FDA grants accelerated approval for SRP-9001 as the first ever gene therapy for Duchenne muscular dystrophy

On 22nd June, 2023, the U.S Food and Drug Administration (FDA) granted accelerated approval to Sarepta Therapeutics’ SRP-9001 (ELEVIDYS, delandistrogene moxeparvovec-rokl) for the treatment of ambulatory pediatric patients aged 4 to 5 years with Duchenne muscular dystrophy (DMD), with a confirmed mutation in the DMD gene. It is the first disease-modifying gene therapy for DMD to be authorized for commercial use.1

DMD is an X-linked, progressive, neuromuscular disease caused by mutations in the DMD gene that disrupts the production of functional dystrophin, an essential protein in muscles.2,3,4 Deficiency of dystrophin leads to the disruption of the dystrophin-associated protein complex (DAPC), which is required to stabilize muscle cell membranes during muscle contraction and prevent damage to muscle fibers.3,4 Without functional dystrophin and DAPC, muscle fibers are prone to injury and develop fibrosis, causing progressive muscle degeneration and loss of function.3,4 Most patients become wheelchair dependent and require respiratory support; eventually, death can occur from cardiac or respiratory failure.3,4

Management of DMD remains challenging due to limited treatment options and no available cure.2,3,4 Symptoms can only be managed through a multidisciplinary medical and rehabilitative approach to improve quality of life and longevity.4 Assisted ventilation and mobility assistance are commonly provided to patients as their disease progresses.4 Angiotensin-converting enzyme (ACE) inhibitors and beta-blockers can be given to manage the cardiac manifestations of DMD.4 The use of glucocorticosteroids is recommended when motor development begins to decline, which requires continuous treatment.3,4 Orthopedic interventions involving physiotherapy focus on preserving weakened muscle function and to prevent the development of limb muscle contractures and scoliosis.4 Given the causative nature of mutations in DMD, the promise of gene therapy as a disease modifying approach has been under significant investigation in recent years.

SRP-9001 (ELEVIDYS, delandistrogene moxeparvovec-rokl) is an adeno-associated virus (AAV)-based gene therapy.1,2 It uses an AAV serotype rh74 (AAVrh74) vector to deliver a gene that encodes for a shortened form of dystrophin called micro-dystrophin, under the control of a muscle-specific promotor, MHCK7, to enhance specificity and expression in the heart and skeletal muscles.2,3 This gene therapy aims to address the underlying cause of DMD by enabling the production of shortened functional dystrophin protein and, thus, maintaining muscle function and delaying progression.3

The approval of SRP-9001 was based on efficacy and safety data from three Phase I and II studies: SRP-9001-101 (NCT03375164), SRP-9001-102 (NCT03769116), and SRP-9001-103 (ENDEAVOR; NCT04626674).1 Study 101 was a completed Phase I/II trial that enrolled 4 male participants aged 4 to 7 years that were treated with a single infusion of SRP-9001.5 The North Star Ambulatory Assessment (NSSA) was used as a standard measurement of motor function. Long-term results showed a positive mean +7.0-point difference above their pre-treatment NSAA baseline scores.5 Total NSAA scores for patients treated with SRP-9001 were 9.9 points (unadjusted means) and 9.4 points (least square means) greater compared to a propensity-weighted external control group (p=0.0125).5

Study 102 is a Phase II trial that enrolled 41 male patients with DMD.5,6 The first part of the study evaluated the safety and expression of micro-dystrophin.  The study achieved its primary biological endpoint of increases in micro-dystrophin expression after 12 weeks.6 Treatment-emergent adverse events (TEAEs) were transient and manageable, with 82% of patients experiencing mild or moderate TEAEs.6 Although patients treated with SRP-9001 did not show a statistically significant increase in total NSAA score (p=0.37) compared to placebo, they outperformed the placebo group at every time point measured and showed a statistically significant improvement in scores from baseline to 48 weeks (p=0.009).6 There was also a statistically significant improvement in NSSA scores at 48 weeks within a subgroup analysis of patients aged 4 to 5 years, compared to the placebo group (+4.3 points versus +1.9 points, respectively; p=0.0172).6 Part 2 of the study was a cross-over phase, where patients originally assigned to placebo received an SRP-9001 infusion. After 48 weeks, SRP-9001-treated patients scored a mean 2 points higher on the NSAA than the external controls, a statistically significant difference (p=0.0009).7 Follow-up is ongoing.

Study 103 (ENDEAVOR) is a Phase Ib trial that assessed the safety and expression of commercially representative SRP-9001 in four cohorts of male patients with DMD.5 The 1-year safety findings were consistent with previous clinical studies with similar reported TEAEs.5 Gene expression data, measured by western blot at 12 weeks, demonstrated successful delivery of SRP-9001 to target cells and an increase in micro-dystrophin levels from baseline.5 Functional results showed improvements in motor function compared to an external control group, assessed by NSAA and timed function tests (TFTs).5

“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, JD, President and Chief Executive Officer of Sarepta Therapeutics, Cambridge, MA1

SRP-9001 is the first and only approved disease-modifying gene therapy for DMD to be authorized for commercial use. The therapy is contraindicated in patients with any deletion in exon 8 and/or exon 9 in the DMD gene.1 Its approval will be verified based on the findings of the post-marketing confirmatory Phase III trial, EMBARK (NCT05096221).1 If the findings are positive, the FDA will consider a non-age restricted label expansion of SRP-9001.8 Another ongoing Phase III trial, ENVISION (NCT05881408), intends to support its globally regulatory approval in non-ambulatory and older ambulatory (aged 8-18 years) patients with DMD.9 Early cost-effectiveness analysis for SRP-9001 revealed it has the potential to be a transformative treatment that prolongs survival for patients with DMD with a substantial increase in overall QALYs (quality-adjusted life years) compared to the current standard of care.3 Other pharmaceutical companies are developing similar gene therapies for DMD and are looking for ways to improve AAV vectors and dosages.2 The approval of SRP-9001 represents a significant milestone advancement in the treatment landscape for DMD.

Written by Lemuel Fulgencio

Reviewed by Juliet Lawrence


  1. Sarepta Therapeutics. Sarepta Therapeutics Announces FDA Approval of ELEVIDYS, the First Gene Therapy to Treat Duchenne Muscular Dystrophy. [Press Release]. 22 Jun 2023. Accessed 28th June 2023.
  2. Deng J, Zhang J, Shi K, et al. Drug development progress in duchenne muscular dystrophy. Front Pharmacol. Jul 2022; 13:950651.
  3. Klimchak AC, Sedita LE, Rodino-Klapac LR, et al. Assessing the value of delandistrogene moxeparvovec (SRP-9001) gene therapy in patients with Duchenne muscular dystrophy in the United States. J Mark Access Health Policy. May 2023; 11(1):2216518.
  4. Duan D, Goemans N, Takeda S, et al. Duchenne muscular dystrophy. Nat Rev Dis Primers. Feb 2021; 7:13.
  5. Sarepta Therapeutics. Sarepta Therapeutics’ Investigational Gene Therapy SRP-9001 for Duchenne Muscular Dystrophy Demonstrates Significant Functional Improvements Across Multiple Studies. [Press Release]. 06 Jul 2023. Accessed 28th June 2023.
  6. Sarepta Therapeutics. Sarepta Therapeutics Announces Top-line Results for Part 1 of Study 102 Evaluating SRP-9001, its Investigational Gene Therapy for the Treatment of Duchenne Muscular Dystrophy. [Press Release]. 07 Jan 2021. Accessed 28th June 2023.
  7. Sarepta Therapeutics. Sarepta Therapeutics’ Gene Therapy SRP-9001 Shows Statistically Significant Functional Improvements Compared to Pre-specified Matched External Control in Part 2 of Study SRP-9001-102 for the Treatment of Duchenne Muscular Dystrophy. [Press Release]. 01 Oct 2022. Accessed 28th June 2023.
  8. Sarepta Therapeutics. Sarepta Therapeutics Announces Update on Regulatory Review of SRP-9001. [Press Release]. 24 May 2023. Accessed 28th June 2023.
  9. Sarepta Therapeutics. SRP-9001-303: ENVISION study enrollment in U.S. [Press Release]. 08 Jun 2023. Accessed 28th June 2023.