{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:55:01Z","timestamp":1792018501647,"version":"4.4.0"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,4,8]],"date-time":"2019-04-08T00:00:00Z","timestamp":1554681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Pegunigalsidase alfa, a novel PEGylated, covalently crosslinked form of \u03b1\u2010galactosidase A developed as enzyme replacement therapy (ERT) for Fabry disease (FD), was designed to increase plasma half\u2010life and reduce immunogenicity, thereby enhancing efficacy compared with available products. Symptomatic adults with FD participated in this open\u2010label, 3\u2010month dose\u2010ranging study, followed by a 9\u2010month extension. Three cohorts were enrolled in a stepwise manner, each receiving increased doses of pegunigalsidase alfa: 0.2, 1.0, 2.0 mg\/kg, via intravenous infusion every other week. Pharmacokinetic analysis occurred on Day 1 and Months 3, 6, and 12. Kidney biopsies at baseline and Month 6 assessed peritubular capillary globotriaosylceramide (Gb3) content. Renal function, cardiac parameters, and other clinical endpoints were assessed throughout. Treatment\u2010emergent adverse events (AEs) and presence of immunoglobulin G (IgG) antidrug antibodies (ADAs) were assessed. Sixteen patients completed 1 year's treatment. Mean terminal plasma half\u2010life (each cohort) ranged from 53 to 121\u2009hours. All 11 male and 1 of 7 female patients presented with classic FD phenotype, in whom renal peritubular capillary Gb3 inclusions were reduced by 84%. Mean estimated glomerular filtration rate was 111\u2009mL\/min\/1.73\u2009m\n                    <jats:sup>2<\/jats:sup>\n                    at baseline, remaining stable throughout treatment. Three patients developed treatment\u2010induced IgG ADAs; following 1 year's treatment, all became ADA\u2010negative. Nearly all treatment\u2010emergent AEs were mild or moderate. One patient withdrew from the study following a serious related AE. Pegunigalsidase alfa may represent an advance in ERT for FD, based on its unique pharmacokinetics and apparent low immunogenicity.\n                  <\/jats:p>","DOI":"10.1002\/jimd.12080","type":"journal-article","created":{"date-parts":[[2019,3,5]],"date-time":"2019-03-05T03:54:11Z","timestamp":1551758051000},"page":"534-544","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":136,"title":["Pegunigalsidase alfa, a novel PEGylated enzyme replacement therapy for Fabry disease, provides sustained plasma concentrations and favorable pharmacodynamics: A 1\u2010year Phase 1\/2 clinical trial"],"prefix":"10.1002","volume":"42","author":[{"given":"Raphael","family":"Schiffmann","sequence":"first","affiliation":[{"name":"Institute of Metabolic Disease 3812 Elm Street  Dallas TX 75226"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozlem","family":"Goker\u2010Alpan","sequence":"additional","affiliation":[{"name":"Lysosomal Disorders Research and Treatment Unit, O&amp;O Alpan LLC  Fairfax Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myrl","family":"Holida","sequence":"additional","affiliation":[{"name":"Medical Genetics\u2010Lysosomal Storage Disorders University of Iowa  Iowa City Iowa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pilar","family":"Giraldo","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras, Hospital de Dia Quiron  Zaragoza Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Barisoni","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Miami  Miami Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert B.","family":"Colvin","sequence":"additional","affiliation":[{"name":"Department of Pathology Boston Massachusetts General Hospital, Harvard Medical School  Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles J.","family":"Jennette","sequence":"additional","affiliation":[{"name":"Department of Pathology University of North Carolina  Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Maegawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics\/Genetics &amp; Metabolism University of Florida  Gainesville Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simeon A.","family":"Boyadjiev","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Section of Genetics, MIND Institute, UC Davis Medical Center  Sacramento 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