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

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

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

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

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

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

In vitro and clinical assessments of muscle specific promoters in driving gene expression and long-term cardiac efficacy in Duchenne muscular dystrophy (ASGCT 2025) - P1, P1/2 | "Three of these products include zildistrogene varoparvovec (SGT-001), an AAV9 vector containing a CK8 promoter, fordaditrogene movaparvovec (PF-06939926), an AAV9 vector containing an hCK promoter, and delandistrogene-moxeparvovec (SRP-9001, ElevidysÒ), an AAVrh74 vector containing a MHCK7 promoter. This two-part study illustrated the Desmin promoter was superior to the others in transfecting skeletal muscle and cardiac function was preserved over time in patients treated with gene therapy. Further studies are needed to test efficacy of each promoter in human cardiomyocytes and additional long term follow up is needed to understand the effects of DMD gene therapy are sustained in cardiac muscle."

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

Long-Term Functional Outcomes and Safety Following Delandistrogene Moxeparvovec Treatment in DMD: EMBARK 2-Year Results (ASGCT 2025) - P3 | "2-year results indicate favorable treatment effect of delandistrogene moxeparvovec on disease progression versus a well-matched EC. Stabilized functional outcomes, prognostic for delaying loss of ambulation, demonstrate durability of treatment. Safety was consistent with prior experience."

Clinical • Duchenne Muscular Dystrophy • Gene Therapies

3-Year Functional Outcomes of Patients With Duchenne Muscular Dystrophy: Pooled Delandistrogene Moxeparvovec Clinical Trial Data vs External Controls (ASGCT 2025) - P1, P1/2 | "Our findings show that treatment with delandistrogene moxeparvovec results in long-term stabilization or slowing of disease progression compared with a rigorously matched EC group, with an increase in between-group divergence over time. Disease Focus of Abstract:Muscular Dystrophy (all forms)"

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

Assessment of Cardiac Outcomes in Delandistrogene Moxeparvovec Clinical Trials for Duchenne Muscular Dystrophy (ASGCT 2025) - P1, P1/2, P3 | "Therapy is generally well tolerated and safe, with no signs of persistent treatment-related cardiac injury. Disease Focus of Abstract:Muscular Dystrophy (all forms)"

Clinical • Cardiovascular • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Inflammation • Muscular Dystrophy

Hepatic-Restricted Microdystrophin Expression Induces Immune Tolerance and Enhances Transgene Expression in Dystrophin-Deficient Mdx Mice (ASGCT 2025) - "µDys9.2 differs from PF-06939926 and SRP-9001 by including the nNOS binding domain, and from SGT-001 by including R3 and excluding R23...Group 1 received the anti-CD20 regimen, followed by AAV-Des-µDys9.2 i.v. administration (1 × 10¹⁴ vg/kg) at eight weeks of age, along with continuous sirolimus dosing until week 12... Hepatic-restricted and nonhepatic µDys9.2 delivery, combined with IMS, enhances transgene expression and immune tolerance in mdx mice, improving efficacy and safety. Disease Focus of Abstract:Rare Diseases"

Preclinical • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Hepatology • Muscular Dystrophy • Rare Diseases • Respiratory Diseases • FOXP3 • IL2RA

Development of muscle tropism AAV capsid by directed evolution (ASGCT 2025) - "Adeno-associated virus (AAV) gene therapy is one of the ideal therapy for single gene disorders such as FDA proved Elevidys for DMD...The high muscle tropism and super low liver target properties may generate an ideal viral vector in the future of gene therapies for muscular single gene disordered diseases. Disease Focus of Abstract:Muscular Dystrophy (all forms)"

Becker Muscular Dystrophy • Duchenne Muscular Dystrophy • Gene Therapies • Genetic Disorders • Muscular Dystrophy • Rare Diseases

Classical Complement Ablation Leads to Divergent Lymphocyte Activation by Antigen Presenting Cells in Response to AAV (ASGCT 2025) - "Blood samples were collected from DMD patients treated with Elevidys (AAV Rh74-microdystrophin) prior to dosing and on days 4, 7, and 14 post dosing, revealing significantly elevated levels of CXCL10 and CCL2 from plasma...Studies are needed to determine if acute inhibition of classical complement results in similar responses. Disease Focus of Abstract:Musculo-Skeletal Disorders"

Musculoskeletal Diseases • C1QA • CCL2 • CD4 • CD8 • CXCL10

Why It Is Still Important to Ensure the Price is Right: Updates to Access Restrictions for Therapies Treating Duchenne Muscular Dystrophy (ISPOR 2025) - "Corticosteroids (Emflaza and Amagree) are excluded as they have significantly different value and price considerations. Coverage criteria aligned to trial criteria is to ensure appropriate use. Duvyzat’s parity access to existing agents is likely a product of similar price-value alignment. If clinical benefit is unclear and price is high (e.g., non-ambulatory Elevidys), there is a prevailing risk of stakeholders adding restrictions (e.g., step edits) or only approving on a case-by-case basis (i.e., non-formulary)."

Duchenne Muscular Dystrophy • Genetic Disorders • Muscular Dystrophy