Sarepta Therapeutics Gains Revised ELEVIDYS Indication After FDA Adds Boxed Warning for Acute Liver Failure

A boxed warning for acute serious liver injury and acute liver failure, added to ELEVIDYS on November 14, 2025, narrows the operational and pharmacovigilance obligations Sarepta Therapeutics and any AAV gene therapy manufacturer must now meet, and sets a visible precedent for how FDA intends to manage post-market safety signals in this modality.

The revised indication restricts delandistrogene moxeparvovec-rokl to ambulatory patients aged 4 and older with a confirmed DMD gene mutation. The change followed an FDA investigation opened June 24, 2025, into deaths due to acute liver failure in non-ambulatory Duchenne muscular dystrophy patients treated with ELEVIDYS. Patients with preexisting liver impairment, defined as GGT greater than 2x the upper limit of normal or elevated total bilirubin not attributable to Gilbert's syndrome, are now explicitly excluded, as are patients with active hepatic viral infection, recent vaccination within four weeks of dosing, or active or recent infection.

For QA directors and regulatory leads managing AAV vector platforms, the CMC Review Memo and the November 2025 approval letter are the documents to read in sequence. The hepatotoxicity signal that drove the indication revision points directly to immunogenicity management, lot-release criteria, and the adequacy of post-infusion monitoring protocols, areas where 21 CFR Part 600 and ICH Q10 quality system requirements intersect with pharmacovigilance obligations. Manufacturers holding BLAs for similar gene therapy products should expect heightened scrutiny of their risk management plans and REMS-adjacent commitments at the next inspection cycle.

The demographic subgroup data referenced in Section 1.1 of the Clinical Review Memo is material for any sponsor conducting comparability assessments or planning label expansions; the ambulatory restriction signals that FDA will weight functional status as a risk-stratification variable in future AAV submissions. Biologics QA teams should also review the updated Medication Guide requirements, which now carry the weight of the boxed warning language and must be reflected in batch documentation and distribution controls.

Sarepta's STN 125781 now carries four approval letters spanning June 2023 through November 2025, a timeline that illustrates how post-market safety data can materially reshape a gene therapy's benefit-risk profile across successive review cycles.

Source: FDA Center for Biologics Evaluation and Research via FDA.gov Vaccines, Blood and Biologics RSS Feed, June 10, 2026.