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Clinical Trial
. 2024 Jan;69(1):93-98.
doi: 10.1002/mus.27955. Epub 2023 Aug 14.

Long-term safety and functional outcomes of delandistrogene moxeparvovec gene therapy in patients with Duchenne muscular dystrophy: A phase 1/2a nonrandomized trial

Jerry R Mendell  1   2 , Zarife Sahenk  1   2   3 , Kelly J Lehman  1 , Linda P Lowes  1   2 , Natalie F Reash  1 , Megan A Iammarino  1 , Lindsay N Alfano  1 , Sarah Lewis  4 , Kathleen Church  1 , Richard Shell  1 , Rachael A Potter  4 , Danielle A Griffin  4 , Mark Hogan  1 , Shufang Wang  4 , Stefanie Mason  4 , Eddie Darton  4 , Louise R Rodino-Klapac  4
Affiliations
Clinical Trial

Long-term safety and functional outcomes of delandistrogene moxeparvovec gene therapy in patients with Duchenne muscular dystrophy: A phase 1/2a nonrandomized trial

Jerry R Mendell et al. Muscle Nerve. 2024 Jan.

Abstract

Introduction/aims: Delandistrogene moxeparvovec is indicated in the United States for the treatment of ambulatory pediatric patients aged 4 through 5 years with Duchenne muscular dystrophy (DMD) with a confirmed mutation in the DMD gene. Long-term delandistrogene moxeparvovec microdystrophin protein (a shortened dystrophin that retains key functional domains of the wild-type protein) expression may positively alter disease progression in patients with DMD. We evaluated long-term safety and functional outcomes of delandistrogene moxeparvovec in patients with DMD.

Methods: An open-label, phase 1/2a, nonrandomized controlled trial (Study 101; NCT03375164) enrolled ambulatory males, ≥4 to <8 years old, with DMD. Patients received a single intravenous infusion (2.0 × 1014 vg/kg by supercoiled quantitative polymerase chain reaction) of delandistrogene moxeparvovec and prednisone (1 mg/kg/day) 1 day before to 30 days after treatment. The primary endpoint was safety. Functional outcomes were change from baseline in North Star Ambulatory Assessment (NSAA) and timed function tests.

Results: Four patients (mean age, 5.1 years) were enrolled. There were 18 treatment-related adverse events; all occurred within 70 days posttreatment and resolved. Mean NSAA total score increased from 20.5 to 27.5, baseline to year 4, with a mean (standard deviation) change of +7.0 (2.9). Post hoc analysis demonstrated a statistically significant and clinically meaningful 9-point difference in NSAA score, relative to a propensity-score-weighted external control cohort (least-squares mean [standard error] = 9.4 [3.4]; P = .0125).

Discussion: Gene transfer therapy with delandistrogene moxeparvovec treatment is well tolerated, with a favorable safety profile. Functional improvements are sustained through 4 years, suggesting delandistrogene moxeparvovec may positively alter disease progression.

Keywords: Duchenne muscular dystrophy; delandistrogene moxeparvovec; dystrophin; gene therapy; microdystrophin; rAAVrh74.

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References

REFERENCES

    1. Bushby K, Finkel R, Birnkrant DJ, et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol. 2010;9:77-93.
    1. Cowen L, Mancini M, Martin A, Lucas A, Donovan J. Variability and trends in corticosteroid use by male United States participants with Duchenne muscular dystrophy in the Duchenne registry. BMC Neurol. 2019;19:84.
    1. Ward LM, Kinnett K, Bonewald L. Proceedings of a Parent Project Muscular Dystrophy Bone Health Workshop: morbidity due to osteoporosis in DMD: the path forward May 12-13, 2016, Bethesda, Maryland, USA. Neuromuscul Disord. 2018;28:64-76.
    1. Patterson G, Conner H, Groneman M, Blavo C, Parmar MS. Duchenne muscular dystrophy: current treatment and emerging exon skipping and gene therapy approach. Eur J Pharmacol. 2023;947:175675.
    1. US Food and Drug Administration. ELEVIDYS™ Highlights of prescribing information. 2023 https://www.fda.gov/media/169679/download. Accessed July 2023

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