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Clinical Trial
. 2025 Oct:285:114664.
doi: 10.1016/j.jpeds.2025.114664. Epub 2025 May 29.

The Mini-COMET Clinical Trial: Safety and Efficacy of Avalglucosidase Alfa after 97 Weeks of Treatment in Children with Infantile-Onset Pompe Disease Previously Treated with Alglucosidase Alfa

David Kronn  1 , James Davison  2 , Alexander Broomfield  2 , Anaïs Brassier  3 , François Labarthe  4 , Si Houn Hahn  5 , Satoko Kumada  6 , Hirotaka Ohki  7 , Sasapin Grace Prakalapakorn  8 , Catherine Wilson  9 , Kristina An Haack  10 , Olivier Huynh-Ba  10 , Susan Richards  11 , Susan Sparks  11 , Swathi Tammireddy  11 , Tianyue Zhou  11 , Yin-Hsiu Chien  12 , Priya S Kishnani  13 ; Mini-COMET investigators
Affiliations
Clinical Trial

The Mini-COMET Clinical Trial: Safety and Efficacy of Avalglucosidase Alfa after 97 Weeks of Treatment in Children with Infantile-Onset Pompe Disease Previously Treated with Alglucosidase Alfa

David Kronn et al. J Pediatr. 2025 Oct.

Abstract

Objective: To evaluate the long-term safety and efficacy of avalglucosidase alfa in children with infantile-onset Pompe disease experiencing clinical decline (cohorts 1 and 2) or suboptimal response (cohort 3) to prestudy alglucosidase alfa.

Study design: The Mini-COMET clinical trial, a phase 2, open-label, ascending-dose, 3-cohort study, has a 25-week primary analysis period (PAP) and an extension treatment period (ETP). In the PAP, cohorts 1 (n = 6) and 2 (n = 5) received avalglucosidase alfa 20 or 40 mg/kg every other week (qow), respectively. Cohort 3 received avalglucosidase alfa 40 mg/kg qow (n = 5) or alglucosidase alfa (prestudy [>6 months] stable dose: 20 mg/kg qow to 40 mg/kg weekly; n = 6). All children completed the PAP and entered the ETP. Children receiving avalglucosidase alfa in the PAP continued the same dose in the ETP. Those receiving alglucosidase alfa in the PAP received avalglucosidase alfa 40 mg/kg qow in the ETP.

Results: At baseline, children were 1-12 years old. Interim data (≥97 weeks) are presented from all 22 children, 20 receiving avalglucosidase alfa 40 mg/kg qow and 2 receiving 20 mg/kg qow in the ETP. Among the 6 who received 20 mg/kg qow avalglucosidase alfa in PAP (cohort 1), 4 had their dose increase to 40 mg/kg qow because of further clinical decline in the ETP. No child died or discontinued at data cutoff. PAP and ETP safety profiles were similar; no treatment-related serious or severe treatment-emergent adverse events occurred. Avalglucosidase alfa was well-tolerated, with no increased safety risk or immunogenicity concerns post-treatment switch. Echocardiography revealed persistent left ventricular mass z score normalization. Compared with baseline, biomarkers of Pompe disease burden decreased, and motor function improved or stabilized.

Conclusions: Results support the positive clinical impact of long-term avalglucosidase alfa in children with infantile-onset Pompe disease.

Trial registration: ClinicalTrials.gov: NCT03019406.

Keywords: OMIM232300; acid α-glucosidase (GAA) deficiency; alglucosidase alfa; autosomal recessive neuromuscular disorder; avalglucosidase alfa; clinical trial; enzyme replacement therapy; extension treatment period; infantile-onset Pompe disease; lysosomal glycogen accumulation; neuromuscular disorder; rare disease.

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Conflict of interest statement

Declaration of Competing Interest This study was funded by Sanofi. David Kronn served as a consultant for Asklepios BioPharmaceutical (AskBio) and Sanofi; served on the advisory board for Asklepios BioPharmaceutical (AskBio) and Sanofi; received grant/research support from Sanofi; served on the speakers bureau for Sanofi; received honoraria for non-CME from Sanofi; and received other financial or material support from Asklepios BioPharmaceutical (AskBio) and Sanofi. James Davison served on the speakers bureau for Recordati Rare Diseases and Sanofi; and received honoraria for non-CME from Recordati Rare Diseases and Sanofi. Alexander Broomfield served as a consultant for Sanofi; served on the advisory board for Sanofi; served on the speakers bureau for Takeda and received honoraria for non-CME from Takeda. Anaïs Brassier served as a consultant for BioMarin, Immedica, and Sanofi; served on the advisory board for BioMarin, Immedica, and Sanofi; and received other financial or material support from Sanofi. Si Houn Hahn is the founder of early-stage spin off company; and received other financial or material support from Key Proteo, Inc. S. Grace Prakalapakorn served as a consultant for Sanofi; and served on the advisory board for Sanofi. Catherine Wilson received consulting fees from Sanofi and Regenxbio. Kristina An Haack is an employee of Sanofi; and owns stock/stock options in Sanofi. Olivier Huynh-Ba is an Employee of Sanofi and owns stock/stock options in Sanofi. Susan Richards is an employee of Sanofi and owns stock/stock options in Sanofi. Susan Sparks is an employee of Sanofi and owns stock/stock options in Sanofi. Swathi Tammireddy is an employee of Sanofi and owns stock/stock options in Sanofi. Tianyue Zhou is an employee of Sanofi and owns stock/stock options in Sanofi. Yin-Hsiu Chien served as a consultant for Amicus; served on the advisory Board for Amicus; received grant/research support from Sanofi; served on the speakers bureau for BioMarin, Sanofi, and Takeda; and received honoraria for non-CME from BioMarin, Sanofi, and Takeda. Priya S. Kishnani served as a consultant for Amicus Therapeutics; served on the advisory Board for Amicus Therapeutics (Pompe Disease Advisory Board), Asklepios BioPharmaceutical (AskBio), Bayer (Advisory Board), Sanofi (Pompe and Gaucher Disease Registry Advisory Board), and Takeda; received grant/research support from Amicus Therapeutics, Pfizer, Sanofi, and Takeda; and received other financial or material support from Amicus Therapeutics, Asklepios BioPharmaceutical (AskBio; has held equity in AskBio and may receive milestone payments related to that equity in the future), Baebies, Maze Therapeutics, and Sanofi.

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