Sarepta has initiated screening and enrollment for Cohort 8 of the ENDEAVOR trial to evaluate prophylactic sirolimus as a strategy to reduce acute liver injury risk during ELEVIDYS gene therapy in non-ambulatory Duchenne muscular dystrophy patients.
Written By: Karthik Teja Macharla, PharmD
Reviewed By: Pharmacally Editorial Team
Sarepta Therapeutics has begun screening and enrolment for Cohort 8 of the ENDEAVOR (Study SRP-9001-103) clinical trial to evaluate an enhanced safety strategy for its gene therapy ELEVIDYS in non-ambulatory patients with Duchenne muscular dystrophy (DMD). The FDA approved dosing in Cohort 8 in November 2025.
The new cohort is designed to investigate whether prophylactic treatment with sirolimus can reduce the risk of acute liver injury (ALI), a known safety concern associated with adeno-associated virus (AAV) gene therapies. Approximately 25 non-ambulatory participants in the United States are expected to enroll in the cohort.
Under the protocol, participants will receive sirolimus for 14 days prior to ELEVIDYS infusion as part of a peri-infusion immunosuppression regimen, which will then continue for 12 weeks after treatment. Researchers will assess the incidence of acute liver injury and levels of ELEVIDYS-derived micro-dystrophin expression at 12 weeks as the primary endpoints.
The launch of Cohort 8 follows safety concerns that emerged in 2025, when serious and fatal cases of acute liver toxicity were reported in non-ambulatory Duchenne patients treated with ELEVIDYS. Those events prompted increased regulatory scrutiny, safety protocol updates, and a re-evaluation of immunosuppression strategies used with AAV gene therapies.
These safety concerns are also reflected in the ELEVIDYS label, where the FDA has included a boxed warning for serious liver injury and acute liver failure associated with treatment.
According to Sarepta, the safety strategy was informed by preclinical data, clinical experience, and input from independent experts in Duchenne muscular dystrophy and liver health.
Louise Rodino-Klapac, Ph.D., president of research & development and technical operations at Sarepta, said the cohort aims to expand understanding of ELEVIDYS in older patients with more advanced disease who have limited treatment options.
ENDEAVOR (NCT04626674) is an open-label Phase 1b study evaluating the safety and expression of ELEVIDYS across multiple patient populations with Duchenne muscular dystrophy. To date, the trial has enrolled 55 participants across seven cohorts, including younger ambulatory patients aged 2 to 7 years, older ambulatory individuals, and non-ambulatory patients.
ELEVIDYS (delandistrogene moxeparvovec-rokl) is a one-time AAV-based gene therapy designed to deliver a micro-dystrophin gene to muscle cells to address the underlying genetic cause of Duchenne muscular dystrophy. The therapy is currently approved for ambulatory patients aged four years and older with confirmed mutations in the DMD gene, and more than 1,200 patients worldwide have received the treatment across clinical trials and real-world use.
Reference
Sarepta Announces that Screening and Enrollment are Underway in ENDEAVOR Cohort 8 to Evaluate Enhanced Immunosuppression Regimen as Part of ELEVIDYS Gene Therapy for Non-Ambulant Individuals with Duchenne, 16 March 2026, Sarepta Announces that Screening and Enrollment are Underway in ENDEAVOR Cohort 8 to Evaluate Enhanced Immunosuppression Regimen as Part of ELEVIDYS Gene Therapy for Non-Ambulant Individuals with Duchenne | Sarepta Therapeutics, Inc.
About the Writer
Karthik Teja Macharla, PharmD is a Pharm.D. graduate with a strong interest in clinical research, pharmacovigilance, and medical writing. In his words, he is passionate about converting complex medical information into clear, evidence-based scientific communication, committed to contributing to patient safety and advancing healthcare through accurate and impactful medical content.