Study to Compare the Efficacy and Safety of Enzyme Replacement Therapies Avalglucosidase Alfa and Alglucosidase Alfa Administered Every Other Week in Patients With Late-onset Pompe Disease Who Have Not Been Previously Treated for Pompe Disease

Summary

Primary Objective: To determine the effect of avalglucosidase alfa treatment on respiratory muscle strength measured by percent (%) predicted forced vital capacity (FVC) in the upright position, as compared to alglucosidase alfa. Secondary Objective: To determine the safety and effect of avalglucosidase alfa treatment on functional endurance (6-minute walk test, inspiratory muscle strength (maximum inspiratory pressure), expiratory muscle strength (maximum expiratory pressure), lower extremity muscle strength (hand-held dynamometry), motor function (Quick Motor Function Test), and health-related quality of life (Short Form-12).

Timeline

Start

2016-11-02

Primary completion

2020-03-19

Completion

2023-05-31

Outcome

Met primary endpoint

paper Non-inferiority was shown because the lower bound of the 95% CI for the difference far exceeded the predefined non-inferiority margin but did not exclude 0 (p=0·0074). PMID 34800399 ↗

release “Avalglucosidase alfa met the primary endpoint demonstrating non-inferiority in improving respiratory function compared to alglucosidase alfa (standard of care) in patients with LOPD.” sanofi.com ↗

Publications

• Kishnani PS, Diaz-Manera J, Illarioshkin S, van der Ploeg AT, Clemens PR, Day JW, Toscano A, Kushlaf H, Ladha S, Attarian S, Carvalho G, Kostera-Pruszczyk A, Erdem-Ozdamar S, Goker-Alpan O, Mozaffar T, Straub V, Roberts M, Haack KA, Huynh-Ba O, Tammireddy S, Periquet M, Thibault N, Zhou T, Dimachkie MM, Schoser B; COMET Investigator Group. Efficacy and safety of avalglucosidase alfa in patients with late-onset Pompe disease after 145 weeks of treatment during the COMET trial. J Neurol. 2025 Aug 16;272(9):581. doi: 10.1007/s00415-025-13266-y.
• Dimachkie MM, Kishnani PS, Ivanescu C, Flore G, Gwaltney C, van der Beek NAME, Hamed A, An Haack K, Pollissard L, Baranowski E, Sparks SE, DasMahapatra P; for COMET Study Group. Measurement Properties of 2 Novel PROs, the Pompe Disease Symptom Scale and Pompe Disease Impact Scale, in the COMET Study. Neurol Clin Pract. 2023 Oct;13(5):e200181. doi: 10.1212/CPJ.0000000000200181. Epub 2023 Aug 8.
• Kishnani PS, Diaz-Manera J, Toscano A, Clemens PR, Ladha S, Berger KI, Kushlaf H, Straub V, Carvalho G, Mozaffar T, Roberts M, Attarian S, Chien YH, Choi YC, Day JW, Erdem-Ozdamar S, Illarioshkin S, Goker-Alpan O, Kostera-Pruszczyk A, van der Ploeg AT, An Haack K, Huynh-Ba O, Tammireddy S, Thibault N, Zhou T, Dimachkie MM, Schoser B; COMET Investigator Group. Efficacy and Safety of Avalglucosidase Alfa in Patients With Late-Onset Pompe Disease After 97 Weeks: A Phase 3 Randomized Clinical Trial. JAMA Neurol. 2023 Jun 1;80(6):558-567. doi: 10.1001/jamaneurol.2023.0552.
• Diaz-Manera J, Kishnani PS, Kushlaf H, Ladha S, Mozaffar T, Straub V, Toscano A, van der Ploeg AT, Berger KI, Clemens PR, Chien YH, Day JW, Illarioshkin S, Roberts M, Attarian S, Borges JL, Bouhour F, Choi YC, Erdem-Ozdamar S, Goker-Alpan O, Kostera-Pruszczyk A, Haack KA, Hug C, Huynh-Ba O, Johnson J, Thibault N, Zhou T, Dimachkie MM, Schoser B; COMET Investigator Group. Safety and efficacy of avalglucosidase alfa versus alglucosidase alfa in patients with late-onset Pompe disease (COMET): a phase 3, randomised, multicentre trial. Lancet Neurol. 2021 Dec;20(12):1012-1026. doi: 10.1016/S1474-4422(21)00241-6.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Avalglucosidase alfa	Protein / enzyme biologic	20 mg/kg	Intravenous
Comparator	alglucosidase alfa	Protein / enzyme biologic	20 mg/kg	Intravenous

Indications