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

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

ELEVIDYS Label Update (Businesswire) - "Following previously communicated steps being taken to strengthen the safety profile of ELEVIDYS, Sarepta is providing an update on on-going engagement with the U.S. Food and Drug Administration (FDA) regarding the ELEVIDYS (delandistrogene moxeparvovec) label. Consistent with other AAV-delivered gene therapies, the FDA has requested that the label include a black box warning for acute liver injury (ALI) and acute liver failure (ALF). Sarepta agrees with this change, which appears to resolve any material issues with the ambulant portion of the ELEVIDYS label."

FDA event • Duchenne Muscular Dystrophy

Preliminary Second Quarter 2025 Financial Highlights (Businesswire) - "For the second quarter ended June 30, 2025, Sarepta reported preliminary financial results: Total net product revenue: $513 million...ELEVIDYS net product revenue: $282 million"

Sales • Duchenne Muscular Dystrophy

Sarepta Refused FDA’s Request to Halt Elevidys Shipments (Bloomberg) - "Sarepta Therapeutics Inc. has refused to pause all shipments of its Elevidys treatment after three deaths were linked to the company’s gene therapies, the Food and Drug Administration said Friday. Two teenage boys died of acute liver failure in recent months after taking Elevidys. They were being treated for Duchenne muscular dystrophy and weren’t able to walk because of the muscle-wasting disease. Separately, the company said Friday that a 51-year-old patient died of acute liver failure last month in an early-stage trial of a gene therapy to treat limb-girdle muscular dystrophy. FDA leaders met with Sarepta, the agency said in a statement , and requested it voluntarily stop all shipments of the drug, which is its biggest product. 'The company refused to do so,' the agency said....Shares of Sarepta tumbled 36% on Friday, to their lowest since 2016. The company has lost about $8.5 billion in value since March 18, when the first patient death was reported."

FDA event • Stock price • Duchenne 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=10 | Recruiting | Sponsor: Sarepta Therapeutics, Inc. | N=16 ➔ 10

Enrollment change • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

FDA Announces Investigation of Deaths Following Treatment With Sarepta’s DMD Gene Therapy Elevidys (CGTLive) - "The FDA has announced that it is investigating the 2 deaths that Sareptha Therapeutics has reported in patients who received treatment with delandistrogene moxeparvovec-rokl (Elevidys), the company’s marketed adeno-associated virus (AAV) vector-based gene therapy for Duchenne muscular dystrophy...Notably, both deaths occurred in patients who were nonambulatory at the time of treatment and both patients had been hospitalized within 2 months of treatment in relation to raised levels of transaminases. Both patients’ deaths were attributed to acute liver failure (ALF). The FDA stated that it is assessing the risk of ALF that results in hospitalization or death after treatment with the gene therapy and whether additional regulatory measures will be necessary."

FDA event • Duchenne Muscular Dystrophy

Pharmacy-directed coordination of gene and high-cost therapies. (PubMed, Am J Health Syst Pharm) - "The creation of a pharmacy-directed program for coordination of gene and high-cost therapies has been crucial to the hospital's success in offering these innovative and potentially life-altering therapies."

Journal • Gene Therapies • Pediatrics

Efficacy of delandistrogene moxeparvovec on Duchenne muscular dystrophy: a systematic review and meta-analysis. (PubMed, Hum Genet) - No abstract available

Journal • Retrospective data • Review • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

ENVISION: A Gene Transfer Therapy Study to Evaluate the Safety and Efficacy of Delandistrogene Moxeparvovec (SRP-9001) in Non-Ambulatory and Ambulatory Participants With Duchenne Muscular Dystrophy (DMD) (clinicaltrials.gov) - P3 | N=148 | Active, not recruiting | Sponsor: Sarepta Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

Second DMD Patient Dies After Treatment with Sarepta Gene Therapy (Genengnews) - "Sarepta Therapeutics said it has temporarily suspended shipments of Elevidys (delandistrogene moxeparvovec-rokl) for infusion in non-ambulatory patients following the second death in three months of a patient with Duchenne muscular dystrophy (DMD) following treatment with the marketed gene therapy. The patient, whose age was not disclosed, was a non-ambulatory individual with DMD...No treatment changes will be implemented for ambulatory patients, Sareota added...Sarepta said it has also voluntarily paused dosing in its Phase III ENVISION trial (SRP-9001-303, NCT05881408) to allow for evaluation of a protocol amendment that would incorporate the enhanced immunosuppressive regimen for the non-ambulatory patient cohort and incorporate any additional feedback from the FDA. The FDA has concurred with the voluntary pause and will need to approve the protocol amendment before screening and dosing can resume in the ENVISION trial, Sarepta added."

Trial suspension • Duchenne Muscular Dystrophy

Some functional improvements in placebo and Delandistrogene moxeparvovec-treated trial participants explained by increased corticosteroid dosing. (PubMed, J Neuromuscul Dis) - No abstract available

Journal

Conservative Management of Acute Myocarditis and Thrombotic Microangiopathy after Elevidys (Delandistrogene Moxeparvovec) (ASGCT 2025) - "Case: He remained ambulatory with current DMD medications of deflazacort 36 mg daily and givinostat (held 2 weeks prior to GT)...Baseline cardiac medications were enalapril, eplerenone, and carvedilol...The day prior, he started 60 mg daily of prednisone for immunosuppression per the label...The next day (Day-4), he reported palpitations while telemetry showed atrial fibrillation, which resolved after 20 minutes of esmolol infusion...Complement blockade with eculizumab was considered for rAAV-associated TMA, but our multispecialty gene therapy team consisting of neurology, cardiology, hematology, and nephrology recommended a conservative watchful waiting approaching... TMA is a poorly understood rAAV toxicity. Complement activation is hypothesized to be a central component of its pathophysiology. However, the scope of rAAV drugs that incite TMA as well as its optimal management remains to be defined."

Late-breaking abstract • Atrial Fibrillation • Cardiovascular • Fibrosis • Gene Therapies • Heart Failure • Hematological Disorders • Hypertension • Inflammation • Muscular Dystrophy • Myositis • Nephrology • Renal Disease • Thrombocytopenia • CST3

Sarepta Provides Update on UK Dosing in ENVISION Study of ELEVIDYS for the treatment of Duchenne Muscular Dystrophy (Sarepta Therap Press Release) - "Sarepta Therapeutics, Inc...shared the following update related to ELEVIDYS (delandistrogene moxeparvovec-rokl), the only approved gene therapy for patients with Duchenne muscular dystrophy....We have received feedback from the Medicines & Healthcare products Regulatory Agency (MHRA) in the United Kingdom (U.K.) that dosing may continue uninterrupted in ENVISION, study SRP-9001-303."

Trial status • Duchenne Muscular Dystrophy