{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T06:07:16Z","timestamp":1784268436320,"version":"3.55.0"},"reference-count":24,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Pompe disease (PD) is a rare, autosomal recessive neuromuscular disorder caused by a deficiency in acid \u03b1\u2010glucosidase. In the Phase 3 COMET trial (NCT02782741), respiratory function was examined in participants with late\u2010onset PD randomized to receive enzyme replacement therapy with alglucosidase alfa (ALG; standard of care) or avalglucosidase alfa (AVA; intervention) in the primary analysis period (PAP). The open\u2010label extended treatment period (ETP) provided long\u2010term data on AVA treatment. This post hoc analysis evaluated respiratory outcomes in participants who received ALG in the PAP (Weeks 0\u201349) and switched to AVA in the ETP (Weeks 49\u2013145). Participants were categorized according to improvement in upright forced vital capacity percent\u2010predicted (FVC) at Week 49. Forty\u2010four participants were included, of whom 20 (45.5%) had \u0394FVC\u2009&gt;\u20090% predicted at Week 49. Among \u0394FVC\u2009&gt;\u20090% predicted participants, FVC improved during the PAP (estimated slope [SE]: 4.0 (1.1) %\/year, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01), and was maintained following switch to AVA in the ETP (0.1 (0.8) %\/year, <jats:italic>p<\/jats:italic>\u2009=\u20090.86). For participants with \u0394FVC\u2009\u2264\u20090% predicted during the PAP (<jats:italic>n<\/jats:italic>\u2009=\u200924; estimated slope [SE]: \u22123.4 (1.0) %\/year, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01), FVC stabilized following switch to AVA (0.3 (0.7) %\/year, <jats:italic>p<\/jats:italic>\u2009=\u20090.70). Slopes in measures of respiratory airflow and inspiratory\/expiratory muscle strength were consistent with these findings. Similar results were observed using \u0394FVC\u2009\u2265\u20093% predicted as a measure of clinically meaningful change. This analysis demonstrates clinically meaningful maintenance in measures of lung volume (FVC) and airflow (forced expiratory volume in 1 s) after switching therapy from ALG to AVA that persists for \u2265\u20092\u2009years and is independent of prior outcomes with ALG.<\/jats:p>","DOI":"10.1002\/jmd2.70033","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:20:21Z","timestamp":1755044421000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Efficacy of Switching Therapy From Alglucosidase Alfa to Avalglucosidase Alfa on Respiratory Function in Participants With Late\u2010Onset Pompe Disease: A Post Hoc Analysis From the <scp>COMET<\/scp> Trial"],"prefix":"10.1002","volume":"66","author":[{"given":"Priya S.","family":"Kishnani","sequence":"first","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics Duke University Medical Center  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Boentert","sequence":"additional","affiliation":[{"name":"Department of Neurology Institute of Translational Neurology, M\u00fcnster University Hospital  M\u00fcnster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Wenninger","sequence":"additional","affiliation":[{"name":"LMU Clinic, Department of Neurology Friedrich\u2010Baur\u2010Institute, University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4879-6071","authenticated-orcid":false,"given":"Kenneth I.","family":"Berger","sequence":"additional","affiliation":[{"name":"Sanofi  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Msihid","sequence":"additional","affiliation":[{"name":"Sanofi  Gentilly France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lasair","family":"O'Callaghan","sequence":"additional","affiliation":[{"name":"Sanofi  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachida","family":"Essadi\u2010Addou","sequence":"additional","affiliation":[{"name":"Sanofi  Gentilly France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Gallego","sequence":"additional","affiliation":[{"name":"Sanofi  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeraj Singh","family":"Rawat","sequence":"additional","affiliation":[{"name":"Sanofi  Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Huynh\u2010Ba","sequence":"additional","affiliation":[{"name":"Sanofi  Gentilly France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Diaz\u2010Manera","sequence":"additional","affiliation":[{"name":"John Walton Muscular Dystrophy Research Centre Newcastle University Centre for Life  Newcastle upon Tyne UK"},{"name":"Neuromuscular Diseases Unit, Neurology Department Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Enfermedades Raras (CIBERER)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2024.1309146"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31324"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-7-73"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1203\/PDR.0b013e3181b24e94"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-020-09936-8"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00241-6"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.2147\/TCRM.S334232"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000008441"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0738-0"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2019.05.27"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.37"},{"key":"e_1_2_12_13_1","unstructured":"ClinicalTrials.gov NCT02782741 Study to Compare the Efficacy and Safety of Enzyme Replacement Therapies Avalglucosidase Alfa and Alglucosidase Alfa Administered Every Other Week in Patients With Late\u2010Onset Pompe Disease Who Have Not Been Previously Treated for Pompe Disease (COMET) https:\/\/clinicaltrials.gov\/study\/NCT02782741."},{"issue":"1","key":"e_1_2_12_14_1","article-title":"Efficacy and Safety of Avalglucosidase Alfa in Participants With Late\u2010Onset Pompe Disease After 145\u2009Weeks' Treatment: Phase 3 COMET Trial","volume":"5","author":"Henderson R. 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