The investigational gene therapy, also known as SRP-9001, was recently backed by the agency’s advisory committee in a tight decision. Its new deadline for review is June 22, 2023.
The FDA has informed Sarepta Therapeutics that it needs more time to review the biologics license application (BLA) for the company’s investigational gene therapy delandistrogene moxeparvovec (also known as SRP-9001) for the treatment of ambulant individuals with Duchenne muscular dystrophy (DMD), according to a company announcement.1 The agency was originally set to review the BLA by May 29, but the need for final label negotiations and postmarketing commitment discussions has pushed the review completion deadline to June 22, 2023.
The company noted in its announcement that it “will remain in a quiet period for the duration of the BLA review.” The decision was made after conversations with the FDA, which has indicated it is working toward potentially granting an accelerated approval for SRP-9001, initially for use in patients aged 4 to 5 years old. If approved, delandistrogene moxeparvovec would be the first gene therapy indicated for DMD.
This decision to push the review follows the recent Cellular, Tissue, and Gene Therapies Advisory Committee (AdComm) meeting that voted—after a back-and-forth discussion—in favor of the therapy’s approval for this indication.2 The committee vote included 8 members voting yes and 6 voting no to the question: Do the overall considerations of benefit and risk, taking into account the existing uncertainties, support Accelerated Approval of SRP-9001—using as a surrogate end point, expression of Sarepta’s microdystrophin at Week 12 after administration of SRP-9001—for the treatment of ambulatory patients with Duchenne muscular dystrophy with a confirmed mutation in the DMD gene?
The BLA is supported by data from the phase 3 EMBARK clinical trial (NCT05096221)—a global, randomized, double-blind, placebo-controlled study. The FDA has noted that it may consider a non–age-restricted expansion of the therapy’s label if EMBARK ultimately meets its objectives. EMBARK is currently expected to be completed later in 2023, with data read out in Q4.
READ MORE: High Dose Fordadistrogene Movaparvovec Improves NSAA, Muscle Volume in Patients With DMD
The trial includes ambulatory individuals with a confirmed DMD mutation within exons 18-79, aged 4 to 7 years. In the first part, patients will be stratified by age at randomization and North Star Ambulatory Assessment (NSAA) total score at screening and then randomly assigned to receive study drug or placebo for 52 weeks. In the second part of the study, patients in both groups will crossover to receive the opposite treatment to what was previously given in part 1 for a 52-week follow-up period.
In addition to EMBARK, results from part 1 of the phase 2 SRP-9001-102 study (Study 102; NCT03769116) also show the therapy’s potential, though the data from the trial showed statistically significant only benefit in subgroups of patients aged 4 to 5 years and not in those aged 6 to 7 years. The AdComm meeting discussed this topic earlier this month, and Sarepta representatives addressed the stratified age results and attributed them to the placebo group not being well matched to the treatment group in the 6- to 7-year-old subgroup in terms of NSAA score. The company noted it is aiming to address these challenges in EMBARK. In Study 102, clinical benefit was deemed clear in both groups when compared with external controls. Additionally, in the phase 1/2 Study 101 (NCT03375164), and the phase 1 ENDEAVOR study (Study 103; NCT04626674), SRP-9001 was deemed well tolerated and yielded clinical improvements and biomarker expression after 1, 2, and 4 years of treatment.3
The AdComm meeting this month itself was the first change of plans for Sarepta, as the company had announced earlier in the year that the agency would not require one, prior to flipping its stance in March 2023. Part of the FDA’s turnaround may be attributed to the degree of discussion on microdystrophin as a surrogate end point late last year and early this year. One portion of the discussion was informed by the Pathway Development Consortium’s paper published in Human Gene Therapy that reviewed and advocated for microdystrophin’s use and the suitability of the accelerated approval pathway.4