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Lookup NU author(s): Professor Volker StraubORCiD, Professor Michela GuglieriORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
The aim of this Phase 1/2, 2-part, multicenter trial was to report clinical safety and efficacy of long-term golodirsen treatment among ambulatory patients with exon 53 skip-amenable Duchenne muscular dystrophy (DMD). Part 1 was a 12-week, randomized, double-blind, placebo-controlled, dose-titration study followed by 9-week safety review. Part 2 was a 168-week, open-label evaluation of golodirsen 30 mg/kg. Part 1 primary endpoint was safety. Part 2 primary endpoints were dystrophin protein expression and 6-minute walk test (6MWT); secondary endpoints were percent predicted forced vital capacity (FVC%p) and safety. Post hoc ambulation analyses used mutation-matched external natural history controls. All patients from Part 1 (golodirsen, n = 8; placebo, n = 4) plus 13 additional patients entered Part 2; 23 completed the study. Adverse events were generally mild, nonserious, and unrelated to golodirsen, with no safety-related discontinuations or deaths. Golodirsen increased dystrophin protein (16.0-fold; P < 0.001) and exon skipping (28.9-fold; P < 0.001). At 3 years, 6MWT change from baseline was -99.0 m for golodirsen-treated patients versus -181.4 m for external controls (P = 0.067), and loss of ambulation occurred in 9% versus 26% (P = 0.21). FVC%p declined 8.4% over 3 years in golodirsen-treated patients, comparing favorably with literature-reported rates. This study provides evidence for golodirsen biologic activity and long-term safety in a declining DMD population and suggests functional benefit versus external controls. Clinical Trial Registration number: NCT02310906.
Author(s): Servais L, Mercuri E, Straub V, Guglieri M, Seferian AM, Scoto M, Leone D, Koenig E, Khan N, Dugar A, Wang X, Han B, Wang D, Muntoni F
Publication type: Article
Publication status: Published
Journal: Nucleic acid therapeutics
Year: 2022
Volume: 32
Issue: 1
Pages: 29-39
Print publication date: 31/01/2022
Online publication date: 17/11/2021
Acceptance date: 17/09/2021
Date deposited: 03/03/2022
ISSN (print): 2159-3337
ISSN (electronic): 2159-334
Publisher: Mary Ann Liebert, Inc. Publishers
URL: https://doi.org/10.1089/nat.2021.0043
DOI: 10.1089/nat.2021.0043
PubMed id: 34788571
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