Sarepta's Elevidys Faces New Challenges and Opportunities

Sarepta Therapeutics has received FDA approval to study an enhanced immunosuppressive regimen for its gene therapy Elevidys, aimed at addressing safety concerns that led to recent label restrictions. This development comes in the wake of significant setbacks for the Duchenne muscular dystrophy (DMD) treatment.

FDA Greenlights New Study Approach

The FDA has given Sarepta the go-ahead to use an enhanced immunosuppressive regimen in Cohort 8 of its Endeavor study. This new approach will involve administering sirolimus before and after Elevidys infusion in non-ambulatory DMD patients or those who can no longer walk independently.

The study aims to enroll approximately 25 non-ambulatory patients who will receive sirolimus infusions for 14 days prior to Elevidys administration and continue for 12 weeks afterward. Primary endpoints will assess the incidence of acute liver injury and Elevidys-dystrophin expression.

Louise Rodino-Klapac, Ph.D., Sarepta's president of R&D and technical operations, stated, "We remain deeply committed to serving all individuals living with Duchenne, including those who have lost the ability to walk." The company plans to initiate the study by the end of this year, with data on primary endpoints expected in the second half of 2026.

Recent Label Restrictions and Safety Concerns

Earlier this month, the FDA limited Elevidys' indication to ambulatory patients aged four and up, removing its previous endorsement for non-ambulatory patients. This decision followed two deaths from acute liver failure in non-ambulatory patients who received the gene therapy.

The updated Elevidys label now includes a boxed warning and new limitations of use. The therapy is not recommended for patients with preexisting liver impairment, recent vaccinations, or recent/active infections. Additionally, patients are advised to remain near an appropriate medical facility for at least two months post-dosing.

Financial Impact and Future Outlook

The safety concerns have significantly impacted Elevidys' sales performance. Third-quarter sales dropped to $131.5 million, a sharp decline from $282 million in the second quarter. Sarepta briefly paused all shipments of the drug in July following an FDA request but was later allowed to resume shipments to ambulatory patients.

Analysts from William Blair view the FDA's approval of the Endeavor study update as a "constructive step" towards addressing safety concerns. If successful, this approach could potentially lead to another label change as early as 2027, potentially restoring a broader patient population for Elevidys.