Safety and efficacy of avalglucosidase alfa in individuals with infantile-onset Pompe disease enrolled in the phase 2, open-label Mini-COMET study: The 6-month primary analysis report.

Autor:	Kishnani PS; Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC. Electronic address: priya.kishnani@duke.edu., Kronn D; Departments of Pathology and Pediatrics, New York Medical College, Valhalla, NY., Brassier A; Reference Center of Inherited Metabolic Diseases, Imagine Institute, Hospital Necker Enfants Malades, APHP, University Paris Descartes, Paris, France., Broomfield A; Willink Biochemical Genetics Unit, Manchester Center for Genomic Medicine, St Mary's Hospital, Central Manchester Foundation Trust, Manchester, United Kingdom., Davison J; Great Ormond Street Hospital NHS Foundation Trust, London, UK and National Institute of Health Research Great Ormond Street Hospital Biomedical Research Centre, London, UK., Hahn SH; Department of Pediatrics, University of Washington School of Medicine, Seattle Children's Hospital, Seattle, WA., Kumada S; Department of Neuropediatrics, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan., Labarthe F; Pediatrics Department, Center for Inborn Errors of Metabolism ToTeM, CHU Tours, and N2C, INSERM U1069, Tours University, Tours, France., Ohki H; Department of Cardiology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan., Pichard S; Reference Center of Inherited Metabolic Diseases, Imagine Institute, Hospital Necker Enfants Malades, APHP, University Paris Descartes, Paris, France., Prakalapakorn SG; Departments of Ophthalmology and Pediatrics, Duke University, Durham, NC., Haack KA; Sanofi, Chilly-Mazarin, France., Kittner B; Sanofi, Bridgewater, NJ., Meng X; Sanofi, Bridgewater, NJ., Sparks S; Sanofi, Cambridge, MA., Wilson C; Sanofi, Cambridge, MA., Zaher A; Sanofi, Laval, Canada., Chien YH; Departments of Medical Genetics and Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
Jazyk:	angličtina
Zdroj:	Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2023 Feb; Vol. 25 (2), pp. 100328. Date of Electronic Publication: 2022 Dec 21.
DOI:	10.1016/j.gim.2022.10.010
Abstrakt:	Purpose: Mini-COMET (NCT03019406; Sanofi) is a phase 2, open-label, ascending-dose, 3-cohort study, evaluating avalglucosidase alfa safety, pharmacokinetics, and efficacy in individuals with infantile-onset Pompe disease aged <18 years who previously received alglucosidase alfa and showed clinical decline (cohorts 1 and 2) or suboptimal response (cohort 3). Methods: During a 25-week primary analysis period, cohorts 1 and 2 received avalglucosidase alfa 20 and 40 mg/kg every other week, respectively, for 6 months, whereas cohort 3 individuals were randomized (1:1) to receive avalglucosidase alfa 40 mg/kg every other week or alglucosidase alfa (current stable dose) for 6 months. Results: In total, 22 individuals were enrolled (cohort 1 [n = 6], cohort 2 [n = 5], cohort 3-avalglucosidase alfa [n = 5], and cohort 3-alglucosidase alfa [n = 6]). Median treatment compliance was 100%. None of the individuals discontinued treatment or died. Percentages of individuals with treatment-emergent adverse events were similar across dose and treatment groups. No serious or severe treatment-related treatment-emergent adverse events occurred. Trends for better motor function from baseline to week 25 were observed for 40 mg/kg every other week avalglucosidase alfa compared with either 20 mg/kg every other week avalglucosidase alfa or alglucosidase alfa up to 40 mg/kg weekly. Conclusion: These data support the positive clinical effect of avalglucosidase alfa in patients with infantile-onset Pompe disease previously declining on alglucosidase alfa. Competing Interests: Conflict of Interest P.S.K. reports advisory board participation for Amicus Therapeutics, Baebies, and Sanofi; receiving consulting fees from Amicus Therapeutics, Asklepios Biopharmaceutical Inc (AskBio), JCR Pharma Co Ltd, Maze Therapeutics, and Sanofi; performing contracted research for Amicus Therapeutics and Sanofi; receiving honoraria from Amicus Therapeutics, AskBio, Maze Therapeutics, and Sanofi; having ownership interest of <5% (stocks, stock options, or other ownership interest excluding diversified mutual funds) in AskBio and Maze Therapeutics; and receiving travel expenses from Amicus Therapeutics and Sanofi. D.K. reports advisory board participation for AskBio and Sanofi; performing contracted research for Sanofi; serving on the Speaker’s bureau for Sanofi; and receiving travel expenses from AskBio and Sanofi. A.Bra. reports advisory board participation for Alexion, Sanofi, and Shire; receiving consulting fees from Alexion; and receiving travel expenses from Alexion, BioMarin, Orphan Europe, Sanofi, and Shire. A.Bro. reports advisory board participation for Sanofi and receiving honoraria from Orchard Therapeutics and Sanofi. J.D. reports advisory board participation for Sanofi, Recordati RRD, and Orchard Therapeutics; receiving consulting fees from bluebird bio Inc; and serving on the Speaker’s bureau for Sanofi, Recordati RRD, and FYMCA Medical Ltd. S.H.H. reports advisory board participation for Alexion Pharmaceutical Inc; performing contracted research for Sanofi; receiving honoraria from Alexion Pharmaceutical Inc; membership of the Seattle Children’s Hospital workforce; serving as temporary CEO of KEY PROTEO, Inc; being an inventor of intellectual property that has been licensed to KEY PROTEO, Inc; being a founder of KEY PROTEO, Inc and having ownership equity interests in the company; and receiving royalties from UpToDate. S.K., F.L., and H.O. declare no conflicts of interest. S.P. reports receiving travel expenses from Sanofi. S.G.P. reports performing contracted research for Sanofi and receiving consulting fees from Sanofi. K.A.H. and her spouse are employees of Sanofi and both have ownership interest of <5% (stocks, stock options, or other ownership interest excluding diversified mutual funds) in Sanofi. B.K. is an employee of Sanofi and has ownership interest of <5% (stocks, stock options, or other ownership interest excluding diversified mutual funds) in Sanofi. X.M. is an employee of TechData Service LLC (contracted to Sanofi). S.S. is an employee of Sanofi and has ownership interest of <5% (stocks, stock options, or other ownership interest excluding diversified mutual funds) in Sanofi. C.W. reports receiving consulting fees from Sanofi and Regenxbio. A.Z. is an employee of Sanofi and has ownership interest of <5% (stocks, stock options, or other ownership interest excluding diversified mutual funds) in Sanofi Canada. Y.-H.C. reports advisory board participation for Amicus Therapeutics and Sanofi; receiving consulting fees from Amicus Therapeutics and Sanofi; performing contracted research for Sanofi; and receiving honoraria from Biogen, Novartis, Sanofi, and Takeda. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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