Efficacy and safety of avalglucosidase alfa in patients with late-onset Pompe disease after 145 weeks of treatment during the COMET trial

Priya S. Kishnani, Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA. priya.kishnani@duke.edu.
Jordi Díaz-Manera, John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK.
Sergey Illarioshkin, Research Center of Neurology, Moscow, Russia.
Ans T. van der Ploeg, Center for Lysosomal and Metabolic Diseases, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Paula R. Clemens, Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
John W. Day, Departments of Neurology and Pediatrics, Stanford University, Stanford, CA, USA.
Antonio Toscano, Department of Clinical and Experimental Medicine, Reference Center for Rare Neuromuscular Disorders, University of Messina, Messina, Italy.
Hani Kushlaf, Department of Neurology & Rehabilitation Medicine and Department of Pathology & Laboratory Medicine, University of Cincinnati, Cincinnati, OH, USA.
Shafeeq Ladha, Gregory W. Fulton ALS and Neuromuscular Center, Barrow Neurological Institute, Phoenix, AZ, USA.
Shahram Attarian, Referral Centre for Neuromuscular Diseases and ALS, Hôpital La Timone, Marseille, France.
Gerson Carvalho, Instituto Chronos de Apoio À Pesquisa, Brasília, DF, Brazil.
Anna Kostera-Pruszczyk, Department of Neurology, Medical University of Warsaw, Warsaw, Poland.
Sevim Erdem-Özdamar, Department of Neurology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
Ozlem Goker-Alpan, Lysosomal and Rare Disorders Research and Treatment Center (LDRTC), Fairfax, VA, USA.
Tahseen Mozaffar, Department of Neurology, University of California, Irvine, Orange, CA, USA.
Volker Straub, John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK.
Mark Roberts, Salford Royal NHS Foundation Trust, Salford, UK.
Kristina An Haack, Sanofi, Chilly-Mazarin, France.
Olivier Huynh-Ba, Sanofi, Chilly-Mazarin, France.
Swathi Tammireddy, Sanofi, Cambridge, MA, USA.
Magali Periquet, Sanofi, Cambridge, MA, USA.
Nathan Thibault, Sanofi, Cambridge, MA, USA.
Tianyue Zhou, Sanofi, Cambridge, MA, USA.
Mazen M. Dimachkie, Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA.
Benedikt Schoser, Friedrich-Baur-Institute, Department of Neurology, LMU Klinikum München, Munich, Germany.

Document Type

Article

Abstract

BACKGROUND AND OBJECTIVES: In the COMET trial, avalglucosidase alfa treatment for late-onset Pompe disease was safe, tolerable and associated with stabilization or improvement in disease parameters through 97 weeks. We report outcomes in the trial extension through 145 weeks of treatment. METHODS: In this phase 3, double-blind, randomized trial, participants with previously untreated late-onset Pompe disease were randomly assigned to receive 20 mg/kg avalglucosidase alfa or alglucosidase alfa every other week for 49 weeks; thereafter, all patients received 20 mg/kg avalglucosidase alfa every other week. For this analysis, efficacy was assessed at 145 weeks and safety to last follow-up (data cutoff: March 11, 2022). RESULTS: Of 100 participants in the double-blind treatment period, 95 entered the open-label extension, and 88 completed ≥ 145 weeks of treatment. At study start, the mean upright FVC percent predicted was similar between treatment arms, and 6MWT distance was greater in the avalglucosidase alfa arm. From baseline to week 145, the LS mean (SE) FVC percent predicted increased by 1.38 (1.22) in the avalglucosidase alfa arm and 1.25 (1.34) in the switch arm. The LS mean (SE) 6MWT distance walked increased by 20.65 (9.60) m and 0.29 (10.42) m, respectively. Potentially treatment-related adverse events were reported in 27 patients (53%) in the avalglucosidase alfa arm and 25 patients (57%) in the switch arm. Anti-drug antibodies declined over time in both arms. CONCLUSIONS: In this randomized clinical trial extension, positive clinical outcomes were maintained for patients taking avalglucosidase alfa for up to 145 weeks with no new safety concerns. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02782741, https://clinicaltrials.gov/ct2/show/NCT02782741 . Registration date: 2016-05-23; Date of first patient enrolled: 2016-11-02.

Medical Subject Headings

Humans; Glycogen Storage Disease Type II (drug therapy); Male; Female; alpha-Glucosidases (therapeutic use, adverse effects, administration & dosage); Double-Blind Method; Middle Aged; Adult; Treatment Outcome; Aged

Publication Date

8-16-2025

Publication Title

Journal of neurology

E-ISSN

1432-1459

Volume

272

Issue

9

First Page

581

PubMed ID

40817977

Digital Object Identifier (DOI)

10.1007/s00415-025-13266-y

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