A 51-year-old patient in Sarepta’s phase 1 limb-girdle muscular dystrophy gene therapy trial died of acute liver failure, marking the third fatality linked to the company’s AAV-based gene therapies. Sarepta CEO Douglas Ingram acknowledged the death but downplayed its material impact. The incident has renewed scrutiny around the risk-benefit profile of Sarepta's gene therapy programs, particularly after previously confirmed deaths in the Duchenne program. Patient advocates and commentators underscore the complexities in managing severe rare diseases, emphasizing the need to balance risks with ongoing urgent unmet needs. The case is likened to the historical Jesse Gelsinger event, raising calls for FDA, industry, and patient groups to collaborate on safety enhancements.