Sarepta Therapeutics permanently closed enrollment in ENVISION, its Phase 3 confirmatory trial of Elevidys for non-ambulatory Duchenne muscular dystrophy patients, on November 5, 2026. The decision follows three patient deaths from acute liver failure in 2025, which led the FDA to strip the non-ambulatory indication. Sarepta now relies on a 25-patient Phase 1b safety study testing immunosuppressive sirolimus pretreatment to seek restored access in early 2027.
Phase 3 ENVISION trial closure details
- ▪Sarepta Therapeutics plans to analyze blinded data collected from Part 1 of the ENVISION trial and share findings with the Duchenne muscular dystrophy community
- ▪The ENVISION study was a global, randomized Phase 3 trial designed to assess clinical benefit in approximately 150 non-ambulatory and older ambulatory Duchenne muscular dystrophy patients
- ▪Sarepta Therapeutics announced on Thursday, November 5, 2026, during its third-quarter earnings call that it will permanently close enrollment in the Phase 3 ENVISION trial of Elevidys
- ▪Sarepta Therapeutics ended ENVISION enrollment after recruiting approximately 90 participants, representing about half of the trial's target sample size
ENDEAVOR Cohort 8 safety study plans
- ▪Sarepta Therapeutics plans to complete ENDEAVOR Cohort 8 enrollment by late 2026 and present 12-week safety and micro-dystrophin expression data to the U.S. FDA in Q1 2027
- ▪ENDEAVOR Cohort 8 participants receive sirolimus for 14 days prior to Elevidys infusion and continue for 12 weeks post-infusion to suppress immune-mediated liver toxicity
- ▪Following the ENVISION trial closure, non-ambulatory Duchenne patients' potential pathway to Elevidys access rests on ENDEAVOR Cohort 8, an open-label Phase 1b safety study enrolling approximately 25 U.S. patients
Elevidys trial patient Deaths and FDA response
- ▪Following three patient fatalities, the U.S. FDA revised Elevidys' label in November 2025 to add a boxed warning for acute liver failure
- ▪The U.S. FDA removed the non-ambulatory Duchenne muscular dystrophy indication from Elevidys' label in November 2025 following three patient fatalities from acute liver failure
- ▪Sarepta said that in March 2025, a young man died from acute liver failure after receiving Elevidys, having also experienced a recent cytomegalovirus infection
- ▪In June 2025, a 15-year-old non-ambulatory patient enrolled in the ENVISION trial died from acute liver failure, prompting Sarepta Therapeutics to pause commercial non-ambulatory shipments and ENVISION dosing
- ▪In July 2025, a third non-ambulatory patient death led the U.S. FDA to request a complete halt of Elevidys distribution and place clinical trials on hold
Mechanisms and prevention of liver toxicity
- ▪A retrospective study presented at the 2026 World Muscle Society Annual Congress reported zero acute liver failure events among patients pretreated with prophylactic sirolimus before Elevidys infusion
- ▪Acute liver failure in AAV gene therapy occurs when CD8+ cytotoxic T lymphocytes attack liver cells displaying AAV viral capsid peptides on their surfaces
- ▪Non-ambulatory Duchenne patients face elevated risk of severe liver immune response due to advanced disease progression, dilated cardiomyopathy, and reduced metabolic reserve
Overview of Duchenne muscular dystrophy and Elevidys
- ▪The U.S. FDA granted accelerated approval to Elevidys in June 2023 based on micro-dystrophin expression in skeletal muscle as a surrogate endpoint
- ▪Elevidys delivers a synthetic micro-dystrophin gene into muscle cells using an adeno-associated virus vector (AAVrh74) designed by Sarepta Therapeutics President of R&D Louise Rodino-Klapac
- ▪Duchenne muscular dystrophy is an X-linked genetic disorder caused by mutations in the dystrophin gene on chromosome Xp21, affecting roughly 1 in 3,500 to 5,000 live male births
Sarepta 2026 financial performance
- ▪Sarepta Therapeutics reported Elevidys net product revenue of $83.5 million for Q3 2026 out of $323.8 million total quarterly net product revenue
- ▪Sarepta Therapeutics raised the low end of its full-year 2026 total net product revenue guidance to between $1.25 billion and $1.3 billion
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