Sarepta Therapeutics Inc. (SRPT) just got the FDA's approval to test a potentially important safety protocol for its gene therapy Elevidys. The agency gave the green light Tuesday for dosing to begin in Cohort 8 of the company's ENDEAVOR study, which will explore whether an immunosuppressant drug can help prevent serious liver complications in Duchenne muscular dystrophy patients.

The Liver Safety Question

Here's the backdrop: Elevidys is currently the only approved gene therapy for Duchenne muscular dystrophy, a devastating genetic disease that progressively weakens muscles. But earlier this year, Sarepta reported three deaths linked to acute liver failure in individuals who received either Elevidys or an investigational gene therapy using the same AAVrh74 platform. One of those fatalities occurred during a clinical trial for limb girdle muscular dystrophy.

Those cases raised obvious concerns about liver safety, which brings us to this new study cohort.

Testing a Protective Approach

Cohort 8 will enroll approximately 25 participants in the U.S. who are non-ambulatory, meaning they cannot walk. The study aims to determine whether administering sirolimus—an immunosuppressant drug—before and after Elevidys infusion can reduce the risk of acute liver injury.

The protocol involves giving patients sirolimus for 14 days before they receive Elevidys, then continuing the immunosuppressant for 12 weeks after the gene therapy infusion. The idea is that sirolimus might dampen the immune response that potentially triggers liver damage.

The study's primary endpoints include measuring the incidence of acute liver injury and assessing Elevidys-dystrophin expression at 12 weeks. Dystrophin is the protein that's missing or deficient in Duchenne patients, and Elevidys is designed to deliver a functional version of it.

The Broader ENDEAVOR Study

This new cohort fits into Sarepta's larger ENDEAVOR study (Study SRP-9001-103), an open-label Phase 1b trial evaluating the expression and safety of Elevidys across multiple patient populations. The study has already enrolled 55 participants across seven cohorts, testing the therapy in younger ambulatory children aged 2-7, older ambulant individuals, and non-ambulatory patients.

The primary endpoint in ENDEAVOR measures the change from baseline in Elevidys micro-dystrophin protein expression at 12 weeks, using western blot analysis. Secondary measures look at micro-dystrophin expression through the percentage of dystrophin-positive muscle fibers.

Progress on Another Front

In related news, Sarepta announced Monday that it's making progress on SRP-1003, an investigational small-interfering RNA therapy for type 1 myotonic dystrophy. The Phase 1/2 multiple ascending dose study has completed its first two cohorts and is moving forward with higher doses.

Cohorts 1 (1.5 mg/kg) and 2 (3 mg/kg) are complete, cohort 3 (4.5 mg/kg) is fully enrolled and ongoing, and patients are currently being dosed in cohort 4 (6 mg/kg). The company plans to initiate dosing in the final cohort, cohort 5 (12 mg/kg), in early 2026.

This progress triggered a $200 million milestone payment to Arrowhead Pharmaceuticals, Inc. (ARWR), which originally developed the therapy.

Sarepta stock was up 1.90% at $19.27 on Tuesday following these announcements.