The U.S. Food and Drug Administration announced it has placed Sarepta Therapeutics investigational gene therapy clinical trials for limb girdle muscular dystrophy on clinical hold following three deaths potentially related to these products and new safety concerns that the study participants are or would be exposed to an unreasonable and significant risk of illness or injury. The FDA has also revoked Sarepta’s platform technology designation.

The FDA leadership also met with Sarepta Therapeutics and requested it voluntarily stop all shipments of Elevidys today. The company refused to do so.  

“ We’ve shown that this FDA takes swift action when patient safety is at risk.” said FDA Commissioner Marty Makary, M.D., M.P.H. “We believe in access to drugs for unmet medical needs but are not afraid to take immediate action when a serious safety signal emerges.”

The three deaths appear to have been a result of acute liver failure in individuals treated with Elevidys or investigational gene therapy using the same AAVrh74 serotype that is used in Elevidys. One of the fatalities occurred during a clinical trial conducted under an investigational new drug application for the treatment of Limb Girdle Muscular Dystrophy.

“Protecting patient safety is our highest priority, and the FDA will not allow products whose harms are greater than benefits. The FDA will halt any clinical trial of an investigational product if clinical trial participants would be exposed to an unreasonable and significant risk of illness or injury,” said Director of the FDA’s Center for Biologics Evaluation and Research Vinay Prasad, M.D., M.P.H.

Elevidys is an adeno-associated virus vector-based gene therapy using Sarepta Therapeutics, Inc.’s AAVrh74 Platform Technology for the treatment of Duchenne muscular dystrophy (DMD). It is designed to deliver into the body a gene that leads to production of Elevidys micro-dystrophin, a shortened protein (138 kDa, compared to the 427 kDa dystrophin protein of normal muscle cells) that contains selected domains of the dystrophin protein present in normal muscle cells. The product is administered as a single intravenous dose.

Duchenne muscular dystrophy is a rare and serious genetic condition which worsens over time, leading to weakness and wasting away of the body’s muscles. The disease occurs due to a defective gene that results in abnormalities in, or absence of, dystrophin, a protein that helps keep the body’s muscle cells intact.

Further, date, the FDA revoked the platform technology designation for Sarepta’s AAVrh74 Platform Technology because, among other things, given the new safety information, the preliminary evidence is insufficient to demonstrate that AAVrh74 Platform Technology has the potential to be incorporated in, or utilized by, more than one drug without an adverse effect on safety.

Elevidys received traditional approval for use in ambulatory DMD patients 4 years of age and older with a confirmed mutation in the DMD gene on June 20, 2024. It was approved for non-ambulatory patients on June 22, 2023 under the accelerated approval pathway. This pathway can allow earlier approval based on an effect on a surrogate endpoint or intermediate clinical endpoint that is reasonably likely to predict clinical benefit, while the company conducts confirmatory studies to verify the predicted clinical benefit. Continued approval for non-ambulatory patients is contingent upon verification and description of clinical benefit in a confirmatory trial. Given the new safety information, The FDA has notified the company that the indication should be restricted to use in ambulatory patients. The FDA is committed to further investigating the safety of the product in ambulatory patients and will take additional steps to protect patients as needed.

The FDA is continuing to investigate the risk of acute liver failure with serious outcomes, including those such as hospitalization and death, following gene therapies using Sarepta’s AAVrh74 Platform Technology, and the need for further regulatory actions.

Broader Spectrum Analysis of FDA's Alert on Sarepta’s AAVrh74 Gene Therapy

The recent FDA investigation into fatalities linked to Sarepta Therapeutics’ AAVrh74 gene therapy products, specifically ELEVIDYS, represents a crucial inflection point for the burgeoning field of gene therapies. As gene therapies evolve from experimental to mainstream clinical applications, the industry's reaction to such adverse events will significantly shape future regulatory frameworks, investor confidence, technological advancements, and public perception.

As of July 18, 2025, three confirmed deaths attributed to acute liver failure related to these gene therapy products underline the importance of stringent oversight and thorough evaluation processes. This scenario highlights both the potential risks and the considerable responsibilities that accompany cutting-edge medical innovations.

Immediate Industry Implications:

• Regulatory Scrutiny Intensifies: The FDA’s immediate suspension of ELEVIDYS and related trials sends a strong signal regarding the importance of safety over speed in drug development. Companies must prepare for stricter regulatory standards, extended approval timelines, and more robust risk mitigation strategies.

• Investor Caution: Investor sentiment towards gene therapy companies will likely experience heightened caution. Risk assessments for biotechnology portfolios will tighten, and increased scrutiny from investors could lead to short-term financial instability within the sector.

• Enhanced Safety Protocols: Industry-wide shifts towards more comprehensive and stringent monitoring procedures, particularly concerning liver function and immunogenic responses, are expected. The demand for detailed preclinical toxicological data will increase significantly.

• Impact on Patient Advocacy and Public Trust: Patient advocacy groups will seek greater transparency and reassurance, demanding clearer communication about potential risks and benefits from gene therapy developers.

Long-term Outlook for Gene Therapy:

• Innovation and Safety Equilibrium: The industry faces a dual challenge—continuing to drive forward innovative treatments while addressing safety concerns more rigorously. This balance will likely redefine development strategies, clinical trial designs, and patient monitoring protocols.

• Technological Advances: The current setbacks might expedite the exploration and adoption of alternative vectors or non-viral delivery methods, potentially leading to safer and more effective solutions. Companies with diversified technological platforms may benefit from this trend.

• Global Regulatory Harmonization: The incident could accelerate international collaboration towards harmonized regulatory standards, reducing variability in safety and efficacy evaluations across different regions.

• Investment in Diagnostic Capabilities: There will be renewed focus and significant investment in developing predictive diagnostic tools, facilitating early detection and prevention of serious adverse effects in clinical settings.

Strategic Recommendations for Industry Stakeholders:

• Enhanced Transparency and Crisis Management: Immediate emphasis should be placed on clear and open communication strategies regarding adverse events and clinical data disclosures to maintain public and investor trust.

• Collaborative Industry Efforts: Industry-wide collaborations to establish and adhere to common safety protocols and standards will be critical in mitigating risks associated with novel therapies.

• Proactive Regulatory Engagement: Companies should proactively engage regulators to anticipate and fulfill evolving regulatory expectations and maintain compliance seamlessly.

The FDA’s recent actions surrounding Sarepta Therapeutics’ gene therapy products serve as a stark reminder of the complex landscape faced by gene therapy developers. While this situation poses significant immediate challenges, it also offers an invaluable opportunity to refine safety protocols, enhance technological innovation, and establish robust regulatory frameworks. Successfully navigating these challenges will determine the pace and sustainability of gene therapy advancements, ensuring patient safety while maximizing therapeutic potential.