FDA Approves Sarepta’s DMD Gene Therapy Elevidys for Expanded Indication

Fact checked by" Matt Hoffman

The gene therapy is now indicated for ambulatory patients aged 4 years and older, and has been granted accelerated approval for nonambulatory patients.

Dough Ingram, president and chief executive officer, Sarepta

Doug Ingram

This is a developing story and will be updated with new information as it becomes available.

The FDA has approved Sarepta Therapeutics’ delandistrogene moxeparvovec-rokl (marketed as Elevidys), an adeno-associated virus (AAV) vector-based gene therapy for patients with Duchenne muscular dystrophy (DMD), for an expanded indication in the disease.1 The therapy is now approved for ambulatory patients (via traditional approval) and nonambulatory patients (via accelerated approval) with a confirmed mutation in the DMD gene who are 4 years of age or older and who do not have any deletion in exon 8 or exon 9 in the gene.

“Representing many years of dedicated research, development, investment and creative energy, the expansion of the Elevidys label to treat Duchenne patients aged 4 and above, regardless of ambulatory status, is a defining moment for the Duchenne community," "Today also stands as a watershed occasion for the promise of gene therapy and a win for science,” Doug Ingram, JD, the president and chief executive officer of Sarepta, said in a statement.1 “At this pivotal moment, I want to give warm thanks to Drs. Jerry Mendell and Louise Rodino-Klapac for their dogged, 20-year pursuit of a gene therapy to treat this ruthless and life-robbing disease, to the FDA for following the scientific evidence to speed delivery of a therapy for a life-threatening rare disease to waiting patients, and to the many clinical investigators and courageous Duchenne families who have participated in the multiple studies that led to this important day.”

Elevidys was originally granted FDA approval under an accelerated approval pathway for a more limited indication on June 22, 2023.2 That original decision limited the therapy's use to 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. Today's decision, which was based on the agency's confirmation of functional benefits, additionally converts the accelerated approval to a traditional approval for patients who are ambulatory. Although it also expands eligibility to nonambulatory patients, the therapy remains under an accelerated approval for patients who are nonambulatory.1 Sarepta noted that ongoing approval for patients who are nonambulatory may depend on the results of ENVISION (Study SRP-9001-303), a phase 3 confirmatory clinical trial evaluating the gene therapy in patients with DMD who are nonambulatory or older and ambulatory.

“Today’s expansion of the Elevidys label represents the culmination of my 50-year pursuit of a treatment for Duchenne patients and, along with my colleague Dr. Louise Rodino-Klapac, a nearly 20-year effort to optimize and develop a gene therapy that could be safely and effectively delivered to muscle,” Jerry Mendell, MD, the coinventor of Elevidys and the senior advisor for Medical Affairs at Sarepta added to the statement.1 “The initial approval of Elevidys was a significant milestone, and the expanded indication means clinicians now have a treatment option for the great majority of boys and young men living with Duchenne. This expansion speaks to the success of the science, the evidence, and the improvements in the trajectory of the disease we have seen to date across studies.”

Elevidy's original approval in 2023 was based upon data from the phase 1/2 SRP-9001-101 (NCT03375164) study, the phase 2 SRP-9001-102 study, and the phase 1 ENDEAVOR study (SRP-9001-103; NCT04626674).2 Changes in expression of microdystrophin, a surrogate end point, informed the approval. Furthermore, in the 20-patient cohort 1 of ENDEAVOR, announced in July 2022, findings showed that SRP-9001-treated patients improved 4 points from their pre-therapy baselines on the North Star Ambulatory Assessment (NSAA) compared with a propensity-weighted external control group (P < .0001) over 1 year.3 These patients demonstrated a 3.8-point (unadjusted means) and 3.2-point (least squared means) improvement that diverged from the natural history of DMD over time.

More recently, results from EMBARK, another phase 3 clinical trial (NCT05096221) evaluating Elevidys in DMD, were presented at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, Maryland, by Damon Asher, MS, PhD, senior director of global medical affairs at Sarepta Therapeutics.4 Notably, EMBARK failed its primary end point. However, key secondary endpoints of change in time to rise (TTR) and time to walk/run 10 meters (10MWR) had small but significant differences from placebo, with a least square mean (LSM) difference of -.64 seconds (standard error [SE], 0.21; P = .0025) on TTR and an LSM of -0.42 seconds (SE, 0.15; P = .0048) on 10MWR.5 A composite, prespecified global statistical test including NSAA, TTR, 10MWR, Stride Velocity 95th Centile, 100MWR, and ascend 4 steps test was statistically significant compared with placebo (P = .0044).4

“What's really going to tell the story is as these patients are followed over longer periods of time," Asher told CGTLive® during the conference. "There’s a lot of challenges in showing efficacy, even with something that may be fairly efficacious, over such a short period of time."

1.Sarepta Therapeutics Announces Expanded US FDA Approval of ELEVIDYS to Duchenne Muscular Dystrophy Patients Ages 4 and Above. News release. Sarepta Therapeutics, Inc. June 20, 2024. Accessed June 20, 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 June 20, 2024. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-fda-approval-elevidys-first-gene
3. Sarepta Therapeutics’ investigational gene therapy SRP-9001 for Duchenne muscular dystrophy demonstrates significant functional improvements across multiple studies. News release. Sarepta Therapeutics, Inc. July 6, 2022. Accessed June 20, 2024. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-investigational-gene-therapy-srp-9001
4. Mendell JR, Muntoni F, McDonald CM, et al. Safety and efficacy of delandistrogene moxeparvovec versus placebo in Duchenne muscular dystrophy: Phase 3 EMBARK primary results. Presented at: ASGCT 27th Annual Meeting, May 7-10; Baltimore, Maryland.
5. 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. Accessed June 20, 2024. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-announces-topline-results-embark-global-0

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