Efficacy and safety of cipaglucosidase alfa plus miglustat in Japanese adults with late-onset Pompe disease: a case series from clinical trials.
7 affiliations
- 1Division of Gene Therapy, Research Center for Medical Sciences, The Jikei University School of Medicine, Tokyo, Japan.
- 2Department of Pediatrics, ISEIKAI International General Hospital, Osaka, Japan.
- 3Division of Child Neurology, Institute of Neurological Science, Tottori University Faculty of Medicine, Yonago, Japan.
- 4Department of Neurology, Kobe City Medical Center General Hospital, Kobe, Japan.
- 5BioMarin Pharmaceutical Japan K.K, Tokyo, Japan.
- 6Amicus Therapeutics UK Ltd, Marlow, UK.
- 7BioMarin UK Ltd, London, UK.
Abstract
Background
The safety and efficacy of cipaglucosidase alfa plus miglustat (cipa+mig) versus alglucosidase alfa plus placebo (alg+pbo) in late-onset Pompe disease (LOPD) were established in the randomised, double-blind, 52-week PROPEL study (NCT03729362) conducted across 24 countries, including Japan. An open-label extension (OLE; NCT04138277) is evaluating long-term cipa+mig outcomes. In Japan, cipa+mig was also available before marketing authorisation in an expanded access study (ATB200-19). This case series summarises the efficacy and safety of cipa+mig in Japanese patients in PROPEL, PROPEL OLE and ATB200-19.Methods
Endpoints included 6-minute walk distance (6MWD), forced vital capacity (FVC), biomarkers and safety. Cipa+mig (20 mg/kg intravenous cipa and 130-260 mg oral mig (weight-based dosing)) and alg+pbo (20 mg/kg intravenous alg and oral pbo) were given biweekly. Patients randomised to alg+pbo in PROPEL received cipa+mig in the OLE. Safety was assessed at every visit, and biomarkers at weeks 2, 4, 6, 12, 26, 38, 52 and every 26 weeks thereafter.Results
Six patients from PROPEL/OLE (cipa+mig, n=2; alg+pbo, n=4; all enrolled in the OLE) and four from ATB200-19 were included. Two patients discontinued treatment: one in the OLE (anaphylactic reaction) and one in ATB200-19 (withdrawal of consent). For evaluable patients (n=8), 6MWD remained stable or improved from baseline to weeks 52 and 104. In PROPEL/OLE, FVC varied with most patients improving with cipa+mig treatment; in ATB200-19, FVC remained stable to week 104. In PROPEL/OLE and ATB200-19, biomarker levels improved or stabilised by week 104, including in the PROPEL switch group, where levels worsened at week 52 but improved after switching to cipa+mig. Seven patients experienced treatment-related adverse events. No deaths occurred.Conclusions
Although the number of patients was small, the efficacy and safety of cipa+mig in Japanese patients from PROPEL/OLE and ATB200-19 were generally sustained and durable responses consistent with positive results in the overall PROPEL population.
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BibTeX
@article{kobayashi2026efficacy,
title = {{Efficacy and safety of cipaglucosidase alfa plus miglustat in Japanese adults with late-onset Pompe disease: a case series from clinical trials.}},
author = {Hiroshi Kobayashi and Aya Narita and Michi Kawamoto and Junjiro Saeki and Ryan Graham and William Kerr},
journal = {BMJ neurology open},
year = {2026},
month = oct,
doi = {10.1136/bmjno-2025-001480},
url = {https://europepmc.org/article/MED/42921145},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Efficacy and safety of cipaglucosidase alfa plus miglustat in Japanese adults with late-onset Pompe disease: a case series from clinical trials.
AU - Hiroshi Kobayashi
AU - Aya Narita
AU - Michi Kawamoto
AU - Junjiro Saeki
AU - Ryan Graham
AU - William Kerr
PY - 2026
DA - 2026/10/16
JO - BMJ neurology open
DO - 10.1136/bmjno-2025-001480
UR - https://europepmc.org/article/MED/42921145
AB - Background The safety and efficacy of cipaglucosidase alfa plus miglustat (cipa+mig) versus alglucosidase alfa plus placebo (alg+pbo) in late-onset Pompe disease (LOPD) were established in the randomised, double-blind, 52-week PROPEL study (NCT03729362) conducted across 24 countries, including Japan. An open-label extension (OLE; NCT04138277) is evaluating long-term cipa+mig outcomes. In Japan, cipa+mig was also available before marketing authorisation in an expanded access study (ATB200-19). This case series summarises the efficacy and safety of cipa+mig in Japanese patients in PROPEL, PROPEL OLE and ATB200-19.Methods Endpoints included 6-minute walk distance (6MWD), forced vital capacity (FVC), biomarkers and safety. Cipa+mig (20 mg/kg intravenous cipa and 130-260 mg oral mig (weight-based dosing)) and alg+pbo (20 mg/kg intravenous alg and oral pbo) were given biweekly. Patients randomised to alg+pbo in PROPEL received cipa+mig in the OLE. Safety was assessed at every visit, and biomarkers at weeks 2, 4, 6, 12, 26, 38, 52 and every 26 weeks thereafter.Results Six patients from PROPEL/OLE (cipa+mig, n=2; alg+pbo, n=4; all enrolled in the OLE) and four from ATB200-19 were included. Two patients discontinued treatment: one in the OLE (anaphylactic reaction) and one in ATB200-19 (withdrawal of consent). For evaluable patients (n=8), 6MWD remained stable or improved from baseline to weeks 52 and 104. In PROPEL/OLE, FVC varied with most patients improving with cipa+mig treatment; in ATB200-19, FVC remained stable to week 104. In PROPEL/OLE and ATB200-19, biomarker levels improved or stabilised by week 104, including in the PROPEL switch group, where levels worsened at week 52 but improved after switching to cipa+mig. Seven patients experienced treatment-related adverse events. No deaths occurred.Conclusions Although the number of patients was small, the efficacy and safety of cipa+mig in Japanese patients from PROPEL/OLE and ATB200-19 were generally sustained and durable responses consistent with positive results in the overall PROPEL population.
SN - 2632-6140
ER -