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Lookup NU author(s): Professor Hanns Lochmuller, Dr Oksana Pogoryelova
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
Objective: To investigate the efficacy and safety of aceneuramic acid extended-release (Ace-ER), a treatment intended to replace deficient sialic acid, in patients with GNE myopathy.Methods: UX001-CL301 was a phase 3, double-blind, placebo-controlled, randomized, international study evaluating the efficacy and safety of Ace-ER in patients with GNE myopathy. Participants who could walk ≥200 meters in a 6-minute walk test at screening were randomized 1:1, and stratified by sex, to receive Ace-ER 6 g/d or placebo for 48 weeks and assessed every 8 weeks. The primary endpoint was change in muscle strength over 48 weeks measured by upper extremity composite (UEC) score. Key secondary endpoints included change in lower extremity composite (LEC) score, knee extensor strength, and GNE myopathy-Functional Activity Scale (GNEM-FAS) mobility domain score. Safety assessments included adverse events (AEs), vital signs, and clinical laboratory results.Results: Eighty-nine patients were randomized (Ace-ER n = 45; placebo n = 44). Change from baseline to week 48 for UEC score between treatments did not differ (least square mean [LSM] Ace-ER -2.25 kg vs placebo -2.99 kg; LSM difference confidence interval [CI] 0.74 [-1.61 to 3.09]; p = 0.5387). At week 48, there was no significant difference between treatments for the change in key secondary endpoints: LEC LSM difference (CI) -1.49 (-5.83 to 2.86); knee extension strength -0.40 (-2.38 to 1.58); and GNEM-FAS mobility domain score -0.72 (-2.01 to 0.57). Gastrointestinal events were the most common AEs.Conclusions: Ace-ER was not superior to placebo in improving muscle strength and function in patients with GNE myopathy.Classification of evidence: This study provides Class I evidence that for patients with GNE myopathy, Ace-ER does not improve muscle strength compared to placebo.
Author(s): Lochmüller H, Behin A, Caraco Y, Lau H, Mirabella M, Tournev I, Tarnopolsky M, Pogoryelova O, Woods C, Lai A, Shah J, Koutsoukos T, Skrinar A, Mansbach H, Kakkis E, Mozaffar T
Publication type: Article
Publication status: Published
Journal: Neurology
Year: 2021
Volume: 92
Issue: 18
Pages: e2109-e2117
Print publication date: 30/04/2019
Online publication date: 25/01/2019
Acceptance date: 04/01/2019
Date deposited: 18/08/2023
ISSN (electronic): 1526-632X
Publisher: American Academy of Neurology (AAN)
URL: https://doi.org/10.1212/WNL.0000000000006932
DOI: 10.1212/WNL.0000000000006932
PubMed id: 31036580
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