Sarepta Therapeutics has issued a critical safety update regarding ELEVIDYS, its gene therapy for Duchenne muscular dystrophy, specifically in light of a second reported fatality due to acute liver failure (ALF) in a non-ambulatory patient. Both instances of ALF have occurred in non-ambulatory individuals, prompting Sarepta to implement immediate and decisive actions to enhance the therapy's safety profile for this specific patient group. These measures include a temporary suspension of ELEVIDYS shipments for non-ambulatory patients, a proactive move to convene an independent panel of Duchenne and liver health experts to evaluate and propose an enhanced immunosuppressive regimen, potentially involving sirolimus, and a voluntary pause in dosing for the non-ambulatory cohort of the ENVISION clinical study (SRP-9001-303) with FDA concurrence. This pause will allow for the integration of the new immunosuppression protocol and regulatory feedback, while treatment for ambulatory patients remains unchanged. Sarepta emphasized its commitment to patient safety and scientific rigor, acknowledging that while elevated liver enzymes are a known class effect of AAV-based gene therapies, the exact mechanism of AAV-related liver toxicity, likely linked to an adaptive immune response, is still being investigated. The company is actively collaborating with the FDA and global health authorities, anticipating potential label updates to reflect the risk of severe ALF and new immune management strategies for non-ambulatory patients.