Clinical Trials for Sarepta Therapeutics’ DMD Therapy to Continue Following Safety Review

CGT LIVE., April 9, 2025- An independent data monitoring committee (DMC) has reviewed Sarepta Therapeutics’ delandistrogene moxeparvovec-rokl (Elevidys), a gene therapy utilizing an adeno-associated virus serotype rh74 (AAVrh74) vector to treat Duchenne muscular dystrophy (DMD). Elevidys delivers a micro-dystrophin gene, encoding a shortened but functional dystrophin protein, to muscle cells, aiming to compensate for the absence of full-length dystrophin caused by DMD mutations. Administered as a single intravenous infusion at a dose of 1.33 x 10¹⁴ vector genomes per kilogram (vg/kg) of body weight, the therapy uses the MHCK7 promoter to drive muscle-specific expression. Based on the totality of evidence, the DMC determined that Elevidys’ benefit-risk profile remains favorable, allowing dosing to continue in three clinical trials without protocol modifications.

This conclusion, supported by Sarepta and its partner Roche, addresses the paused enrollment and dosing of Elevidys in the EU, which impacted the Phase 1 Study 104 (NCT06241950), Phase 2 ENVOL (NCT06128564; Study 302), and Phase 3 ENVISION (NCT05881408; Study 303) trials. The European Medicines Agency (EMA) requested this pause following the March 2025 report of a young male patient in the U.S. who died from acute liver failure (ALF) after receiving Elevidys. The DMC’s review of this case was initiated at the request of EU authorities. Sarepta plans to submit relevant data to EU regulators within a week of April 4, 2025, anticipating that the pauses will not significantly delay the trials’ timelines.

Roche emphasized its dedication to patient safety, stating, “We are working closely with the EMA and will share updates as they become available.” Acute liver injury is a known potential adverse event associated with AAV-based gene therapies like Elevidys and is listed in its prescribing information. However, this fatal case of ALF represents a previously unreported severity of liver injury for Elevidys, which has treated over 800 patients to date. Sarepta noted that the patient had a recent cytomegalovirus (CMV) infection, which may have contributed to the outcome by causing CMV hepatitis, a condition that can exacerbate liver damage. The company plans to update Elevidys’ prescribing information to include this event, though it does not consider it a new safety signal.