Sarepta's DMD Gene Therapy Elevidys Faces Setback After Second Patient Death

Sarepta Therapeutics' gene therapy for Duchenne muscular dystrophy (DMD), Elevidys, has encountered a significant setback following the death of a second patient due to acute liver failure. The incident has prompted the company to suspend treatment for certain patient groups and reevaluate its safety protocols, sending shockwaves through the gene therapy landscape.

Second Fatal Case Raises Alarm

Sarepta and its ex-U.S. partner Roche reported the death of a 15-year-old non-ambulatory patient in the Phase III ENVISION study on Sunday. This follows a similar incident in March, marking the second fatality among over 900 patients treated with Elevidys globally. Both cases involved non-ambulatory patients who developed acute liver failure, a known risk associated with adeno-associated virus (AAV) vector-based gene therapies.

In response, Sarepta has taken swift action:

• Suspended Elevidys administration to non-ambulatory patients in the U.S. commercial setting
• Paused dosing in the ENVISION trial, which serves as the confirmatory study for Elevidys' accelerated approval
• Assembled an independent expert panel to develop an enhanced immunosuppression regimen, potentially including the drug sirolimus

Roche has discontinued Elevidys use in commercial non-ambulatory patients outside the U.S., while European regulators had previously placed holds on three Elevidys trials following the first death report.

Implications for Gene Therapy Landscape

The incidents have raised concerns about the broader gene therapy field, which has been experiencing what BlueRock Therapeutics CEO Seth Ettenberg described as a "cold winter." Several other gene therapy programs have reported safety issues, including those from Rocket Pharmaceuticals, Neurogene, and Beam Therapeutics.

Jefferies analyst Andrew Tsai noted that the second death has worsened Elevidys' benefit-risk profile, potentially affecting both non-ambulatory and ambulatory patient groups. The uncertainty surrounding Elevidys' future is compounded by the recent appointment of Vinay Prasad, Ph.D., as director of the FDA's Center for Biologics Evaluation and Research (CBER), who had previously criticized the therapy's approval under former director Peter Marks.

Financial and Regulatory Repercussions

The news has had immediate financial consequences for Sarepta:

• Stock price plummeted nearly 50% on Monday morning
• Company suspended its revenue guidance, with an update expected in the Q2 earnings report
• Previous 2025 revenue projection lowered to $2.3-$2.6 billion from up to $3.1 billion

The incident adds another chapter to Elevidys' contentious regulatory history. The therapy received accelerated approval in 2023 and 2024 for progressively broader patient populations, despite mixed clinical results and internal FDA disagreements.

As the gene therapy community grapples with these developments, the focus shifts to enhancing safety protocols and maintaining public confidence in this promising yet complex field of medicine. The outcome of Sarepta's efforts to mitigate risks and the regulatory response will likely have far-reaching implications for the future of gene therapy development and approval processes.