FDA Issues New Boxed Warning, Limiting ELEVIDYS to Ambulatory DMD

The United States Food and Drug Administration (US FDA) has approved new safety warnings for Sarepta’s delandistrogene moxeparvovec-rokl (ELEVIDYS) for Duchenne muscular dystrophy (DMD), restricting the indication to ambulatory patients.1

According to a November 14, 2025, FDA communication, the therapy received substantial labeling revisions, including a Boxed Warning describing the risk of serious liver injury, acute liver failure, or fatal outcomes.

“The FDA is requiring the manufacturer to conduct a postmarketing observational study to further assess the risk of serious liver injury,” said the FDA in a statement. “The study will enroll approximately 200 patients with DMD and follow them for at least 12 months after administration of Elevidys, with periodic liver function assessments.”1

Delandistrogene moxeparvovec-rokl was the first approved gene therapy to treat DMD, a rare, progressive genetic disorder, for use in patients ≥4 years of age. The single-dose, adeno-associated virus-based gene therapy is designed to address the lack of dystrophin protein driven by mutations in the dystrophin gene (DMD).1,2

“We want to thank the FDA for their thorough and collaborative review,” said Louise Rodino-Klapac, PhD, the president of research & development and technical operations at Sarepta Therapeutics. “Completion of the safety labeling change for ELEVIDYS will ensure that families and healthcare professionals have clear information, supported by a Medication Guide, to help understand these updates and guide treatment decisions.”3

The therapy received initial FDA approval in June 2023 based on results from the global, randomized, double-blind, placebo-controlled phase 3 EMBARK trial, which met a surrogate endpoint of increased microdystrophin in individuals 4-5 years of age with DMD and no significant pre-existing antibody titers or contraindications.4

In June 2025, following 2 reports of fatal acute liver failure in non-ambulatory pediatric males with DMB who had received delandistrogene moxeparvovec-rokl, the FDA issued a CBER Safety Communication and halted distribution of the drug.2

Sarepta released a statement in response, emphasizing patient safety and well-being as their top priority in July 2025 and noting delandistrogene moxeparvovec-rokl as the only approved gene therapy available to patients impacted by DMD. At the time, the drug had been indicated for use in ambulatory and non-ambulatory patients with a confirmed mutation in the DMD gene.2

Subsequent investigation into the 2 reported fatal cases showed markedly elevated liver enzymes and hospitalization 2 months post-treatment. A non-fatal case of acute liver injury showed mesenteric vein thrombosis, bowel ischemia/ necrosis, and portal hypertension.1

The November 2025 FDA update includes additional safety-specific information and monitoring recommendations for clinicians and patients. The updated guidance recommends weekly liver monitoring for ≥3 months post-treatment and for patients to remain near an appropriate medical facility for ≥ 2 months after infusion.

The new labeling emphasizes that corticosteroid therapy may suppress immune function, increasing susceptibility to infections and serious complications including death and advises weekly testing for troponin-I to detect cardiac injury for 1 month following treatment. Patients are advised to contact a clinician if they exhibit yellowing of the skin or eyes, miss or vomit corticosteroid doses, or notice a change in mental status.

The therapy is not recommended for use in individuals with preexisting liver impairment, recent vaccinations, or recent/active infections, or patients with deletions involving DMD exons 8 and/or 9.

References

1. FDA Approves New Safety Warning and Revised Indication that Limits Use for Elevidys Following Reports of Fatal Liver Injury. FDA. Published online November 14, 2025. Accessed November 14, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-new-safety-warning-and-revised-indication-limits-use-elevidys-following-reports-fatal?utm_medium=email&utm_source=govdelivery.

2. Sarepta Therapeutics Provides Clarifying Statement on ELEVIDYS | Sarepta Therapeutics, Inc. Sarepta Therapeutics, Inc. Published 2025. Accessed November 14, 2025. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-provides-clarifying-statement-elevidys

3. Sarepta Announces FDA’s Approval of Updated ELEVIDYS Prescribing Information | Sarepta Therapeutics, Inc. Sarepta Therapeutics, Inc. Published 2025. Accessed November 14, 2025. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-announces-fdas-approval-updated-elevidys-prescribing

4. Johnson V. FDA Approves Sarepta’s Landmark DMD Gene Therapy Elevidys. Cgtlive.com. Published June 22, 2023. Accessed November 14, 2025. https://www.cgtlive.com/view/fda-approves-sarepta-s-landmark-dmd-gene-therapy-elevidys