capivasertib-to-faslodex-reduces-breast-cancer-progression
- AstraZeneca PLC (AZN)
Iptacopan
Darovasertib Combination Therapy with Crizotinib
Capivasertib Plus FASLODEX® (fulvestrant)
Novartis investigational iptacopan provides clinically meaningful increases in hemoglobin levels in complement-inhibitor-naïve patients with PNH
Dec 08, 2022
- Phase III APPOINT-PNH study of investigational oral monotherapy iptacopan met its primary endpoint; second positive Phase III topline readout for iptacopan in paroxysmal nocturnal hemoglobinuria (PNH)1
- Topline APPOINT-PNH data were consistent with APPLY-PNH readout and showed a significant proportion of complement-inhibitor-naïve patients treated with iptacopan achieved clinically meaningful increases in hemoglobin levels vs. baseline without the need for blood transfusions1
- PNH has a significant unmet need not addressed by anti-C5 therapies; despite treatment with anti-C5s, a large proportion of people with PNH remain anemic, fatigued and dependent on blood transfusions2-5
- APPOINT-PNH data to be presented at upcoming medical meeting and included in iptacopan PNH global regulatory 2023 submissions
Basel, December 8, 2022 —
Novartis today announced the Phase III APPOINT-PNH study (NCT04820530) of investigational oral monotherapy iptacopan in complement-inhibitor-naïve (including anti-C5 therapies) adults with PNH met its primary endpoint1. Topline results showed a significant proportion of patients treated with iptacopan (200 mg twice daily) achieved clinically meaningful hemoglobin-level increases of 2 g/dL or more from baseline without the need for blood transfusions at 24 weeks1.
In the study, the safety profile of iptacopan monotherapy was consistent with previously reported data1,6,7. Detailed data will be presented at an upcoming medical meeting and included as part of global regulatory submissions in 2023.
“We are very encouraged by the results of the complement-inhibitor-naïve data from the Phase III APPOINT-PNH trial,” said David Soergel, M.D., Global Head, Cardiovascular, Renal and Metabolism Development Unit, Novartis. “This second iptacopan readout for PNH underscores the robust potential for this therapy, enabling us to submit a broad regulatory package with the goal of iptacopan potentially becoming the first oral monotherapy for PNH.”
Topline results for the pivotal Phase III APPLY-PNH study were recently announced8. It met its two primary endpoints, with iptacopan demonstrating superiority over anti-C5 therapies (eculizumab or ravulizumab) in adults with PNH experiencing residual anemia despite prior anti-C5 treatment8. The study showed a statistically significant and clinically meaningful increase in the proportion of iptacopan-treated patients achieving 2 g/dL or more hemoglobin-level increases from baseline, and 12 g/dL or more hemoglobin levels, both without the need for blood transfusions at 24 weeks, compared to anti-C5 therapies8.
Novartis is grateful to the patients and clinical investigators whose time, trust and commitment made this PNH research possible, and is excited to continue to explore the potential of iptacopan as the first oral monotherapy option for patients with PNH.
Iptacopan is also being investigated in Phase III studies for the complement-mediated kidney diseases (CMKDs) C3 glomerulopathy (APPEAR-C3G [NCT04817618]), IgA nephropathy (APPLAUSE-IgAN [NCT04578834]), and atypical hemolytic uremic syndrome (APPELHUS [NCT04889430]), as well as in a number of additional indications in Phase II9-11.
Following presentation of the Phase III APPLY-PNH iptacopan data at ASH, Novartis will host an investor conference call on December 13, 2022 at 18:30 CET / 12:30 ET. A simultaneous webcast may be accessed by visiting the Novartis website at https://www.novartis.com/investors/event-calendar, and a replay will be available after the call.
About the study
APPOINT-PNH (NCT04820530) is a Phase III, multinational, multicenter, open-label, single-arm study to evaluate the efficacy and safety of twice-daily, oral iptacopan monotherapy (200 mg) in adult PNH patients who are naïve to complement inhibitor therapy, including anti-C5 therapies (e.g., eculizumab or ravulizumab)12.
The primary endpoint was to assess the proportion of participants achieving an increase in hemoglobin levels from baseline of 2 g/dL or more in the absence of red blood cell (RBC) transfusions at 24 weeks12. Secondary endpoints include the proportion of participants achieving sustained hemoglobin levels of 12 g/dL or more in the absence of RBC transfusions, transfusion avoidance defined as the proportion of participants who remain free from transfusions, average change in hemoglobin levels, average percent change in lactate dehydrogenase (LDH) levels, rate of breakthrough hemolysis, average change in absolute reticulocyte counts, change in fatigue, and rates of major adverse vascular events12.
About paroxysmal nocturnal hemoglobinuria (PNH)
PNH is a rare, chronic and serious complement-mediated blood disorder2. People with PNH have an acquired mutation in some of their hematopoietic stem cells (which are located in the bone marrow and can grow and develop into RBCs, white blood cells and platelets) that causes them to produce RBCs that are susceptible to premature destruction by the complement system2,3. This leads to intravascular hemolysis (destruction of RBCs within blood vessels) and extravascular hemolysis (destruction of RBCs mostly in the spleen and liver), which cause anemia (low levels of circulating RBCs), thrombosis (formation of blood clots), fatigue and other debilitating symptoms that can impact people’s quality of life2,3.
It is estimated that approx. 10-20 people per million worldwide live with PNH2. Although PNH can develop at any age, it is often diagnosed in people between 30-40 years old13,14.
PNH has a significant unmet need not addressed by anti-C5 therapies (eculizumab or ravulizumab): despite treatment with anti-C5s, a large proportion of people with PNH remain anemic, fatigued and dependent on blood transfusions2-5.
About iptacopan
Iptacopan is an investigational first-in-class, orally administered targeted factor B inhibitor of the alternative complement pathway6,7,15. It acts upstream of the C5 terminal pathway, preventing not only intravascular but also extravascular hemolysis in PNH6,7,15. In doing so, iptacopan targets a key part of the biology responsible for PNH while offering an oral monotherapy option6,7,15.
Discovered at the Novartis Institutes for BioMedical Research, iptacopan is currently in development for a number of other complement-mediated diseases (CMDs) where significant unmet needs exist, including kidney diseases C3G, IgAN, atypical hemolytic uremic syndrome (aHUS), membranous nephropathy (MN), lupus nephritis (LN), and blood disorders immune thrombocytopenic purpura (ITP) and cold agglutinin disease (CAD).
Based on disease prevalence, unmet need and data from Phase II studies, iptacopan has received FDA Breakthrough Therapy Designation in PNH, orphan drug designations from the FDA and EMA in PNH and C3G, EMA PRIME designation for C3G, and EMA orphan drug designation in IgAN16-19.
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 108,000 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 is on Twitter. Sign up to follow @Novartis at https://twitter.com/novartisnews
For Novartis multimedia content, please visit https://www.novartis.com/news/media-library
For questions about the site or required registration, please contact media.relations@novartis.com
Novartis iptacopan comes out successful in 2nd phase 3 trial rare blood disorder
Dec. 08, 2022 5:05 AM ET
By: Ravikash, SA News Editor
Novartis (NYSE:NVS) said its oral drug iptacopan met the main goal of a phase 3 trial in certain patients with paroxysmal nocturnal hemoglobinuria (PNH) in a phase 3 trial.
https://www.novartis.com/clinicaltrials
Zuranolone (SAGE-217/BIIB125)
Darovasertib Combination Therapy with Crizotinib
Darovasertib Combination Therapy with Crizotinib
December 6, 2022
Sage Therapeutics and Biogen Complete Rolling Submission of New Drug Application for Zuranolone in the Treatment of Major Depressive Disorder and Postpartum Depression
Zuranolone is being evaluated as a short course, rapid-acting, oral medication for major depressive disorder (MDD) and postpartum depression (PPD)
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Dec. 6, 2022-- Sage Therapeutics, Inc. (Nasdaq: SAGE) and Biogen Inc. (Nasdaq: BIIB) announced the completion of the rolling submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for zuranolone in the treatment of major depressive disorder (MDD) and postpartum depression (PPD). Zuranolone is an investigational drug being evaluated as a rapid-acting, once-daily, 14-day oral short course treatment in adults with MDD and PPD. The submission completes the NDA filing that was initiated earlier this year.
This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20221205005815/en/
In the clinical development program to date, zuranolone showed rapid and sustained improvement of depressive symptoms with a generally well-tolerated and consistent safety profile. Zuranolone, a neuroactive steroid, has a novel mechanism of action as a positive allosteric modulator of GABA-A receptors. In people with depression, it may help to rapidly rebalance dysregulated neuronal networks to help restore brain function. Zuranolone targets brain networks responsible for functions such as mood, arousal, behavior, and cognition.
“Based on the data in the LANDSCAPE and NEST programs, we believe that zuranolone has the potential to be a meaningful new therapy for depression,” said Priya Singhal, M.D., M.P.H., Head of Global Safety and Regulatory Sciences and Interim Head of R&D at Biogen. “We look forward to working with the FDA as this filing progresses.”
“Mental health is a highly underserved area with an urgent unmet need for innovative therapies. We need to rethink how MDD and PPD are treated. Existing treatments often take weeks to months to provide symptom relief, and patients may need to cycle through multiple treatment options to fully address their symptoms. People with MDD and PPD deserve better,” said Laura Gault, M.D., Ph.D., Chief Medical Officer at Sage. “We believe that zuranolone, if approved, could evolve the way depression is treated and this submission brings us one step closer to that goal.”
The NDA submission includes data from the LANDSCAPE and NEST development programs for zuranolone. The LANDSCAPE program includes five studies of zuranolone in adults with MDD (MDD-201B, MOUNTAIN, SHORELINE, WATERFALL, and CORAL Studies). The NEST program includes two studies of zuranolone in adult women with PPD (ROBIN and SKYLARK Studies).
Zuranolone was granted Fast Track Designation by the FDA in 2017 and Breakthrough Therapy in 2018 for MDD. The FDA also granted Fast Track Designation for PPD in 2022.
About zuranolone
Zuranolone (SAGE-217/BIIB125) is a once-daily, 14-day, investigational drug in development for the treatment of major depressive disorder (MDD) and postpartum depression (PPD). Zuranolone is an oral neuroactive steroid (NAS) GABA-A receptor positive allosteric modulator (PAM). The GABA system is the major inhibitory signaling pathway of the brain and central nervous system and contributes to regulating brain function. Zuranolone has been granted Fast Track and Breakthrough Therapy Designation for MDD and Fast Track Designation for PPD by the U.S. Food & Drug Administration.
Zuranolone is being evaluated in the LANDSCAPE and NEST clinical development programs. The two development programs include multiple studies examining use of zuranolone in several thousand people with a variety of dosing, clinical endpoints, and treatment paradigms. The LANDSCAPE program includes five studies of zuranolone in people with MDD (MDD-201B, MOUNTAIN, SHORELINE, WATERFALL, and CORAL Studies). The NEST program includes two placebo-controlled studies of zuranolone in women with PPD (ROBIN and SKYLARK Studies). Additionally, Shionogi completed a Phase 2 study of zuranolone in Japan in people with MDD.
About Sage Therapeutics
Sage Therapeutics is a biopharmaceutical company fearlessly leading the way to create a world with better brain health. Our mission is to pioneer solutions to deliver life-changing brain health medicines, so every person can thrive. For more information, please visit www.sagerx.com.
About Biogen
As pioneers in neuroscience, Biogen discovers, develops, and delivers worldwide innovative therapies for people living with serious neurological diseases as well as related therapeutic adjacencies. One of the world’s first global biotechnology companies, Biogen was founded in 1978 by Charles Weissmann, Heinz Schaller, Sir Kenneth Murray, and Nobel Prize winners Walter Gilbert and Phillip Sharp. Today, Biogen has a leading portfolio of medicines to treat multiple sclerosis, has introduced the first approved treatment for spinal muscular atrophy, and developed the first and only approved treatment to address a defining pathology of Alzheimer’s disease. Biogen is also commercializing biosimilars and focusing on advancing one of the industry’s most diversified pipelines in neuroscience that will transform the standard of care for patients in several areas of high unmet need.
We routinely post information that may be important to investors on our website at www.biogen.com. Follow us on social media - Twitter, LinkedIn, Facebook, YouTube.
View source version on businesswire.com: https://www.businesswire.com/news/home/20221205005815/en/
Source: Sage Therapeutics, Inc.
Sage, Biogen complete rolling filing with FDA for depression therapy zuranolone
Dec. 06, 2022 7:20 AM ET
By: Ravikash, SA News Editor
- Sage Therapeutics (NASDAQ:SAGE) and Biogen (NASDAQ:BIIB) completed a rolling submission of a new drug application (NDA) with the U.S. Food and Drug Administration (FDA) for approval of zuranolone to treat major depressive disorder (MDD) and postpartum depression (PPD).
- https://seekingalpha.com/news/3914235-sage-biogen-complete-rolling-filing-with-fda-for-depression-therapy-zuranolone
- Biogen Inc. (BIIB), SAGE
- https://www.sagerx.com/
- https://www.sagerx.com/programs-research/pipeline
Darovasertib Combination Therapy with Crizotinib
Darovasertib Combination Therapy with Crizotinib
Darovasertib Combination Therapy with Crizotinib
IDEAYA Biosciences Receives Fast Track Designation for Darovasertib Combination Therapy with Crizotinib for the Treatment of Metastatic Uveal Melanoma
- Fast Track designation granted by U.S. FDA for evaluation of darovasertib in combination with crizotinib in adult patients being treated for metastatic uveal melanoma (MUM)
- Enables darovasertib / crizotinib development program to access expedited regulatory review processes, including potential eligibility for accelerated approval / priority review
SOUTH SAN FRANCISCO, Calif., Dec. 5, 2022 /PRNewswire/ --
IDEAYA Biosciences, Inc. (NASDAQ: IDYA), a synthetic lethality focused precision medicine oncology company committed to the discovery and development of targeted therapeutics, announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to IDEAYA's development program investigating darovasertib, a potential first-in-class protein kinase C (PKC) inhibitor, for use in combination with crizotinib, an investigational cMET inhibitor, for the treatment of adult patients with metastatic uveal melanoma.
"We are extremely pleased to receive the U.S. FDA Fast Track designation as we prepare to initiate a potential Phase 2/3 registrational trial to evaluate the darovasertib and crizotinib combination in patients with MUM. The Fast Track designation acknowledges MUM as a serious condition and the potential for the darovasertib / crizotinib combination to treat this unmet medical need," said Dr. Darrin Beaupre, Senior Vice President and Chief Medical Officer at IDEAYA Biosciences.
Fast Track is a U.S. FDA process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. Under the Fast Track designation, the darovasertib / crizotinib development program in MUM is eligible for various expedited regulatory review processes, including generally more frequent FDA interactions (e.g., meetings, written communications), potential eligibility for rolling review of a New Drug Application (NDA) and potential accelerated approval and priority review of an NDA.
Darovasertib was previously also designated as an Orphan Drug by the U.S. FDA in Uveal Melanoma (UM), including in MUM, entitling IDEAYA to certain potential tax credits, exemptions from user fees, and statutory marketing exclusivity.
IDEAYA is targeting initiation of a potential registration-enabling trial for the darovasertib and crizotinib combination in MUM in Q1 2023, subject to FDA feedback and guidance.
IDEAYA is also planning to initiate a company-sponsored Phase 1 clinical trial in Q4 2022 to evaluate darovasertib monotherapy in neoadjuvant UM patients. The preliminary development approach contemplates clinical endpoints such as organ preservation and/or vision preservation proximal to primary interventional treatments. Additional information on the company's plans to evaluate darovasertib, including scientific insights and clinical development opportunities in the neoadjuvant setting, will be highlighted in an Investor R&D Day webcast being hosted by IDEAYA on December 12, 2022, at 8:00 am - 9:30 am ET. Registration is available at https://ir.ideayabio.com/events or https://lifescievents.com/event/ideaya-rd-day/.
About IDEAYA Biosciences
IDEAYA is a synthetic lethality-focused precision medicine oncology company committed to the discovery and development of targeted therapeutics for patient populations selected using molecular diagnostics. IDEAYA's approach integrates capabilities in identifying and validating translational biomarkers with drug discovery to select patient populations most likely to benefit from its targeted therapies. IDEAYA is applying its early research and drug discovery capabilities to synthetic lethality – which represents an emerging class of precision medicine targets.
SOURCE IDEAYA Biosciences, Inc.
IDEAYA wins FDA fast track status for melanoma treatment
Dec. 05, 2022 6:37 AM ET
IDEAYA Biosciences, Inc. (IDYA)PFE
By: Dulan Lokuwithana, SA News Editor
- Oncology-focused biotech IDEAYA Biosciences (NASDAQ:IDYA) announced Monday that the FDA granted Fast Track designation for its experimental drug darovasertib in metastatic uveal melanoma (MUM) as a combination therapy.
- Accordingly, the regulatory benefits related to FDA’s Fast Track designation will be applicable for darovasertib, a protein kinase C inhibitor, in combination with Pfizer’s (PFE) lung cancer therapy crizotinib as a treatment for adults with MUM.
- https://seekingalpha.com/news/3913825-idya-stock-on-watch-after-fda-fast-track-status-for-melanoma-treatment
- IDEAYA Biosciences, Inc. (IDYA)PFE
- https://www.ideayabio.com/pipeline/
biotecHOPE™ 2022
ANAVEX®2-73 (BLARCAMESINE)
ANAVEX®2-73 (BLARCAMESINE)
ANAVEX®2-73 (BLARCAMESINE)
ANAVEX®2-73 (BLARCAMESINE) PHASE 2B/3 STUDY MET PRIMARY AND KEY SECONDARY ENDPOINTS,
SHOWING STATISTICALLY SIGNIFICANT REDUCTION OF CLINICAL DECLINE IN GLOBAL CLINICAL STUDY OF PATIENTS WITH EARLY ALZHEIMER’S DISEASE
- Robust, Statistically Significant and Clinically Meaningful Absolute Improvement in Cognitive Function as Measured by ADAS-Cog and ADCS-ADL
- Key Secondary Endpoint CDR-SB Also Met, Demonstrating Statistically Significant Results
- Plan to Meet with Regulatory Authorities to Determine Next Steps
NEW YORK –December 1, 2022
Anavex Life Sciences Corp. (“Anavex” or the “Company”) (Nasdaq: AVXL), a clinical-stage biopharmaceutical company developing differentiated therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders including Alzheimer’s disease, Parkinson’s disease, Rett syndrome and other central nervous system (CNS) disorders, today announced positive topline results from its Phase 2b/3 ANAVEX®2-73-AD-004 clinical trial of oral ANAVEX®2-73 (blarcamesine) for the treatment of mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) and mild AD (collectively known as early AD). ANAVEX®2-73 met the primary endpoints ADAS-Cog[1] and ADCS-ADL[2] and key secondary endpoint CDR-SB[3] with statistically significant results. Next step, in light of this data, is meeting with regulatory authorities to discuss this data in the context of ongoing development with an aim to bring this therapy to patients in Europe, Asia-Pacific, and the U.S.
ANAVEX®2-73 (blarcamesine) is an orally available, small-molecule activator of the sigma-1 receptor (SIGMAR1), which, data suggest, is pivotal to restoring neural cell homeostasis and promoting neuroplasticity.[4]
ANAVEX®2-73-AD-004 was a randomized, double-blind, multicenter, placebo-controlled 509 patient Phase 2b/3 study (randomized 1:1:1 to mid or high dose of ANAVEX®2-73 or placebo), for the treatment of early Alzheimer’s disease over 48 weeks. Top line data will be presented later today in the late breaking oral communication presentation at the Clinical Trials on Alzheimer’s Disease (CTAD) Congress 2022, December 1, 2022, at 4:30pm PT in San Francisco, CA. Further analysis of the data remains ongoing, and the Company plans to submit the data for publication in a peer-reviewed medical journal. The open-label extension study ATTENTION-AD will continue to follow participants over a 96 week period.
ANAVEX®2-73 treatment met the primary endpoints and reduced clinical decline on the global cognitive and functional scales over 48 weeks in the analysis of the Intent-to-treat (ITT) population.
ANAVEX®2-73 demonstrated visible improvement in patients with Alzheimer’s disease. Patients treated with ANAVEX®2-73 were 84% more likely, to have improved cognition by ADAS-Cog score change of -0.50 points or better from baseline to end of treatment than patients on placebo, Odds Ratio = 1.84 (p = 0.015). On average, patients, who improved cognitively with ANAVEX®2-73 treatment, improved by ADAS-Cog cognition score of -4.03 points. ANAVEX®2-73 treatment was 167% more likely to improve function compared with placebo, at a clinically meaningful improvement of ADCS-ADL score change of +3.5 points or better, Odds Ratio = 2.67 (p=0.0255). This reflects a robust improved and clinically meaningful outcome in cognition and function from baseline.
Additionally, treatment with ANAVEX®2-73 statistically significantly reduced cognitive decline, measured with ADAS-Cog, compared to placebo at end of treatment by 45%, representing a treatment difference in mean score change of -1.85 points (p=0.033).
ANAVEX®2-73 treatment also met the secondary endpoint of reduction in clinical decline of cognition and function assessed by the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) compared to placebo, by a treatment difference in mean score change of -0.42 points (p=0.040), representing 27% reduction in the ITT population.
ANAVEX®2-73 (blarcamesine) was generally safe and well tolerated. The incidence of treatment emergent adverse events (TEAEs) was similar in the active and placebo arms with dizziness being the most common TEAE. TEAEs ≥7.5% threshold were predominantly mild or moderate. No clinically significant changes in vital signs, laboratory values and ECG parameters in active and placebo arms were observed. Safety findings in the study were consistent with the known safety profile of ANAVEX®2-73.
In addition to safety and efficacy demonstrated on the primary and key secondary endpoints, a pre-specified analysis of patients without SIGMAR1 gene mutation provides further confidence of the robustness of the SIGMAR1 activation in the treatment of neurodegenerative diseases. Approximately 80% of the total worldwide population lack a SIGMAR1 gene mutation.[5] ANAVEX®2-73 was more efficacious in this pre-specified population. This effect is consistent with prior clinical trials of ANAVEX®2-73.[6]
“People living with Alzheimer’s disease desperately need new therapies and I am truly impressed with the outcome of this study, which demonstrated reversal of cognitive decline,” said A/Professor Stephen Macfarlane, FRANZCP, Head of Clinical Services at the Dementia Centre, HammondCare and Principal Investigator. “These results complement and are consistent with findings from the previously completed Alzheimer’s disease Phase 2a ANAVEX®2-73 trial, which also demonstrated therapeutic effect on cognition and function. ANAVEX®2-73 might be a very much needed solution for many patients with Alzheimer’s disease.”
“We are very pleased to see such positive clinical data in patients with Alzheimer’s disease, which is otherwise a progressive disease, thereby emphasizing the potentially significant implications these findings have for patients, caregivers, and healthcare systems worldwide,” said Edward R Hammond, MD, PhD, MPH, Chief Medical Officer of Anavex. “We intend to discuss these findings with regulatory authorities in the context of the ongoing clinical development of ANAVEX®2-73 in this indication, with the goal of providing a much-needed treatment to the millions of patients living with Alzheimer’s disease.”
“The successful results of the ANAVEX®2-73-AD-004 clinical trial would not be possible without the truly motivated and dedicated study participants, their families and caregivers and the clinical investigators around the world. We thank all the people involved in the study for their invaluable contributions,” said Christopher U. Missling, PhD, President and Chief Executive Officer of Anavex. “These clinical study findings confirm the robustness of the ANAVEX precision medicine platform, and we look forward to advancing ANAVEX®2-73 as a potential new treatment option for Alzheimer’s disease while we continue to focus on the effect of ANAVEX®2-73 leveraging this approach to drug development to provide intelligent solutions beyond many traditional neurology trials in disease areas with high unmet needs.”
Economic Burden of Alzheimer's Disease[7]
Alzheimer's disease is the most common cause of dementia and the fifth leading cause of death in adults older than 65 years. The estimated total healthcare costs for the treatment of Alzheimer's disease in 2020 were estimated at $305 billion, with the cost expected to increase to more than $1 trillion as the population ages. Most of the direct costs of care for Alzheimer's disease are attributed to skilled nursing care, home healthcare, and hospice care. Indirect costs of care, including quality of life and informal caregiving, are likely underestimated, and are associated with significant negative societal and personal burdens.
About Anavex Life Sciences Corp.
Anavex Life Sciences Corp. (Nasdaq: AVXL) is a publicly traded biopharmaceutical company dedicated to the development of novel therapeutics for the treatment of neurodegenerative and neurodevelopmental disorders, including Alzheimer's disease, Parkinson's disease, Rett syndrome, and other central nervous system (CNS) diseases, pain, and various types of cancer. Anavex's lead drug candidate, ANAVEX®2-73 (blarcamesine), has successfully completed a Phase 2a clinical trial for Alzheimer's disease, a Phase 2 proof-of-concept study in Parkinson's disease dementia, and both a Phase 2 and a Phase 3 study in adult patients with Rett syndrome. ANAVEX®2-73 is an orally available drug candidate that restores cellular homeostasis by targeting sigma-1 and muscarinic receptors. Preclinical studies demonstrated its potential to halt and/or reverse the course of Alzheimer's disease. ANAVEX®2-73 also exhibited anticonvulsant, anti-amnesic, neuroprotective, and anti-depressant properties in animal models, indicating its potential to treat additional CNS disorders, including epilepsy. The Michael J. Fox Foundation for Parkinson's Research previously awarded Anavex a research grant, which fully funded a preclinical study to develop ANAVEX®2-73 for the treatment of Parkinson's disease. ANAVEX®3-71, which targets sigma-1 and M1 muscarinic receptors, is a promising clinical stage drug candidate demonstrating disease-modifying activity against the major hallmarks of Alzheimer's disease in transgenic (3xTg-AD) mice, including cognitive deficits, amyloid, and tau pathologies. In preclinical trials, ANAVEX®3-71 has shown beneficial effects on mitochondrial dysfunction and neuroinflammation. Further information is available at www.anavex.com. You can also connect with the company on Twitter, Facebook, Instagram, and LinkedIn.
Anavex's drug improves cognitive function in Alzheimer's patients, meets main goal of trial
Dec. 02, 2022 6:53 AM ET
Anavex Life Sciences Corp. (AVXL)
By: Ravikash, SA News Editor12 Comments
Anavex Life Sciences (NASDAQ:AVXL) said its oral drug ANAVEX2-73 (blarcamesine) met the main goal of improvement in cognitive function in patients with early Alzheimer's disease (AD) in a phase 2B/3 trial.
Anavex Life Sciences Corp. (AVXL)
https://www.anavex.com/therapeutic-candidates
Donanemab
ANAVEX®2-73 (BLARCAMESINE)
ANAVEX®2-73 (BLARCAMESINE)
Lilly Shares Positive Donanemab Data in First Active Comparator Study in Early Symptomatic Alzheimer's Disease
November 30, 2022
- Brain amyloid clearance (<24.1 Centiloids) was achieved in 37.9% of donanemab-treated participants compared with 1.6% of Aduhelm® (aducanumab-avwa)-treated patients at 6 months
- Donanemab reduced brain amyloid plaque levels vs. baseline by 65.2% compared with 17.0% for Aduhelm® at 6 months
SAN FRANCISCO, Nov. 30, 2022 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) has announced that donanemab met all primary and secondary endpoints for the 6-month primary outcome analysis in the Phase 3 TRAILBLAZER-ALZ 4 study, providing the first active comparator data on amyloid plaque clearance in patients with early symptomatic Alzheimer's disease treated with amyloid-targeting therapies. These data comparing donanemab to Aduhelm® * (aducanumab-avwa) to assess superiority on amyloid plaque reduction were shared at the 15th Clinical Trials on Alzheimer's Disease (CTAD) conference. Donanemab is an investigational antibody that targets a modified form of beta amyloid plaque called N3pG.
Through the FDA's accelerated approval pathway, the FDA has recognized that the reduction of amyloid beta plaque is a biomarker reasonably likely to predict clinical benefit in the treatment of early Alzheimer's disease.
"The purpose of this first ever active comparator trial of amyloid lowering agents was to answer important questions about potential differences in amyloid plaque reduction," said Mark Mintun, M.D., group vice president of pain and neurodegeneration research and development, Eli Lilly and Company. "These data reinforce our confidence in donanemab's unique mechanism of action based on reductions in key biomarkers of Alzheimer's disease, amyloid plaque and plasma phosphorylated tau (P-tau). Importantly, this was also the first study to obtain ARIA rates side by side using identical methods for ARIA assessment in the same patient population, demonstrating the ability to disconnect rate of plaque clearance from rate of ARIA incidence."
In the co-primary outcomes, brain amyloid plaque clearance, defined as achieving brain amyloid plaque levels of <24.1 Centiloids, was achieved in 37.9% of donanemab-treated participants (25 of 66) compared with 1.6% of Aduhelm-treated patients (1 of 64) at 6 months; in the intermediate tau subpopulation, 38.5% of donanemab-treated participants (10 of 26) reached brain amyloid clearance compared with 3.8% of Aduhelm-treated participants (1 of 26) by 6 months. In a key secondary outcome, donanemab reduced brain amyloid levels vs. baseline by 65.2% compared with 17.0% for Aduhelm at 6 months. In an exploratory outcome, donanemab, but not aducanumab-avwa, treatment significantly reduced plasma P-tau217 at 6 months compared to baseline.
The safety profile of both treatments was consistent with their previously published studies. ARIA was the most common treatment emergent adverse event in both groups. In the aducanumab-avwa group, the incidence of total ARIA was 26.1% with 4.3% being symptomatic. In the donanemab group, the incidence of total ARIA was 25.4% with 2.8% being symptomatic. For both treatments, all symptomatic cases were related to ARIA-E.
"It is encouraging to see that donanemab produced significant reduction of amyloid build up in the brain and P-tau in the blood after 6 months. This suggests that this treatment modified the biology of Alzheimer's disease early on in treatment," said Stephen Salloway, MD, associate director of the Center for Alzheimer's Disease Research at Brown University, who presented the findings. "It is also notable in TRAILBLAZER-ALZ 4 that the higher amyloid clearance by donanemab compared to aducanumab-avwa at 6 months was not associated with a higher rate of ARIA."
TRAILBLAZER-ALZ 4 is ongoing and will have 12-month and 18-month secondary analyses. The study is one of five studies that comprise the clinical program to evaluate the efficacy and safety of donanemab. In August, Lilly announced that the FDA accepted the donanemab application for review, with Priority Review designation, for Alzheimer's disease under the accelerated approval pathway.
About TRAILBLAZER-ALZ 4 Study
TRAILBLAZER-ALZ 4 (LY3002813) is a multicenter, randomized, open-label Phase 3 study of that enrolled 148 patients aged 50 to 85 with early symptomatic AD who met entry criteria including a Clinical Dementia Rating (CDR)-Global Score of 0.5 or 1 and gradual and progressive change in memory function for more than six months, among other criteria. Donanemab and Aduhelm are administered via intravenous infusions every four weeks for up to 18 months. Donanemab is administered until evidence of plaque clearance via positron emission tomography (PET) at 6, 12, or 18 months. Aduhelm is administered through the duration of the study according to its approved label. The studies' co-primary endpoints are superiority on, as measured by PET scan: the percentage of participants who reach complete amyloid plaque clearance and the percentage of participants who reach complete amyloid plaque clearance in the intermediate tau subpopulation at 6 months.
Lilly previously announced and published in the New England Journal of Medicine (NEJM) results from the Phase 2 TRAILBLAZER-ALZ study in March 2021. In June 2021, Lilly announced that the FDA had granted Breakthrough Therapy designation for donanemab based on the TRAILBLAZER-ALZ data.
About Alzheimer's Disease
Alzheimer's disease is a fatal illness that causes progressive decline in memory and other aspects of cognition. Dementia due to Alzheimer's disease is the most common form of dementia, accounting for 60 to 80 percent of all cases1. There are currently over 55 million people living with dementia around the world, with numbers expected to increase to nearly 139 million by 20502. Over 10 million new cases of dementia are diagnosed each year worldwide, implying one new case every 3.2 seconds, and a significant increase in the caregiving burden placed on society and families. In the US alone, there was an increase of nearly 10 million new caregivers from 2015 to 20203. The current annual societal and economic cost of dementia is estimated at $1.3 trillion, an amount that is expected to double by 2030 unless we find a way to slow the disease2.
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
© Lilly USA, LLC 2022. ALL RIGHTS RESERVED.
View original content to download multimedia:https://www.prnewswire.com/news-releases/lilly-shares-positive-donanemab-data-in-first-active-comparator-study-in-early-symptomatic-alzheimers-disease-301690725.html
SOURCE Eli Lilly and Company
Lilly posts Phase 3 data to compare its Alzheimer’s drug vs. Biogen’s
Dec. 01, 2022 7:15 AM ET
Eli Lilly and Company (LLY), BIIB, ESALF, ESALY
By: Dulan Lokuwithana, SA News Editor
Eli Lilly (NYSE:LLY) shared data from a Phase 3 trial for its Alzheimer's disease donanemab, comparing its performance against Aduhelm, an FDA-approved Alzheimer's therapy developed by Biogen (NASDAQ:BIIB) and Eisai (OTCPK:ESALF) (OTCPK:ESALY)
Eli Lilly and Company (LLY), BIIB, ESALF, ESALY
https://www.clinicaltrials.gov/ct2/show/NCT05508789
November 30, 2022
VLA15
ANAVEX®2-73 (BLARCAMESINE)
batiraxcept (AVB-500)
Valneva and Pfizer Report Six-Month Antibody Persistence Data in Children and Adults for Lyme Disease Vaccine Candidate
December 1, 2022
- Antibody levels remained above baseline six months after completion of a three-dose (Month 0-2-6) or a two-dose (Month 0-6) vaccination schedule
- Higher antibody levels were observed in the three-dose vaccination schedule versus the two-dose vaccination schedule, further validating the use of this schedule in the ongoing Phase 3 study
- There were no safety concerns observed in this six-month observational follow up
New York & Saint-Herblain (France), December 1, 2022 – Pfizer Inc. (NYSE: PFE) and Valneva SE (Nasdaq: VALN; Euronext Paris: VLA) today reported antibody persistence data six months after the completion of a three-dose (Month 0-2-6) or a two-dose (Month 0-6) vaccination schedule with their Lyme disease vaccine candidate, VLA15 in both children and adults. This is the first time antibody persistence data are reported in pediatric populations for this vaccine candidate.
Following positive immunogenicity and safety data for Phase 2 study VLA15-221 in April 2022[1], Valneva and Pfizer evaluated the persistence of antibodies six months after the Month 0-2-6 and the Month 0-6 vaccination schedule with VLA15 in healthy adults and pediatric participants (5 to 65 years of age). Data were collected in 96 healthy adults and 81 pediatric participants (5-17 years of age) for the Month 0-2-6 vaccination schedule and in 84 healthy adults and 78 pediatric participants (5-17 years of age) for the Month 0-6 schedule.
As observed in previous clinical studies with VLA15, antibody levels declined over time in all study groups but remained above baseline, confirming their persistence six months after completion of both vaccination schedules. Overall, antibody levels remained higher with the three-dose vaccination schedule compared to the two-dose schedule. Geometric mean fold rise (GMFRs) compared to baseline were 1.9-fold for Serotype 1 (ST1) to 3.2-fold Serotype 2 (ST2) across all age groups in the Month 0-2-6 vaccination schedule. The highest GMFRs were reported in the 5 to 11 years old age group, with GMFR levels at 2.8-fold (ST1) to 6.6-fold (ST2).
These results further validate the use of the three-dose vaccination schedule which is also included in the Phase 3 protocols for all participants.
No vaccine-related serious adverse events (SAEs) and no safety concerns were observed in this six-month observational follow up.
Juan Carlos Jaramillo M.D., Chief Medical Officer of Valneva, said, “We are pleased with these antibody persistence data that further validate the use of the three-dose vaccination schedule in our ongoing Phase 3 study and the acceptable safety and tolerability profiles of our vaccine candidate. Lyme disease continues to spread, representing a high unmet medical need that impacts the lives of many in the Northern Hemisphere, and each new report of positive data takes us a step closer to potentially bringing this vaccine to both adults and children who could benefit from it.”
Earlier this year, Pfizer and Valneva initiated a Phase 3 clinical study, Vaccine Against Lyme for Outdoor Recreationists (VALOR) (NCT05477524), to investigate the efficacy, safety and immunogenicity of VLA15[2]. Approximately 6,000 participants 5 years of age and older will receive three doses of VLA15 180 µg or saline placebo as a primary vaccination series followed by one booster dose of VLA15 or saline placebo (1:1 ratio). Enrollment is ongoing in Europe and the United States and expected to be completed in the second quarter of 2023. To learn more, visit www.pfizerclinicaltrials.com/nct05477524. To achieve the required pediatric safety database, Pfizer and Valneva are planning to initiate a complementary Phase 3 clinical study in early December 2022 to collect additional VLA15 safety data in participants 5 to 17 years of age.
“Rates of Lyme disease continue to increase globally, underscoring the importance of a vaccine that may help protect both adults and children,” said Annaliesa Anderson, Ph.D., Senior Vice President and Chief Scientific Officer of Vaccine Research & Development at Pfizer. “These six-month antibody persistence data are encouraging, and we hope that the data generated from the Phase 3 studies will further support the positive evidence for VLA15 to date.”
Pending successful completion of the Phase 3 studies, Pfizer could potentially submit a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) and Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) in 2025.
About VLA15
VLA15 is the only Lyme disease vaccine candidate currently in clinical development. This investigational multivalent protein subunit vaccine uses an established mechanism of action for a Lyme disease vaccine that targets the outer surface protein A (OspA) of Borrelia burgdorferi, the bacteria that cause Lyme disease. OspA is a surface protein expressed by the bacteria when present in a tick. Blocking OspA inhibits the bacterium’s ability to leave the tick and infect humans. The vaccine covers the six most common OspA serotypes expressed by the Borrelia burgdorferi sensu lato species that are prevalent in North America and Europe. VLA15 has demonstrated a strong immune response and satisfactory safety profile in pre-clinical and clinical studies so far. Valneva and Pfizer entered into a collaboration agreement in April 2020 to co-develop VLA15, with updates to the terms within this agreement made in June 2022.3,4 The terms of the collaboration agreement include a $25 million milestone payment made to Valneva upon Pfizer’s initiation of the Phase 3 study. The program was granted Fast Track designation by the U.S. FDA in July 2017.5
About Clinical Study VLA15-221
VLA15-221 is a randomized, observer-blind, placebo-controlled Phase 2 study. It is the first clinical study with VLA15 which enrolled a pediatric population (5-17 years old).
585 healthy participants received VLA15 at two different immunization schedules (month 0-2-6 [N=190] or month 0-6 [N=187]) or three doses of placebo (month 0-2-6 [N=208]). Vaccine recipients received VLA15 at a dose of 180 µg, which was selected based on data generated in the two previous Phase 2 studies. The main safety and immunogenicity readout was performed one month after the primary vaccination series. A subset of participants will receive a booster dose of VLA15 or placebo at month 18 (booster phase) and will be followed for three additional years to monitor antibody persistence.
VLA15 is tested as an alum-adjuvanted formulation and administered intramuscularly. The study is being conducted at U.S. sites located in areas where Lyme disease is endemic and has enrolled both volunteers with a cleared past infection with Borrelia burgdorferi as well as Borrelia burgdorferi-naïve volunteers.
About Lyme Disease
Lyme disease is a systemic infection caused by Borrelia burgdorferi bacteria transmitted to humans by infected Ixodes ticks.6 It is considered the most common vector-borne illness in the Northern Hemisphere.7 While the true incidence of Lyme disease is unknown, it is estimated to annually affect approximately 476,000 people in the United States and 130,000 people in Europe.8,9 Early symptoms of Lyme disease (such as a gradually expanding erythematous rash called Erythema migrans or more nonspecific symptoms like fatigue, fever, headache, mild stiff neck, arthralgia or myalgia) are often overlooked or misinterpreted. Left untreated, the disease can disseminate and cause more serious complications affecting the joints (arthritis), the heart (carditis) or the nervous system.9 The medical need for vaccination against Lyme disease is steadily increasing as the geographic footprint of the disease widens.8
About Valneva SE
Valneva is a specialty vaccine company focused on the development and commercialization of prophylactic vaccines for infectious diseases with significant unmet medical need. The Company takes a highly specialized and targeted approach to vaccine development and then applies its deep understanding of vaccine science to develop prophylactic vaccines addressing these diseases. Valneva has leveraged its expertise and capabilities both to commercialize three vaccines and to rapidly advance a broad range of vaccine candidates into and through the clinic, including candidates against Lyme disease and the chikungunya virus.
Pfizer, Valneva Lyme disease vaccine shows antibodies even 6-month after vaccination
Dec. 01, 2022 6:16 AM ET
By: Ravikash, SA News Editor1 Comment
Pfizer (NYSE:PFE) and Valneva (NASDAQ:VALN) said their Lyme disease vaccine VLA15 showed antibody levels remained above baseline six months after vaccination in a phase 2 trial.
https://valneva.com/research-development/lyme-disease/
https://clinicaltrials.gov/ct2/show/NCT04801420
batiraxcept (AVB-500)
batiraxcept (AVB-500)
batiraxcept (AVB-500)
Press Release
Nov 29, 2022
Aravive Announces Fast Track Designation of Batiraxcept for Treatment of ccRCC
FDA decision based on new Phase 1b data: Objective Response Rate (ORR) of 57% and median Progression-Free Survival (PFS) of 11.4 months in patients with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who have progressed after 1 or 2 prior lines of immuno-oncology (IO)- and vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI)-based therapies
HOUSTON, Nov. 29, 2022 (GLOBE NEWSWIRE) -- Aravive, Inc. (Nasdaq: ARAV, “the Company”), a late clinical-stage oncology company developing targeted therapeutics to treat metastatic disease, today announced the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation to the company’s lead program, batiraxcept, for treatment of patients with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who have progressed after 1 or 2 prior lines of systemic therapy that include both immuno-oncology (IO)-based and vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI)-based therapies (either in combination or sequentially).
Fast Track is a process designed to facilitate the development and expedite the review of investigational drugs to treat serious conditions and fill an unmet medical need. Drugs that receive Fast Track designation may be eligible for more frequent communications and meetings with the FDA to discuss the drug's development plan, including the design of the proposed clinical trials, use of biomarkers and the extent of data needed to support approval. Drugs with Fast Track Designation may also qualify for accelerated and priority review of new drug applications if relevant criteria are met.
The Fast Track Designation was based on new data submitted to the agency from the P1b clear cell renal cell cancer (ccRCC) study (AVB500-RCC-003; NCT04300140). As of September 26, 2022, 26 previously treated (second line or greater) patients with ccRCC have been treated with batiraxcept in the Phase 1b portion of a Phase 1b/2 trial at doses of 15 mg/kg (n=16) and 20 mg/kg (n=10), plus cabozantinib 60 mg daily. There were no dose limiting toxicities observed at either dose. Clinical data from this study demonstrate that batiraxcept has the potential to increase the clinical activity of cabozantinib in patients with metastatic ccRCC who have progressed following IO- and VEGF-TKI-based therapies (N=14 of the 26 patients) as the Objective Response Rate (ORR) was 57% and median Progression-Free Survival (PFS) was 11.4 months in this population.
“The majority of patients with kidney cancer develop resistance to frontline treatment and there is a clinical need for novel agents to improve upon treatment options in the refractory setting,” said Kathryn Beckermann, M.D., Ph.D., Assistant Professor, Division of Hematology and Oncology, Vanderbilt University Medical Center, and lead investigator for the trial. “Response rates to single agent targeted kinase inhibitors are approximately 30% with a PFS of approximately 7 months. The early data seen with batiraxcept including biomarker development, response rate, and progression-free survival are promising.”
“A review of the literature suggests that the clinical activity of cabozantinib is lower in those patients who have progressed following a VEGF-TKI-based therapy compared to patients who have progressed on IO or IO/IO therapy. Since preclinical data published by Xiao in 20191 observed that batiraxcept may restore TKI sensitivity, it makes sense that the combination of batiraxcept and cabozantinib may exhibit its greatest impact in those patients who have failed prior VEGF-TKI therapies,” said Gail McIntyre, Ph.D., DABT, Chief Executive Officer of Aravive. “Understanding the P1b ccRCC data has allowed us to identify the most appropriate patient population in which to evaluate batiraxcept in combination with cabozantinib and potentially the quickest path to approval in this population with an unmet medical need.”
_______________
1 Cancer Res 2019;79:5758–68
About Aravive
Aravive, Inc. is a late clinical-stage oncology company developing targeted therapeutics to treat metastatic disease. Our lead product candidate, batiraxcept (formerly AVB-500), is an ultra-high affinity decoy protein that binds to GAS6, the sole ligand that activates AXL, thereby inhibiting metastasis and tumor growth, and restoring sensitivity to anti-cancer agents. Batiraxcept has been granted Fast Track Designation by the U.S. FDA and Orphan Drug Designation by the European Commission in platinum-resistant recurrent ovarian cancer. Batiraxcept is in an active registrational Phase 3 trial in platinum resistant ovarian cancer (NCT04729608), a Phase 1b/2 trial in clear cell renal cell carcinoma (NCT04300140), and a Phase 1b/2 trial in pancreatic adenocarcinoma (NCT04983407). The Company is based in Houston, Texas and received a Product Development Award from the Cancer Prevention & Research Institute of Texas (CPRIT) in 2016. Additional information at www.aravive.com.
Aravive gains on FDA Fast Track status for lead program
Nov. 29, 2022 7:42 AM ET
By: Dulan Lokuwithana, SA News Editor
- Clinical-stage oncology company Aravive, Inc. (NASDAQ:ARAV) added ~7% pre-market Tuesday after announcing that the FDA granted Fast Track Designation to its lead program, batiraxcept, as a treatment for certain kidney cancer patients.
- https://seekingalpha.com/news/3911854-arav-stock-gains-on-fda-fast-track-status-for-lead-program
- Aravive, Inc. (ARAV)
- https://aravive.com/pipeline/
- https://aravive.com/
XENLETA® (lefamulin)
batiraxcept (AVB-500)
XENLETA® (lefamulin)
Nabriva Therapeutics Announces Positive Topline Results from Phase 1 Trial of XENLETA® (lefamulin) in Adult Patients with Cystic Fibrosis
November 28, 2022 at 7:01 AM EST
- PK Data and Safety Profile Consistent with Previous Studies in Healthy Subjects –
- Results Support Potential Utility of Lefamulin in Patients with Cystic Fibrosis -
DUBLIN, Ireland and FORT WASHINGTON, Pa., Nov. 28, 2022 (GLOBE NEWSWIRE) -- Nabriva Therapeutics plc (NASDAQ: NBRV), a biopharmaceutical company engaged in the commercialization and development of innovative anti-infective agents to treat serious infections, announced positive topline results from their Phase 1 clinical trial that assessed the safety and pharmacokinetics (PK) of oral and intravenous (IV) XENLETA® (lefamulin) in adult patients with cystic fibrosis (CF).
“We are excited to share positive topline results from this important study of XENLETA in patients with CF,” said Christine Guico-Pabia, M.D., MBA, MPH, Nabriva’s Chief Medical Officer. “The data indicate that the PK of XENLETA in CF patients is consistent with that observed in previous single-dose healthy volunteer studies evaluating the approved oral and IV dosing for adults with community-acquired bacterial pneumonia (CABP). In addition, XENLETA was well-tolerated and the adverse event profile in CF patients was consistent with that described across our clinical program.
Dr. Guico-Pabia added, “XENLETA has been demonstrated to be a potent anti-staphylococcal antibiotic in in vitro and clinical studies, including against methicillin-resistant S. aureus (MRSA). There are limited treatment options for the management of bacterial exacerbations in CF patients caused by S. aureus and the results of this study support the potential utility of XENLETA in this difficult to treat patient population. We would like to thank the study participants, investigators, and the Cystic Fibrosis Foundation for their support of this important study and look forward to sharing the complete results with the medical community in the first half of 2023.”
About the Trial
The Phase 1 trial is an open-label, randomized, single-dose, crossover study to assess the safety and pharmacokinetics of oral (600 mg) and IV (150 mg) XENLETA in adult patients with cystic fibrosis. The dosing utilized in this study is consistent with the FDA approved dosage for the treatment of adults with CABP.
More information can be found at ClinicalTrials.gov -NCT05225805.
About Nabriva Therapeutics plc
Nabriva Therapeutics is a biopharmaceutical company engaged in the commercialization and development of innovative anti-infective agents to treat serious infections. Nabriva Therapeutics received U.S. Food and Drug Administration approval for XENLETA® (lefamulin injection, lefamulin tablets), the first systemic pleuromutilin antibiotic for community-acquired bacterial pneumonia (CABP). Nabriva Therapeutics is also developing CONTEPO™ (fosfomycin) for injection, a potential first-in-class epoxide antibiotic for complicated urinary tract infections (cUTI), including acute pyelonephritis. Nabriva entered into an exclusive agreement with subsidiaries of Merck & Co. Inc., Kenilworth, N.J., USA to market, sell and distribute SIVEXTRO® (tedizolid phosphate) in the United States and certain of its territories.
About XENLETA
XENLETA (lefamulin) is a first-in-class semi-synthetic pleuromutilin antibiotic for systemic administration in humans discovered and developed by the Nabriva Therapeutics team. It is designed to inhibit the synthesis of bacterial protein, which is required for bacteria to grow. XENLETA’s binding occurs with high affinity, high specificity and at molecular sites that are different than other antibiotic classes. Efficacy of XENLETA was demonstrated in two multicenter, multinational, double-blind, double-dummy, non-inferiority trials assessing a total of 1,289 patients with CABP. In these trials, XENLETA was compared with moxifloxacin and in one trial, moxifloxacin with and without linezolid. Patients who received XENLETA had similar rates of efficacy as those taking moxifloxacin alone or moxifloxacin plus linezolid. The most common adverse reactions associated with XENLETA included diarrhea, nausea, reactions at the injection site, elevated liver enzymes, and vomiting. For more information, please visit www.XENLETA.com.
Indication and Important Safety Information
Indication
XENLETA is a pleuromutilin antibacterial indicated for the treatment of adults with community-acquired bacterial pneumonia (CABP) caused by the following susceptible microorganisms: Streptococcus pneumoniae, Staphylococcus aureus (methicillin-susceptible isolates), Haemophilus influenzae, Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydophila pneumoniae.
Usage
To reduce the development of drug-resistant bacteria and maintain the effectiveness of XENLETA and other antibacterial drugs, XENLETA should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.
Important Safety Information
CONTRAINDICATIONS
XENLETA is contraindicated in patients with known hypersensitivity to XENLETA or pleuromutilins.
XENLETA tablets are contraindicated for use with CYP3A4 substrates that prolong the QT interval.
Please see Full Prescribing Information for XENLETA at www.XENLETA.com.
Source: Nabriva Therapeutics US, Inc
Nabriva gains after announcing Phase 1 data for cystic fibrosis candidate
Nov. 28, 2022 10:07 AM ET
Nabriva Therapeutics plc (NBRV)
By: Dulan Lokuwithana, SA News Editor
- Ireland-based pharma Nabriva Therapeutics (NASDAQ:NBRV) rose ~15% on Monday morning after announcing results from a Phase 1 trial for its antibiotic Xenleta in adults with cystic fibrosis (CF).
- https://seekingalpha.com/news/3911601-nbrv-stock-gains-after-announcing-phase-1-data-for-cystic-fibrosis-candidate
- Nabriva Therapeutics plc (NBRV)
- https://www.xenleta.com/
- https://www.nabriva.com/
axs-05
batiraxcept (AVB-500)
XENLETA® (lefamulin)
axsome therapeutics announces axs-05 achieves primary endpoint in the accord phase 3 trial in alzheimer’s disease agitation
November 28, 2022
AXS-05 statistically significantly delayed time to relapse of Alzheimer’s disease agitation versus placebo (p=0.014, primary endpoint)
AXS-05 statistically significantly prevented relapse of Alzheimer’s disease agitation versus placebo (p=0.018, key secondary endpoint)
Statistically significant improvement in Alzheimer’s disease agitation, as measured by the CMAI total score, starting at Week 1 with open-label AXS-05 (p<0.001 vs baseline, all timepoints)
Improvement in Alzheimer’s disease agitation, assessed by the modified Alzheimer’s Disease Cooperative Study-CGIC scale, achieved by 66% of patients at 2 weeks and 86% at 5 weeks
Improvement in Alzheimer’s disease agitation, assessed by the PGI-C scale, achieved by 68% of patients at 2 weeks and 89% at 5 weeks
No treatments are currently approved for Alzheimer’s disease agitation
NEW YORK, Nov. 28, 2022 (GLOBE NEWSWIRE) -- Axsome Therapeutics, Inc. (NASDAQ: AXSM), a biopharmaceutical company developing and delivering novel therapies for the management of central nervous system (CNS) disorders, today announced that AXS-05, a novel, oral, investigational NMDA receptor antagonist with multimodal activity, met the primary and key secondary endpoints in the ACCORD (Assessing Clinical Outcomes in Alzheimer’s Disease Agitation) Phase 3 trial, by substantially and statistically significantly delaying the time to relapse and preventing relapse of agitation in patients with Alzheimer’s disease, as compared to placebo. The ACCORD study was a double-blind, placebo-controlled, multi-center, randomized withdrawal, U.S. trial which treated 178 patients with Alzheimer’s disease agitation. Patients achieving a sustained clinical response after open-label treatment with AXS-05 were randomized (n=108) in a 1:1 ratio to continue treatment with AXS-05 or to discontinue AXS-05 and switch to placebo. AXS-05 has been granted Breakthrough Therapy designation by the U.S. Food and Drug Administration (FDA) for the treatment of Alzheimer’s disease agitation. There are currently no FDA-approved treatments for Alzheimer’s disease agitation.
AXS-05 met the primary endpoint by substantially and statistically significantly delaying the time to relapse of agitation symptoms as compared to placebo, with a hazard ratio for time to relapse of 0.275 (p=0.014), representing a 3.6-fold lower risk of relapse compared to placebo. AXS-05 also met the key secondary endpoint of relapse prevention, based on the rates of relapse during the double-blind treatment period (7.5% of AXS-05 patients vs. 25.9% of placebo patients, p=0.018). Relapse was defined as a ≥10-point worsening in the CMAI total score from randomization or a CMAI total score greater than that at study entry; or hospitalization or other institutionalization due to agitation associated with Alzheimer’s disease.
With open-label treatment with AXS-05, patients experienced rapid, substantial, and statistically significant improvement compared to baseline in agitation symptoms. Statistically significant improvement on the Cohen Mansfield Agitation Inventory (CMAI) was seen with open-label AXS-05 treatment at all timepoints starting at Week 1 (p<0.001), with mean reductions from baseline of 11.0 points at Week 2 (p<0.001), and 20.6 points at Week 5 (p<0.001). Improvements were also significant with open-label AXS-05 treatment on all CMAI subscales including the Physically Aggressive subscale at all timepoints (p<0.001).
Jeffrey Cummings, MD, ScD, Director Emeritus of the Cleveland Clinic Lou Ruvo Center for Brain Health, and Chambers Professor of Brain Science at the University of Nevada Las Vegas said, “Agitation is one of the most troubling and consequential aspects of Alzheimer’s disease for patients and their caregivers as it is associated with early nursing home placement, accelerated cognitive decline, and increased mortality. The results of the ACCORD trial demonstrate convincing clinical activity for AXS-05 on agitation associated with Alzheimer’s disease based on both a significant delay in symptom relapse as well as a reduction of relapse compared to placebo. Treatment with AXS-05 during the open-label period in a large cohort of patients resulted in rapid and clinically meaningful improvements in Alzheimer’s disease agitation. The improvements were especially notable since they were seen on the aggressive symptom subscales of the agitation measures. Agitation occurs in the majority of patients with Alzheimer’s disease and there are currently no treatments approved for this condition. AXS-05 could potentially fill this high unmet medical need for patients and their caregivers, if approved, based on the observed positive efficacy and favorable safety and tolerability results.”
Rapid and substantial improvement in Alzheimer’s disease agitation was reported by both clinicians and caregivers on global measures. Clinicians reported improvement in agitation in 66.3% of patients at Week 2 and 86.3% at Week 5 after treatment with AXS-05, as assessed using the modified Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change for Agitation (mADCS-CGIC). Caregivers reported improvement in agitation in 67.5% of patients at Week 2 and 89.3% at Week 5 after treatment with AXS-05, as assessed using the Patient Global Impression of Change (PGI-C) rated by the caregiver.
Caregiver distress and burden, patient quality of life, and depressive symptoms were all statistically significantly improved compared to baseline after patients were treated with open-label AXS-05. Caregiver distress was assessed using the NPI Agitation and Aggression Caregiver Distress score (p<0.001, at Weeks 4 and 8). Caregiver burden was assessed using the Zarit Burden Interview (ZBI) (p=0.006 at Week 4, p=0.003 at Week 8). Patient quality of life was assessed using the caregiver rated Quality of Life Alzheimer’s Disease (QoL-AD) scale (p<0.001 at Week 4, p=0.013 at Week 8). Depressive symptoms were assessed using the Cornell Scale for Depression in Dementia (CSDD) (p<0.001, at Weeks 4 and 8).
Herriot Tabuteau, MD, Chief Executive Officer of Axsome said, “With the positive results from ACCORD, AXS-05 has now demonstrated efficacy in the treatment of Alzheimer’s disease agitation in two well-controlled trials. In addition to the strong results versus placebo in the double-blind period, results from the open-label period evidenced rapid, substantial, and significant improvements in Alzheimer’s disease agitation versus baseline with AXS-05 treatment. The ACCORD results complement, and are consistent with, those from the previously completed positive ADVANCE-1 trial. We intend to discuss these findings with the FDA in the context of the ongoing clinical development of AXS-05 in this indication, with the goal of providing a much needed treatment to the millions of patients living with Alzheimer’s disease agitation and their caregivers.”
The rates of adverse events observed in the double-blind period were 28.3% in the AXS-05 group and 22.2% in the placebo group. Discontinuations in the double-blind period due to adverse events were low (0% for AXS-05 and 1.9% for placebo). One serious adverse event was reported in the AXS-05 group (faecaloma), which was determined by the investigator to be not related to study medication, and 2 serious adverse events were reported in the placebo group (cardiac arrest, femur fracture). Falls were reported in 4 patients in the AXS-05 group, none of which were associated with serious adverse events and all of which were determined by the investigators to be not related to study medication, and in 2 patients in the placebo group, one of which was associated with a femur fracture. One death was reported in the placebo group. There was no evidence of cognitive decline for patients treated with AXS-05 as shown by the Mini-Mental State Examination (MMSE), a widely utilized measure of general cognitive function. Treatment with AXS-05 was not associated with sedation.
AXS-05 was granted Breakthrough Therapy designation for the treatment of Alzheimer's disease agitation by the FDA in June 2020. The FDA Breakthrough Therapy designation was supported by the positive results of the ADVANCE-1 trial. A Breakthrough Therapy designation is granted to potentially expedite development and review timelines for a promising investigational medicine when preliminary clinical evidence indicates it may demonstrate substantial improvement on one or more clinically significant endpoints over available therapies for a serious or life-threatening condition.
Open-label Period Results Summary
A total of 178 patients were treated with open-label AXS-05 for up to 9 weeks and assessed for efficacy. The primary timepoint for open-label efficacy assessments was 5 weeks, and the key secondary timepoint was 2 weeks. P-values were calculated versus baseline.
- The mean CMAI total score was 70.9 at baseline.
- Treatment with AXS-05 was associated with a mean reduction from baseline in the CMAI total score of 6.7 points at Week 1, 11.0 points at Week 2, and 20.6 points at Week 5 (p<0.001 for all).
- Clinical response on the CMAI (defined as ≥30% reduction from baseline) after treatment with AXS-05 was achieved by 21.8% of patients at Week 1, 40.4% of patients at Week 2, and 70.0% of patients at Week 5.
- Treatment with AXS-05 was also associated with improvements on all CMAI subscales including the Physically Aggressive subscale at all timepoints (p<0.001).
- Improvement in Alzheimer’s disease agitation, assessed using the clinician rated mADCS-CGIC, was achieved by 47.1% of patients at Week 1, 66.3% of patients at Week 2, and 86.3% of patients at Week 5, after treatment with AXS-05.
- Improvement in Alzheimer’s disease agitation, assessed using the caregiver rated PGI-C, was achieved by 51.2% of patients at Week 1, 67.5% of patients at Week 2, and 89.3% of patients at Week 5, after treatment with AXS-05.
- Caregiver distress, assessed using the NPI Agitation and Aggression Caregiver Distress score, was significantly reduced after treatment with AXS-05 (p<0.001, at Weeks 4 and 8).
- Caregiver burden, assessed using the ZBI, was significantly reduced after treatment with AXS-05 (p=0.006 at Week 4, p=0.003 at Week 8).
- Patient quality of life, assessed using the caregiver rated QoL-AD scale, was significantly improved after treatment with AXS-05 (p<0.001 at Week 4, p=0.013 at Week 8).
- Depressive symptoms, assessed using the CSDD, were significantly reduced after treatment with AXS-05 (p<0.001, at Weeks 4 and 8).
Double-blind Period Results Summary
A total of 108 patients were randomized, 53 to continued treatment with AXS-05, and 55 switched to placebo. The mean CMAI total scores at randomization were 43.7 and 44.9 for the AXS-05 and placebo groups respectively.
- AXS-05 met the primary endpoint by substantially and statistically significantly delaying the time to relapse of Alzheimer’s disease agitation as compared to placebo (hazard ratio for time to relapse of 0.275, p=0.014), demonstrating a 3.6-fold lower risk of relapse compared to placebo.
- AXS-05 met the key secondary endpoint by preventing relapse of Alzheimer’s disease agitation as compared to placebo, with 7.5% of AXS-05 patients relapsing versus 25.9% of patients switched to placebo (p=0.018).
- The rates of adverse events in the double-blind period were 28.3% in the AXS-05 group and 22.2% in the placebo group. Discontinuations in the double-blind period due to adverse events were low (0% for AXS-05 and 1.9% for placebo).
About the ACCORD Study
ACCORD (Assessing Clinical Outcomes in Alzheimer’s Disease Agitation) was a Phase 3, randomized, double-blind, placebo-controlled, multi-center trial to evaluate efficacy and safety of AXS-05 in patients with Alzheimer’s disease (AD) agitation. Patients with a diagnosis of probable Alzheimer’s disease and clinically meaningful agitation associated with their disease were enrolled into a 9-week, open-label period, during which they were treated with AXS-05 and monitored for a sustained clinical response. Sustained clinical response was defined as a ≥30% improvement from baseline in the Cohen-Mansfield Agitation Inventory (CMAI) total score and improvement on the PGI-C (score of ≤3) that are both maintained for at least 4 consecutive weeks.
Patients who experienced a sustained clinical response during the open-label treatment period were then randomized in a 1:1 ratio, to continue treatment with AXS-05 or to switch to placebo treatment, in a double-blind fashion for up to 26 weeks. Treatment was continued until either a relapse of agitation symptoms or the end of the 26-week double-blind period, whichever occurred first. Relapse was defined as a ≥10-point worsening in the CMAI total score from randomization or a CMAI total score greater than that at study entry; or hospitalization or other institutionalization due to agitation associated with Alzheimer’s disease.
A total of 178 patients were enrolled into the open-label period and treated with AXS-05, and 108 patients were randomized to continue on AXS-05 (n=53) or to switch to placebo (n=55). The mean Cohen-Mansfield Agitation Inventory (CMAI) total score at baseline study entry was 70.9. The mean CMAI total scores at randomization were 43.7 (AXS-05) and 44.9 (placebo). The minimum score on the CMAI is 29, corresponding to the total absence of symptoms, with higher scores corresponding to greater agitation. The primary endpoint in the study was time from randomization to relapse of Alzheimer’s disease agitation calculated by the Kaplan-Meier estimates and the hazard ratio. The key secondary endpoint, to assess relapse prevention, was the percentage of patients who relapsed. The primary timepoint for open-label efficacy assessments was Week 5 and the key secondary timepoint was Week 2. P-values for the open-label period were calculated versus baseline.
About AXS-05
AXS-05 (dextromethorphan-bupropion) is a novel, oral, patent protected, investigational N-methyl-D-aspartate (NMDA) receptor antagonist with multimodal activity under development for the treatment of Alzheimer’s disease (AD) agitation and other central nervous system (CNS) disorders. AXS-05 utilizes a proprietary formulation and dose of dextromethorphan and bupropion, and Axsome’s metabolic inhibition technology, to modulate the delivery of the components. The dextromethorphan component of AXS-05 is an uncompetitive NMDA receptor antagonist, also known as a glutamate receptor modulator, and a sigma-1 receptor agonist. The bupropion component of AXS-05 serves to increase the bioavailability of dextromethorphan, and is a norepinephrine and dopamine reuptake inhibitor. AXS-05 is covered by a robust patent estate extending out at least to 2037-2040. AXS-05 was granted FDA Breakthrough Therapy designation for the treatment of Alzheimer’s disease agitation in June 2020. AXS-05 is not approved by the FDA for the treatment of AD agitation.
About Axsome Therapeutics, Inc.
Axsome Therapeutics, Inc. is a biopharmaceutical company developing and delivering novel therapies for central nervous system (CNS) conditions that have limited treatment options. Through development of therapeutic options with novel mechanisms of action, we are transforming the approach to treating CNS conditions. At Axsome, we are committed to developing products that meaningfully improve the lives of patients and provide new therapeutic options for physicians. For more information, please visit the Company’s website at axsome.com. The Company may occasionally disseminate material, nonpublic information on the company website.
Source: Axsome Therapeutics, Inc.
Axsome says candidate for Alzheimer’s agitation met main goal in late-stage trial
Nov. 28, 2022 7:22 AM ET
Axsome Therapeutics, Inc. (AXSM)
By: Dulan Lokuwithana,
SA News Editor3 Comments
Axsome Therapeutics (NASDAQ:AXSM) jumped ~20% pre-market Monday after the neurology-focused biopharma announced that its candidate for Alzheimer’s disease (AD) agitation AXS-05 met the main goal in a Phase 3 trial.
Axsome Therapeutics, Inc. (AXSM)
https://www.axsome.com/axs-portfolio/pipeline/about-axs-05
SRP-9001
tetravalent dengue vaccine candidate (TAK-003)
tetravalent dengue vaccine candidate (TAK-003)
Sarepta Therapeutics Announces That U.S. FDA has Accepted for Filing and Granted Priority Review for the Biologics License Application for SRP-9001, Sarepta’s Gene Therapy for the Treatment of Ambulant Individuals with Duchenne Muscular Dystrophy
11/28/22 7:00 AM EST
– Regulatory action date of May 29, 2023
– SRP-9001 would be the first gene therapy for Duchenne, a one-time treatment designed to treat the underlying cause of DMD by delivering a functional shortened dystrophin to muscle
CAMBRIDGE, Mass., Nov. 28, 2022 (GLOBE NEWSWIRE) -- Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, today announced that the U.S. Food and Drug Administration (FDA) has accepted the Company's Biologics License Application (BLA) seeking accelerated approval of SRP-9001 (delandistrogene moxeparvovec) for the treatment of ambulant individuals with Duchenne muscular dystrophy. SRP-9001 has been granted Priority Review by the FDA, with a regulatory action date of May 29, 2023.
“We are delighted to announce that the FDA has accepted Sarepta’s BLA for SRP-9001 for filing and priority review,” said Doug Ingram, president and chief executive officer, Sarepta Therapeutics. “Duchenne is a relentlessly degenerative and invariably fatal disease, robbing children of muscle and function hourly and daily. Our BLA submission for an accelerated approval, along with the FDA’s acceptance of that BLA for filing and review, is a tremendously important milestone in our effort to bring a potentially life-changing gene therapy to Duchenne patients as rapidly as possible and we look forward to working with the FDA through the review process.”
SRP-9001 is an investigational gene therapy for Duchenne being developed in partnership with Roche. Duchenne is characterized by a mutation in the dystrophin gene that results in the lack of dystrophin, which acts as a shock absorber for muscle at the membrane. SRP-9001 is designed to treat the proximate cause of Duchenne by delivering to muscle a gene that codes for a shortened, functional form of dystrophin. In addition to a wealth of pre-clinical evidence, the BLA for SRP-9001 included efficacy and safety data from Study SRP-9001-103 (also known as ENDEAVOR), as well as from Studies SRP-9001-101 and SRP-9001-102, and an integrated analysis across these three clinical studies comparing functional results to a propensity-score-weighted external control (EC). In clinical results from more than 80 treated patients, SRP-9001 has demonstrated positive results at multiple time points, including one-, two- and up to four-years after treatment, in addition to demonstrating a consistent safety profile.
In addition to Studies SRP-9001-101, SRP-9001-102 and SRP-9001-103, SRP-9001 is also being studied in EMBARK (Study SRP-9001-301), a global, randomized, double-blind, placebo-controlled clinical trial of SRP-9001 which has recruited 125 participants with Duchenne between the ages of 4 to 7. EMBARK is fully enrolled with results expected by the end of 2023. Sarepta has proposed EMBARK as the post-marketing confirmatory trial for SRP-9001.
About SRP-9001 (delandistrogene moxeparvovec)
SRP-9001 (delandistrogene moxeparvovec) is an investigational gene transfer therapy intended to deliver SRP-9001 to muscle tissue for the targeted production of functional components of dystrophin. Sarepta is responsible for global development and manufacturing for SRP-9001 and plans to commercialize SRP-9001 in the United States upon receiving FDA approval. In December 2019, Roche partnered with Sarepta to combine Roche’s global reach, commercial presence and regulatory expertise with Sarepta’s gene therapy candidate for Duchenne to accelerate access to SRP-9001 for patients outside the United States.
About Sarepta Therapeutics
Sarepta is on an urgent mission: engineer precision genetic medicine for rare diseases that devastate lives and cut futures short. We hold leadership positions in Duchenne muscular dystrophy (DMD) and limb-girdle muscular dystrophies (LGMDs), and we currently have more than 40 programs in various stages of development. Our vast pipeline is driven by our multi-platform Precision Genetic Medicine Engine in gene therapy, RNA and gene editing. For more information, please visit www.sarepta.com or follow us on Twitter, LinkedIn, Instagram and Facebook.
Sarepta/Roche gene therapy for Duchenne gets FDA priority review
Nov. 28, 2022 7:43 AM ET
Sarepta Therapeutics, Inc. (SRPT), RHHBY, RHHBF
By: Dulan Lokuwithana, SA News Editor
- Sarepta Therapeutics (NASDAQ:SRPT) announced Monday that the FDA accepted its marketing application for gene therapy candidate SRP-9001 it develops with Roche (OTCQX:RHHBY) (OTCQX:RHHBF) under the agency’s priority review.
- https://seekingalpha.com/news/3911535-sareptaroche-gene-therapy-for-duchenne-gets-fda-priority-review
- Sarepta Therapeutics, Inc. (SRPT), RHHBY, RHHBF
- https://www.sarepta.com/products-pipeline/pipeline
tetravalent dengue vaccine candidate (TAK-003)
tetravalent dengue vaccine candidate (TAK-003)
tetravalent dengue vaccine candidate (TAK-003)
Takeda’s Biologics License Application (BLA) for Dengue Vaccine Candidate (TAK-003) Granted Priority Review by U.S. Food and Drug Administration
November 22, 2022
- TAK-003 is Being Evaluated for the Prevention of Dengue Disease Caused by Any Dengue Virus Serotype in Individuals 4 Years Through 60 Years of Age
OSAKA, Japan and CAMBRIDGE, Massachusetts, November 22, 2022 – Takeda (TSE:4502/NYSE:TAK) today announced that the U.S. Food and Drug Administration (FDA) has accepted and granted priority review of the Biologics License Application (BLA) for TAK-003, the company’s investigational dengue vaccine candidate. In the U.S., TAK-003 is being evaluated for the prevention of dengue disease caused by any dengue virus serotype in individuals 4 years through 60 years of age.
Dengue is a mosquito-borne virus endemic in more than 125 countries, including the U.S. territories of Puerto Rico, the U.S. Virgin Islands and American Samoa.1,2 Incidence of dengue has increased globally over the past two decades and is a leading cause of fever among travelers returning from Latin America, the Caribbean and Southeast Asia.3
“If approved, we believe TAK-003 has the potential to become an important dengue prevention option for healthcare providers, and we continue to be encouraged by our discussions with the FDA,” said Gary Dubin, M.D., president of the Global Vaccine Business Unit at Takeda. “This year, of the 888 dengue infections in the U.S., 96% were a result of travel to dengue endemic areas. Of the 316 dengue infections in U.S. endemic territories, 97% were locally transmitted.4 At Takeda, we are guided by our commitment to serving these affected populations and are fully committed to working with the FDA to advance this filing.”
The TAK-003 BLA is supported by safety and efficacy data from the pivotal Phase 3 Tetravalent Immunization against Dengue Efficacy Study (TIDES) trial, where the dengue vaccine candidate met its primary endpoint by preventing 80.2% of symptomatic dengue cases at 12 months.5,6 In addition, TAK-003 met its secondary endpoint by preventing 90.4% of hospitalizations at 18 months, and in an exploratory analysis, it demonstrated protection against dengue fever through 4.5 years (54 months) after vaccination. The TIDES exploratory analyses showed that throughout the 4.5-year study follow-up, TAK-003 prevented 84% of hospitalized dengue cases and 61% of symptomatic dengue cases in the overall population, including both seropositive and seronegative individuals.
Currently, TAK-003 has not been approved by the FDA or any other health authority outside of Indonesia. Following the approval of TAK-003 in Indonesia, Takeda will continue to progress regulatory filings in other dengue-endemic and non-endemic countries. In October 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended the approval of Takeda’s dengue vaccine candidate, TAK-003, for the prevention of dengue disease caused by any serotype in individuals four years of age and older in Europe and in dengue-endemic countries participating in the parallel EU-M4all procedure. The final step in the path to approval in Europe is a Marketing Authorization decision from the EMA, which is expected in the coming months. Regulatory reviews will also progress in dengue-endemic countries in Latin America and Asia.
About TAK-003
Takeda's tetravalent dengue vaccine candidate (TAK-003) is based on a live-attenuated dengue serotype 2 virus, which provides the genetic “backbone” for all four vaccine viruses.7 Clinical Phase 2 data in children and adolescents showed that TAK-003 induced immune responses against all four dengue serotypes, in both seropositive and seronegative participants, which persisted through 48 months after vaccination.8 The pivotal Phase 3 TIDES trial met its primary endpoint of overall vaccine efficacy (VE) against virologically confirmed dengue (VCD) at 12 months follow-up and all secondary endpoints at 18 months follow-up for which there were a sufficient number of dengue cases, including VE against hospitalized dengue and VE in baseline seropositive and baseline seronegative individuals. Safety results from the studies' integrated analysis showed that the rates of Serious Adverse Events (SAEs) were 6.21% in the TAK-003 Group, and 7.56% in the Placebo Group.9 Most frequent unsolicited AEs were nasopharyngitis, upper respiratory tract infection, viral upper respiratory tract infection, viral infection, and pyrexia.
About the Phase 3 TIDES (DEN-301) Trial
The double-blind, randomized, placebo-controlled Phase 3 TIDES trial is evaluating the safety and efficacy of two doses of TAK-003 in the prevention of laboratory-confirmed symptomatic dengue fever of any severity and due to any of the four dengue virus serotypes in children and adolescents.10 Study participants were randomized 2:1 to receive two doses of TAK-003 0.5 mL or placebo on months 0 and 3, administered subcutaneously. The study is comprised of five parts. Part 1 and the primary endpoint analysis evaluated vaccine efficacy (VE) and safety through 12 months after the second dose. Part 2 continued for an additional six months to complete the assessment of the secondary endpoints of VE by serotype, baseline serostatus and disease severity, including VE against hospitalized dengue. Part 3 evaluated VE and long-term safety by following participants for an additional two and a half to three years, as per World Health Organization (WHO) recommendations.5 Part 4 will evaluate efficacy and safety for 13 months following booster vaccination, and Part 5 will evaluate long-term efficacy and safety for one year after completion of Part 4.
The trial is taking place at sites in dengue-endemic areas in Latin America (Brazil, Colombia, Panama, the Dominican Republic and Nicaragua) and Asia (Philippines, Thailand and Sri Lanka) where there are unmet needs in dengue prevention and where severe dengue is a leading cause of serious illness and death among children.5 Baseline blood samples were collected from all individuals participating in the trial to allow for evaluation of safety and efficacy based on serostatus. Takeda and an independent Data Monitoring Committee of experts are actively monitoring safety on an ongoing basis.
About Takeda
Takeda is a global, values-based, R&D-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 R&D efforts on four therapeutic areas: Oncology, Rare Genetics and Hematology, Neuroscience, and Gastroenterology (GI). We also make targeted R&D 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 R&D 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 https://www.takeda.com.
Takeda dengue vaccine gets FDA priority review
Nov. 23, 2022 7:16 AM ET
Takeda Pharmaceutical Company Limited (TAK)
By: Dulan Lokuwithana, SA News Editor
- Takeda (NYSE:TAK) announced that the U.S. Food and Drug Administration (FDA) accepted and granted the priority review for the Biologics License Application (BLA) it submitted for the investigational dengue vaccine candidate TAK-003.
- A live-attenuated vaccine, TAK-003, is currently undergoing the FDA review for the prevention of dengue disease in those aged 4 - 60 years.
- https://seekingalpha.com/news/3910929-takeda-dengue-vaccine-gets-fda-priority-review
- Takeda Pharmaceutical Company Limited (TAK)
- https://www.takeda.com/what-we-do/research-and-development/our-pipeline/
- https://www.takeda.com/
ARV-471
tetravalent dengue vaccine candidate (TAK-003)
Epcoritamab (DuoBody®-CD3xCD20)
Arvinas Announces ARV-471 Achieves a Clinical Benefit Rate of 38% in Evaluable Patients and Continues to Show a Favorable Tolerability Profile in its Phase 2 Expansion Trial (VERITAC)
November 22, 2022
ARV-471 continues to show activity in heavily pre-treated patients with locally advanced or metastatic ER+/HER2- breast cancer
Median progression free survival of 3.7 months in all patients and 5.7 months in patients with ESR1 mutant tumors support the initiation of two Phase 3 registrational trials
NEW HAVEN, Conn., Nov. 22, 2022 (GLOBE NEWSWIRE) -- Arvinas, Inc. (Nasdaq: ARVN) today announced initial results from the Phase 2 cohort expansion portion (VERITAC) of a phase 1/2 study with ARV-471, a novel PROTAC® estrogen receptor (ER) protein degrader. ARV-471 is being co-developed with Pfizer Inc. (NYSE: PFE) for the treatment of patients with locally advanced or metastatic ER positive / human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) breast cancer.
This disclosure was originally planned for December 8, 2022. However, on November 21, 2022, the 2022 San Antonio Breast Cancer Symposium (SABCS) incorrectly published the abstract, omitting a key safety data table, and inadvertently released the corresponding full data presentation on the SABCS website. These full data are scheduled to be presented on December 8, 2022 at 9:00 a.m. CT in an oral presentation titled “ARV-471, a PROTAC® estrogen receptor (ER) degrader in advanced ER-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer: phase 2 expansion (VERITAC) of a phase 1/2 study.”
As a result of the early release of the full data presentation, Arvinas will host a conference call and webcast today, November 22, 2022, at 4:30 p.m. ET to discuss these data. Those wishing to examine the data in more detail are welcome to access our 8K filed last evening located here.
In the VERITAC trial, ARV-471 shows a favorable tolerability profile and demonstrates a clinical benefit rate of 38% (total n=71) (CBR: rate of confirmed complete response, confirmed partial response, or stable disease > 24 weeks), the primary endpoint in the trial. These results are consistent with the Phase 1 portion of this trial.
Patients in VERITAC had a median of four lines of prior therapies, in a population where 100% of patients were treated with prior cyclin-dependent kinase (CDK4/6) inhibitors, 79% with prior fulvestrant, and 73% with prior chemotherapy.
At the time of data cutoff (June 6, 2022), ARV-471 administered at 200 mg (n=35) and 500 mg (n=36) demonstrated:
- Antitumor activity in 100% CDK4/6 inhibitor-pretreated patients, as measured by a CBR of 38% (total n=71) in all patients and 51.2% in patients with mutant ESR1 tumors (n=41).
- Preliminary median progression-free survival (mPFS) of 3.7 months, a key secondary endpoint, in all evaluable patients and 5.7 months in patients with mutant ESR1 tumors (n=41).
- A favorable tolerability profile, with the majority of treatment-related adverse events (TRAEs) reported as Grade 1 or 2.
“I’m gratified to see the continued differentiated profile of ARV-471 and its potential to become an important new standard of care for patients with ER+/HER2- breast cancer,” said John Houston, Ph.D., President and Chief Executive Officer at Arvinas. “The positive VERITAC results, in a heavily pre-treated population in which 100% of the patients received at least one prior CDK4/6 inhibitor and many who had progressed on or after chemotherapy, and fulvestrant, reinforce our confidence in ARV-471 as we prepare to initiate two pivotal trials, with the goal of working to give patients and physicians a potential new option in the fight against breast cancer.”
“These data validate the early data which led us to enter into the collaboration with Arvinas and give us the confidence needed to initiate two Phase 3 registrational trials," said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology and Rare Disease, Pfizer Global Product Development.
ARV-471 Clinical Update
Study Design
VERITAC is the Phase 2 cohort expansion portion of a Phase 1/2 single-arm trial of ARV-471 alone and in combination with palbociclib in patients with ER+/HER2- locally advanced or metastatic breast cancer (mBC) (NCT04072952). In VERITAC, patients were treated with either 200 mg or 500 mg ARV-471 with a primary endpoint of CBR (CR, PR or SD > 24 weeks). Secondary endpoints include ORR, DOR, PFS and OS as well as safety (AEs) and pharmacokinetics.
Enrollment
As of the data cut-off date of June 6, 2022, 71 patients with locally advanced or metastatic ER+/HER2- breast cancer in the VERITAC expansion cohort were treated once-daily with oral doses of ARV-471 at 200 mg (n=35) or 500 mg (n=36).
- 100% of patients were previously treated with CDK 4/6 inhibitors
- 79% of patients were previously treated with fulvestrant
- 73% of patients were previously treated with chemotherapy
- 45% received chemotherapy in the metastatic setting
Efficacy Data
Clinical benefit rate (the primary endpoint, defined as a confirmed complete response, partial response, or stable disease ≥ 24 weeks) in all patients (n=71) and in patients with tumors harboring ESR1 mutations (n=41):
- All patients (200 mg and 500 mg, n=71): 38%
- Patients with tumors harboring ESR1 mutations (n=41): 51.2%
- Patients with ESR1 wild-type tumors (n=25): 20%
- All patients at 200 mg (n=35): 37.1%
- Patients with tumors harboring ESR1 mutations (n=19): 47%
- All patients at 500 mg (n=36): 39%
- Patients with tumors harboring ESR1 mutations (n=22): 55%
Progression free survival
- All patients receiving 200 mg or 500 mg qd ARV-471 (n=71): median 3.7 months
- Patients with mutant ESR1 tumors (n=41): median 5.7 months
- Patients receiving 200 mg qd ARV-471 (n=35): median 3.5 months
- Patients with mutant ESR1 tumors (n=19): median 5.5 months
- At the time of the data cutoff, data for 500 mg cohort were immature and therefore not included in a separate analysis
About ARV-471
ARV-471 is an investigational, orally-bioavailable PROTAC® protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with locally advanced or metastatic ER+/HER2- breast cancer.
In preclinical studies, ARV-471 demonstrated near-complete ER degradation in tumor cells, induced robust tumor shrinkage when dosed as a single agent in multiple ER-driven xenograft models, and showed superior anti-tumor activity when compared to a standard of care agent, fulvestrant, both as a single agent and in combination with a CDK4/6 inhibitor. In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialization of ARV-471; Arvinas and Pfizer will equally share worldwide development costs, commercialization expenses, and profits.
About Arvinas
Arvinas is a clinical-stage biotechnology company dedicated to improving the lives of patients suffering from debilitating and life-threatening diseases through the discovery, development, and commercialization of therapies that degrade disease-causing proteins. Arvinas uses its proprietary PROTAC® Discovery Engine platform to engineer proteolysis targeting chimeras, or PROTAC® targeted protein degraders, that are designed to harness the body’s own natural protein disposal system to selectively and efficiently degrade and remove disease-causing proteins. In addition to its robust preclinical pipeline of PROTAC® protein degraders against validated and “undruggable” targets, the company has three investigational clinical-stage programs: bavdegalutamide (ARV-110) and ARV-766 for the treatment of men with metastatic castration-resistant prostate cancer; and ARV-471 for the treatment of patients with locally advanced or metastatic ER+/HER2- breast cancer. For more information, visit www.arvinas.com.
Pfizer, Arvinas breast cancer therapy hits 38% clinical benefit in Phase 2 trial
Nov. 22, 2022 8:17 AM ET
By: Dulan Lokuwithana, SA News Editor
Arvinas, Inc (NASDAQ:ARVN) announced Tuesday early results from its Phase 2 cohort expansion portion of a Phase 1/2 study for protein degrader ARV-471 it co-develops with Pfizer (NYSE:PFE), indicating a clinical benefit rate of 38% among breast cancer patients.
https://clinicaltrials.gov/ct2/show/NCT04072952
https://www.arvinas.com/research-and-development/
Epcoritamab (DuoBody®-CD3xCD20)
ELAHERE™ (mirvetuximab soravtansine-gynx)
Epcoritamab (DuoBody®-CD3xCD20)
Genmab Announces U.S. Food and Drug Administration Accepts for Priority Review Biologics License Application (BLA) for Epcoritamab (DuoBody®-CD3xCD20) for the Treatment of Relapsed/Refractory Large B-Cell Lymphoma (LBCL)
Nov 21, 2022 at 2:00 PM CET
Media Release
COPENHAGEN, Denmark; November 21, 2022
- Epcoritamab BLA accepted for FDA Priority review; FDA action date is May 21, 2023
- Epcoritamab could become the first subcutaneous bispecific antibody approved for the treatment of LBCL
- BLA submission supported by positive EPCORE™ NHL-1 trial results
Genmab A/S (Nasdaq: GMAB) today announced that the U.S. Food and Drug Administration (FDA) has accepted for Priority Review the Biologics License Application (BLA) for subcutaneous epcoritamab (DuoBody®-CD3xCD20), an investigational bispecific antibody, for the treatment of patients with relapsed/refractory large B-cell lymphoma (LBCL) after two or more lines of systemic therapy. Under the Prescription Drug User Fee Act (PDUFA), the FDA has set a target action date of May 21, 2023.
The BLA submission is based on safety and preliminary efficacy data from the LBCL cohort of the pivotal EPCORE™ NHL-1 open-label, multi-center phase 2 clinical trial evaluating epcoritamab in patients with relapsed, progressive or refractory CD20+ mature B-cell non-Hodgkin lymphoma (B-NHL). These results were presented in a late-breaking oral presentation as a part of the Presidential Symposium at the 27th Annual Meeting of the European Hematology Association (EHA2022), in Vienna, Austria.
“We are pleased that the BLA for epcoritamab has been accepted for Priority Review by the FDA, accelerating the pathway for approval and bringing us one step closer to potentially delivering a novel treatment option to relapsed and refractory LBCL patients who are in need of additional treatment options,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. “Together with our partner, AbbVie, we recognize the unmet need for safe, effective and accessible treatments for patients with B-cell malignancies and we believe that epcoritamab has the potential to become a core therapy in this patient population.”
Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies' oncology collaboration. The companies will share commercial responsibilities in the U.S. and Japan, with AbbVie responsible for further global commercialization. The companies are committed to evaluating epcoritamab as a monotherapy, and in combination, across lines of therapy in a range of hematologic malignancies, including an ongoing phase 3, open-label, randomized clinical trial evaluating epcoritamab as a monotherapy in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) (NCT: 04628494) and a phase 3, open-label clinical trial evaluating epcoritamab in combination in patients with relapsed/refractory follicular lymphoma (FL) (NCT: 05409066).
In October 2022, the European Medicines Agency validated for review a Marketing Authorization Application (MAA) for epcoritamab for the treatment of patients with relapsed/refractory DLBCL– a major subtype of LBCL – after two or more lines of systemic therapy.
Based on the existing agreement, this milestone triggers a USD 80 million milestone payment from AbbVie. The milestone payment will not impact Genmab’s 2022 financial guidance provided on November 9, 2022.
About the EPCORE™ NHL-1 Trial
EPCORE™ NHL-1 is an open-label, multi-center safety and preliminary efficacy trial of epcoritamab including a phase 1 first-in-human, dose escalation part; a phase 2 expansion part; and a