Sarepta Therapeutics Inc. (NASDAQ: SRPT) has started screening and enrollment for Cohort 8 of its ENDEAVOR study to evaluate an enhanced immunosuppression regimen for ELEVIDYS gene therapy in non-ambulatory Duchenne muscular dystrophy patients.

The cohort will enroll approximately 25 non-ambulatory participants in the United States who will receive sirolimus as part of a protocol designed to reduce acute liver injury risk associated with AAV gene therapy. The immunosuppression regimen includes 14 days of sirolimus dosing before ELEVIDYS administration and continues for 12 weeks after infusion.

Primary endpoints include incidence of acute liver injury and ELEVIDYS-dystrophin expression at 12 weeks. The approach is based on preclinical data and clinical experience, including guidance from specialists in Duchenne and liver health.

"Individuals with non-ambulatory Duchenne face profound unmet need and fewer treatment options," said Louise Rodino-Klapac, president of research and development at Sarepta. "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."

ELEVIDYS carries a boxed warning for acute serious liver injury and acute liver failure. Fatal acute liver failure has occurred in non-ambulatory patients treated with ELEVIDYS in clinical and post-marketing settings.

The ENDEAVOR study is an open-label Phase 1b study that has enrolled 55 participants across seven cohorts. ELEVIDYS has been administered to over 1,200 patients globally in clinical and real-world settings, according to the company's press release.