Sarepta Reports Second Death of DMD Gene Therapy Recipient

Rare Daily Staff

Sarepta Therapeutics reported a second death from acute liver failure in a person treated with Elevidys, its approved gene therapy for the rare neuromuscular condition Duchenne muscular dystrophy.

The cases of acute liver failure to date have both occurred in non-ambulatory individuals with Duchenne. Sarepta extends its deepest sympathies to the affected families and care teams.

In response, the company outlined steps to strengthen the safety profile of Elevidys in non-ambulatory patients. It said it is taking proactive steps to mitigate the risk of acute liver failure in non-ambulatory patients. This includes convening an independent group of leading experts in Duchenne and liver health to consider an enhanced immunosuppression regimen for Elevidys. The panel will evaluate data and assess the proposed regimen, which includes sirolimus and is supported by preclinical data demonstrating the effectiveness of additional immunosuppression in moderating liver enzyme elevations, a key factor in mitigating potential safety events.

Sarepta said it will share the panel’s recommendations with the U.S. Food and Drug Administration, and implementation of any new regimen will be subject to FDA guidance and approval.

It is also temporarily suspending shipments of Elevidys for non-ambulatory patients while an enhanced immunosuppressive regimen is evaluated, discussed with regulatory bodies, and implemented.

The company said no treatment changes are being proposed for ambulatory patients, and the current practice of administering corticosteroids before and after Elevidys infusion, along with post-treatment monitoring, remains the unchanged.

Sarepta has voluntarily paused dosing in the ENVISION clinical study, a confirmatory trial required under the FDA’s accelerated approval pathway for non-ambulatory patients. The company said the FDA concurs with its decision. The pause will allow for the evaluation of a protocol amendment to incorporate an enhanced immunosuppressive regimen for the non-ambulatory patient cohort and to incorporate any additional feedback from the FDA. Regulatory alignment is needed before screening and dosing in ENVISION may resume.

“Our paramount priority is the safety and well-being of the patients we serve,” said Louise Rodino-Klapac, chief scientific officer and head of research and development at Sarepta. “We are taking immediate, decisive steps to better understand and mitigate the risk of acute liver failure, including enhancing the immunosuppressive regimen, for those with Duchenne who are non-ambulatory.”