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Open Access 01-12-2023 | Diseases of the neuromuscular synapses and muscles | Research

Efficacy confirmation study of aceneuramic acid administration for GNE myopathy in Japan

Authors: Madoka Mori-Yoshimura, Naoki Suzuki, Masahisa Katsuno, Masanori P. Takahashi, Satoshi Yamashita, Yasushi Oya, Atsushi Hashizume, Shinichiro Yamada, Masayuki Nakamori, Rumiko Izumi, Masaaki Kato, Hitoshi Warita, Maki Tateyama, Hiroshi Kuroda, Ryuta Asada, Takuhiro Yamaguchi, Ichizo Nishino, Masashi Aoki

Published in: Orphanet Journal of Rare Diseases | Issue 1/2023

Abstract

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).

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Title: Efficacy confirmation study of aceneuramic acid administration for GNE myopathy in Japan
Authors: Madoka Mori-Yoshimura
Naoki Suzuki
Masahisa Katsuno
Masanori P. Takahashi
Satoshi Yamashita
Yasushi Oya
Atsushi Hashizume
Shinichiro Yamada
Masayuki Nakamori
Rumiko Izumi
Masaaki Kato
Hitoshi Warita
Maki Tateyama
Hiroshi Kuroda
Ryuta Asada
Takuhiro Yamaguchi
Ichizo Nishino
Masashi Aoki
Publication date: 01-12-2023
Publisher: BioMed Central
Keyword: Diseases of the neuromuscular synapses and muscles
Published in: Orphanet Journal of Rare Diseases / Issue 1/2023
Electronic ISSN: 1750-1172
DOI: https://doi.org/10.1186/s13023-023-02850-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Efficacy confirmation study of aceneuramic acid administration for GNE myopathy in Japan

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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