PT  - JOURNAL ARTICLE
AU  - Hanns Lochmüller
AU  - Anthony Behin
AU  - Yoseph Caraco
AU  - Heather Lau
AU  - Massimiliano Mirabella
AU  - Ivailo Tournev
AU  - Mark Tarnopolsky
AU  - Oksana Pogoryelova
AU  - Catherine Woods
AU  - Alexander Lai
AU  - Jinay Shah
AU  - Tony Koutsoukos
AU  - Alison Skrinar
AU  - Hank Mansbach
AU  - Emil Kakkis
AU  - Tahseen Mozaffar
TI  - A phase 3 randomized study evaluating sialic acid extended-release for GNE myopathy
AID  - 10.1212/WNL.0000000000006932
DP  - 2019 Apr 30
TA  - Neurology
PG  - e2109--e2117
VI  - 92
IP  - 18
4099  - http://n.neurology.org/content/92/18/e2109.short
4100  - http://n.neurology.org/content/92/18/e2109.full
SO  - Neurology2019 Apr 30; 92
AB  - 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.6MWT=6-minute walk test; Ace-ER=aceneuramic acid extended-release; AE=adverse event; CI=confidence interval; GNEM-DMP=GNE myopathy disease monitoring program; GNEM-FAS=GNE myopathy–Functional Activity Scale; HHD=hand-held dynamometer; LE=lower extremity; LEC=lower extremity composite; LSM=least squares mean; ManNAc=N-acetyl-d-mannosamine; SA=sialic acid; SAE=serious adverse event; UE=upper extremity; UEC=upper extremity composite