Roche, Sarepta halt Elevidys use following second patient death

Sarepta Therapeutics and Roche have halted the commercial and clinical use of Elevidys gene therapy for non-ambulatory Duchenne muscular dystrophy (DMD) patients, following a second case of fatal acute liver failure.

In the commercial setting, non-ambulatory patients should no longer receive Elevidys. In the clinical trial setting, enrollment and dosing of non-ambulatory patients will be immediately paused until additional risk mitigation measures are implemented in the study protocol, according to a Roche press release. 

In a separate press release, Sarepta said it is working to immediately convene an independent group of experts in Duchenne and liver health to consider an enhanced immunosuppression regimen for Elevidys. This 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.

The two fatal acute liver failure (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. Outside of Europe, dosing will be paused, effective immediately, for the ENVISION trial. The dosing restrictions will also go into effect for future dosing of commercial non-ambulatory patients.

According to Roche, the benefit-risk of Elevidys treatment in ambulatory Duchenne patients remains positive and treatment guidance is unchanged.

Sarepta sold the ex-U.S. commercialization rights to Elevidys to Roche in 2019, retaining the U.S. rights. Roche and Sarepta jointly manage the clinical studies.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.