Sarepta Undergoes Major Restructuring, Prioritizes siRNA After Gene Therapy Pipeline Pivot

Sarepta Therapeutics is undergoing a major strategic restructuring, including laying off 36% of its workforce, aiming for $400 million in annual savings. The company is pivoting its pipeline, discontinuing most AAV gene therapy programs for limb-girdle muscular dystrophy to prioritize its siRNA platform (for myotonic dystrophy type 1, idiopathic pulmonary fibrosis, and Huntington’s disease), while seeking partners for deprioritized assets and continuing its collaboration with Arrowhead Pharmaceuticals.

This restructuring comes as Sarepta faces significant challenges regarding its flagship Duchenne muscular dystrophy (DMD) AAV gene therapy, Elevidys. The FDA has requested a black box warning for acute liver injury on Elevidys’ label, following two patient deaths from acute liver failure. This led Sarepta to halt Elevidys administration to non-ambulatory patients in the U.S. commercial setting and pause its Phase 3 ENVISION trial, seeking FDA approval for an enhanced immunosuppressive regimen.

Despite these setbacks, Sarepta’s stock surged over 30% postmarket after the announcement, as investors viewed the black box warning as preferable to a market withdrawal. While analysts anticipate near-term revenue headwinds for Elevidys, confidence in Sarepta’s long-term debt repayment ability appears to have increased. CEO Douglas Ingram stated the restructuring is a proactive measure to ensure the company’s “long term viability” and patient-centric mission. Alongside the layoffs, Sarepta announced leadership team changes, including new Chief Commercial, Operating, Financial, and Scientific Officers, and a new President of R&D and Technical Operations.