{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T17:27:08Z","timestamp":1787851628613,"version":"build-2784847793"},"reference-count":41,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T00:00:00Z","timestamp":1698624000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014923","name":"CymaBay Therapeutics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Seladelpar is a potent and selective peroxisome proliferator\u2010activated receptor\u2010\u03b4 agonist that targets multiple cell types involved in primary biliary cholangitis (PBC), leading to anti\u2010cholestatic, anti\u2010inflammatory and anti\u2010pruritic effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To evaluate the\u00a0long\u2010term safety and efficacy of seladelpar in patients with PBC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In an open\u2010label, international, long\u2010term extension study, patients with PBC completing seladelpar lead\u2010in studies continued treatment. Seladelpar was taken orally once daily at doses of 5 or 10\u2009mg with dose adjustment permitted for safety or tolerability. The primary analysis was for safety and the secondary efficacy analysis examined biochemical markers of cholestasis and liver injury. The study was terminated early due to the unexpected histological findings in a concurrent study for non\u2010alcoholic steatohepatitis, which were subsequently found to predate treatment. Safety and efficacy data were analysed through 2\u2009years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>There were no serious treatment\u2010related adverse events observed among 106 patients treated with seladelpar for up to 2\u2009years. There were four discontinuations for safety, one possibly related to seladelpar. Among 53 patients who completed 2\u2009years of seladelpar, response rates increased from years 1 to 2 for the composite endpoint (alkaline phosphatase [ALP] &lt;1.67\u2009\u00d7\u2009ULN, \u226515% decrease in ALP, and total bilirubin \u2264ULN) and ALP normalisation from 66% to 79% and from 26% to 42%, respectively. In those with elevated bilirubin at baseline, 43% achieved normalisation at year 2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Seladelpar was safe, and markedly improved biochemical markers of cholestasis and liver injury in patients with PBC. These effects were maintained or improved throughout the second year. Clinicaltrials.gov: NCT03301506; Clinicaltrialsregister.eu: 2017\u2010003910\u201016.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apt.17755","type":"journal-article","created":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:55:25Z","timestamp":1698713725000},"page":"186-200","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Open\u2010label, clinical trial extension: Two\u2010year safety and efficacy results of seladelpar in patients with primary biliary cholangitis"],"prefix":"10.1111","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4874-7010","authenticated-orcid":false,"given":"Marlyn J.","family":"Mayo","sequence":"first","affiliation":[{"name":"Division of Digestive and Liver Diseases, Department of Internal Medicine University of Texas Southwestern  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5547-6020","authenticated-orcid":false,"given":"John M.","family":"Vierling","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Gastroenterology and Hepatology, Department of Surgery, Division of Abdominal Transplantation Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3906-6811","authenticated-orcid":false,"given":"Christopher L.","family":"Bowlus","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology University of California Davis School of Medicine  Sacramento California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5498-6037","authenticated-orcid":false,"given":"Cynthia","family":"Levy","sequence":"additional","affiliation":[{"name":"Division of Digestive Health and Liver Diseases University of Miami Miller School of Medicine  Miami Florida USA"},{"name":"Schiff Center for Liver Diseases University of Miami  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6736-2255","authenticated-orcid":false,"given":"Gideon M.","family":"Hirschfield","sequence":"additional","affiliation":[{"name":"Toronto Centre for Liver Disease  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy W.","family":"Neff","sequence":"additional","affiliation":[{"name":"Covenant Metabolic Specialists LLC  Sarasota and Fort Myers Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Galambos","sequence":"additional","affiliation":[{"name":"Digestive Healthcare of Georgia  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8666-3849","authenticated-orcid":false,"given":"Stuart C.","family":"Gordon","sequence":"additional","affiliation":[{"name":"Division of Hepatology, Henry Ford Health Wayne State University School of Medicine  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian B.","family":"Borg","sequence":"additional","affiliation":[{"name":"Southern Therapy and Advanced Research LLC  Jackson Mississippi USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8285-2204","authenticated-orcid":false,"given":"Stephen A.","family":"Harrison","sequence":"additional","affiliation":[{"name":"Radcliffe Department of Medicine University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4374-4507","authenticated-orcid":false,"given":"Paul J.","family":"Thuluvath","sequence":"additional","affiliation":[{"name":"Institute of Digestive Health and Liver Diseases Mercy Medical Center  Baltimore Maryland USA"},{"name":"Department of Medicine University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9588-9364","authenticated-orcid":false,"given":"Aparna","family":"Goel","sequence":"additional","affiliation":[{"name":"Department of Medicine Stanford University  Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3575-6516","authenticated-orcid":false,"given":"Mitchell L.","family":"Shiffman","sequence":"additional","affiliation":[{"name":"Liver Institute of Virginia, Bon Secours Mercy Health  Richmond and Newport News Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0919-4468","authenticated-orcid":false,"given":"Mark G.","family":"Swain","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E. 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