The FDA is assessing the need for “further regulatory action” on Sarepta’s Duchenne muscular dystrophy gene therapy in the aftermath of two patient deaths, though the regulator has not yet specified what action this could be.
After two patient deaths in recent months, the FDA has opened an investigation into Sarepta Therapeutics’ Duchene muscular dystrophy gene therapy Elevidys, the regulator announced Tuesday.
In particular, the FDA is probing the risk of acute liver failure possibly associated with Elevidys. The two deaths were linked to elevated liver enzymes, for which both patients had to be hospitalized “less than two months” after receiving the gene therapy.
The FDA is now “evaluating the need for further regulatory action,” though it has not yet specified what kinds of actions those might be.
Sarepta reported the first Elevidys patient death in March, attributing it to acute liver failure that the company at the time said was of a severity “not previously reported for Elevidys.” The company maintained that liver injury is a known side effect of Elevidys and of gene therapies that use adeno-associated virus vectors—and that Elevidys’ benefit-risk profile “remains positive.”
Earlier this month, Sarepta revealed that a second patient on Elevidys had died, likewise due to acute liver failure. In an investor call to discuss the development, CEO Doug Ingram again pointed out that “liver injury is a known risk of AAV therapies, historically,” adding that currently all clinical-stage gene therapies use this delivery platform. Both patients were non-ambulatory teenagers.
After the second patient’s death, Sarepta enacted a series of safety efforts for Elevidys, including convening an independent panel of experts to assess the need for and possibly implement an “enhanced immunosuppression regimen” for the gene therapy, according to its press announcement earlier this month. Sarepta has also suspended Elevidys shipments for non-ambulatory patients.
Sarepta shares have crashed some 80% since March.
Duchenne muscular dystrophy is an inherited muscular disorder characterized by delayed development in kids, motor difficulties, skeletal deformities and impaired pulmonary function. It is caused by mutations in the dystrophin gene, which in turn leads to the progressive weakening and degeneration of muscle fibers. Elevidys addresses the underlying cause of the disorder by delivering a shorter but functioning copy of the dystrophin gene.
The FDA granted Elevidys accelerated approval in June 2023. A year later, the regulator converted this to full approval, allowing its use in patients 4 years and older.
Peter Marks, former director of the Center for Biologics Evaluation and Research (CBER), had a heavy hand in Elevidys’ approval. Reporting from STAT News in June 2024 revealed that Marks overruled objections from his review staff, ultimately signing off on the full approval of the gene therapy.
This move was met by criticism from some experts and observers—including from Marks’ successor, current CBER chief Vinay Prasad. Writing in a blog post in August 2024, Prasad questioned Marks’ interference: “Why should a top FDA official unilaterally approve an expensive gene therapy?”
