Elevidys (delandistrogene moxeparvovec-rokl) / Sarepta Therap, Nationwide Children's, Roche - LARVOL DELTA

Sarepta Therapeutics (SRPT) announced…that it has gotten approval from the Food and Drug Administration (FDA) for an enhanced immunosuppressive regimen that is designed to mitigate the risk of acute liver injury (ALI) and acute liver failure (ALF) for patients undergoing AAV gene therapy (InvestorsObserver) - "The biotech company will be testing a dosing regimen as part of a study cohort for its Elevidys gene therapy that's administered to patients with Duchenne muscular dystrophy...This dosing regimen involves testing to see whether administering sirolimus prior to and after Elevidys can reduce ALI, which is a known risk associated with AAV gene therapy...Sarepta will enroll 25 non-ambulatory patients in the US as part of its cohort study."

FDA event • Trial status • Duchenne Muscular Dystrophy

Drug-induced liver injury: a real-world pharmacovigilance study using the FDA adverse event reporting system database 2004-2024. (PubMed, Ann Hepatol) - "Our study summarized a reported culprit-drug list of DILI by comprehensively reviewing the liver injury-related reports in the FAERS database, and highlighted the prominent position of antineoplastic agents in reporting frequency, risk signal strength ranking, number of positive signal drugs, and high-risk drug distribution, suggesting that we may need to pay more attention to the liver injury risk of antineoplastic agents in clinical practice."

Adverse events • Journal • Real-world evidence • Hepatology • Liver Failure • Oncology

Real-world experience with gene therapy in Duchenne muscular dystrophy center readiness and patients safety: report from Qatar. (PubMed, Gene Ther) - "Delandistrogene moxeparvovec (Elevidys) received accelerated approval from the U.S. Food and Drug Administration in June 2023 for ambulatory children aged 4-5 years with a confirmed diagnosis of Duchenne Muscular Dystrophy...Recognizing the complexities involved in treating older Duchenne Muscular Dystrophy patients, a standardized protocol for pre- and post-infusion care was implemented. Our findings highlight the positive clinical outcomes of gene therapy for Duchenne Muscular Dystrophy patients in Qatar."

Journal • Real-world evidence • Cardiovascular • CNS Disorders • Congestive Heart Failure • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Heart Failure • Muscular Dystrophy

A Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) Following Imlifidase Infusion in Participants With Duchenne Muscular Dystrophy (DMD) Determined to Have Pre-existing Antibodies to Recombinant Adeno-Associated Virus Serotype (rAAVrh74) (clinicaltrials.gov) - P1 | N=5 | Terminated | Sponsor: Sarepta Therapeutics, Inc. | Trial completion date: Oct 2027 ➔ Oct 2025 | Enrolling by invitation ➔ Terminated | Trial primary completion date: Jan 2026 ➔ Oct 2025; Study is being terminated due to a business decision.

Trial completion date • Trial primary completion date • Trial termination • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

FDA adds strongest warning to Sarepta gene therapy for Duchenne’s muscular dystrophy linked to 2 patient deaths (ABC News) - "The infused therapy from Sarepta Therapeutics will carry a boxed warning — the most serious type — alerting doctors and patients to the risk of potentially fatal liver failure with the treatment, the FDA said in a release...The one-time therapy, Elevidys, has been under FDA scrutiny since the company reported the first of two deaths of teenage boys in March...In addition to the boxed warning, the FDA is also limiting the drug's approved use to patients who are 4 years old and up and can still walk."

FDA event • Duchenne Muscular Dystrophy

ENVOL: A Gene Delivery Study to Evaluate the Safety and Expression of Delandistrogene Moxeparvovec in Participants Under the Age of Four With Duchenne Muscular Dystrophy (DMD) (clinicaltrials.gov) - P2 | N=21 | Recruiting | Sponsor: Hoffmann-La Roche | Trial completion date: May 2033 ➔ Jan 2034 | Trial primary completion date: May 2033 ➔ Jan 2034

Trial completion date • Trial primary completion date • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy • TRA

Caregiver-reported Patient Experiences with Duchenne Muscular Dystrophy: Qualitative In-trial Interviews 1 Year After Delandistrogene Moxeparvovec in the Pivotal EMBARK Trial. (PubMed, Neurol Ther) - P3 | "These findings underscore the importance of maintaining stability or achieving minimal improvements in treatment outcomes for patients with DMD. Parental experiences and perceptions provided additional insight beyond clinical outcome assessment measures, offering a complementary subjective perspective on treatment impact."

Interview • Journal • CNS Disorders • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

Incidence and Clinical Significance of Immune-mediated Myocarditis after Gene Replacement Therapy: a Systematic Reviewew and Meta-Analysis (AHA 2025) - "In VigiBase, myocarditis occurred in relation to Delandistrogene Moxeparvovec (1/16(6%)) and Onasemnogene Abeparvovec (14/217 (6%)). Six percent of patients treated with AAV gene therapy experienced immune mediated myocarditis, most of which were early onset and clinically mild... Six percent of patients treated with AAV gene therapy experienced immune mediated myocarditis, most of which were early onset and clinically mild. One death occurred in the settings of a capillary leak-syndrome and cardiac dysfunction. These findings underscore the relative rarity of clinically significant cardiac sequale."

Retrospective data • Cardiovascular • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Hepatology • Inflammation • Movement Disorders • Muscular Atrophy • Muscular Dystrophy • Myositis • Rare Diseases

Improving rAAV production: key adenoviral elements and their impact on vector yield and quality (ESGCT 2024) - "Recombinant Adeno-associated viruses (AAVs) are one of the most used viral vectors for gene therapy, with several products already on the market (e.g., Hemgenix, Roctavian, Elevidys). A smaller plasmid, without adenoviral structural proteins was generated, allowing a similar or better rAAV production across all tested serotypes. The knowledge generated from this study will ultimately facilitate the development of improved strategies for the large-scale production of high-titer and high-quality rAAV vectors, thereby advancing the gene therapy field."

Gene Therapies

Reversal of Acute Liver Injury Following Delandistrogene Moxeparvovec Gene Therapy Using Sirolimus and Immunoglobulin. (PubMed, Pediatr Neurol) - No abstract available

Journal • Gene Therapies • Hepatology • Liver Failure

Real-World Outcomes of Delandistrogene Moxeparvovec Gene Therapy: Motor Outcomes and Emerging Safety Concerns. (PubMed, Mol Ther) - "The cohort had improvements in year 1 motor function assessments relative to baseline, including a statistically significant median 4-point increase in North Star Ambulatory Assessment score; however, important confounding factors, e.g. baseline corticosteroid use, limit interpretation and will be important to control for in future real-world data sets. Additional follow-up is required to determine long-term safety and motor outcomes with unclear generalizability of our results."

Journal • Real-world evidence • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Hepatology • Liver Failure • Muscular Dystrophy

Dystrophinopathies. (PubMed, Continuum (Minneap Minn)) - "Two patient deaths in the spring of 2025 were deemed related to delandistrogene moxeparvovec use in nonambulatory patients, and dosing in these patients has been paused...Elevated transaminases in the setting of elevated creatine kinase with normal γ-glutamyl transferase and speech delay or autism in boys are less common initial presentations. Genetic testing is typically the next step in diagnosis and, depending on the nature of the variation and predicted severity of the phenotype, can guide the choice of treatment."

Journal • Review • Autism Spectrum Disorder • Becker Muscular Dystrophy • Cardiomyopathy • Cardiovascular • Developmental Disorders • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

Anaphylaxis During Delandistrogene Moxeparvovec Infusion Therapy in a Boy With Duchenne Muscular Dystrophy. (PubMed, Muscle Nerve) - No abstract available

Journal • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

HORIZON: A Gene Transfer Therapy to Evaluate the Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) Following Therapeutic Plasma Exchange (Plasmapheresis) in Participants With Duchenne Muscular Dystrophy (DMD) and Pre-existing Antibodies to AAVrh74 (clinicaltrials.gov) - P1 | N=3 | Terminated | Sponsor: Sarepta Therapeutics, Inc. | N=10 ➔ 3 | Trial completion date: Aug 2026 ➔ Aug 2025 | Recruiting ➔ Terminated | Trial primary completion date: Nov 2025 ➔ Aug 2025; Study is being terminated due to a business decision.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

Engineering Targeted Gene Delivery Systems for Primary Hereditary Skeletal Myopathies: Current Strategies and Future Perspectives. (PubMed, Biomedicines) - "Clinically, AAV-based therapies (e.g., Elevidys® for DMD, Zolgensma® for SMA) demonstrate functional improvements, though immune responses and hepatotoxicity remain concerns. Future directions focus on AI-driven vector design, hybrid systems (AAV-exosomes), and standardized manufacturing to achieve "single-dose, lifelong cure" paradigms for muscular disorders."

Journal • Review • Gene Therapies • Metabolic Disorders • Muscular Dystrophy • Myositis • Pompe Disease

Gene therapy for Duchenne muscular dystrophy. (PubMed, Brain Dev) - "Delandistrogene moxeparvovec, the first FDA-approved gene therapy for DMD, has demonstrated transgene expression and potential functional improvement in early phase trials, although its long-term efficacy, durability, and safety remain unconfirmed...Future studies focus on overcoming vector size limitations by using dual/triple AAV systems or non-viral platforms, improving muscle tropism through capsid and promoter engineering, and expanding eligibility through desensitization protocols. This review provides an integrated overview of the current progress, challenges, and future perspectives in gene therapy for DMD, with the aim of supporting its safe and effective clinical implementation."

Journal • Review • Cardiovascular • CNS Disorders • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Hepatology • Immunology • Inflammation • Liver Failure • Muscular Dystrophy • Myositis

Sarepta Therapeutics (SRPT) Declines Again On EMA Recommendation to Refuse ELEVIDYS Marketing Authorization, Securities Class Action Pending – Hagens Berman (GlobeNewswire) - "The EMA Concluded That ELEVIDYS Lacks Efficacy: On July 24, 2025, the EMA released a statement regarding ELEVIDYS. The agency reported that data from a key study involving 125 children between the ages of four and seven failed to demonstrate that the drug had a significant effect on movement abilities after a year."

EMA filing • Duchenne Muscular Dystrophy

AAV microdystrophin gene replacement therapy for Duchenne muscular dystrophy: progress and prospects. (PubMed, Gene Ther) - "In 2023, Elevidys (Sarepta Therapeutics) received accelerated approval based on levels of dystrophin as a surrogate biomarker...A separate microdystrophin therapy, PF-06939926 (Pfizer) was discontinued for both efficacy and safety reasons (including the deaths of two clinical trial participants). Solid Biosciences, Genethon, REGENXBIO, and Insmed continue to develop microdystrophin therapies differing in transgene structure, promoter sequences, and AAV serotype. Here we describe recent progress in AAV-microdystrophin therapeutics development, and discuss the challenges facing such approaches, including pre-existing anti-capsid immunity, anti-transgene immunity, the unknown functionality of microdystrophin transgenes, transduction of muscle stem cells, and long-term transgene persistence."

Journal • Review • Developmental Disorders • Duchenne Muscular Dystrophy • Genetic Disorders • Hepatology • Liver Failure • Muscular Dystrophy

ENDURE: An Observational Study Comparing Delandistrogene Moxeparvovec With Standard of Care in Participants With Duchenne Muscular Dystrophy (clinicaltrials.gov) - P=N/A | N=500 | Enrolling by invitation | Sponsor: Sarepta Therapeutics, Inc. | Recruiting ➔ Enrolling by invitation

Enrollment status • HEOR • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

Roche provides regulatory update on Elevidys gene therapy for Duchenne muscular dystrophy in the EU (GlobeNewswire) - "Roche...announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a negative opinion on the conditional marketing authorisation (CMA) for Elevidys (delandistrogene moxeparvovec) for ambulatory individuals aged three to seven years with Duchenne muscular dystrophy (DMD). Given the high unmet need in DMD, Roche plans to continue to work with the EMA to explore a potential path forward....The CHMP opinion is based on data from the largest and broadest gene therapy clinical programme in DMD to date, including results from the pivotal Phase III EMBARK study that showed treatment with Elevidys provided sustained stabilisation or slowing of disease progression, and a consistent and manageable safety profile in ambulatory patients."

CHMP • Duchenne Muscular Dystrophy

ELEVIDYS - Enhanced Safety Efforts (Businesswire) - "The Committee aligned on an enhanced immunosuppressive regimen with sirolimus for ELEVIDYS in non-ambulant patients. Sarepta will submit the finding of the expert panel and proposed protocol to the FDA imminently and will discuss a proposal to gather data on the regimen in a new cohort (Cohort 8) of the ENDEAVOR study (Study SRP-9001-103) as a pathway to re-establish dosing in the non-ambulant setting. Additionally, Sarepta is assessing real-world data generation opportunities for ambulant patients through investigator-initiated trials."

Clinical • Duchenne Muscular Dystrophy

FDA Investigating Sarepta's Elevidys® after Second Patient Dies. (PubMed, Hum Gene Ther) - No abstract available

Journal

Delandistrogene Moxeparvovec Gene Therapy in Individuals With Duchenne Muscular Dystrophy: Evidence in Focus: Report of the AAN Guidelines Subcommittee. (PubMed, Neurology) - No abstract available

Journal • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

FDA Informs Sarepta That It Recommends That Sarepta Remove Its Pause and Resume Shipments of ELEVIDYS for Ambulatory Individuals With Duchenne Muscular Dystrophy (Businesswire) - "Sarepta Therapeutics...announced that the U.S. Food and Drug Administration (FDA) notified Sarepta that it may lift its voluntary pause on shipments of ELEVIDYS (delandistrogene moxeparvovec) for ambulatory patients with Duchenne. Sarepta will resume shipping ELEVIDYS to sites of care for treatment of ambulatory patients with Duchenne imminently....FDA’s review of the safety data in the ambulatory population included the case of an 8-year-old in Brazil whose death was deemed unlikely to be related to treatment with ELEVIDYS by the Brazilian health authorities. FDA’s investigation has concluded the death was unrelated to treatment with ELEVIDYS and confirmed that Sarepta can resume shipments."

FDA event • Duchenne Muscular Dystrophy

Sarepta Therapeutics Announces Voluntary Pause of ELEVIDYS Shipments in the U.S. (Businesswire) - "Today, Sarepta Therapeutics notified the U.S. Food and Drug Administration (FDA) of its decision to voluntarily and temporarily pause all shipments of ELEVIDYS (delandistrogene moxeparvovec) for Duchenne muscular dystrophy in the United States, effective close of business Tuesday, July 22, 2025. This proactive step will allow Sarepta the necessary time to respond to any requests for information and allow Sarepta and FDA to complete the ELEVIDYS safety labeling supplement process. The Company looks forward to a collaborative, science-driven review process and dialogue with the FDA."

FDA event • Duchenne Muscular Dystrophy