Delandistrogene Moxeparvovec Gene Therapy in Ambulatory Patients (Aged ≥4 to <8 Years) with Duchenne Muscular Dystrophy: 1-Year Interim Results from Study SRP-9001-103 (ENDEAVOR).

Autor: Zaidman CM; Department of Neurology, Washington University in St. Louis, St. Louis, MO, USA., Proud CM; Children's Hospital of the King's Daughters, Norfolk, VA, USA., McDonald CM; University of California Davis Health, Sacramento, CA, USA., Lehman KJ; Center for Gene Therapy, Nationwide Children's Hospital, Columbus, OH, USA., Goedeker NL; Department of Neurology, Washington University in St. Louis, St. Louis, MO, USA., Mason S; Sarepta Therapeutics, Inc., Cambridge, MA, USA., Murphy AP; Roche Products Ltd, Welwyn Garden City, UK., Guridi M; F. Hoffmann-La Roche Ltd, Basel, Switzerland., Wang S; Sarepta Therapeutics, Inc., Cambridge, MA, USA., Reid C; Roche Products Ltd, Welwyn Garden City, UK., Darton E; Sarepta Therapeutics, Inc., Cambridge, MA, USA., Wandel C; F. Hoffmann-La Roche Ltd, Basel, Switzerland., Lewis S; Sarepta Therapeutics, Inc., Cambridge, MA, USA., Malhotra J; Sarepta Therapeutics, Inc., Cambridge, MA, USA., Griffin DA; Sarepta Therapeutics, Inc., Cambridge, MA, USA., Potter RA; Sarepta Therapeutics, Inc., Cambridge, MA, USA., Rodino-Klapac LR; Sarepta Therapeutics, Inc., Cambridge, MA, USA., Mendell JR; Center for Gene Therapy, Nationwide Children's Hospital, Columbus, OH, USA.; The Ohio State University, Columbus, OH, USA.
Jazyk: angličtina
Zdroj: Annals of neurology [Ann Neurol] 2023 Nov; Vol. 94 (5), pp. 955-968. Date of Electronic Publication: 2023 Sep 07.
DOI: 10.1002/ana.26755
Abstrakt: Objective: Delandistrogene moxeparvovec is approved in the USA for the treatment of ambulatory patients (4-5 years) with Duchenne muscular dystrophy. ENDEAVOR (SRP-9001-103; NCT04626674) is a single-arm, open-label study to evaluate delandistrogene moxeparvovec micro-dystrophin expression, safety, and functional outcomes following administration of commercial process delandistrogene moxeparvovec.
Methods: In cohort 1 of ENDEAVOR (N = 20), eligible ambulatory males, aged ≥4 to <8 years, received a single intravenous infusion of delandistrogene moxeparvovec (1.33 × 10 14  vg/kg). The primary endpoint was change from baseline (CFBL) to week 12 in delandistrogene moxeparvovec micro-dystrophin by western blot. Additional endpoints evaluated included: safety; vector genome copies; CFBL to week 12 in muscle fiber-localized micro-dystrophin by immunofluorescence; and functional assessments, including North Star Ambulatory Assessment, with comparison with a propensity score-weighted external natural history control.
Results: The 1-year safety profile of commercial process delandistrogene moxeparvovec in ENDEAVOR was consistent with safety data reported in other delandistrogene moxeparvovec trials (NCT03375164 and NCT03769116). Delandistrogene moxeparvovec micro-dystrophin expression was robust, with sarcolemmal localization at week 12; mean (SD) CFBL in western blot, 54.2% (42.6); p < 0.0001. At 1 year, patients demonstrated stabilized or improved North Star Ambulatory Assessment total scores; mean (SD) CFBL, +4.0 (3.5). Treatment versus a propensity score-weighted external natural history control demonstrated a statistically significant difference in least squares mean (standard error) CFBL in North Star Ambulatory Assessment, +3.2 (0.6) points; p < 0.0001.
Interpretation: Results confirm efficient transduction of muscle by delandistrogene moxeparvovec. One-year post-treatment, delandistrogene moxeparvovec was well tolerated, and demonstrated stabilized or improved motor function, suggesting a clinical benefit for patients with Duchenne muscular dystrophy. ANN NEUROL 2023;94:955-968.
(© 2023 Sarepta Therapeutics and The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
Databáze: MEDLINE
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