FDA Advisory Committee to Review Sarepta Therapeutics’ Gene Therapy for Duchenne Muscular Dystrophy amid Safety and Efficacy Concerns

Ahead of the upcoming US FDA advisory committee meeting, concerns have been raised about the clinical trials, manufacturing, and preclusive nature of Sarepta Therapeutics' gene therapy for Duchenne muscular dystrophy (DMD).[0] The therapy, known as SRP-9001, is designed to address the underlying cause of DMD through the targeted production of functional components of dystrophin in muscle tissue.[1] DMD is a rare, fatal neuromuscular genetic disease that affects approximately one in every 3,500-5,000 newborn males worldwide.[2] The condition is characterized by a mutation that leads to a lack of dystrophin and muscle loss, resulting in weakness that worsens over time and most patients die by their early 20s.[3]

The FDA released briefing documents raising concerns about the therapy's ability to safely and effectively treat patients.[3] FDA staff reviewers noted that the clinical trial data did not provide clear evidence of clinical benefit and that the gene therapy might pose safety risks, such as liver injury, and that patients who receive it might be ineligible for other clinical trials.[4] The FDA plans to decide whether to approve SRP-9001 by May 29, although the agency is not required to follow its advisory committee's advice, but it often does.[5]

Sarepta presented a complicated mix of results from animal and human studies in support of its application for accelerated approval of SRP-9001.[6] Dr. Craig McDonald from the University of California, Davis, who testified on behalf of the company, said that there is evidence micro-dystrophin levels after treatment are a good measure of its effectiveness, and that Sarepta does have preliminary evidence the treatment is, in fact, helpful.[6] However, critics have raised concerns that confirmatory trials for drugs that have received accelerated approval can take years, and have sometimes been delayed, which results in expensive drugs with uncertain efficacy remaining on the market for years.[7]

The FDA advisory committee will discuss the clinical implications of Sarepta's findings to date, as well as the potential risks, benefits, and uncertainties of accelerated approval of SRP-9001.[1] The panel will vote on whether the benefits and risks support an accelerated approval of SRP-9001 based on microdystrophin expression.[8] The agency is expected to decide by the end of May, and while the FDA is not bound by the recommendations of its outside advisers, it usually follows them.[6]

The decision on SRP-9001 is crucial for the patient community, who are in urgent need of new therapies. DMD is a debilitating and life-threatening disease that affects thousands of boys globally, and there is currently no known cure. With the May 29 action date fast approaching, Sarepta will work collaboratively with the FDA to complete the review of its BLA for SRP-9001.[9]

0. “Sarepta Therapeutics Halted Ahead of FDA Decision” TipRanks, 12 May. 2023, https://www.tipranks.com/news/sarepta-therapeutics-halted-ahead-of-fda-decision

1. “FDA advisory meeting on DMD gene therapy SRP-9001 livestreams May…” Muscular Dystrophy News, 11 May. 2023, https://musculardystrophynews.com/news/fda-advisory-meeting-dmd-gene-therapy-srp-9001-livestreams-may-12/

2. “Sarepta Therapeutics Announces Positive Vote from U.S. FDA Advisory Committee Meeting for SRP-9001 Gene …” ACROFAN USA, 12 May. 2023, https://us.acrofan.com/detail.php?number=826558

3. “FDA Briefing Documents Question Safety, Efficacy of Sarepta’s DMD Gene Therapy” BioSpace, 10 May. 2023, https://www.biospace.com/article/fda-briefing-documents-question-safety-efficacy-of-sarepta-s-dmd-gene-therapy/

4. “FDA Staff Raises Issues For Sarepta's Duchenne Gene Therapy Data, Analyst Says Issues Known, Expects Positive …” Investing.com UK, 10 May. 2023, https://uk.investing.com/news/stock-market-news/fda-staff-raises-issues-for-sareptas-duchenne-gene-therapy-data-analyst-says-issues-known-expects-positive-vote-3016036

5. “Sarepta's Duchenne Gene Therapy Does Not Have ‘Unambiguous Evidence,' FDA Staff Says” Medpage Today, 10 May. 2023, https://www.medpagetoday.com/neurology/generalneurology/104449

6. “FDA advisers narrowly back first gene therapy for muscular dystrophy” WUSF Public Media, 12 May. 2023, https://wusfnews.wusf.usf.edu/2023-05-12/fda-advisers-narrowly-back-first-gene-therapy-for-muscular-dystrophy

7. “FDA's ‘accelerated approval' pathway for drugs is important but imperfect” Washington Examiner, 3 May. 2023, https://www.washingtonexaminer.com/opinion/fda-approval-pathway-for-drugs-important-but-imperfect

8. “FDA Panel Votes in Favor of Gene Therapy SRP-9001 for Duchenne Muscular Dystrophy In Tight Decision” Neurology Live, 12 May. 2023, https://www.neurologylive.com/view/fda-panel-votes-in-favor-of-gene-therapy-srp-9001-for-duchenne-muscular-dystrophy

9. “FDA advisers narrowly back accelerated approval of Sarepta gene therapy” MarketWatch, 12 May. 2023, https://www.marketwatch.com/story/fda-advisers-narrowly-back-accelerated-approval-of-sarepta-gene-therapy-501badb9

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