A recent AAN Evidence in Focus article reviews the current evidence on delandistrogene moxeparvovec, a one-time gene therapy approved by the FDA in June 2024 for treating Duchenne muscular dystrophy (DMD) in patients aged four and older. The therapy delivers a miniaturized dystrophin gene using a viral vector but has shown limited evidence of effectiveness, with key clinical trials failing to meet primary motor function goals. While it may slightly slow functional decline, its benefits are difficult to separate from those of concurrent high-dose steroids. Serious side effects, including muscle and heart inflammation, liver injury, and risk of death, require close monitoring. The treatment, which costs $3.2 million, does not cure DMD or definitively improve lifespan or quality of life, underscoring the need for further long-term studies.

This review evaluates current evidence on delandistrogene moxeparvovec for Duchenne muscular dystrophy (DMD), analyzing six clinical trials, including two Class I studies that did not meet primary motor outcomes. While some secondary outcomes showed minor improvements, they lacked statistical significance. Safety concerns included immune-related side effects such as myocarditis and liver toxicity, and one death has been reported. Despite limited efficacy, the FDA approved the drug based on safety and secondary data. Ongoing monitoring and further research are needed to assess long-term outcomes and guide clinical use.

Key Concepts

Etiology & Genetics

  • X-linked progressive muscle disease
  • Caused by pathogenic variants in the DMD gene
  • Results in absence of functional dystrophin protein

Prognosis and Traditional Management

  • Improved with:
    • Multidisciplinary care
    • Use of corticosteroids

    Advances in Disease-Modifying Therapies

    Antisense Oligonucleotide (ASO) Therapies

    • Target restoration of the reading frame via exon skipping

    Challenges in Gene Therapy for DMD

    • DMD gene:
      • Contains 79 exons
      • 14-kb transcript — too large for AAV vectors (~5 kb capacity)

      Delandistrogene Moxeparvovec (Elevidys) – Gene Therapy for DMD

      Composition

      • Recombinant AAV vector (rAAVrh74)
      • Encodes a microdystrophin transgene
      • Produces a truncated protein (~138 kDa vs. 427 kDa normal dystrophin)

      Regulatory Status

      • Initial FDA Accelerated Approval:
        • June 22, 2023
        • Ambulatory boys aged 4–5 years

        Evidence Summary: Delandistrogene Moxeparvovec in Duchenne Muscular Dystrophy (DMD)

        Search Results
        A systematic literature search of PubMed, Cochrane, Clinicaltrials.gov, and the World Health Organization's International Clinical Trials Registry Platform for published articles and clinical trials on treatment of DMD with delandistrogene moxeparvovec was conducted on July 31, 2024

        • Full approval: Ambulatory boys aged 4+ years
        • Accelerated approval: Nonambulatory boys with DMD

        Primary Outcome Measure

        • Initial search: 36 articles → 7 full-text reviewed → 5 articles included.
        • Updated search: 23 articles → 1 additional included.
        • ClinicalTrials.gov + FDA: 6 total trials identified; 4 had published data.

        Key Trials with Available Data

        • North Star Ambulatory Assessment (NSAA):
          • 17-item scale (0 = unable, 1 = assisted, 2 = independent).
          • Healthy peak score: 34 by age 4.
          • DMD trajectory: improvement to ~age 6, followed by decline (~3.7 points/year post age 7).
          • Minimal Clinically Important Difference (MCID): 2.3–3.5 points.

          Summary of Efficacy

          Trial IDDesignClassNSAA DifferenceMeets MCID?Notes
          NCT03375164 Phase 1/2a, nonrandomized III +9.4 (4 years) Yes (exploratory) Post-hoc, small sample
          NCT03769116 Phase 2, RCT I/III +0.8 (overall) No Age 4–5: +2.5 points (near MCID)
          ENDEAVOR Phase 1b, open-label III +3.2 (1 year) Yes Interim data, external comparator
          EMBARK Phase 3, RCT I +0.65 (52 weeks) No Primary endpoint not met

          Conclusion

          • NCT03375164 – Phase 1/2a (Single-Site, Nonrandomized)
            • Sample: 4 boys, age 4–8.
            • Dose: 2.0×10¹⁴ vg/kg, IV; plus prednisone 1 mg/kg/day.
            • Outcomes:
              • 1-year follow-up: exploratory motor outcomes (Class IV).
              • 4-year post-hoc comparison: LSM NSAA difference = +9.4 points vs. external control (Class III).

              Safety Summary: Delandistrogene Moxeparvovec in DMD

              Patient Exposure

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              Information
              Published:27 May 2025
              Modified: 27 May 2025