FDA Approves SRP-9001 as First Gene Therapy for Duchenne Muscular Dystrophy

NeurologyLiveAugust 2023
Volume 6
Issue 4

Marketed as Elevidys, the gene therapy is approved for ambulatory pediatric patients aged 4 to 5 with Duchenne based on expression of micro-dystrophin.

Jerry Mendell, MD, pediatric neurologist and principal investigator in the Center for Gene Therapy at Nationwide Children's Hospital

Jerry Mendell, MD

The FDA has approved Sarepta Therapeutics’ investigational gene therapy SRP-9001, otherwise known as delandistrogene moxeparvovec, for the treatment of ambulatory patients with Duchenne muscular dystrophy (DMD) with a confirmed mutation in the DMD gene. Marketed as Elevidys, it becomes the first approved gene therapy for DMD, a neuromuscular condition that causes progressive weakness and loss of skeletal and heart muscles.1

An AAV vector-based gene therapy, SRP-9001's indication is for ambulatory pediatric patients aged 4 to 5 years with DMD. The therapy is contraindicated for patients with any deletion in exon 8 and/or exon 9 in the DMD gene. Approved under the accelerated approval pathway, Sarepta will continue to reinforce the agent’s efficacy in the ongoing phase 3 EMBARK study (NCT05096221), which is set to complete in late 2023 and have data read out in early 2024.

"Duchenne is a relentlessly progressive, degenerative disease, robbing children of muscle function," Jerry Mendell, MD, pediatric neurologist and principal investigator in the Center for Gene Therapy at Nationwide Children's Hospital, said in a statement.1 "The increases in Elevidys dystrophin expression and the functional results that we see can make a difference in the lives of our patients."

In its release, the FDA concluded that an increase in the surrogate end point—expression of microdystrophin—is reasonably likely to predict clinical benefit in individuals 4 to 5 years of age with DMD who do not have significant pre-existing antibody titers against the AAVrh74 vector or have other contraindications based on the inclusion criteria of the clinical trials.

The decision came months after the FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee voted that the current data on the agent was sufficient enough to warrant approval.2 The committee answered on 4 discussion topics, the first of which asked whether the agent’s impact on microdystrophin, considered a surrogate biomarker, would be reasonably likely to predict clinical benefit. In the hearing, panelists weighed in on data from the biologics license application of SRP-9001, which was comprised of 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).

Study 101 was the first-in-human study, featuring 4 ambulatory individuals with DMD aged 4 to 7 years old. Study 102, the only double-blind, placebo-controlled study used to support SRP-9001, was a crossover trial that included 41 individuals aged 4 to 7 years old. Part 1 of the crossover study, a 48-week period, assessed 3 different doses while Part 2, an additional 48 weeks, acted as a functional open-label period. Study 103 had the most diverse patient population, with 20 ambulatory individuals aged 4 to 7 years old, 7 ambulatory patients aged 8 to 17, 6 nonambulatory patients, and 7 ambulatory patients aged between 3 and 4 years old.

Based on available data, do you agree with the FDA's decision to limit Elevidys's indication to those aged 4 to 5 years?


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 NSAA compared with a propensity-weighted external control group (P <.0001) over a 1-year period. 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.3

Announced at the same time, longer follow-up data from 4 patients in Study 101 demonstrated a 7-point improvement above pretreatment baselines on the NSAA, a 9.9-point unadjusted means and a 9.4-point least squared means vs a propensity weighted external control (P = .0125) at 4 years. An integrated analysis of 52 patients across all 3 studies also showed that at 1 year, patients treated with the gene therapy at the target dose improved 3.1 points (unadjusted means) and 2.4 points (least squared means) on NSAA versus propensity-weighted external controls (P <.0001).

"The approval of Elevidys is a watershed moment for the treatment of Duchenne. Elevidys is the first and only gene therapy approved for Duchenne, and this approval brings us closer to our goal of bringing forward a treatment that provides the potential to alter the trajectory of this degenerative disease," Doug Ingram, president and chief executive officer of Sarepta, said in a statement.1 "As we prepare to launch Elevidys, we should acknowledge and celebrate the decades of dedication and work from the patient community, families, clinicians, and our Sarepta colleagues that resulted in today’s approval. Our confirmatory trial, EMBARK, should read out in the fourth quarter of this year. If EMBARK confirms the benefits seen in our prior trials, Sarepta will move rapidly to submit a BLA supplement to expand the approved label as broadly as good science permits."

In recent years, the treatment landscape for DMD has grown exponentially. In 2016, the FDA approved eteplirsen (Exondys 51; Sarepta), a treatment for patients amenable to exon 51 skipping, as the first approved therapy for the disease. Since then, there have been 4 other approvals, including 2 agents—viltolarsen (Viltepso; NS Pharma) and golodirsen (Vyondys; Sarepta)—that are indicated for patients with a confirmed mutation amenable to exon 53 skipping. Deflazacort (Emflaza; PTC Therapeutics), a derivative of prednisone, was approved for DMD in patients 2 years of age and older in 2017 as well. The most recent approval came in 2021, with the FDA greenlighting Sarepta’s casimersen (Amondys 45), an antisense oligonucleotide, for patients amenable to skipping exon 45.

Shortly after the decision, Natalie Goedeker, CPNP, a nurse practitioner in neurology in the Neuromuscular Division at Washington University in St Louis, who presented Delphi panel recommendations for the management of the adverse events associated with therapy at the 2023 Muscular Dystrophy Association Clinical and Scientific Conference, spoke with NeurologyLive® for a special episode of the Mind Moments podcast about the approval. Check out her insight from the episode below.


1. Sarepta Therapeutics announces FDA approval of Elevidys, the first gene therapy to treat Duchenne muscular dystrophy. News release. June 22, 2023. Accessed June 22, 2023. https://www.businesswire.com/news/home/20230622454844/en/
2. FDA Peripheral and Central Nervous System Drugs Advisory Committee Meeting. May 12, 2023. Accessed May , 2023.
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 2023 https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-investigational-gene-therapy-srp-9001
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