FDA Considers Withdrawing Sarepta's Duchenne Gene Therapy Amid Safety Concerns

The U.S. Food and Drug Administration (FDA) is contemplating the potential withdrawal of Sarepta Therapeutics' gene therapy Elevidys from the market following a series of patient deaths linked to liver toxicity. This development marks a significant setback for the treatment of Duchenne muscular dystrophy (DMD) and raises questions about the safety of certain gene therapies.

FDA Signals Stronger Action on Elevidys

FDA Commissioner Martin Makary revealed in an interview with Bloomberg News that the agency is assessing whether Elevidys should remain on the U.S. market. This statement comes after two teenage patients treated with Elevidys died from acute liver failure, prompting Sarepta to pause shipments to non-ambulatory patients in June.

The situation escalated further when a third death was reported in a 51-year-old patient who received SRP-9004, an investigational gene therapy for limb-girdle muscular dystrophy that uses the same underlying platform as Elevidys. Although this death was not directly related to Elevidys, it has intensified concerns about the safety of Sarepta's gene therapy approach.

In response to these events, the FDA is reportedly planning to request that Sarepta voluntarily halt all shipments of Elevidys, not just those to non-ambulatory patients. An FDA spokesperson confirmed that a federal official is "taking a hard look at pulling it from the market."

Sarepta's Challenges and Market Response

The news has had a significant impact on Sarepta Therapeutics. The company's stock plummeted more than 35% following the reports, with shares trading at $13.9 as of Friday afternoon. The broader biotech market, as measured by the XBI index, also experienced a 1.9% decline in correlation with Sarepta's stock drop.

These developments come on the heels of Sarepta's announcement of a major restructuring, including the layoff of approximately 500 employees and the addition of a black box warning for Elevidys regarding liver risks. The company has been criticized for not disclosing the third patient death during its investor call on Wednesday, leading to questions about transparency.

Sarepta CEO Douglas Ingram defended the company's actions, stating that the death was "neither material nor relevant" to the information shared on Wednesday and asserting that Sarepta has been "extraordinarily transparent."

Regulatory Scrutiny and Implications for Gene Therapy

The controversy surrounding Elevidys extends beyond recent safety concerns. Its initial accelerated approval in June 2023 was contentious, with former Center for Biologics Evaluation and Research (CBER) director Peter Marks overruling negative opinions from FDA review teams.

The current situation has reignited debates about the approval process for gene therapies and the balance between providing access to potentially life-changing treatments and ensuring patient safety. The FDA's actions regarding Elevidys could have far-reaching implications for the development and regulation of gene therapies, particularly those using adeno-associated virus (AAV) vectors, which have been linked to liver toxicity.

As the FDA continues its investigation and deliberations, the future of Elevidys and similar gene therapies remains uncertain. The pharmaceutical industry and patient communities are closely watching for the agency's next steps, which could reshape the landscape of treatments for rare genetic disorders.