Sarepta Gains Complete Approval and Expanded Label for DMD Gene Therapy
Sarepta The FDA announced on Thursday that Sarepta Therapeutics’ gene therapy Elevidys will now be available to Duchenne muscular dystrophy (DMD) patients aged 4 and older, irrespective of their ability to walk. This decision broadens the previous accelerated approval, which was limited to ambulatory patients aged four and five.
In this latest decision, the FDA granted full approval for all patients aged 4 and above with a confirmed DMD gene mutation, while providing accelerated approval for non-ambulatory patients. The continued approval for non-ambulatory patients is dependent on the outcomes of an ongoing Phase III trial.
The FDA highlighted that Sarepta‘s evidence demonstrated a verified clinical benefit. Although the initial study did not meet its primary endpoint, the evaluation of secondary and exploratory endpoints was sufficiently compelling to confirm a clinical benefit.
Sarepta Will Pfizer’s DMD Setback Affect Sarepta’s Pending FDA Decision?
Last week, Pfizer faced a significant setback when its experimental gene therapy for Duchenne muscular dystrophy (DMD), fordadistrogene movaparvovec, failed to show improvement in motor function compared to a placebo in boys aged four to seven during a late-stage trial. This Phase III trial failure for Pfizer comes just days before the FDA’s anticipated June 21 decision on whether to extend the use and grant full approval for a similar treatment from Sarepta Therapeutics, Elevidys, which is currently the only approved gene therapy for DMD.
Despite concerns about Elevidys’ efficacy, analysts predict that the FDA will approve a label expansion and full approval, though the extent of this access remains uncertain. Pfizer’s recent Phase III trial failure echoes the challenges faced by Elevidys, which also did not meet its primary endpoint in a late-stage trial.
In June 2023, the FDA made a controversial decision to grant accelerated approval to Elevidys, marking it as the first gene therapy for Duchenne muscular dystrophy (DMD). This approval currently applies to 4- and 5-year-olds, despite Elevidys not meeting the primary functional endpoint. The decision was based on data indicating that the therapy increased expression of the micro-dystrophin protein, a biomarker deemed “reasonably likely to predict clinical benefit” for DMD patients in this age group who can walk.
Sarepta has now submitted a supplemental Biologics License Application (BLA) to expand Elevidys’ label by removing age and ambulation restrictions, while also seeking to transition from accelerated to traditional approval. This move faces stricter regulatory scrutiny, especially as Sarepta has not released study data for older patients. Nevertheless, analysts consulted by BioSpace remain generally optimistic about Elevidys’ future.
According to Uy Ear, vice president of U.S. healthcare biotechnology at Mizuho Securities, setbacks in one drug’s development do not necessarily delay FDA decisions on others. Despite Pfizer’s recent Phase III trial disappointment with CIFFREO, which did not achieve primary and secondary endpoints like 10-meter run/walk velocity and time to rise from floor velocity, analysts remain optimistic about Sarepta’s prospects. They believe the FDA’s ongoing label negotiation with Sarepta for Elevidys should proceed unaffected by Pfizer’s trial results, although specific data supporting this optimism were not provided.
Kostas Biliouris, director and equity research analyst at BMO Capital Markets, explained to BioSpace that the setback was specific to the drug itself. He noted that Sarepta achieved its crucial secondary goals whereas Pfizer did not. Biliouris suggested that these outcomes increase the pressure on the FDA to approve Elevidys and potentially broaden its approved uses, given its current status as the sole option in the foreseeable future.
Regarding safety, Biliouris emphasized a significant distinction between the two gene therapies. Unlike Elevidys, Pfizer’s fordadistrogene movaparvovec has encountered notable safety issues. Pfizer recently reported a patient death during the Phase II DAYLIGHT DMD study, and in December 2021, the company had to halt screening and dosing in a Phase Ib study due to an unexpected patient death.
Tim Lugo, biotechnology group head at William Blair, highlighted in correspondence with BioSpace that while the FDA evaluates Elevidys based on its efficacy and safety profile, the failure of what was anticipated to be a leading program underscores the importance of regulatory adaptability.
During a recent public advisory committee meeting, concerns were raised about the long-term effectiveness of gene therapies like Elevidys, questioning their “one and done” nature and potential complications in dosing subsequent therapies once Elevidys is on the market. The recent setbacks have prompted discussions about the timeline for future submissions to the FDA. Despite acknowledging Elevidys’ limitations, some argue that expanding its access could stimulate further development of therapies for Duchenne muscular dystrophy (DMD).
In contrast, the failure of Pfizer’s program is seen as advantageous for Sarepta due to the continued high unmet need in the DMD community and the scarcity of treatment options. Elevidys is currently approved for children aged 4 and 5, representing only a small fraction of the DMD population, leaving a significant number without viable treatment options. Estimates suggest approximately 300 to 400 boys are born with DMD annually in the U.S., with a similar number succumbing to the disease each year.
Looking ahead, there is optimism about new gene therapies under development for DMD, though questions remain about their efficacy and duration of benefit. Discussions about Elevidys potentially expanding its market indicate a current patient pool of 300 to 400, with thousands more lacking access, suggesting a substantial market opportunity.
Overall, stakeholders anticipate Elevidys’ approval and potential label expansion to have a profound impact on Sarepta, potentially paving the way for further advancements in DMD treatment.