FDA to investigate Elevidys deaths

The U.S. FDA is investigating the risk of acute liver failure with serious outcomes following treatment with Sarepta Therapeutics’ Elevidys gene therapy and is evaluating the need for further regulatory action.

The agency did not elaborate on what “further regulatory action” could entail.

Earlier this month, Sarepta and ex-U.S. commercialization partner Roche halted the commercial and clinical use of Elevidys for non-ambulatory Duchenne muscular dystrophy (DMD) patients, following a second case of fatal acute liver failure (ALF).

The two fatal ALF cases occurred in non-ambulatory patients, out of a total of approximately 140 non-ambulatory patients treated with Elevidys globally to date. Following the first case of fatal ALF, reported in March, European regulators requested that Roche and Sarepta put temporary clinical holds on three Elevidys studies, which are still in effect.

In both cases, the patients presented with elevated transaminases and were hospitalized less than two months after treatment with Elevidys. While acute liver injury is a known possible side effect of Elevidys — as well as of other AAV-mediated gene therapies — acute liver failure leading to death represents a severity of acute liver injury not previously reported for Elevidys.

Elevidys is a single-dose AAV-based gene transfer therapy for intravenous infusion designed to address the underlying genetic cause of Duchenne — mutations or changes in the DMD gene that result in the lack of dystrophin protein — through the delivery of a transgene that codes for the targeted production of Elevidys micro-dystrophin in skeletal muscle.

The FDA granted accelerated approval for Elevidys in June 2023 for ambulatory pediatric patients aged 4-5 years who have a confirmed mutation in the DMD gene. A year later, the agency approved a label expansion for Elevidys to include all individuals, regardless of ambulatory status, with DMD with a confirmed mutation in the DMD gene who are at least 4 years of age.