Sarepta Therapeutics (SRPT) Status Update summary

Safety update and incident response

• Two non-ambulatory patients in the ENVISION study died from acute liver failure after Elevidys/ELEVIDYS treatment, prompting a pause in the study and suspension of commercial shipments for non-ambulatory patients.

• Acute liver failure is extremely rare, limited to non-ambulatory individuals, and has not shown correlation with total dose; dosing remains weight-based.

• Immediate actions include pausing the ENVISION study, suspending shipments, and preparing protocol amendments for enhanced immunosuppression.

• Ongoing discussions with the FDA may lead to a label update reflecting severe acute liver failure risk and immune management strategies.

• Ambulatory patient protocol remains unchanged, with corticosteroids and liver monitoring continuing.

Enhanced immunosuppression and risk mitigation strategy

• A new regimen including sirolimus, a T-cell inhibitor, is being developed to mitigate immune-mediated liver inflammation and reduce liver enzyme elevations.

• Preclinical data in non-human primates and animal studies show sirolimus suppresses immune response to AAV, reduces inflammatory response, and maintains gene expression in target tissues.

• The protocol for sirolimus use will be finalized with input from an expert panel and the FDA, aiming for rapid implementation.

• Shipments for non-ambulatory patients remain suspended until the risk mitigation plan is approved and implemented.

• Ambulatory patients continue under the existing protocol with corticosteroids and monitoring.

Impact on guidance and operations

• Revenue guidance has been suspended due to the pause in non-ambulatory dosing; an update will be provided in the next quarterly call.

• The ambulatory/non-ambulatory split among treated patients shifted from 85/15% to 70/30% this year, reflecting broader label use.

• Financial discipline and cost structure review are planned to address the operational impact.

• An investor call is scheduled for June 16, 2025, to discuss the safety update and business outlook.