Sarepta Gains FDA Expansion for Duchenne Gene Therapy Elevidys

The FDA has broadened the label for Sarepta’s Duchenne muscular dystrophy (DMD) gene therapy, Elevidys, exactly a year after it was initially granted accelerated approval. This expansion now includes all DMD patients aged 4 and above, marking a significant milestone for both the company and patients suffering from this genetic disorder. Originally, Elevidys was approved only for ambulatory boys aged 4 to 5.

The FDA’s decision came after confirming the functional benefits of Elevidys. It has now received traditional approval for ambulatory patients and accelerated approval for non-ambulatory patients. However, the continued approval for non-ambulatory patients is conditional upon the verification of clinical benefits in a confirmatory trial.

Doug Ingram, CEO of Sarepta, referred to this development as "a defining moment for the Duchenne community," highlighting the potential of gene therapy and its benefits for science. Analyst Tim Lugo from William Blair described it as a "transformational" milestone for both Sarepta and DMD patients. He expects the expanded label to drive significant revenue growth for the company, estimating product revenues to reach $3 billion in 2025 and $5 billion in 2027, before a decline in 2028.

The label expansion came eight months after Sarepta disclosed that the EMBARK pivotal study did not achieve its primary endpoint, falling short in the North Star Ambulatory Assessment (NSAA), which measures motor function. Despite this setback, Sarepta emphasized the "clinically meaningful" effects observed in secondary endpoints of the trial, such as improvements in the time taken to rise from the floor, changes in a 10-meter walk or run time, and increased dystrophin protein expression triggered by Elevidys.

Following the trial results, Ingram argued that the study demonstrated Elevidys’s potential to alter the course of DMD and that the company aimed for the broadest possible label. Initial investor reactions were negative, with Sarepta’s share price plummeting by 41% after the EMBARK topline results were revealed. However, investor confidence rebounded as Elevidys achieved commercial success, generating $334 million in sales during its first three quarters on the market.

Investor concerns were further alleviated when the FDA prioritized the review of the Elevidys expansion application in February and decided not to hold an advisory committee meeting as part of the review process. By the time markets opened on Friday, Sarepta's shares had surged by 38% to $170, recovering from the previous dip to $110.

The journey to Elevidys’s initial approval was fraught with challenges, including clinical holds in 2018 and 2021 due to safety concerns. Even after an advisory committee voted 8-6 to recommend approval, the FDA delayed its decision by a month.

The expanded approval is particularly gratifying for Jerry Mendell, M.D., Sarepta's senior advisor for medical affairs, and Louise Rodino-Klapac, Ph.D., the company’s chief scientific officer. Mendell, who discovered Elevidys, expressed that this event marks the culmination of his 50-year pursuit of a treatment for Duchenne patients and nearly 20 years of effort to develop a safe and effective gene therapy.

Elevidys works by delivering a micro-dystrophin-encoding gene into a patient’s muscle tissue, prompting the production of the micro-dystrophin protein. This protein is crucial for patients who cannot produce it properly, leading to progressive muscle weakness. Priced at $3.2 million for a one-time treatment, Elevidys aims to transform the disease into a milder form.

As part of its collaboration with Roche, established in 2019, Sarepta handles regulatory approval, commercialization, and manufacturing of Elevidys in the U.S., while Roche is responsible for regulatory approval and commercialization in the rest of the world.