Sarepta Aims for Expanded Label, Larger DMD Gene Therapy Market

Sarepta Therapeutics is on the verge of obtaining full FDA approval and a label expansion for its gene therapy, Elevidys. The therapy has been scrutinized for its high cost and clinical effectiveness. Elevidys received accelerated approval in June 2023 for treating Duchenne muscular dystrophy (DMD) in patients aged 4 to 5, generating over $200 million in revenue last year and an additional $133.9 million in the first quarter this year. However, opinions vary on its benefits to patients.

DMD, a severe form of inherited muscular dystrophy, is caused by mutations in the dystrophin gene, leading to muscle degeneration and weakness. Debra Miller, CEO of CureDuchenne, described Elevidys as a significant breakthrough for families involved in trials, showing positive effects for patients. Michael Kelly, the organization's chief scientific officer, praised the FDA for its courageous decision to grant accelerated approval, emphasizing the strong demand from parents of young children for the therapy.

Uy Ear, vice president of U.S. healthcare—biotechnology at Mizuho Securities, highlighted the impressive uptake of Elevidys. However, he noted that patients are typically diagnosed around the age of five, close to the current cutoff for the therapy, necessitating a label expansion to maintain the drug's momentum. Sarepta aims to make Elevidys accessible to all DMD patients, irrespective of age or ambulatory status.

If the FDA grants full approval and a label expansion, the impact on DMD patients will be substantial. Kelly noted that full approval would also facilitate the approval of other DMD drugs in the pipeline. However, some experts have raised concerns about the gene therapy's clinical effectiveness and cost. David Rind, chief medical officer of the Institute for Clinical and Economic Review (ICER), pointed out that Elevidys missed its primary efficacy endpoint in two studies but still received approval. The FDA, in briefing documents, indicated that measuring micro-dystrophin levels in muscle tissue only provided information about the transgene product's expression, not its pharmacologic effect on the disease pathway.

Rind expressed skepticism about micro-dystrophin as an effective biomarker, suggesting that a more controlled, long-term trial is necessary to determine Elevidys' benefits. He also criticized the therapy's $3.2 million per dose price, highlighting the lack of a pricing regulation scheme in the U.S. Despite these concerns, the FDA is likely to proceed with an expanded indication, a move Rind described as unfortunate but possible.

Kelly acknowledged the regulatory challenges but emphasized the reported benefits from patients and parents. Ear noted the absence of major safety concerns with Elevidys so far, though it is still early to identify potential issues. Rind questioned why the therapy failed in clinical trials if it is as effective as some reports suggest.

Sarepta did not immediately respond to a comment request. Overall, experts expect the gene therapy to receive full approval, with Kelly emphasizing the importance of giving patients the choice in treatment decisions. The DMD community would find it difficult to accept if full approval and a label extension are not granted.