Sarepta Gains FDA Nod for Study to De-Risk Key Gene Therapy Elevidys
Company to test new drug regimen aimed at mitigating severe liver injury risk that prompted an FDA black box warning and restricted the drug's use.
Sarepta Therapeutics (NASDAQ: SRPT) has received clearance from the U.S. Food and Drug Administration to initiate a new clinical study for its flagship gene therapy, Elevidys, aimed at addressing the severe safety concerns that have constrained the drug's market potential. The company's shares traded up 1.7% to $19.23 in morning trading following the announcement.
The FDA approved the commencement of Cohort 8 within the ongoing ENDEAVOR study. This new phase will investigate whether co-administering the immunosuppressant sirolimus with Elevidys can mitigate the risk of acute serious liver injury, a side effect that has proven fatal in some patients. This development is a critical step for Sarepta as it seeks to re-establish confidence in what is currently the only approved gene therapy for Duchenne muscular dystrophy (DMD), a rare and fatal genetic disorder.
The urgency of this new study is underscored by the significant safety issues that have plagued Elevidys. The therapy's label includes a black box warning—the FDA's most stringent safety alert—for acute liver injury and acute liver failure. This warning was implemented after several tragic cases, including fatal outcomes in non-ambulatory pediatric patients treated with the therapy, according to reports on the updated drug label. These events led the FDA to narrow the drug's indication, restricting its use to ambulatory DMD patients aged four and older and removing non-ambulatory patients from the approved population.
In an official statement, Sarepta confirmed the new study will enroll approximately 25 non-ambulatory participants in the United States. The trial is designed to "evaluate an enhanced immunosuppressive regimen" with the specific goal of reducing the risk of acute liver injury. "Sarepta plans to initiate Cohort 8 before the end of 2025, with primary endpoint data collection anticipated in the second half of 2026," the company stated in its press release. The primary endpoints will be the incidence of liver injury and the expression of micro-dystrophin, the crucial protein Elevidys is designed to produce, at 12 weeks.
Success in this cohort could pave the way for Sarepta to potentially regain access to the non-ambulatory patient population, a significant expansion of the commercial opportunity for Elevidys. The company noted that decisions on resuming commercial dosing for this group will be made in collaboration with the FDA after reviewing the study's data.
Wall Street analysts reacted positively to the news, viewing it as a proactive and necessary step to de-risk the therapy. Analysts at Mizuho recently upgraded Sarepta's stock from "Neutral" to "Outperform" with a $26 price target, citing strong demand and favorable insurance coverage despite the safety overhang. Similarly, Bernstein SocGen Group raised its price target from $18 to $20, attributing the change to higher estimates for Elevidys following solid third-quarter results and the recent label updates, as reported by Investing.com.
For Sarepta, which has a market capitalization of nearly $2 billion, the commercial success of Elevidys is paramount. The therapy represents a multi-billion dollar market opportunity, but its trajectory has been hampered by the balance between its therapeutic promise and its documented risks. The updated FDA label already mandates rigorous weekly liver function testing for at least three months after administration. The potential inclusion of sirolimus represents a new strategy to manage the therapy's toxicities more effectively.
The path forward for Elevidys remains complex. The company must demonstrate to regulators, physicians, and patients that this new regimen can provide a sufficient safety margin. The results from Cohort 8 in late 2026 will be a pivotal catalyst for the company and its shareholders, determining whether one of the most promising treatments for Duchenne muscular dystrophy can overcome its most significant hurdle.