Eagerly awaiting the FDA's final decision on Sarepta's novel micro-dystrophin gene therapy (SRP-9001, "Elevydis") for Duchenne muscular dystrophy, the medical community and Duchenne patients can finally celebrate the conditional approval of the first gene therapy granted under an accelerated approval pathway. Still, the true efficacy of the drug has yet to be proven in a large scale clinical trial, prompting the FDA to constrain the label until more data becomes available. Regardless, this is a historical event and a clear indication that the FDA has taken a pro-approval stance on gene therapies for rare, intractable diseases.
Sarepta's new gene therapy, marketed under the name "Elevydis", contains the DNA encoding a truncated form of the dystrophin protein, which confers muscle cells their structure and function. Mutations to the dystrophin gene cause non-functional forms to be expressed, resulting in severe muscle weakness and systemic malfunction in predominantly young males (12 years and less). In theory, providing a replacement dystrophin gene could restore muscle function and decrease morbidity and mortality in the ~250,000 patients that suffer in the USA alone.
The FDA deliberations began back in May when the Cellular, Tissue and Gene Therapies Advisory Committee gave a controversial recommendation for approval, voting 8-6 in favor of conditional approval. While not beholden to Advisory Committee (AdComm) recommendations, the FDA typically votes in alignment with their expert opinion. Originally slated for May 29th, the FDA pushed back their decision date by 3 weeks, a sign that the dissent within the approval committee was not easy to resolve.
Approval is not an all-or-nothing phenomenon, and negotiations can be made to ameliorate the concerns that hold up the deliberation process. Concern over the efficacy of the micro-dystrophin variant of the full-length gene combined with safety concerns over the novel viral delivery mechanism were weighed against the potential clinical benefit in a patient population that lacks effective treatment options. Ultimately, the FDA decided on conditional approval for children 4-5 years of age, a subgroup that did show significantly elevated dystrophin levels in Sarepta's open-label clinical study ("Endeavor") of SRP-9001 in 20 participants ages 4-7. Full approval will be contingent on the results of their ongoing double-blind placebo-controlled Phase 3 ("Embark") study of the drug in 120 participants ages 4-7, which will measure a clinically meaningful benefit using the North Star Ambulatory Assessment total score to assess motor function (instead of just micro-dystrophin levels).
“The approval of Elevidys is a watershed moment for the treatment of Duchenne. Elevydis is the first and only gene therapy approved for Duchenne, and this approval brings us closer to our goal of bringing forward a treatment that provides the potential to alter the trajectory of this degenerative disease."
In addition to the Embark confirmatory trial, Sarepta is also launching a large-scale placebo-controlled study ("Envision") to examine Elevydis' efficacy in an older and non-ambulatory patient population.
We note that the SRPT chart shows evidence of a double-top forming recently near the $160 level, and the share price has come under heavy pressure since the FDA deferred its decision on SRP-9001 by one month. It will be critical for SRPT shares to hold the major support level at $120.
Author does not own shares of Sarepta at the time this article was published, but may choose to buy and sell shares in the future.
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