Efficacy confirmation study of aceneuramic acid administration for GNE myopathy in Japan.
Aceneuramic acid
Efficacy confirmation study
GNE myopathy
Ultra-orphan disease
Journal
Orphanet journal of rare diseases
ISSN: 1750-1172
Titre abrégé: Orphanet J Rare Dis
Pays: England
ID NLM: 101266602
Informations de publication
Date de publication:
11 08 2023
11 08 2023
Historique:
received:
03
05
2023
accepted:
02
08
2023
medline:
14
8
2023
pubmed:
12
8
2023
entrez:
11
8
2023
Statut:
epublish
Résumé
A rare muscle disease, GNE myopathy is caused by mutations in the GNE gene involved in sialic acid biosynthesis. Our recent phase II/III study has indicated that oral administration of aceneuramic acid to patients slows disease progression. We conducted a phase III, randomized, placebo-controlled, double-blind, parallel-group, multicenter study. Participants were assigned to receive an extended-release formulation of aceneuramic acid (SA-ER) or placebo. Changes in muscle strength and function over 48 weeks were compared between treatment groups using change in the upper extremity composite (UEC) score from baseline to Week 48 as the primary endpoint and the investigator-assessed efficacy rate as the key secondary endpoint. For safety, adverse events, vital signs, body weight, electrocardiogram, and clinical laboratory results were monitored. A total of 14 patients were enrolled and given SA-ER (n = 10) or placebo (n = 4) tablets orally. Decrease in least square mean (LSM) change in UEC score at Week 48 with SA-ER (- 0.115 kg) was numerically smaller as compared with placebo (- 2.625 kg), with LSM difference (95% confidence interval) of 2.510 (- 1.720 to 6.740) kg. In addition, efficacy was higher with SA-ER as compared with placebo. No clinically significant adverse events or other safety concerns were observed. The present study reproducibly showed a trend towards slowing of loss of muscle strength and function with orally administered SA-ER, indicating supplementation with sialic acid might be a promising replacement therapy for GNE myopathy. ClinicalTrials.gov (NCT04671472).
Sections du résumé
BACKGROUND
A rare muscle disease, GNE myopathy is caused by mutations in the GNE gene involved in sialic acid biosynthesis. Our recent phase II/III study has indicated that oral administration of aceneuramic acid to patients slows disease progression.
METHODS
We conducted a phase III, randomized, placebo-controlled, double-blind, parallel-group, multicenter study. Participants were assigned to receive an extended-release formulation of aceneuramic acid (SA-ER) or placebo. Changes in muscle strength and function over 48 weeks were compared between treatment groups using change in the upper extremity composite (UEC) score from baseline to Week 48 as the primary endpoint and the investigator-assessed efficacy rate as the key secondary endpoint. For safety, adverse events, vital signs, body weight, electrocardiogram, and clinical laboratory results were monitored.
RESULTS
A total of 14 patients were enrolled and given SA-ER (n = 10) or placebo (n = 4) tablets orally. Decrease in least square mean (LSM) change in UEC score at Week 48 with SA-ER (- 0.115 kg) was numerically smaller as compared with placebo (- 2.625 kg), with LSM difference (95% confidence interval) of 2.510 (- 1.720 to 6.740) kg. In addition, efficacy was higher with SA-ER as compared with placebo. No clinically significant adverse events or other safety concerns were observed.
CONCLUSIONS
The present study reproducibly showed a trend towards slowing of loss of muscle strength and function with orally administered SA-ER, indicating supplementation with sialic acid might be a promising replacement therapy for GNE myopathy.
TRIAL REGISTRATION NUMBER
ClinicalTrials.gov (NCT04671472).
Identifiants
pubmed: 37568154
doi: 10.1186/s13023-023-02850-y
pii: 10.1186/s13023-023-02850-y
pmc: PMC10416530
doi:
Substances chimiques
N-Acetylneuraminic Acid
GZP2782OP0
Banques de données
ClinicalTrials.gov
['NCT04671472']
Types de publication
Randomized Controlled Trial
Multicenter Study
Clinical Trial, Phase III
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
241Informations de copyright
© 2023. Institut National de la Santé et de la Recherche Médicale (INSERM).
Références
Orphanet J Rare Dis. 2014 Oct 11;9:150
pubmed: 25303967
BMJ Neurol Open. 2022 Dec 1;4(2):e000362
pubmed: 36483092
Hum Mol Genet. 2007 Nov 15;16(22):2669-82
pubmed: 17704511
J Neuromuscul Dis. 2016 Mar 3;3(1):49-66
pubmed: 27854209
J Neuromuscul Dis. 2023;10(4):555-566
pubmed: 37125562
Neuromuscul Disord. 2018 Feb;28(2):158-168
pubmed: 29305133
Nat Med. 2009 Jun;15(6):690-5
pubmed: 19448634
J Biol Chem. 2004 Mar 19;279(12):11402-7
pubmed: 14707127
Nat Genet. 2001 Sep;29(1):83-7
pubmed: 11528398
J Neurol Sci. 1981 Jul;51(1):141-55
pubmed: 7252518
Front Neurol. 2022 Oct 18;13:1002310
pubmed: 36330422
Genet Med. 2021 Nov;23(11):2067-2075
pubmed: 34257421
Hum Mutat. 2014 Aug;35(8):915-26
pubmed: 24796702
Neurology. 2002 Dec 10;59(11):1689-93
pubmed: 12473753
J Neurol Sci. 1984 Apr;64(1):33-43
pubmed: 6737002
Neurology. 2003 Jul 8;61(1):145; author reply 145
pubmed: 12847185
J Neuromuscul Dis. 2021;8(2):225-234
pubmed: 33459658
Neurology. 2019 Apr 30;92(18):e2109-e2117
pubmed: 31036580
Neurol Genet. 2019 Feb 01;5(1):e308
pubmed: 30842975
Neuromuscul Disord. 2014 May;24(5):380-6
pubmed: 24656604
Curr Opin Neurol. 2022 Oct 1;35(5):629-636
pubmed: 35959526
J Neurol Neurosurg Psychiatry. 2015 Apr;86(4):385-92
pubmed: 25002140