{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T14:01:53Z","timestamp":1785506513668,"version":"3.56.0"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Klinikum der Universit\u00e4t M\u00fcnchen"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Pompe disease, also known as glycogen storage disease type II, is a rare, progressive lysosomal storage disorder caused by pathogenic variants in the\n                      <jats:italic>GAA<\/jats:italic>\n                      gene. Enzyme replacement therapy has transformed the natural history of the disease; however, with three agents now approved \u2014 alglucosidase alfa, avalglucosidase alfa, and cipaglucosidase alfa plus miglustat \u2014 clinicians lack a consensus quantitative framework for determining when a patient has left the zone of therapeutic stability and requires treatment reassessment, escalation, or switching.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A structured synthesis was conducted of Phase 2 and Phase 3 randomized controlled trials, open-label extension studies, registry analyses, real-world observational datasets, switching studies, scoping review evidence on global diagnostic and epidemiological variation, and consensus recommendations evaluating approved enzyme replacement therapies for Pompe disease, with an emphasis on late-onset Pompe disease. Outcome domains evaluated included forced vital capacity percentage predicted, six-minute walk test distance, urinary hexose tetrasaccharide, serum creatine kinase, maximal inspiratory and expiratory pressures, anti-drug antibody titers, functional motor scales, and patient-reported outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Across LOTS, COMET and its 97- and 145-week extensions, PROPEL and ATB200-07, ATB200-02, the STIG real-world cohort, the International Pompe Registry, European Pompe Consortium start\u2013switch\u2013stop criteria, post hoc PROPEL switching analyses, real-world alglucosidase-to-avalglucosidase switching data, and the first multicenter real-world analysis of switching to next-generation enzyme replacement therapies, a coherent therapeutic corridor of stability emerges. Forced vital capacity change within approximately\u2009\u2212\u20091% to +\u20095% per year defines the respiratory stability corridor; a confirmed decline exceeding 5% over 12 months constitutes an alarm threshold. For the six-minute walk test, stabilization within approximately\u2009\u00b1\u200925\u00a0m of the peak is an adequate response, whereas a confirmed decline of more than 25\u00a0m from the peak is actionable. Biomarker improvement or normalization of urinary hexose tetrasaccharide and creatine kinase is achievable with next-generation enzyme replacement therapies and serves as an early surrogate of enhanced lysosomal glycogen clearance. Multicenter real-world switching data indicate that transitions between enzyme replacement therapy preparations are generally feasible and associated with clinical stability in late-onset Pompe disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This formal, multi-domain therapeutic corridor of stability for enzyme replacement therapy in Pompe disease is grounded in available Phase 2, Phase 3, extension, registry, consensus, and real-world evidence. The framework supports structured monitoring, timely reassessment of treatment, and personalized management for patients receiving long-term enzyme replacement therapy. Prospective validation with standardized monitoring is required.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial number<\/jats:title>\n                    <jats:p>Not applicable.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-026-04518-9","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T16:55:37Z","timestamp":1785257737000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Defining the therapeutic corridor of stability in enzyme replacement therapy for Pompe disease: a position statement"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2757-8131","authenticated-orcid":false,"given":"Benedikt","family":"Schoser","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"4518_CR1","volume-title":"The Online Metabolic and Molecular Bases of Inherited Disease","author":"AJJ Reuser","year":"2019","unstructured":"Reuser AJJ, Hirschhorn R, Kroos MA. Pompe disease: glycogen storage disease type II, acid alpha-glucosidase deficiency. In: Valle DL, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA, editors. The Online Metabolic and Molecular Bases of Inherited Disease. New York: McGraw-Hill; 2019."},{"key":"4518_CR2","doi-asserted-by":"publisher","unstructured":"Giugliani R, Solomon F, Kushlaf H, Wright E, Haselkorn T, Zanoteli E, Schoser B. Global variations in diagnostic methods and epidemiological estimates in Pompe disease: findings from a scoping review. Orphanet J Rare Dis. 2025;20(1):216. https:\/\/doi.org\/10.1186\/s13023-025-03679-3. PMID: 40329343.","DOI":"10.1186\/s13023-025-03679-3"},{"issue":"15","key":"4518_CR3","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1056\/NEJMoa0909859","volume":"362","author":"AT van der Ploeg","year":"2010","unstructured":"van der Ploeg AT, Clemens PR, Corzo D, Escolar DM, Florence J, Groeneveld GJ, et al. 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STIG study: real-world data of long-term outcomes of adults with Pompe disease under enzyme replacement therapy with alglucosidase alfa. J Neurol. 2021;268(7):2482\u201392. https:\/\/doi.org\/10.1007\/s00415-021-10409-9.","journal-title":"J Neurol"},{"issue":"12","key":"4518_CR6","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.1016\/S1474-4422(21)00241-6","volume":"20","author":"J Diaz-Manera","year":"2021","unstructured":"Diaz-Manera J, Kishnani PS, Kushlaf H, Ladha S, Mozaffar T, Straub V, et al. Safety and efficacy of avalglucosidase alfa versus alglucosidase alfa in patients with late-onset Pompe disease (COMET): a phase 3, randomised, multicentre trial. 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This Position Statement is a synthesis of published data and does not involve original research on human participants or animals.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Benedikt Schoser has participated in the following advisory boards for Alnylam, Avidity, Bayer, Dyne, Sanofi, Souffle. Research grants held for EU Horizon 2022 COMPASS-NMD, EU Horizon 2022 PALADIN, and EU Horizon 2022 Entry-DM. Speaker\u2019s honoraria for Amicus, Alexion, Argenx, Dyne, Kedrion, and Sanofi.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"259"}}