Evidence map›Paper›PMID 40817977›Full record

Trial reportJournal of neurology2025

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, Jordi Díaz-Manera, Sergey Illarioshkin, Ans T van der Ploeg, Paula R Clemens, John W Day, Antonio Toscano, Hani Kushlaf, Shafeeq Ladha, Shahram Attarian and 16 more

Registry-linked trialAbstract readRandomized Controlled TrialClinical Trial, Phase III
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02782741 (A Phase 3 Randomized, Multicenter, Multinational, Double-blinded Study Comparing the Efficacy and Safety of Repeated Biweekly Infusions of Avalglucosidase Alfa), which is not on this map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02782741 phase3completednot on this map

A Phase 3 Randomized, Multicenter, Multinational, Double-blinded Study Comparing the Efficacy and Safety of Repeated Biweekly Infusions of Avalglucosidase Alfa (neoGAA, GZ402666) and Alglucosidase Alfa in Treatment naïve Patients With Late-onset Pompe Disease

TypeinterventionalSponsorGenzyme, a Sanofi CompanyRan2016 to 2023Enrolled101ConditionsGlycogen Storage Disease Type II, Pompe's DiseaseArmsAvalglucosidase alfa (GZ402666), Alglucosidase alfa (GZ419829)
3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Trial
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  5. Article
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  7. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

26 authors.

Priya S KishnaniDivision of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA. priya.kishnani@duke.edu.
Jordi Díaz-ManeraJohn Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK.
Sergey IllarioshkinResearch Center of Neurology, Moscow, Russia.
Ans T van der PloegCenter for Lysosomal and Metabolic Diseases, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Paula R ClemensDepartment of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
John W DayDepartments of Neurology and Pediatrics, Stanford University, Stanford, CA, USA.
Antonio ToscanoDepartment of Clinical and Experimental Medicine, Reference Center for Rare Neuromuscular Disorders, University of Messina, Messina, Italy.
Hani KushlafDepartment of Neurology & Rehabilitation Medicine and Department of Pathology & Laboratory Medicine, University of Cincinnati, Cincinnati, OH, USA.
Shafeeq LadhaGregory W. Fulton ALS and Neuromuscular Center, Barrow Neurological Institute, Phoenix, AZ, USA.
Shahram AttarianReferral Centre for Neuromuscular Diseases and ALS, Hôpital La Timone, Marseille, France.
Gerson CarvalhoInstituto Chronos de Apoio À Pesquisa, Brasília, DF, Brazil.
Anna Kostera-PruszczykDepartment of Neurology, Medical University of Warsaw, Warsaw, Poland.
Sevim Erdem-ÖzdamarDepartment of Neurology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
Ozlem Goker-AlpanLysosomal and Rare Disorders Research and Treatment Center (LDRTC), Fairfax, VA, USA.
Tahseen MozaffarDepartment of Neurology, University of California, Irvine, Orange, CA, USA.
Volker StraubJohn Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK.
Mark RobertsSalford Royal NHS Foundation Trust, Salford, UK.
Kristina An HaackSanofi, Chilly-Mazarin, France.
Olivier Huynh-BaSanofi, Chilly-Mazarin, France.
Swathi TammireddySanofi, Cambridge, MA, USA.
Magali PeriquetSanofi, Cambridge, MA, USA.
Nathan ThibaultSanofi, Cambridge, MA, USA.
Tianyue ZhouSanofi, Cambridge, MA, USA.
Mazen M DimachkieDepartment of Neurology, University of Kansas Medical Center, Kansas City, KS, USA.
Benedikt SchoserFriedrich-Baur-Institute, Department of Neurology, LMU Klinikum München, Munich, Germany.
COMET Investigator Group

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesIn 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.

methodsIn 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).

resultsOf 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.

conclusionsIn 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 registrationClinicalTrials.gov, NCT02782741, https://clinicaltrials.gov/ct2/show/NCT02782741 . Registration date: 2016-05-23; Date of first patient enrolled: 2016-11-02.

Indexed as

alpha-GlucosidasesGlycogen Storage Disease Type IIAdultAgedDouble-Blind MethodFemaleHumansMaleMiddle AgedTreatment Outcomealpha-GlucosidasesGAA protein, humanAcid α-glucosidase deficiencyAlglucosidase alfaAvalglucosidase alfaLate-onset Pompe disease

Identifiers

PMID40817977
PMCPMC12357813

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.