Written By: Pharmacally Medical News Desk
Sarepta Therapeutics has announced that the U.S. Food and Drug Administration (FDA) has approved the initiation of Cohort 8 in its ongoing ENDEAVOR clinical study. This phase 1b study aims to evaluate an enhanced immunosuppressive regimen as part of the ELEVIDYS (delandistrogene moxeparvovec) gene therapy treatment specifically for non-ambulatory individuals living with Duchenne muscular dystrophy (DMD). The approval marks a critical development toward increasing the safety and accessibility of gene therapy in this high-risk patient population who have lost the ability to walk.
ENDEAVOR trial also (Study 9001-103) Cohort 8 will incorporate an enhanced immunosuppressive protocol that includes administration of sirolimus before and after ELEVIDYS infusion. The regimen begins with 14 days of sirolimus prior to dosing and continues for 12 weeks post-treatment. This strategy is designed to mitigate severe immune reactions and reduce the risk of acute liver injury (ALI), a serious side effect previously observed in non-ambulatory Duchenne patients receiving the gene therapy. Management of liver safety remains utmost important, as cases of acute liver failure had led to temporary commercial holds for the non-ambulatory population. Primary endpoints for this cohort include monitoring the incidence of ALI and assessing dystrophin expression 12 weeks after dosing.
ELEVIDYS is currently the only approved gene therapy designed to address the underlying cause of Duchenne muscular dystrophy by delivering a micro-dystrophin gene to skeletal and cardiac muscles. Since its approval, ELEVIDYS has been administered to over a thousand patients worldwide across clinical trials and real-world settings, primarily in ambulatory individuals aged four years and older.
ELEVIDYS has been linked to serious acute liver injury (ALI) in non-ambulatory patients. In 2025, two fatal cases of acute liver failure in non-ambulatory pediatric DMD patients following ELEVIDYS treatment were reported, leading the FDA to investigate these deaths and ultimately issue a boxed warning highlighting the risk of serious liver injury and acute liver failure. As a result, Sarepta voluntarily suspended U.S. distribution of ELEVIDYS for non-ambulatory patients starting June 2025, shortly after which the FDA placed a formal request to halt shipments to this patient group and suspended clinical dosing. This suspension followed concerns over elevated liver enzymes, hospitalization, and life-threatening complications such as mesenteric vein thrombosis in affected patients.
Louise Rodino-Klapac, Ph.D., president of research & development and technical operations at Sarepta, stated that Cohort 8 of the ENDEAVOR study will evaluate incorporating sirolimus into the immunosuppression regimen to reduce acute liver injury risk and restore treatment access for non-ambulatory individuals with Duchenne. She added that dosing is planned to start by the end of 2025, with primary endpoint data collection expected in the second half of 2026.
The company is working closely with the FDA to ensure that decisions regarding resumption of commercial dosing for non-ambulatory patients are based on comprehensive data and prioritize patient safety.
Impact on Duchenne Treatment Landscape
The FDA’s approval of the enhanced immunosuppression cohort in the ENDEAVOR study is an important step toward making ELEVIDYS gene therapy safer and more accessible for non-ambulatory Duchenne patients, who have limited treatment options. Sarepta’s approach to reducing immune and liver-related side effects may set a new standard for gene therapies in rare neuromuscular diseases.
References
Sarepta Announces Approval to Begin ENDEAVOR Cohort 8 to Evaluate Enhanced Immunosuppression Regimen as Part of ELEVIDYS Gene Therapy for Non-Ambulant Individuals with Duchenne, 25 November 2025, Sarepta, https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-announces-approval-begin-endeavor-cohort-8-evaluate