The ground shook for Sarepta Therapeutics, Inc. (NASDAQ:SRPT) last week as the U.S. Food and Drug Administration (FDA), alarmed by a third patient death tied to its gene therapy platform, pulled a rare move: requesting a voluntary halt to Elevidys shipments. The company’s response? A resounding “no,” igniting a major regulatory clash with severe implications for patients and investors alike.

The upheaval began on Friday when the U.S. Food and Drug Administration (FDA) made a rare and impactful announcement: it had placed Sarepta’s investigational gene therapy clinical trials for limb girdle muscular dystrophy (LGMD) on a clinical hold. This decision stemmed from serious safety concerns, including three patient deaths potentially linked to these products, indicating that study participants faced or would be exposed to an unreasonable and significant risk of illness or injury.

In light of these developments, the FDA also formally requested Sarepta to voluntarily halt all shipments of Elevidys, the company’s approved gene therapy. However, in a move that set the stage for a major regulatory clash with severe implications for both patients and investors, Sarepta definitively refused this request.

Also Read: Did The FDA Make A Mistake? Sarepta’s Elevidys Approval Under Scrutiny

The three fatalities, which prompted the FDA’s strong action, have resulted from acute liver failure in individuals who had received either Elevidys or an investigational gene therapy utilizing the same AAVrh74 serotype, a viral vector used in gene delivery. Notably, one of these deaths occurred during a clinical trial for LGMD, conducted under an investigational new drug application.

Adding to Sarepta’s challenges, the FDA further revoked the platform technology designation for the company’s AAVrh74 Platform Technology. This designation, typically granted to technologies with broad therapeutic promise that can streamline regulatory review, was rescinded because, given the new safety information, the preliminary evidence was deemed insufficient to demonstrate that the AAVrh74 Platform Technology could be incorporated into or utilized by multiple drugs without adverse effects on safety.

Elevidys had received traditional approval in June 2024 for ambulatory Duchenne muscular dystrophy (DMD) patients aged four years and older with a confirmed DMD gene mutation. Previously, in June 2023, it secured accelerated, conditional approval for non-ambulatory DMD patients. However, continued approval for non-ambulatory patients is contingent upon verification of clinical benefit through confirmatory trials.

With the emergence of this new safety data, the FDA notified Sarepta that Elevidys’s indication should now be restricted solely to ambulatory patients. The FDA is continuing its investigation into the risk of acute liver failure, including severe outcomes such as hospitalization and death, associated with gene therapies employing Sarepta’s AAVrh74 Platform Technology, and is prepared to take further regulatory actions as necessary.

Despite the FDA’s stance, Sarepta issued a statement on Friday affirming its decision to continue shipping Elevidys to the ambulatory patient population. The company asserted that its “comprehensive scientific interpretation of the data… shows no new or changed safety signals in the ambulant patient population.” Sarepta also expressed its commitment to ongoing discussions and information sharing with the FDA to advance their “shared purpose of protecting patient safety and informed access to care.”

The company clarified that the most recent fatal event occurred in a Phase 1 clinical trial for an investigational gene therapy called SRP-9004, which is designed to treat a different condition, LGMD Type 2D. Sarepta emphasized that SRP-9004 is administered at a different dose and manufactured using a distinct process from Elevidys. Furthermore, the LGMD study participant who passed away was not treated with Elevidys, and dosing for the SRP-9004 trial had already concluded at the time of death. Sarepta reported this acute liver failure (ALF) event as a life-threatening case to the FDA on June 20 and subsequently notified the agency of the death on July 3.

Looking ahead, Sarepta plans to submit the findings of an expert panel and a proposed protocol to the FDA. They will also discuss a proposal to collect additional data on a modified treatment regimen in a new cohort (Cohort 8) of the ENDEAVOR study (Study SRP-9001-103). This is intended as a pathway to re-establish dosing for non-ambulant patients in the future.

Price Action: As of Monday’s premarket session, Sarepta’s stock was down 6.79% at $13.12, reflecting the ongoing concerns and market reaction to these significant developments.

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