Genethon’s Post

Atamyo Therapeutics has announced the US Food and Drug Administration (FDA) has awarded Fast Track Designation for ATA-100, an AAV-based gene therapy for the treatment LGMDR9 in Phase 1/2 clinical trials in the US and Europe. In the clinical trial of ATA-100 for the LGMDR9, the company said enrollment progress is on track and the first 2 patients in the second high-dose cohort have been treated. Updated results of the clinical trials will be presented at the 29th International Annual Congress of the World Muscle Society (WMS) in Prague (8-12 October 2024). The designation was requested based on the potential for ATA-100 to address an unmet medical need for LGMDR9, a serious and debilitating condition that affects young adults and leads to loss of ambulation within 10 to 15 years. Preliminary data from the ongoing European Phase 1b/2b study were submitted in support of the application. The clinical trials (EudraCT 2021-004276-33, NCT105224505) are multicenter Phase 1/2 studies evaluating safety, pharmacodynamics, efficacy, and immunogenicity of intravenous ATA-100, a single-dose Adeno-Associated Virus (AAV) vector carrying the human FKRP transgene. The studies will consist of two phases: an open-label dose escalation phase (Stage 1) and a double-blind placebo controlled, randomized phase (Stage 2). Enrollment of the first low-dose cohort of the study in Europe (protocol code ATA-001-FKRP) is completed with promising initial functional results and two patients have already been treated in the high-dose cohort. ATA-100 has been overall well tolerated to date in all treated patients with no unexpected safety signal. Updated results of the clinical trials will be presented through an oral presentation at the 29th International Annual Congress of the World Muscle Society (WMS) in Prague, October 8 to 12, 2024. “This new Fast Track Designation in the US and the good clinical progress of our LGMD-R9 program confirms its life-changing potential for patients affected by LGMD-R9,” said Stephane Degove, Chief Executive Officer and Co-Founder of Atamyo Therapeutics. “We look forward to sharing ATA-100 updated clinical trial results with the community in October,” he added. To read the complete press release: https://lnkd.in/guNrXECN For more information about Atamyo visit our website: atamyo.com #genetherapy #LGMD #musculardystrophy

📈𝘽𝙞𝙤𝙥𝙝𝙖𝙧𝙢𝙖 𝘽𝙪𝙡𝙡𝙚𝙩𝙞𝙣: 𝙎𝙩𝙖𝙮 𝘼𝙝𝙚𝙖𝙙 𝙬𝙞𝙩𝙝 𝙏𝙝𝙚𝙨𝙚 5 𝙍𝙚𝙖𝙙𝙨 📚 📌 SpringWorks Therapeutics (Nasdaq: SWTX), a commercial-stage biopharmaceutical company specializing in severe rare diseases and cancer, has completed the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA). The NDA is for mirdametinib, an investigational MEK inhibitor, intended for treating pediatric and adult patients with neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN). 📌  Precision BioSciences, Inc. (Nasdaq: DTIL), an advanced gene editing company using its novel proprietary ARCUS® platform to develop in vivo gene editing therapies, has been added to the Russell Microcap® Index. This inclusion follows the conclusion of the 2024 Russell indexes annual reconstitution, which became effective after the close of U.S. markets on June 28, 2024. 📌 Amneal Pharmaceuticals (Nasdaq: AMRX) has announced the addition of omalizumab, referencing XOLAIR®, to its biosimilar pipeline. Omalizumab is a humanized monoclonal antibody targeting free immunoglobulin E (IgE), used to treat chronic conditions like severe persistent allergic asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), food allergies, and chronic spontaneous urticaria. Developed by Kashiv BioSciences, LLC, the biosimilar is currently in a Phase III clinical trial, which began in Q3 2023. 📌 Humacyte (Nasdaq: HUMA) has received the FDA’s Regenerative Medicine Advanced Therapy (RMAT) designation for their investigational Acellular Tissue Engineered Vessel (ATEV) for advanced peripheral artery disease (PAD). Alongside this, the FDA has cleared a new Investigational New Drug (IND) application for the PAD indication. 📌 Legend Biotech (NASDAQ: LEGN), a global leader in cell therapy, announced positive overall survival results from CARTITUDE-4, an ongoing Phase 3 study evaluating CARVYKTI® (cilta-cel) versus PVd or DPd in adult patients with relapsed and lenalidomide-refractory multiple myeloma. CARVYKTI® showed statistically significant and clinically meaningful improvement in overall survival (OS) in the pre-specified second interim analysis. Safety results aligned with CARVYKTI®'s established profile, with no new safety signals identified. #biotechnews #biotech #biopharma #biopharmanews

« The FDA’s Center for Drug Evaluation and Research (CDER) approved 55 new drugs in 2023, as the small molecule and biologic pharmacopoeia continues to grow. This cohort is nearly 50% bigger than the new approval class of 2022, which fell below the approval trend line. (…) The FDA’s Center for Biologic Evaluation and Research (CBER) kept the pace up too, approving a growing number of cell and gene therapies, vaccines and blood products in 2023. This included the first CRISPR–Cas9-based gene editing product, two vaccines for respiratory syncytial virus (RSV) and a burst of gene therapies. By therapeutic area, oncology continues to accumulate the most approvals. CDER gave a green light to 13 (24%) new cancer therapies in 2023. Neurology came in second, with 9 (16%) approvals, also in line with recent trends. Infectious diseases and haematology tied for third, with 5 (9%) apiece. By modality, the medical toolbox continues to get more diverse. 2023 saw an increase in the number of nucleotide-based therapeutics, including a second RNA-aptamer product. On the antibody front, 4 T-cell engaging bispecifics arrived. » Mullard, Nature Reviews Drug Discovery, 2024

FDA Mandates Enhanced Warning Labels for CAR-T Therapies The Food and Drug Administration (FDA) has directed the inclusion of new black box warnings for CAR-T cell therapies due to emerging reports of T-cell malignancies, some of which resulted in fatal outcomes. This precautionary measure is specifically applicable to BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies. Since 2017, CAR-T therapies have demonstrated significant and lasting responses in patients with lymphoma, leukemia, or multiple myeloma. While existing warnings already highlight the potential risk of secondary malignancies associated with CAR-T therapies, the FDA, in letters dated January 19th to CAR-T therapy manufacturers, mandated the inclusion of boxed warnings—considered the most robust form of labeled cautionary information. CAR T-cell therapy employs T cells, crucial in directing the immune response, to customize cancer treatments for individual patients. This process involves collecting the patient's own T cells, modifying them in a laboratory to introduce chimeric antigen receptors (CARs) on their surface. These CARs are engineered to target and attach to specific antigens found on cancer cells. As of now, six CAR-T therapies are approved in the United States: Kymriah (tisagenlecleucel) Yescarta (brexucabtagene autoleucel) Carvykti (ciltacabtagene autoleucel) Breyanzi (lisocabtagene maraleucel) Abecma (idecabtagene vicleucel) Tecartus (brexucabtagene autoleucel) The FDA initiated an investigation into CAR-positive lymphoma in November, prompted by reports of T-cell malignancies from both clinical trials and post-marketing adverse event reporting. Despite these concerns, FDA officials emphasized that the benefits of CAR-T treatments, approved for lymphoma, leukemia, and multiple myeloma, outweigh the potential risks. In a briefing update on January 8th, Dr. Peter Marks, director of the FDA's Center for Biologics Evaluation and Research, stressed the importance of continuous monitoring of clinical trial participants and post-approval CAR-T patients throughout their entire lives. This ongoing vigilance aims to identify any new malignancies and test for the presence of the CAR gene when such occurrences arise. The International Society for Cell and Gene Therapy has published an expert consensus statement on CAR-T risks, supporting ongoing evaluation while endorsing the continued accessibility of these therapies. The statement acknowledges that CAR-T cell immunotherapies have been administered to 34,000 patients worldwide, with 20 reported cases of T cell malignancies. However, additional information is needed to comprehensively understand the associated risks, including patient characteristics, genetic mutations, and the timing of malignancy development.

2023 FDA approvals - second highest new drug approvals in 30 years! #fdaapproval It is fantastic to see that 55 new drugs have been approved last year and great article in Nature Reviews Drug Discovery below for further reading.   My personal highlights among many are some of the new first-in-class and first-in-modality products, e.g. 🔷 the AKT inhibitor, capivasertib (Truqap) targeting the PI3K–AKT–mTOR signaling pathway for HER2- metastatic breast cancer 🔷 the γ-secretase inhibitor, nirogacestat (Ogsiveo), for rare desmoid tumors 🔷 the GPRC5D × CD3-targeted T-cell engager, talquetamab (Talvey), for multiple myeloma 🔷 the small-molecule inhibitor of the complement factor B, iptacopan (Fabhalta) as oral monotherapy for patients with paroxysmal nocturnal haemoglobinuria 🔷 the hypoxia-inducible factor prolyl hydroxylase inhibitor, daprodustat (Jesduvroq), for anemia caused by chronic kidney disease There were other interesting approvals in neurology (e.g for ALS, Alzheimer’s disease or Friedreich’s ataxia) and products approved based on novel surrogate biomarkers or single-arm phase II studies. Further, FDA's  Center for Biologics Evaluation and Research (CBER) approved a number of cell and gene therapies #cellandgenetherapy, vaccines and blood products in 2023. For example 🔸 the first CRISPR–Cas9-based gene editing therapy #crisprcas9 , exagamglogene autotemcel (Casgevy) indicated for sickle cell disease. 🔸 the first cell therapy for patients with type 1 diabetes patients made from donor-derived islet cells, donislecel (Lantidra) 🔸 two vaccines for respiratory syncytial virus (Arexvy and Abrysvo) and a novel antibody, nirsevimab (Beyfortus) for the prevention of RSV in infants 🔸 live fecal microbiota spores, (Vowst), a microbiome therapeutic to treat recurring Clostridioides difficile infections The field and #innovations are rapidly progressing- there will be more to come in #2024 with novel agents addressing high unmet medical needs and something to look forward to! #drugdevelopment https://lnkd.in/eQuXqZcb

2023 FDA approvals and Forecast for 2024 decision by FDA The FDA approved 55 novel therapeutics in 2023, the second highest count in the past 30 years. The FDA’s Center for Drug Evaluation and Research (CDER) approved 55 new drugs in 2023, as the small molecule and biologic pharmacopoeia continues to grow. This cohort is nearly 50% bigger than the new approval class of 2022, which fell below the approval trend line. The 10-year rolling average for new CDER approvals now stands at 46 per year, the highest it has been in over 20 years. The nadir was 2010, when this average bottomed out at 25 per year. The FDA’s Center for Biologic Evaluation and Research (CBER) kept the pace up too, approving a growing number of cell and gene therapies, vaccines and blood products in 2023. This included the first CRISPR–Cas9-based gene editing product, two vaccines for respiratory syncytial virus (RSV) and a burst of gene therapies  https://lnkd.in/eQ-CbZvp

From the initial breakthrough in a Phase III CRISPR trial to the promising results of another Alzheimer’s disease drug in slowing disease progression, 2023 marked significant milestones in clinical trials. As reported by GlobalData’s Pharmaceutical Intelligence Centre, a total of 22,338 clinical trials kicked off in 2023. The primary focus of these trials was oncology, closely followed by central nervous system-related trials. Among the trials initiated, the largest share (36%) belonged to Phase II trials. Additionally, 7,183 clinical trials concluded during the year, with 6,234 successfully completed and 777 terminated. Key Highlights: 🧠Eli Lilly and Company’s donanemab published successful Ph 3 trial results for Alzheimer’s disease 🔬Vertex Pharmaceuticals and CRISPR Therapeutics – positive results came from three Ph 3 studies studying the gene therapy exa-cel (which will be branded as Casgevy)  💉Eli Lilly and Company secures another spot on the list, this time with its obesity medication Zepbound (tirzapetide), showcasing efficacy outcomes superior to its primary competitor, Novo Nordisk’s Wegovy 💊First biologic for COPD – Regeneron and Sanofi announced positive results from a Ph 3 NOTUS trial, investigating chronic obstructive pulmonary disease. If approved, it will be the first approved biologic for the disease Looking forward to seeing what 2024 has to offer - lots of exciting new approved therapies I hope! 😊

📰 Pharma Today: Weekly Newsletter (July 30 - August 6, 2024) 🧬 𝗧𝗵𝗲𝗿𝗮𝗽𝗲𝘂𝘁𝗶𝗰 𝗜𝗻𝗻𝗼𝘃𝗮𝘁𝗶𝗼𝗻𝘀 - 💉 Roche initiates a Phase 2 trial for an injectable GLP-1 therapy, showing potential in diabetes treatment.    - 💊 Vertex Pharmaceuticals reports positive Phase 2 results for VX-548, a non-opioid pain management drug, emphasizing its effectiveness and safety. - 🧬 Johnson & Johnson secures FDA approval for a novel multiple myeloma treatment, advancing the field of antibody-drug conjugates (ADCs). - 🌟 Eisai US provides additional data on Leqembi, reinforcing its potential in treating Alzheimer's disease. - 💊 BioNTech SE & Regeneron's mRNA cancer therapy demonstrates positive outcomes in Phase 2 trials, a significant advancement in oncology. ✅ 𝗥𝗲𝗴𝘂𝗹𝗮𝘁𝗼𝗿𝘆 𝗔𝗽𝗽𝗿𝗼𝘃𝗮𝗹𝘀 - ⚡ Adaptimmune has won accelerated FDA approval for Tecelra (afami-cel), a treatment for metastatic or unresectable synovial sarcoma. - 🌍 Novo Nordisk receives MHRA approval for a new indication of Wegovy in the UK, expanding its use in weight management. - 💉 Pfizer obtains EU approval for its hemophilia B gene therapy, highlighting the potential for gene-based treatments. - 👌 GSK Wins Broad Label Expansion for Jemperli in First-Line Endometrial Cancer - 📕 Zevra Therapeutics’s NPC Drug to Face Newly Formed FDA Adcomm - 📱 Abbott Laboratories issues a medical device correction for FreeStyle Libre 3 sensors, addressing a reported defect. 🏢 𝗖𝗼𝗿𝗽𝗼𝗿𝗮𝘁𝗲 𝗗𝗲𝘃𝗲𝗹𝗼𝗽𝗺𝗲𝗻𝘁𝘀 - 💼 Sanofi files a lawsuit against Sarepta Therapeutics over patent disputes related to Duchenne muscular dystrophy gene therapy. - ✂ Bristol Myers Squibb cuts 117 jobs in New Jersey amid organizational restructuring, indicating a broader trend of cost optimization in the industry. - 💰 Pfizer announces a $150 million upgrade to its Melbourne manufacturing plant, set to become a leading facility for antimicrobial production. - 🔬 Boehringer Ingelheim acquires Nerio Therapeutics for up to $1.3 billion, enhancing its oncology portfolio. - 💼 GSK and Flagship Pioneering form a partnership to develop ten new drugs, aiming to expand their pipeline significantly. - 💼 Skye Bioscience Inc. partners with Beacon Biosignals to explore treatments for obesity-related conditions, including sleep apnea. - 🌍 Merck, AstraZeneca, and Gilead Sciences compete in the ADC market, each advancing their respective TROP2-targeted therapies. Stay updated with the latest pharmaceutical innovations and industry movements. See u next week for more insights!

How to Develop a Drug in a Rare Disease? When it comes to drug development in rare diseases, there are certain hurdles that must be taken compared to more prevalent diseases: 1.    Target Discovery: Understanding the intricate biology underlying a disease is crucial for identifying effective treatment targets. However, in rare diseases both the etiology of the disease as well as the link to manifesting symptoms are often incompletely understood, making it difficult to find targeted treatments. Novel technologies like next-generation sequencing offer promise in unraveling the genetic basis of many rare diseases, paving the way for targeted interventions, including new modalities with long-lasting effects such as gene therapies and RNA-based therapeutics. 2.    Preclinical Research: Preclinical Drug Development typically involves extensive laboratory and animal studies to assess safety, efficacy and pharmacological properties. Yet, accurately modeling rare diseases in laboratory settings necessitates a comprehensive understanding of their pathophysiology, which can be challenging given the limited disease knowledge and the lack of predictiveness of models for novel modalities, when it comes to long-term efficacy and safety. 3.    Clinical Research: Clinical Development involves testing safety in healthy volunteers (or sometimes in patients) in Phase I, efficacy in a smaller number of patients in Phase II and confirming findings compared to placebo or SoC in a large and preferably diverse group in Phase III. Given small number of patients with a rare disease, often with low diagnostic accuracy, it can be challenging to recruit an adequate cohort for clinical trials across these phases. Moreover, in case of severe phenotypes, common to rare diseases, the use of a placebo group can be unethical. Innovative trial designs, decentralization and implementation of real-world evidence (RWE) can help overcome those challenges. 4.    Market Entry: With a small patient pool, orphan drugs may in themselves not be commercially attractive for developers, often leading to higher prices to ensure economic viability. Specific orphan instruments offer additional incentives, such as prolonged market exclusivity or developers venturing into the orphan space. For newer, high-priced modalities such as gene therapies, payers and pharma players are exploring new reimbursement models. Moreover, patients and families sometimes take active roles in advocating for the reimbursement of expensive but life-saving drugs.   5.    Post marketing commitments: The journey of drug development extends into the realm of post-marketing surveillance and collection of a body of RWE. Especially for novel technologies such as gene and cell therapies, RWE emerges as a crucial tool in evaluating long-term safety and efficacy, complementing traditional clinical trial data. Active collaboration with patients and advocacy groups is important for successful post-marketing strategies.    

Today, Orum Therapeutics and Vertex Pharmaceuticals announced a significant deal. Orum Therapeutics, a leader in Degrader-Antibody Conjugates (DACs), has its lead asset ORM-5029 (HER2-GSPT1 degrader) in Phase 1 clinical trials, while its ORM-6151 (CD33-GSPT1 degrader) was acquired by BMS last November. Although both assets are anticancer agents, this deal with Vertex represents an intriguing expansion of Targeted Protein Degradation (TPD) and DACs into non-oncological fields. How does Vertex intend to leverage Orum Therapeutics' TPD²® Technology? In collaboration with CRISPR Therapeutics, Vertex has successfully commercialized CASGEVY, an ex vivo CRISPR/Cas9 gene editing therapy for Sickle Cell Disease (SCD) and Transfusion-Dependent Beta Thalassemia (TDBT). For gene-edited cells to engraft successfully in vivo, we must eliminate existing hematopoietic stem cells (HSCs). Conventional bone marrow transplant therapies rely on high-dose chemotherapy. Physicians employing CASGEVY-based treatment use busulfan, an alkylating agent. However, busulfan's non-specific HSC depletion can cause severe myelosuppression and hepatic endothelial damage, potentially leading to complications such as hepatic veno-occlusive disease. Consequently, many developers are striving to replace high-dose chemotherapy-based conditioning regimens with more selective agents. A notable example was Magenta Therapeutics' MGTA-117 (anti-CD117 ADC), which combined a CD117-targeting antibody with amanitin (an RNA polymerase II inhibitor) payload. Magenta Therapeutics developed it for conditioning in AML patients eligible for stem cell transplant, but the company halted its development due to lethal toxicity in clinical trials. Conversely, Beam Therapeutics, using a base editing approach, employs a unique strategy to reduce busulfan dependence. Beam's ESCAPE strategy genetically modifies a specific CD117 epitope on transplanted HSCs, preventing anti-CD117 antibody binding. These edited HSCs remain unaffected by anti-CD117 antibodies while retaining normal growth and survival through SCF binding. Unedited native HSCs have their SCF-CD117 interaction disrupted by anti-CD117 antibodies, leading to their elimination.