FDA Expands Use of Sarepta's Duchenne Gene Therapy

The Food and Drug Administration (FDA) has significantly expanded the application of Elevidys, the first gene therapy for Duchenne muscular dystrophy (DMD), a progressive and fatal muscle-wasting disease primarily affecting boys. This decision marks a considerable broadening of the therapy's use, although questions about its efficacy remain.

Elevidys, developed by Sarepta Therapeutics, is now available to individuals with DMD who are at least four years old and have mutations in a specific gene, regardless of their ability to walk. The FDA also shifted Elevidys from conditional approval to full approval for ambulatory patients, meaning its availability is no longer dependent on further tests. For non-ambulatory patients, approval is contingent on the results of an ongoing Phase 3 study called Envision.

Peter Marks, head of the FDA's Center for Biologics Evaluation and Research, played a crucial role in the decision. He overruled other FDA reviewers and officials who were concerned about negative data from Elevidys tests and whether the therapy's biological effects would translate into real benefits. Marks concluded that the benefits of Elevidys outweighed the risks.

Previously, in June, Elevidys was approved only for a specific group: boys aged 4 to 5. This group is estimated to be around 400 individuals in the U.S. annually. The recent approval expands the therapy's reach to about 80% of DMD patients, potentially boosting sales for Sarepta, which already has seen cumulative sales of $334 million. However, sales growth has recently plateaued. With a list price of $3.2 million, Elevidys ranks among the world's most expensive medicines.

DMD is a debilitating disease that leads to the gradual loss of muscle function, typically resulting in the inability to walk during teenage years and heart or lung complications by the 30s. There is no cure for DMD, and current treatments such as steroids and exon-skipping drugs only modestly slow the disease's progression. Recently, the FDA approved a non-steroidal pill aimed at delaying muscle loss and reducing inflammation.

Gene therapy, including Elevidys, has been developed in hopes of offering a more effective treatment by halting or even reversing the disease's progression. Elevidys works by helping the body produce a miniature form of the dystrophin protein, which is deficient in DMD patients. Despite producing levels of this protein thought to be beneficial, Elevidys has faced scrutiny due to mixed results from clinical tests and its failure to show significant benefits in a Phase 2 placebo-controlled trial.

In a meeting last year, FDA advisers struggled with the effectiveness of Elevidys and the evidence linking its biological effects to real benefits, narrowly recommending its approval. Marks again had to overrule other reviewers to secure conditional approval, based on the therapy's potential to predict a benefit. This conditional approval remains at risk if an ongoing confirmatory study yields negative results.

The FDA's decision has faced criticism, with some experts arguing that the agency has stretched the definition of surrogate outcomes, which are used to predict clinical benefits. This criticism echoes past controversies over the FDA's accelerated approvals, including for Sarepta's exon-skipping drugs.

Elevidys also comes with safety concerns. Some patients who received the therapy experienced serious side effects, such as liver damage and muscle weakness. Similar gene therapies from Pfizer and Solid Biosciences have faced safety issues, including a recent case where a young boy in a Pfizer trial died of cardiac arrest a year after treatment.

Despite these setbacks, Wall Street analysts remain optimistic about Elevidys, noting that it shows benefits on multiple secondary measures in testing and hasn't faced the same safety issues as other therapies. While not flawless, Elevidys is considered the most promising first-generation gene therapy for DMD currently on or near the market. Other potential therapies from companies like Regenxbio and Solid Biosciences are still years away from possible approval.