{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:49:38Z","timestamp":1791924578940,"version":"4.3.4"},"reference-count":32,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T00:00:00Z","timestamp":1694995200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>An approved therapy for nonalcoholic steatohepatitis (NASH) and fibrosis remains a major unmet medical need.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To investigate the histological and metabolic benefits of pegozafermin, a glycoPEGylated FGF21 analogue, in subjects with biopsy\u2010confirmed NASH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This proof\u2010of\u2010concept, open\u2010label, single\u2010cohort study, part 2 of a phase 1b\/2a clinical trial, was conducted at 16 centres in the United States. Adults (age 21\u201375\u2009years) with NASH (stage 2 or 3 fibrosis, NAS\u22654) and magnetic resonance imaging proton density fat fraction (MRI\u2010PDFF) \u22658% received subcutaneous pegozafermin 27\u2009mg once weekly for 20\u2009weeks. Primary outcomes were improvements in liver histology, and safety and tolerability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 20 enrolled subjects, 19 completed the study. Twelve subjects (63%) met the primary endpoint of \u22652\u2010point improvement in NAFLD activity score with \u22651\u2010point improvement in ballooning or lobular inflammation and no worsening of fibrosis. Improvement of fibrosis without worsening of NASH was observed in 26% of subjects, and NASH resolution without worsening of fibrosis in 32%. Least\u2010squares mean relative change from baseline in MRI\u2010PDFF was \u221264.7% (95% CI: \u221271.7, \u221257.7; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). Significant improvements from baseline were also seen in serum aminotransferases, noninvasive fibrosis tests, serum lipids, glycaemic control and body weight. Adverse events (AEs) were reported in 18 subjects (90%). The most frequently reported AEs were mild\/moderate nausea and diarrhoea. There were no serious AEs, discontinuations due to AEs, or deaths.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Pegozafermin treatment for 20\u2009weeks had beneficial effects on hepatic and metabolic parameters and was well tolerated in subjects with NASH. <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>: NCT04048135.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.17709","type":"journal-article","created":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T07:49:36Z","timestamp":1695023376000},"page":"1005-1015","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Clinical trial: Effects of pegozafermin on the liver and on metabolic comorbidities in subjects with biopsy\u2010confirmed nonalcoholic steatohepatitis"],"prefix":"10.1111","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9872-2391","authenticated-orcid":false,"given":"Naim","family":"Alkhouri","sequence":"first","affiliation":[{"name":"Arizona Liver Health  Chandler Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald","family":"Lazas","sequence":"additional","affiliation":[{"name":"ObjectiveHealth\/Digestive Health Research  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohit","family":"Loomba","sequence":"additional","affiliation":[{"name":"University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan P.","family":"Frias","sequence":"additional","affiliation":[{"name":"Velocity Clinical Research  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shibao","family":"Feng","sequence":"additional","affiliation":[{"name":"89bio Inc.  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