Sarepta Therapeutics will be investigating the potential of using an immunosuppressant both before and after treatment with Elevidys (delandistrogene moxeparvovec-rokl) in a bid to avoid potentially fatal adverse events associated with its flagship gene therapy.
The US Food and Drug Administration (FDA) has given Sarepta approval to enrol a new cohort (Cohort 8) in the Phase Ib ENDEAVOR trial (NCT04626674). The cohort will enrol 25 non-ambulant patients with Duchenne muscular dystrophy (DMD) who will receive sirolimus – an immunosuppressant – both 14 days before and for 12 weeks after treatment with Elevidys.
Go deeper with GlobalData
Discover B2B Marketing That Performs
Combine business intelligence and editorial excellence to reach engaged professionals across 36 leading media platforms.
Primary endpoints include incidence of acute liver injury (ALI) and Elevidys-dystrophin expression at 12 weeks. The approach is based on preclinical data and shaped by real-world clinical experience, including guidance from independent specialists in DMD and liver health.
Data from Cohort 8 will be used to determine whether these infusions can reduce the risk of ALI, a known risk associated with adeno-associated virus (AAV) gene therapy. ALI has been associated with the death of two patients who were non-ambulatory after treatment with the gene therapy. Sarepta said that the onset of ALI typically begins within eight weeks of Elevidys administration.
Following the deaths, the FDA and Sarepta agreed to a pause on certain Elevidys trials, as well as the company temporarily stopping sales of the gene therapy after pressure from the agency. These pauses have since been lifted.
Dr Louise Rodino-Klapac, president of research & development and technical operations at Sarepta, said that the company plans to initiate enrolment into the cohort by the end of 2025 and, pending enrolment, complete primary endpoint data could be available in the second half of 2026.
US Tariffs are shifting - will you react or anticipate?
Don’t let policy changes catch you off guard. Stay proactive with real-time data and expert analysis.
By GlobalDataRodino-Klapac added: “Guided by real-world experience, external clinician expertise, and FDA input, cohort 8 of the ENDEAVOR study will evaluate integrating sirolimus into our immunosuppression approach, with the goals of mitigating the risk of acute liver injury and restoring access for non-ambulant individuals living with DMD.”
Elevidys remains available as appropriate to ambulatory individuals ages four and over, as per an updated label announced earlier in November 2025. The new label has added a boxed warning for the risk of acute serious liver injury (ALI) and acute liver failure (ALF), as well as the therapy no longer being approved for use in the non-ambulatory indication.
This comes just days after Sarepta terminated a Phase I trial (NCT06241950) of Elevidys in combination with Hansa Biopharma’s Idefirix (imlifidase). The study was investigating whether treatment with Idefirix could broaden the patients eligible to receive the gene therapy.
Cell & Gene therapy coverage on Clinical Trials Arena is supported by Cytiva.
Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content.
