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

Priya S Kishnani; David Kronn; Anaïs Brassier; Alexander Broomfield; James Davison; Si Houn Hahn; Satoko Kumada; François Labarthe; Hirotaka Ohki; Samia Pichard; S Grace Prakalapakorn; Kristina An Haack; Barbara Kittner; Xianzhang Meng; Susan Sparks; Catherine Wilson; Atef Zaher; Yin-Hsiu Chien; Mini-COMET Investigators

doi:10.1016/j.gim.2022.10.010

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

Genet Med. 2023 Feb;25(2):100328. doi: 10.1016/j.gim.2022.10.010. Epub 2022 Dec 21.

Authors

Priya S Kishnani¹, David Kronn², Anaïs Brassier³, Alexander Broomfield⁴, James Davison⁵, Si Houn Hahn⁶, Satoko Kumada⁷, François Labarthe⁸, Hirotaka Ohki⁹, Samia Pichard³, S Grace Prakalapakorn¹⁰, Kristina An Haack¹¹, Barbara Kittner¹², Xianzhang Meng¹², Susan Sparks¹³, Catherine Wilson¹³, Atef Zaher¹⁴, Yin-Hsiu Chien¹⁵; Mini-COMET Investigators

Affiliations

¹ Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC. Electronic address: [email protected].
² Departments of Pathology and Pediatrics, New York Medical College, Valhalla, NY.
³ Reference Center of Inherited Metabolic Diseases, Imagine Institute, Hospital Necker Enfants Malades, APHP, University Paris Descartes, Paris, France.
⁴ Willink Biochemical Genetics Unit, Manchester Center for Genomic Medicine, St Mary's Hospital, Central Manchester Foundation Trust, Manchester, United Kingdom.
⁵ Great Ormond Street Hospital NHS Foundation Trust, London, UK and National Institute of Health Research Great Ormond Street Hospital Biomedical Research Centre, London, UK.
⁶ Department of Pediatrics, University of Washington School of Medicine, Seattle Children's Hospital, Seattle, WA.
⁷ Department of Neuropediatrics, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan.
⁸ Pediatrics Department, Center for Inborn Errors of Metabolism ToTeM, CHU Tours, and N2C, INSERM U1069, Tours University, Tours, France.
⁹ Department of Cardiology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
¹⁰ Departments of Ophthalmology and Pediatrics, Duke University, Durham, NC.
¹¹ Sanofi, Chilly-Mazarin, France.
¹² Sanofi, Bridgewater, NJ.
¹³ Sanofi, Cambridge, MA.
¹⁴ Sanofi, Laval, Canada.
¹⁵ Departments of Medical Genetics and Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.

PMID: 36542086
DOI: 10.1016/j.gim.2022.10.010

Abstract

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.

Keywords: Acid α-glucosidase (GAA) deficiency; Alglucosidase alfa; Avalglucosidase alfa; Enzyme replacement therapy; Infantile-onset Pompe disease.

Publication types

Randomized Controlled Trial
Clinical Trial, Phase II
Research Support, Non-U.S. Gov't

MeSH terms

Cohort Studies
Enzyme Replacement Therapy / adverse effects
Glycogen Storage Disease Type II* / drug therapy
Humans
Forschung
Treatment Outcome
alpha-Glucosidases / adverse effects

Substances

alpha-Glucosidases

Associated data

ClinicalTrials.gov/NCT03019406