Sarepta’s Bid for Expanded Indication for DMD Gene Therapy Elevidys Now Under Priority Review by the FDA

The FDA has granted priority review to Sarepta Therapeutics’ efficacy supplement to its biologics license application (BLA) for delandistrogene moxeparvovec (marketed as Elevidys), a gene therapy for patients with Duchenne muscular dystrophy (DMD).¹ The Prescription Drug User Fee Act date for the FDA’s decision on the supplement has been set for June 21, 2024.

Via the efficacy supplement, Sarepta is seeking to remove requirements related to age and ambulatory-status from the indication for Elevidys. Currently, the gene therapy is approved for use in ambulatory patients aged 4 through 5 years with DMD and a confirmed mutation in the DMD gene, excluding patients with any deletion in exon 8 and/or exon 9.² Furthermore, the company is aiming to convert Elevidys’s status as an accelerated approval product to a traditional approval product with the efficacy supplement.¹ Sarepta noted that the FDA gave confirmation that it is not planning to hold an advisory committee meeting related to the efficacy supplement.

"We are pleased to announce that FDA has accepted and filed Sarepta’s efficacy supplement to evaluate broadening the approved indication of Elevidys by removing age and ambulation restrictions and converting the approval from accelerated to traditional,” Doug Ingram, JD, the president and chief executive officer of Sarepta, said in a statement.¹ “We are particularly grateful for the Division’s prompt engagement and commitment to expediency by granting priority review and setting a June 21 review goal date. Understanding that every day matters to families living with Duchenne, we will work with our regulatory counterparts to successfully complete this review as rapidly as possible."

Elevidys was originally granted FDA approval for its current indication on June 22, 2023.² The decision was primarily based upon data from the SRP-9001-102 (NCT03769116) and SRP-9001-103 (ENDEAVOR; NCT04626674) clinical trials.¹ Meanwhile, the global, randomized, double-blind, placebo-controlled phase 3 EMBARK clinical trial (NCT05096221) is generating postmarketing data.

Sarepta has previously noted that it would consider seeking a non–age-restricted expansion of the therapy’s label if EMBARK ultimately meets its objectives.² In October 2023, the company announced topline results from EMBARK showing that it had failed its primary end point of statistically significant change in North Star Ambulatory Assessment (NSAA) scores at week 52 compared to placebo.³ Treated patients improved 2.6 points on NSAA total score compared to 1.9 points in placebo-treated patients for a 0.65-point difference (n = 125; P =. 24). Although, key secondary end points of change in time to rise (TTR) and 10-meter walk test (10MWT) compared to placebo were statistically significant across all age groups.

“First of all, every EMBARK measure favors this therapy Elevidys,” Ingram said during a conference call on the data. “Every key secondary end point is strongly statistically significant, as are all of the age subgroup analyses in the key secondary end points, even though they were not in fact powered to be statistically significant. Across all of the end points that most powerfully predict loss of ambulation (TTR, 10MWT, 4-stair climb), Elevidys is powerfully statistically significant. On the issue of clinical meaningfulness, literature notes arise time that slows beyond 5 seconds is the single most predictive metric for early loss of ambulation and Elevidys reduces those odds by literally over 90%. While we did not hit statistical significance on NSAA, it is clear, you can look at the curves and see it, this is because NSAA was simply not as sensitive as the various time tests and indeed, too insensitive to pick up a decline in the 6-7-year-old age group in 52 weeks and every other timed metric detected in these degenerating boys.”

REFERENCES
1. Sarepta therapeutics announces U.S. FDA acceptance of an efficacy supplement to expand the Elevidys indication. News release. Sarepta Therapeutics, Inc. February 16, 2024. Accessed February 16, 2024.https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-us-fda-acceptance-efficacy?_ga=2.242068545.254033713.1708093077-1826905377.1708093076
2. Sarepta Therapeutics Announces FDA Approval of ELEVIDYS, the First Gene Therapy to Treat Duchenne Muscular Dystrophy. News release. Sarepta Therapeutics. June 22, 2023. Accessed February 16, 2024. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-fda-approval-elevidys-first-gene
3. Sarepta Therapeutics announces topline results from EMBARK, a global pivotal study of ELEVIDYS gene therapy for Duchenne muscular dystrophy. News release. Sarepta Therapeutics. October 30, 2023. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-topline-results-embark-global-0