NYMC Faculty Publications

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, Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC. Electronic address: priya.kishnani@duke.edu.
David Kronn, Departments of Pathology and Pediatrics, New York Medical College, Valhalla, NY.
Anaïs Brassier, Reference Center of Inherited Metabolic Diseases, Imagine Institute, Hospital Necker Enfants Malades, APHP, University Paris Descartes, Paris, France.
Alexander Broomfield, Willink Biochemical Genetics Unit, Manchester Center for Genomic Medicine, St Mary's Hospital, Central Manchester Foundation Trust, Manchester, United Kingdom.
James Davison, Great Ormond Street Hospital NHS Foundation Trust, London, UK and National Institute of Health Research Great Ormond Street Hospital Biomedical Research Centre, London, UK.
Si Houn Hahn, Department of Pediatrics, University of Washington School of Medicine, Seattle Children's Hospital, Seattle, WA.
Satoko Kumada, Department of Neuropediatrics, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan.
François Labarthe, Pediatrics Department, Center for Inborn Errors of Metabolism ToTeM, CHU Tours, and N2C, INSERM U1069, Tours University, Tours, France.
Hirotaka Ohki, Department of Cardiology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
Samia Pichard, Reference Center of Inherited Metabolic Diseases, Imagine Institute, Hospital Necker Enfants Malades, APHP, University Paris Descartes, Paris, France.
S Grace Prakalapakorn, Departments of Ophthalmology and Pediatrics, Duke University, Durham, NC.
Kristina An Haack, Sanofi, Chilly-Mazarin, France.
Barbara Kittner, Sanofi, Bridgewater, NJ.
Xianzhang Meng, Sanofi, Bridgewater, NJ.
Susan Sparks, Sanofi, Cambridge, MA.
Catherine Wilson, Sanofi, Cambridge, MA.
Atef Zaher, Sanofi, Laval, Canada.
Yin-Hsiu Chien, Departments of Medical Genetics and Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.

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Genetics in Medicine

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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.