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

ACUTE DECLINE IN BONE HEALTH IN THREE BOYS WITH DUCHENNE MUSCULAR DYSTROPHY FOLLOWING GENE THERAPY (WRMC 2026) - "His GC pulse was prednisone for 18 wks: mean dose 89 mg/d (1.4 mg/kg/d). To our knowledge, this is the first report of worsening bone health in boys with DMD following gene therapy. All three patients developed new fragility fractures and increased obesity; two had a decline in BMD within months of high-dose GC pulses with delandistrogene moxeparvovec. Important additional risk factors may include delayed puberty and interruptions in IV BP."

Gene therapy • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy • Musculoskeletal Diseases • Obesity • Orthopedics • Osteoporosis • Rheumatology

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=13 | Active, not recruiting | Sponsor: Hoffmann-La Roche | Recruiting ➔ Active, not recruiting | N=21 ➔ 13 | Trial primary completion date: Jan 2034 ➔ Feb 2030

Enrollment change • Enrollment closed • Trial primary completion date • Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy

EXPEDITION: A Long-term Follow-up Study of Participants Who Received Delandistrogene Moxeparvovec (SRP-9001) in a Previous Clinical Study (clinicaltrials.gov) - P3 | N=400 | Enrolling by invitation | Sponsor: Sarepta Therapeutics, Inc. | Trial completion date: Nov 2030 ➔ Oct 2033 | Trial primary completion date: Nov 2030 ➔ Oct 2033

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

Two-Year Outcomes Following Delandistrogene Moxeparvovec Treatment in Ambulatory Patients with Duchenne Muscular Dystrophy: Phase 3 EMBARK Trial. (PubMed, Neurol Ther) - P3 | "At 2 years, stabilization or slowing of DMD disease progression was observed in ambulatory male patients with DMD aged 4 to < 8 years receiving delandistrogene moxeparvovec versus a matched EC cohort. Safety was consistent with EMBARK 1-year data and manageable with appropriate monitoring."

Journal • P3 data • CNS Disorders • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy

ENDEAVOR: A Gene Transfer Therapy Study to Evaluate the Safety of and Expression From Delandistrogene Moxeparvovec (SRP-9001) in Participants With Duchenne Muscular Dystrophy (DMD) (clinicaltrials.gov) - P1 | N=83 | Recruiting | Sponsor: Sarepta Therapeutics, Inc. | Active, not recruiting ➔ Recruiting | N=55 ➔ 83 | Trial completion date: Jul 2026 ➔ Feb 2028 | Trial primary completion date: Jul 2024 ➔ Dec 2027

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

Safety and efficacy of commercially administered elevidys (delandistrogene moxeparvovec-rokl). (PubMed, Mol Ther) - No abstract available

Journal

Gene therapy in Duchenne muscular dystrophy. (PubMed, Arch Pediatr) - "In 2023, delandistrogene moxeparvovec (Sarepta/Roche) received accelerated approval from the U.S. Food and Drug Administration for ambulatory pediatric patients, marking the first regulatory authorization of a gene therapy for DMD. By contrast, fordadistrogene movaparvovec (Pfizer) showed encouraging biomarker results but was associated with immune-mediated serious adverse events, including thrombotic microangiopathy cases and patient deaths due to acute liver failure, ultimately leading to program discontinuation. Other investigational candidates-GNT0004 (Généthon), SGT-003 (Solid Biosciences), and RGX-202 (Regenxbio)-incorporate distinct promoter designs and microdystrophin cassettes and are currently in early- to mid-phase evaluation...Gene therapy management also raises difficult economic and logistical challenges for healthcare systems. Balancing rapid patient access to potentially disease-modifying therapies with rigorous scientific and regulatory..."

Journal • Review • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Hepatology • Liver Failure • Muscular Dystrophy • Myositis • Pediatrics

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