Sarepta's Duchenne Gene Therapy Faces Setbacks in Europe Amid Safety Concerns

Clinical Trials Halted Following Patient Death

Sarepta Therapeutics and its partner Roche have suspended three clinical trials of their Duchenne muscular dystrophy (DMD) gene therapy, Elevidys, in Europe. This decision comes in response to a request from the European Medicines Agency (EMA) following the death of a 16-year-old patient in the United States who suffered acute liver failure after receiving the treatment.

The paused trials include the Phase 3 Envision study, evaluating Elevidys in boys aged 8 to 17; Roche's Phase 2 Envol study, investigating the therapy in babies and newborns; and Sarepta's Phase 1 Study 104, examining Elevidys in boys ages 4 to 9 with pre-existing antibodies to a particular serotype. The suspension affects all EU countries, with the Envol study also halted in the UK.

Roche stated in a letter to the World Duchenne Organization that the trials will remain on hold until "analysis into the cause of death is complete." Meanwhile, four U.S.-based Elevidys studies continue to progress.

Safety Concerns and Market Impact

The patient death has raised concerns about the safety of adeno-associated virus (AAV) vector-based gene therapies. While serious liver injury is a known risk of Elevidys, the severity of this case—acute liver failure leading to death—represents a new level of concern. Sarepta disclosed that the deceased patient had a recent cytomegalovirus infection, which may have been a contributing factor.

This incident has had a significant impact on Sarepta's market position, with the company's share price dropping by 42% since the announcement. Despite these setbacks, some analysts remain optimistic about Elevidys' long-term prospects. Leerink Partners noted that while the therapy has "taken a reputational hit," they believe "the pendulum seems to have swung too far" in terms of market reaction.

Regulatory Landscape and Future Outlook

Elevidys received accelerated approval in the United States in June 2023 for boys ages 4 and 5, with the FDA expanding its label in June 2024 to include all DMD patients aged 4 and up. These approvals have been controversial, as neither was based on a trial that met its primary endpoint.

Despite the challenges, Elevidys has seen strong sales, indicating a significant unmet need in the DMD patient population. In the fourth quarter, Sarepta reported revenue of $383 million from Elevidys, a 110% increase from the previous quarter. Leerink Partners projects Elevidys sales to reach $2 billion this year.

As the investigation into the patient death continues, the pharmaceutical industry watches closely to see how this development will affect the future of gene therapies for rare diseases. The outcome of this analysis could have far-reaching implications for the development and regulation of similar treatments in the pipeline.