Despite the FDA review teams initially leaning against approving Sarepta’s Duchenne muscular dystrophy (DMD) gene therapy, a memo reveals that Peter Marks, M.D., Ph.D., who is responsible for overseeing the agency’s gene therapy review, disagreed with the staff’s interpretations. As a result, Sarepta’s Elevidys, a DMD gene therapy with a price tag of $3.2 million, received long-awaited accelerated approval on Friday, albeit for a limited patient population.
Internal documents reveal that the FDA’s review teams were leaning towards rejecting Sarepta’s gene therapy for Duchenne muscular dystrophy (DMD). However, Peter Marks, M.D., Ph.D., who oversees the agency’s gene therapy review process, disagreed with the staff’s interpretations, as shown in a memo.
Sarepta’s highly anticipated gene therapy for Duchenne muscular dystrophy, called Elevidys, has finally received accelerated approval, but with restrictions on the patient population.
As the director of the FDA’s Center for Biologics Evaluation and Research (CBER), Marks concurred with the review teams’ assessment of Elevidys’ product quality and safety. However, he differed in his interpretation of the efficacy data, specifically in the 4 to 5 years old group, as stated in a memo.
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In April, it was reported that Marks became aware of the internal objections and intervened. Instead of making an immediate decision, Marks sought external input by organizing an advisory committee meeting, according to Stat. During the meeting in May, experts voted 8 to 6 in favor of granting accelerated approval to Elevidys, also known as SRP-9001.
Marks carefully examined reviews and recommendations on the drug from various FDA branches, including the Office of Therapeutic Products (OTP) and the Office of Compliance and Biologics Quality (OCBQ), among others, before reaching his decision.
The director concluded that the data provided by Sarepta in its application demonstrated “substantial evidence of effectiveness.” He highlighted an exploratory analysis that revealed a significant improvement on the North Star Ambulatory Assessment (NSAA) scale, a measure of functional skills, in the Elevidys group compared to the placebo group in the 4-5 age group.
Although the sample size for that specific data was small, Marks argued that the positive outcome on the NSAA scale aligns with the expression of micro-dystrophin protein in Elevidys. Considering the high unmet need in DMD and the compelling evidence, Marks determined that the therapy meets the criteria for accelerated approval in the specified age group.
However, Marks acknowledged that the data in the 6-7 years old group suggested the possibility of decreased effectiveness. He attributed this to the natural progression of the disease after age 6. This further justified the approval in the younger age group to ensure that patients do not miss the window of opportunity for the clinical benefits of the treatment.
“In light of the unmet medical need, the severity of the disease, and its progressive and irreversible nature that begins in early childhood, it is reasonable to accept some level of uncertainty regarding effectiveness.”
The effectiveness of the therapy has been a subject of extensive debate, with even advisors who voted in favor of approval expressing concerns about the strength of the clinical evidence, as noted by the director. Prior to the advisory meeting, the FDA expressed hesitations in its briefing documents, stating that the studies did not provide clear evidence that the treatment was likely beneficial for the specific patient population.
