Long-term safety and efficacy of cipaglucosidase alfa plus miglustat in individuals living with Pompe disease: an open-label phase I/II study (ATB200-02).

Autor: Byrne BJ; University of Florida, Gainesville, FL, USA. barry.byrne@ufl.edu., Schoser B; Friedrich-Baur-Institute at the Department of Neurology, LMU University Hospital, LMU Munich, Munich, Germany., Kishnani PS; Duke University Medical Center, Durham, NC, USA., Bratkovic D; PARC Research Clinic, Royal Adelaide Hospital, Adelaide, SA, Australia., Clemens PR; Department of Neurology, University of Pittsburgh School of Medicine and VA Pittsburgh Healthcare System, Pittsburgh, PA, USA., Goker-Alpan O; Lysosomal and Rare Disorders Research and Treatment Center, Fairfax, VA, USA., Ming X; Neurology, Rutgers New Jersey Medical School, Newark, NJ, USA.; Guam Regional Medical City, Dededo, Guam., Roberts M; Salford Royal NHS Foundation Trust, Salford, UK., Vorgerd M; Department of Neurology, University Hospital Bergmannsheil, Heimer Institute for Muscle Research, Bochum, Germany., Sivakumar K; Neuromuscular Clinic and Research Center, Phoenix, AZ, USA., van der Ploeg AT; Erasmus MC University Medical Center, Rotterdam, Netherlands., Goldman M; Amicus Therapeutics, Inc., Princeton, NJ, USA., Wright J; Amicus Therapeutics, Inc., Princeton, NJ, USA., Holdbrook F; Amicus Therapeutics, Inc., Princeton, NJ, USA., Jain V; Amicus Therapeutics, Inc., Princeton, NJ, USA., Benjamin ER; Amicus Therapeutics, Inc., Princeton, NJ, USA., Johnson F; Amicus Therapeutics, Inc., Princeton, NJ, USA., Das SS; Amicus Therapeutics, Inc., Princeton, NJ, USA., Wasfi Y; Amicus Therapeutics, Inc., Princeton, NJ, USA., Mozaffar T; University of California, Irvine, Irvine, CA, USA.
Jazyk: angličtina
Zdroj: Journal of neurology [J Neurol] 2024 Apr; Vol. 271 (4), pp. 1787-1801. Date of Electronic Publication: 2023 Dec 06.
DOI: 10.1007/s00415-023-12096-0
Abstrakt: Cipaglucosidase alfa plus miglustat (cipa + mig) is a novel, two-component therapy for Pompe disease. We report data from the Phase I/II ATB200-02 study for up to 48 months of treatment. Four adult cohorts, including one non-ambulatory ERT-experienced (n = 6) and three ambulatory cohorts, (two enzyme replacement therapy [ERT]-experienced cohorts [2-6 years (n = 11) and ≥ 7 years (n = 6)]), one ERT-naïve cohort (n = 6), received 20 mg/kg intravenous-infused cipa plus 260 mg oral mig biweekly. Change from baseline (CFBL) for multiple efficacy endpoints at 12, 24, 36, and 48 months, pharmacodynamics, pharmacokinetics, safety, and immunogenicity data were assessed. Six-minute walking distance (% predicted) improved at 12, 24, 36, and 48 months: pooled ambulatory ERT-experienced cohorts, mean(± standard deviation [SD]) CFBL: 6.1(± 7.84), n = 16; 5.4(± 10.56), n = 13; 3.4(± 14.66), n = 12; 5.9(± 17.36), n = 9, respectively; ERT-naïve cohort: 10.7(± 3.93), n = 6; 11.0(± 5.06), n = 6; 9.0(± 7.98), n = 5; 11.7(± 7.69), n = 4, respectively. Percent predicted forced vital capacity was generally stable in ERT-experienced cohorts, mean(± SD) CFBL - 1.2(± 5.95), n = 16; 1.0(± 7.96), n = 13; - 0.3(± 6.68), n = 10; 1.0(± 6.42), n = 6, respectively, and improved in the ERT-naïve cohort: 3.2(± 8.42), n = 6; 4.7(± 5.09), n = 6; 6.2(± 3.35), n = 5; 8.3(± 4.50), n = 4, respectively. Over 48 months, CK and Hex4 biomarkers improved in ambulatory cohorts. Overall, cipa + mig was well tolerated with a safety profile like alglucosidase alfa. ATB200-02 results show the potential benefits of cipa + mig as a long-term treatment option for Pompe disease. Trial registration number: NCT02675465 January 26, 2016.
(© 2023. The Author(s).)
Databáze: MEDLINE
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