CAMBRIDGE, Mass. — Sarepta Therapeutics, Inc. (NASDAQ: SRPT) announced that screening and enrollment have begun for Cohort 8 of the ENDEAVOR clinical study, which will evaluate an enhanced immunosuppression regimen as part of treatment with its gene therapy ELEVIDYS for non-ambulant individuals with Duchenne muscular dystrophy.
Cohort 8 of the ENDEAVOR study will assess whether prophylactic treatment with sirolimus can help reduce the risk of acute liver injury associated with adeno-associated virus (AAV) gene therapy. Approximately 25 non-ambulatory participants in the United States are expected to enroll in the cohort.
Participants will receive sirolimus beginning prior to ELEVIDYS infusion and continuing afterward as part of a safety protocol designed to mitigate the risk of acute liver injury and acute liver failure, complications that have been associated with AAV gene therapies in non-ambulatory patients.
The regimen will include 14 days of peri-infusion sirolimus dosing before ELEVIDYS administration and will continue for 12 weeks after infusion. The primary endpoints include the incidence of acute liver injury and levels of ELEVIDYS micro-dystrophin expression at 12 weeks following treatment.
“We are proud to announce that clinical trial sites are now open and actively recruiting non-ambulatory individuals with Duchenne to participate in ENDEAVOR Cohort 8,” said Louise Rodino-Klapac, Ph.D., president of research & development and technical operations at Sarepta. “Individuals with non-ambulatory Duchenne face profound unmet need and fewer treatment options. Cohort 8 of ENDEAVOR is expected to build on the dystrophin expression data generated with ELEVIDYS to-date while deepening our understanding of its safety profile in older patients with more advanced disease so we can urgently advance this treatment option for them.”
The approach is based on preclinical data and clinical experience, including input from independent specialists in Duchenne muscular dystrophy and liver health.
The ENDEAVOR study, also known as Study SRP-9001-103, is an open-label Phase 1b trial evaluating the safety and expression of ELEVIDYS across multiple patient groups. The study has enrolled 55 participants across seven cohorts, including younger ambulatory patients aged 2 to 7, older ambulatory individuals, and non-ambulatory patients.
The primary endpoint of the study is the change from baseline in the quantity of ELEVIDYS micro-dystrophin protein expression measured by western blot at 12 weeks. Secondary measures include changes in the percentage of dystrophin-positive muscle fibers.
ELEVIDYS (delandistrogene moxeparvovec-rokl) is a single-dose gene therapy delivered via intravenous infusion that is designed to address the underlying genetic cause of Duchenne muscular dystrophy. The therapy uses an adeno-associated virus vector to deliver a gene that produces a shortened form of dystrophin, known as micro-dystrophin, in skeletal muscle.
The therapy is currently approved for the treatment of ambulatory patients aged 4 and older with Duchenne muscular dystrophy who have a confirmed mutation in the DMD gene. Sarepta said ELEVIDYS has been administered to more than 1,200 patients worldwide in clinical trials and real-world settings.
