Sarepta Therapeutics has secured full FDA approval for Elevidys, a gene therapy targeting Duchenne muscular dystrophy (DMD), expanding its availability to all patients aged 4 and older with a confirmed mutation in the DMD gene. This decision arrives on the heels of a setback for Pfizer, whose experimental DMD gene therapy, fordadistrogene movaparvovec, failed to meet its primary endpoint in a Phase III trial. The FDA's decision marks a significant milestone for DMD patients, offering a potentially transformative treatment option for a broader population.
Regulatory Path and Clinical Evidence
The FDA's decision includes full approval for ambulatory patients and accelerated approval for non-ambulatory patients, the latter being contingent upon the results of an ongoing Phase III study. The agency stated that the clinical benefit of Elevidys had been verified based on the evidence provided by Sarepta. Despite the original study missing its primary endpoint, the review of secondary and exploratory endpoints was compelling enough to demonstrate a clinical benefit.
In June 2023, Elevidys received accelerated approval for 4- and 5-year-olds, even though it had missed its primary functional endpoint. This initial approval was based on data showing increased expression of the micro-dystrophin protein, a biomarker deemed reasonably likely to predict clinical benefit in young, ambulatory DMD patients.
Market Impact and Unmet Need
The expanded approval addresses a significant unmet need in the DMD community. The previous label limited Elevidys to a small fraction (approximately 3%) of the total DMD population. With the new label, a much larger patient group now has access to this gene therapy. Experts estimate that around 300 to 400 boys are born with DMD each year in the U.S., and the disease claims approximately 400 lives annually.
Kostas Biliouris, director and equity research analyst at BMO Capital Markets, noted that Pfizer's failure puts pressure on the FDA to approve Elevidys and expand its label, given the limited treatment options available. Tim Lugo, the group head for biotechnology at William Blair, added that the failure of a potential "next-in-line" program highlights the need for flexibility in regulatory decisions.
Financial Implications and Future Prospects
Analysts predict substantial market potential for Elevidys. Sarepta has estimated peak sales of $4 billion. Biliouris' model, focusing on the population aged four through seven years, estimates peak revenues reaching around $3 billion, assuming Sarepta reaches about 50% of the addressable population. The total market value for DMD in the U.S. is estimated to be around $30 billion, considering the premium pricing for Elevidys.
Uy Ear, vice president of U.S. healthcare biotechnology at Mizuho Securities, emphasized the need for more potent treatments and a better understanding of the long-term benefits of gene therapies for DMD. While the statistical significance of functional endpoint improvements is evident, the magnitude of these differences warrants further investigation.
The full approval and label expansion for Elevidys are expected to significantly impact Sarepta and drive further innovation in DMD therapies.
