Sarepta Ends Trial for Duchenne Treatment

Sarepta Therapeutics has confirmed that it will permanently close enrollment in the ENVISION Phase 3 trial, which was intended to confirm the efficacy of Elevidys (delandistrogene moxeparvovec-rokl) for non-ambulatory Duchenne muscular dystrophy patients. The decision comes after three patients died from acute liver failure during the trial.

The ENVISION trial was a global, randomized, double-blind, placebo-controlled study designed to demonstrate that micro-dystrophin expression translated into measurable clinical benefit for non-ambulatory patients. However, the trial was put on hold after the three patient deaths, and Sarepta has now decided not to resume enrollment.

Background on Duchenne Muscular Dystrophy

Duchenne muscular dystrophy is a rare, X-linked genetic disease caused by mutations or deletions in the dystrophin gene. It affects roughly 1 in every 3,500 to 5,000 males born worldwide, with an estimated 15,000-20,000 patients in the United States. The disease is characterized by progressive muscle degeneration, leading to loss of ambulation and eventually death.

Elevyds, the first gene therapy approved for Duchenne, works by delivering a synthetic micro-dystrophin gene directly into muscle cells using an adeno-associated virus (AAV) as the delivery vehicle. However, the full dystrophin gene is too large to fit inside any viral vector, so Sarepta’s researchers engineered a shortened but functional version.

Regulatory Implications

The closure of the ENVISION trial creates a problem for the FDA, which had required Sarepta to complete the trial as a condition of the accelerated approval of Elevidys for non-ambulatory patients. The FDA’s accelerated approval framework is designed to speed access to treatments for serious conditions with unmet need, but it requires confirmatory evidence of clinical benefit.

Sarepta is now pursuing an alternative path, enrolling approximately 25 non-ambulatory patients in an open-label Phase 1b trial called ENDEAVOR Cohort 8. The trial tests whether adding sirolimus, an immunosuppressant, to the Elevidys protocol can prevent acute liver failure. The primary endpoints are the incidence of acute liver injury and micro-dystrophin expression at 12 weeks.

Sarepta’s CEO, Michael Severino, announced the formal end of the ENVISION trial during the company’s third-quarter 2026 earnings call, citing operational and technical barriers accumulated during the extended hold as key factors in the decision. The company will analyze the blinded data already collected from Part 1 of the study and share findings with the Duchenne community.

Enrollment in ENDEAVOR Cohort 8 is on track to complete by the end of 2026, with FDA engagement planned for the first quarter of 2027 once 12-week safety and efficacy data are in hand.

The company’s commitment to serving non-ambulatory individuals with Duchenne remains steadfast, according to Louise Rodino-Klapac, Sarepta’s president of research and development. The closure of the ENVISION trial is a setback, but the sirolimus path offers a glimmer of hope for patients who have already lost the ability to walk.

Regulatory Holds and Shipment Suspension Follow Fatal Liver Events

Sarepta maintained that the overall risk-benefit balance stayed favorable despite the labeled danger of acute liver injury. In June 2025, a second non-ambulatory participant, a 15-year-old, died from acute liver failure while enrolled in ENVISION. A third fatality in July triggered the FDA to formally request a complete halt to Elevidys distribution and all ongoing trials, sending Sarepta’s shares down roughly 40 percent.

All three deaths occurred in patients who could no longer walk, a group that typically exhibits advanced cardiac, respiratory and metabolic complications. Roughly half of 18-year-old Duchenne individuals develop dilated cardiomyopathy, further straining hepatic function during immune challenges. Compromised breathing and altered metabolic reserves reduce the liver’s ability to withstand immune-mediated injury, making severe outcomes more likely. The company responded by halting Elevidys shipments to non-ambulatory patients and pausing all ENVISION dosing worldwide.

AAV vectors use a viral capsid that the immune system identifies as foreign, prompting CD8⁺ cytotoxic T-cell activity against liver cells displaying capsid fragments. In younger, healthier individuals, this response is typically manageable and does not lead to fatal liver injury. The pattern of deaths among non-ambulatory participants has clarified the biological mechanism behind the adverse events. Ambulatory patients remained unaffected, allowing their label to keep traditional approval status.

Regulatory Context and Precedents

Regulators have cited the 2022 Omnibus legislation as the basis for recent withdrawals of accelerated approvals when confirmatory data fall short. That statute granted the agency clearer authority to act swiftly, a power exercised in oncology cases during the prior two years.

Financial Outlook and Next Steps

Investors will watch the February 28 PDUFA meeting for the antisense oligonucleotide candidates, as a positive outcome could provide a financial cushion while the ENDEAVOR data are evaluated. The timing of that meeting aligns with the anticipated release of the 12-week safety and micro-dystrophin expression results from the sirolimus cohort.