A narrow FDA AdComm vote in favor of accelerated approval for Sarepta’s first-in-class gene transfer therapy illustrates challenges faced by regulators, payers and developers as a wave of innovative genetic treatments for rare diseases comes to market.
A U.S. Food and Drug Administration advisory committee’s narrow 8-6 vote in favor of recommending accelerated approval for a first-in-class gene transfer therapy was welcomed by Duchenne muscular dystrophy (DMD) patients and caregivers. The vote shows a regulatory agency grappling with the question of how to evaluate truly novel therapeutics for rare diseases where longitudinal data are not available.
“In recent years, FDA has increasingly shown an openness to surrogate endpoints as the basis for approval of a therapy,” said Bethany Kiernan, Director of Healthcare Research Analytics for Infectious, Niche and Rare Diseases at Clarivate. “The fact that the committee said, albeit not overwhelmingly, that efficacy data from Sarepta’s surrogate endpoint was good enough to support accelerated approval is interesting and very positive, especially for a disease like muscular dystrophy where there remains such high unmet need.”
For payers, however, the vote in favor of Sarepta Therapeutics’ SRP-9001 added urgency to the task of shoring up value assessment and utilization management practices. Payers in the United States are increasingly incorporating health economics outcomes research into their decision-making, inking outcomes-based contracts with manufacturers and, for DMD therapeutics, weighing the value of single versus chronic treatment for the disease, as the recent Clarivate report Five key trends in gene therapy approvals and access found.
An earlier Sarepta DMD drug, the antisense oligonucleotide (ASO) treatment EXONDYS 51, was priced at $300,000 a year for the average patient when it won FDA approval in 2016. The rare and inexorably fatal muscle wasting disease affects approximately one in every 3,500-5,000 newborn males worldwide, with symptoms typically first appearing in infants and toddlers. Most patients must use a wheelchair by the time they are in their teens.
Weighing unmet need against cost
Sarepta’s modest pricing of EXONDYS 51 surprised Wall Street – analysts had anticipated a higher sticker price for the injectable. With 11 gene therapies already approved payers are bracing for impact as Cortellis Competitive Intelligence™ data identifies another 30 in late-stage pipelines.
Unlike EXONDYS 51 and Sarepta’s two other ASOs, which target specific mutations on the dystrophin gene and require repeated treatments, SRP-9001 can be administered to patients with a broader range of mutations and is delivered in a single dose. It is also currently being tested for ambulatory patients, typically pre-teens who have not yet lost a lot of muscle function. A March 2022 Access & Reimbursement study by Clarivate found that many Managed Care Organization executives remain uncertain about covering these emerging DMD treatments, making collection of real world evidence a critical factor in securing access for patients. Payers are also eyeing a variety of stringent utilization management measures to prevent unnecessary care and rein in costs.
“With gene therapies, like any specialized treatment, payers are going to be very stringent in making sure patients meet the criteria for treatment, given the cost they’re carrying,” said Kiernan. “However, because this is a genetic condition and there’s a definitive diagnosis, hopefully that means the process will be relatively straightforward for patients and physicians.”
Prior authorizations are a top concern for neurologists when it comes to prescribing these next generation DMD gene treatments, as highlighted in the Access & Reimbursement survey, followed by excessive out-of-pocket costs, restrictions to the most severe cases and reauthorization roadblocks. Given the progressive nature of the disease, time-to-treatment will be of the essence for this wave of DMD therapeutics, should they win marketing approval. (Pfizer and Solid Biosciences have candidates in late-stage development too).
“With muscular dystrophy, genetic testing and other established diagnostic tests means that kids are often identified early on,” said Kiernan. “The Muscular Dystrophy Association and parents are very vocal and from the access side, there will be a push to accelerate that process as much as possible.”
To learn more about the challenges faced by payers, regulators and biopharmas working to bring safe and effective gene therapeutics to patients, please read the Clarivate report, Five key trends in gene therapy approval and access.