TY - JOUR
T1 - Aceneuraminic acid for distal myopathy
AU - Aoki, Masashi
N1 - Publisher Copyright:
© 2025, Japanese Pharmacological Society. All rights reserved.
PY - 2025
Y1 - 2025
N2 - Distal myopathy with rimmed vacuoles (GNE myopathy) is an incurable disease that develops after the late teens, progresses slowly, and has no effective treatment. It is inherited in an autosomal recessive manner, and the number of patients in Japan is estimated to be around 400. The causative gene was revealed to be GNE, the rate-limiting enzyme in the sialic acid biosynthesis pathway, and non-clinical studies demonstrated the effectiveness of sialic acid. Tohoku University Hospital conducted an investigator-initiated phase I trial with aceneuraminic acid in 2010. After that, trials were conducted overseas, and a phase II trial using acenoiraminic acid sustained-release tablets confirmed that muscle strength in the upper limbs had recovered, and the drug progressed to a phase III trial. In Japan, a Phase II/III study was conducted at five domestic facilities using the same protocol as the overseas Phase III study, and efficacy and safety were confirmed. However, Phase III trials overseas failed to show efficacy and development was discontinued. An additional confirmation study was conducted in Japan, and as a result of confirming reproducibility, the product was approved for manufacturing and sales in March 2024, ahead of the rest of the world. This is a successful example of the development of a therapeutic drug for an ultra-orphan disease, which is said to be difficult to develop, and is expected to lead to early treatment for patients.
AB - Distal myopathy with rimmed vacuoles (GNE myopathy) is an incurable disease that develops after the late teens, progresses slowly, and has no effective treatment. It is inherited in an autosomal recessive manner, and the number of patients in Japan is estimated to be around 400. The causative gene was revealed to be GNE, the rate-limiting enzyme in the sialic acid biosynthesis pathway, and non-clinical studies demonstrated the effectiveness of sialic acid. Tohoku University Hospital conducted an investigator-initiated phase I trial with aceneuraminic acid in 2010. After that, trials were conducted overseas, and a phase II trial using acenoiraminic acid sustained-release tablets confirmed that muscle strength in the upper limbs had recovered, and the drug progressed to a phase III trial. In Japan, a Phase II/III study was conducted at five domestic facilities using the same protocol as the overseas Phase III study, and efficacy and safety were confirmed. However, Phase III trials overseas failed to show efficacy and development was discontinued. An additional confirmation study was conducted in Japan, and as a result of confirming reproducibility, the product was approved for manufacturing and sales in March 2024, ahead of the rest of the world. This is a successful example of the development of a therapeutic drug for an ultra-orphan disease, which is said to be difficult to develop, and is expected to lead to early treatment for patients.
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U2 - 10.1254/fpj.24090
DO - 10.1254/fpj.24090
M3 - Review article
C2 - 39756906
AN - SCOPUS:85214765759
SN - 0015-5691
VL - 160
SP - 48
EP - 52
JO - Folia Pharmacologica Japonica
JF - Folia Pharmacologica Japonica
IS - 1
ER -