Sarepta Therapeutics Adds Black Box Warning to Elevidys, Announces Major Restructuring

Sarepta Therapeutics, a Cambridge, Massachusetts-based biotech company, has announced significant changes to its gene therapy for Duchenne muscular dystrophy (DMD) and a major corporate restructuring. These developments come in the wake of two patient deaths linked to the treatment and reflect the company's efforts to address safety concerns while refocusing its strategic priorities.

Black Box Warning Added to Elevidys

Following the deaths of two teenage patients with DMD who were treated with Elevidys, Sarepta has added a black box warning to the gene therapy. The warning specifically addresses the risks of acute liver injury and acute liver failure, known adverse effects associated with adeno-associated virus (AAV) vector-based gene therapies.

The company had previously insisted that Elevidys' benefit-risk ratio remained positive after the first patient death in March. However, the occurrence of a second fatality in June, also linked to acute liver failure, prompted Sarepta to temporarily halt shipments for non-ambulatory patients while it reassessed its approach to immunosuppression in this patient group.

Corporate Restructuring and Pipeline Reprioritization

In a strategic move announced Wednesday afternoon, Sarepta revealed plans to lay off approximately 500 employees, representing more than a third of its workforce. This decision comes as part of a broader restructuring effort aimed at focusing the company's resources on "high-impact programs" and prioritizing "potentially best-in-class siRNA platform assets."

Key aspects of the restructuring include:

• Focusing on programs for facioscapulohumeral muscular dystrophy, idiopathic pulmonary fibrosis, and Huntington's disease
• Pausing several other programs, including most gene therapies in development for limb-girdle muscular dystrophy (LGMD)
• Continuing plans to submit a biologics license application for SRP-9003 for LGMD type 2E/R4 in the second half of this year

Sarepta CEO Doug Ingram stated, "Faced with environmental changes, we have decided to act decisively, implementing a focused strategy to ensure Sarepta remains a vibrant, financially enduring, patient-centric organization dedicated to improving the lives of those with rare genetic diseases."

The company expects these changes to generate significant cost savings, including approximately $120 million in annual cash cost savings by 2026 through the layoffs and about $300 million in annual non-personnel cost savings through pipeline reprioritization starting next year.

Resumption of Elevidys Shipments and FDA Investigation

Despite the setbacks, Sarepta has completed an expert committee review to establish a protocol for additional prophylactic immunosuppression in non-ambulatory patients. The company plans to submit this protocol to the FDA "imminently" with the goal of resuming Elevidys shipments to this patient group.

It's worth noting that the FDA has opened an investigation into the gene therapy following the second patient death. The outcome of this investigation could have significant implications for the future of Elevidys and Sarepta's gene therapy program.

Despite these challenges, Sarepta reported that its DMD portfolio, including Elevidys, generated $513 million in revenue for the second quarter of the year.