By Fineline Cube 
The U.S. Food and Drug Administration (FDA) announced a Boxed Warning for Elevidys, Sarepta Therapeutics’ (NASDAQ: SRPT) gene‑therapy for Duchenne Muscular Dystrophy (DMD), co‑developed with Roche. The warning restricts the indication to ambulatory patients aged four years and older and removes the label for non‑ambulatory, late‑stage or wheelchair‑dependent patients.
The FDA also mandates a black‑box label stating that Elevidys can cause fatal serious liver injury and acute liver failure (ALF).
Regulatory Action Summary
| Action | Effective Date | Scope | Key Safety Message |
|---|---|---|---|
| Boxed Warning | 14 Nov 2025 | All U.S. marketed Elevidys vials | “May cause fatal serious liver injury and acute liver failure.” |
| Indication Change | 14 Nov 2025 | Restricted to ambulatory DMD patients ≥ 4 years | Non‑ambulatory use removed |
| EMA Status | Mar 2025 – Jul 2025 | Phase III trial suspended; CHMP negative opinion | Conditional approval for ambulatory 3‑7 yr patients rejected |
Elevidys – Product Overview
- Therapeutic Class: Recombinant AAV‑mediated gene therapy delivering a micro‑dystrophin transgene.
- Administration: Single intravenous infusion (≈ 0.5 mL/kg).
- Mechanism: Enables muscle cells to express a truncated dystrophin protein that restores ~ 10‑15 % of normal function, applicable to any pathogenic DMD mutation.
- Approved Indication (pre‑warning): All DMD patients, ambulatory and non‑ambulatory, ages 4 years and older.
Safety Concerns & Recent Events
- Fatal Liver Event (EU): In March 2025, the European Medicines Agency (EMA) halted a Phase III trial after a patient outside the trial’s inclusion criteria suffered acute liver failure and died following Elevidys infusion.
- CHMP Negative Opinion (Jul 2025): The Committee for Medicinal Products for Human Use recommended against conditional approval for ambulatory DMD patients aged 3‑7 years, citing insufficient safety data.
- U.S. Boxed Warning: The FDA now requires enhanced liver‑function monitoring pre‑ and post‑infusion, and a Risk Evaluation and Mitigation Strategy (REMS) for all prescribers.
Market Impact
- Revenue Outlook: Elevidys had generated ≈ US$350 million in 2024 U.S. sales. The restriction to a narrower patient pool (≈ 30 % of the original DMD population) could cut 2025‑2026 revenue forecasts by $120‑150 million.
- Stock Reaction: Sarepta shares fell 6.8 % in after‑hours trading on the announcement; Roche (NYSE: RHHBY) saw a 4.2 % decline.
- Competitive Landscape: The warning opens a window for next‑generation micro‑dystrophin candidates (e.g., Pfizer’s PF‑06939926) and exon‑skipping therapies to capture market share.
Forward‑Looking Statements
This brief contains forward‑looking statements regarding regulatory actions, safety monitoring requirements, and financial impacts of Elevidys. Actual results may differ due to risks including additional safety findings, further regulatory actions, and competitive developments.-Fineline Info & Tech