FDA Pushes Back Decision Date for Duchenne Gene Therapy SRP-9001


Submitted under the accelerated approval pathway, if approved, SRP-9001 would become the first marketed gene therapy specific for Duchenne muscular dystrophy.

In a company update, Sarepta Therapeutics announced that the FDA has informed it will need additional time to complete the review of SRP-9001, a gene therapy in development for Duchenne muscular dystrophy (DMD). It anticipates that the review will be complete by June 22, 2023.1

Sarepta noted in its announcement that the agency has indicated that it is working toward potentially granting an accelerated approval for SRP-9001, using the phase 3 EMBARK study (NCT05096221) as a confirmatory trial. If approved, the therapy would become the first gene therapy on the market for DMD, with an indication for patients between 4 and 5 years old; however, the FDA may entertain a non-age-restricted expansion of the SRP-9001 label if EMBARK meets its objectives.

EMBARK is set to complete later this year and have data read out in the fourth quarter of 2023. This phase 3, randomized, double-blind, 2-part, placebo-controlled study assesses SRP-9001 in ambulatory individuals with a confirmed DMD mutation within exons 18-79, aged 4 to 7 years. In part 1, patients will be stratified by age at randomization and North Star Ambulatory Assessment (NSAA) total score at screening and randomized to receive SRP-9001 or placebo for a 52-week stretch. In part 2, a 52-week follow-up period, patients in both groups will crossover to receive the opposite treatment to what was previously given in part 1.

SRP-9001, or delandistrogene moxeparvovec, is an AAV vector-based gene therapy designed to address the underlying cause of DMD through the targeted production of functional components of dystrophin in muscle tissue. The agent’s biologics license application (BLA) was supported by several studies, including the phase 1/2 SRP-9001-101 (NCT03375164), the phase 2 SRP-9001-102 study, and the phase 1 ENDEAVOR study (SRP-9001-103; NCT04626674).2

READ MORE: Potential Path for Phase 3 Study of AOC 1001 in Myotonic Dystrophy Becomes Clear After FDA Ease’s Clinical Hold

In early May, the FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee voted that the current data on SRP-9001 was sufficient enough to warrant approval. Voting 8­–6 (8 Yes; 6 No; 0 Abstain) in favor of the agent, the panel was asked whether SRP-9001 was deserving of accelerated approval, while considering the benefits and risks of the treatment, and using micro-dystrophin expression at week 12 as a surrogate biomarker.3

The committee answered on 4 discussion topics, the first of which asked whether SRP-9001’s impact on microdystrophin, considered a surrogate biomarker, would be reasonably likely to predict clinical benefit. In the second discussion topic, those on the committee commented on the clinical significance of SRP-9001’s impact on certain exploratory subgroups, specifically patients between 4 and 5 years old in Study 102 (NCT03769116), the only randomized, double-blind, placebo-controlled study used to support the therapy. In the final topic, members of the committee discussed the potential benefits, risks, and uncertainties that may be associated with the administration of SRP-9001 in ambulatory patients with DMD with a confirmed mutation in the DMD gene.

As gene therapies are new to neurology, the FDA also brought up safety concerns, and the potential cross–reactivity to future gene therapies. To address some of these issues, Sarepta proposed several risk mitigations, including pre- and post-infusion monitoring of liver enzymes, weekly troponin monitoring during the first month of treatment, weekly platelet monitoring during the first 2 weeks, and long-term follow-up to better characterize safety concerns.

1. Sarepta Therapeutics announces update on regulatory review of SRP-9001. News release. May 24, 2023. Accessed May 24, 2023. https://www.businesswire.com/news/home/20230523006142/en/Sarepta-Therapeutics-Announces-Update-on-Regulatory-Review-of-SRP-9001#:~:text=New%20regulatory%20action%20date%20is%20June%2022%2C%202023&text=Following%20discussions%20with%20FDA%2C%20the,ages%204%2D5%20years%20old.
2. Sarepta Therapeutics announces that U.S. FDA has accepted for filing and granted priority review for the biologics license application for SRP-9001, Sarepta’s gene therapy for the treatment of ambulant individuals with Duchenne muscular dystrophy. News reelase Sarepta Therapeutics. November 28, 2022. May 24, 2023 https://www.globenewswire.com/news-release/2022/11/28/2563009/0/en/Sarepta-Therapeutics-Announces-That-U-S-FDA-has-Accepted-for-Filing-and-Granted-Priority-Review-for-the-Biologics-License-Application-for-SRP-9001-Sarepta-s-Gene-Therapy-for-the-Tr.html
3. FDA Peripheral and Central Nervous System Drugs Advisory Committee Meeting. May 12, 2023. Accessed May 12, 2023.
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