{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T08:28:31Z","timestamp":1790497711584,"version":"4.1.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","license":[{"start":{"date-parts":[[2018,8,30]],"date-time":"2018-08-30T00:00:00Z","timestamp":1535587200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatology Communications"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:p>Patients with primary biliary cholangitis (PBC) who had an inadequate response to ursodiol have few treatment options. Alkaline phosphatase (ALP) and bilirubin levels correlate with the risk of liver transplant or death in PBC patients. Fibroblast growth factor (FGF) 19 is a hormone that acts directly in the liver to regulate bile acid synthesis. We evaluated NGM282, an engineered analogue of FGF19, for the treatment of PBC. In this 28\u2010day, double\u2010blind, placebo\u2010controlled phase 2 trial, 45 PBC patients who had an inadequate response to ursodiol were randomly assigned 1:1:1 to receive subcutaneous daily doses of either NGM282 at 0.3 mg (n = 14), 3 mg (n = 16), or placebo (n = 15). The primary endpoint was a change in ALP from baseline after 28 days of treatment. At day 28, ALP was significantly reduced with NGM282 treatment at both 0.3 mg (least\u2010squares mean \u201351.0 IU\/L [standard error (SE) 15.4]) and 3 mg (\u201366.0 IU\/L [SE 16.0]) versus placebo (3.3 IU\/L [SE 14.8]), with least\u2010squares mean differences of \u201354.3 IU\/L (95% confidence interval \u2013104.2 to \u20134.5; <jats:italic toggle=\"yes\">P<\/jats:italic> = 0.0149) and \u201369.3 IU\/L (95% confidence interval \u2013120.5 to \u201318.3; <jats:italic toggle=\"yes\">P<\/jats:italic> = 0.0030), respectively. Fifty percent (7 of 14) of patients receiving NGM282 0.3 mg and 46% (6 of 13) of those receiving NGM282 3mg achieved 15% or greater reduction in ALP levels from baseline, compared with 7% (1 of 15) of patients receiving placebo. NGM282 also significantly reduced serum concentrations of transaminases and immunoglobulins. Most adverse events were grade 1 (mild) to grade 2 (moderate) in severity, with gastrointestinal disorders more frequent in the NGM282 treatment groups. No worsening of pruritus was observed with NGM282 treatment. <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> NGM282 administered for 28 days resulted in significant improvements in ALP and transaminase levels compared with placebo, with an acceptable safety profile in patients with PBC. (<jats:italic toggle=\"yes\">Hepatology Communications<\/jats:italic> 2018; 00:000\u2010000)<\/jats:p>","DOI":"10.1002\/hep4.1209","type":"journal-article","created":{"date-parts":[[2018,8,30]],"date-time":"2018-08-30T19:21:53Z","timestamp":1535656913000},"page":"1037-1050","source":"Crossref","is-referenced-by-count":118,"title":["NGM282 for Treatment of Patients With Primary Biliary Cholangitis: A Multicenter, Randomized, Double\u2010Blind, Placebo\u2010Controlled Trial"],"prefix":"10.1097","volume":"2","author":[{"given":"Marlyn J.","family":"Mayo","sequence":"first","affiliation":[{"name":"University of Texas,Southwestern Medical Center,Dallas,Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan J.","family":"Wigg","sequence":"additional","affiliation":[{"name":"Flinders Medical Center,Adelaide,South Australia,Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara A.","family":"Leggett","sequence":"additional","affiliation":[{"name":"Royal Brisbane and Women's Hospital and School of Medicine,University of Queensland,Brisbane,Queensland,Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hays","family":"Arnold","sequence":"additional","affiliation":[{"name":"Digestive Research Center,San Antonio,Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J.","family":"Thompson","sequence":"additional","affiliation":[{"name":"St. Vincent's Hospital,Melbourne,VIC,Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Weltman","sequence":"additional","affiliation":[{"name":"Nepean Hospital,Sydney,New South Wales,Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth J.","family":"Carey","sequence":"additional","affiliation":[{"name":"Mayo Clinic\u2013Arizona,Scottsdale,Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Muir","sequence":"additional","affiliation":[{"name":"Duke University,Durham,North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Ling","sequence":"additional","affiliation":[{"name":"NGM Biopharmaceuticals Inc.,South San Francisco,California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Rossi","sequence":"additional","affiliation":[{"name":"NGM Biopharmaceuticals Inc.,South San Francisco,California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex M.","family":"DePaoli","sequence":"additional","affiliation":[{"name":"NGM Biopharmaceuticals Inc.,South San Francisco,California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2018,8,30]]},"reference":[{"key":"hep41209-bib-0001-20240114","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1016\/S0140-6736(15)00154-3","article-title":"Primary biliary cirrhosis","volume":"386","year":"2015","journal-title":"Lancet"},{"key":"hep41209-bib-0002-20240114","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.jhep.2017.03.022","article-title":"EASL clinical practice guidelines: the diagnosis and management of patients with primary biliary cholangitis","volume":"67","year":"2017","journal-title":"J Hepatol"},{"key":"hep41209-bib-0003-20240114","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1002\/hep.22906","article-title":"Primary biliary cirrhosis","volume":"50","year":"2009","journal-title":"Hepatology"},{"key":"hep41209-bib-0004-20240114","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1053\/j.gastro.2014.08.029","article-title":"Levels of alkaline phosphatase and bilirubin are surrogate end points of outcomes of patients with primary biliary cirrhosis: an international follow\u2010up study","volume":"147","year":"2014","journal-title":"Gastroenterology"},{"key":"hep41209-bib-0005-20240114","doi-asserted-by":"crossref","first-page":"S25","DOI":"10.1016\/j.jhep.2015.02.023","article-title":"New paradigms in the treatment of hepatic cholestasis: from UDCA to FXR, PXR and beyond","volume":"62","year":"2015","journal-title":"J Hepatol"},{"key":"hep41209-bib-0006-20240114","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1056\/NEJM199405123301903","article-title":"Ursodiol for the long\u2010term treatment of primary biliary cirrhosis. The UDCA\u2010PBC Study Group","volume":"330","year":"1994","journal-title":"N Engl J Med"},{"key":"hep41209-bib-0007-20240114","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1016\/S0140-6736(10)61965-4","article-title":"Primary biliary cirrhosis","volume":"377","year":"2011","journal-title":"Lancet"},{"key":"hep41209-bib-0008-20240114","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1056\/NEJMoa1509840","article-title":"A placebo\u2010controlled trial of obeticholic acid in primary biliary cholangitis","volume":"375","year":"2016","journal-title":"N Engl J Med"},{"key":"hep41209-bib-0009-20240114","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/S2468-1253(17)30246-7","article-title":"Seladelpar (MBX\u20108025), a selective PPAR\u2010delta agonist, in patients with primary biliary cholangitis with an inadequate response to ursodeoxycholic acid: a double\u2010blind, randomised, placebo\u2010controlled, phase 2, proof\u2010of\u2010concept study","volume":"2","year":"2017","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"hep41209-bib-0010-20240114","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1159\/000371670","article-title":"Bile acids as hormones: the FXR\u2010FGF15\/19 pathway","volume":"33","year":"2015","journal-title":"Dig Dis"},{"key":"hep41209-bib-0011-20240114","doi-asserted-by":"crossref","first-page":"S120","DOI":"10.1194\/jlr.R800026-JLR200","article-title":"Fifty years of advances in bile acid synthesis and metabolism","volume":"50","year":"2009","journal-title":"J Lipid Res"},{"key":"hep41209-bib-0012-20240114","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1053\/j.gastro.2011.10.028","article-title":"Selective activation of nuclear bile acid receptor FXR in the intestine protects mice against cholestasis","volume":"142","year":"2012","journal-title":"Gastroenterology"},{"key":"hep41209-bib-0013-20240114","first-page":"247ra100","article-title":"A nontumorigenic variant of FGF19 treats cholestatic liver diseases","volume":"6","year":"2014","journal-title":"Sci Transl Med"},{"key":"hep41209-bib-0014-20240114","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1016\/S0002-9440(10)61177-7","article-title":"A mouse model of hepatocellular carcinoma: ectopic expression of fibroblast growth factor 19 in skeletal muscle of transgenic mice","volume":"160","year":"2002","journal-title":"Am J Pathol"},{"key":"hep41209-bib-0015-20240114","doi-asserted-by":"crossref","first-page":"3306","DOI":"10.1158\/0008-5472.CAN-14-0208","article-title":"Separating tumorigenicity from bile acid regulatory activity for endocrine hormone FGF19","volume":"74","year":"2014","journal-title":"Cancer Res"},{"key":"hep41209-bib-0016-20240114","doi-asserted-by":"crossref","first-page":"15433","DOI":"10.1038\/ncomms15433","article-title":"Non\u2010cell\u2010autonomous activation of IL\u20106\/STAT3 signaling mediates FGF19\u2010driven hepatocarcinogenesis","volume":"8","year":"2017","journal-title":"Nat Commun"},{"key":"hep41209-bib-0017-20240114","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1002\/hep.28257","article-title":"Engineered fibroblast growth factor 19 reduces liver injury and resolves sclerosing cholangitis in Mdr2\u2010deficient mice","volume":"63","year":"2016","journal-title":"Hepatology"},{"key":"hep41209-bib-0018-20240114","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1016\/S0140-6736(18)30474-4","article-title":"NGM282 for treatment of non\u2010alcoholic steatohepatitis: a multicentre, randomised, double\u2010blind, placebo\u2010controlled, phase 2 trial","volume":"391","year":"2018","journal-title":"Lancet"},{"key":"hep41209-bib-0019-20240114","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1111\/j.1365-2133.2009.09586.x","article-title":"The 5\u2010D itch scale: a new measure of pruritus","volume":"162","year":"2010","journal-title":"Br J Dermatol"},{"key":"hep41209-bib-0020-20240114","doi-asserted-by":"crossref","first-page":"497","DOI":"10.2340\/00015555-1265","article-title":"Visual analogue scale: evaluation of the instrument for the assessment of pruritus","volume":"92","year":"2012","journal-title":"Acta Derm Venereol"},{"key":"hep41209-bib-0021-20240114","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1136\/gut.2005.065862","article-title":"Development, validation, and evaluation of the PBC\u201040, a disease specific health related quality of life measure for primary biliary cirrhosis","volume":"54","year":"2005","journal-title":"Gut"},{"key":"hep41209-bib-0022-20240114","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1053\/j.gastro.2014.12.005","article-title":"Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid","volume":"148","year":"2015","journal-title":"Gastroenterology"},{"key":"hep41209-bib-0023-20240114","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1002\/hep.29569","article-title":"A randomized trial of obeticholic acid monotherapy in patients with primary biliary cholangitis","volume":"67","year":"2018","journal-title":"Hepatology"},{"key":"hep41209-bib-0025-20240114","first-page":"CD000551","article-title":"Ursodeoxycholic acid for primary biliary cirrhosis","volume":"12","year":"2012","journal-title":"Cochrane Database Syst Rev"},{"key":"hep41209-bib-0026-20240114","first-page":"CD003778","article-title":"Glucocorticosteroids for primary biliary cirrhosis","year":"2005","journal-title":"Cochrane Database Syst Rev"},{"key":"hep41209-bib-0027-20240114","first-page":"CD004385","article-title":"Methotrexate for primary biliary cirrhosis","year":"2010","journal-title":"Cochrane Database Syst Rev"},{"key":"hep41209-bib-0028-20240114","first-page":"CD004789","article-title":"D\u2010penicillamine for primary biliary cirrhosis","year":"2004","journal-title":"Cochrane Database Syst Rev"},{"key":"hep41209-bib-0029-20240114","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.2147\/TCRM.S113052","article-title":"New developments in the treatment of primary biliary cholangitis\u2014role of obeticholic acid","volume":"13","year":"2017","journal-title":"Ther Clin Risk Manag"},{"key":"hep41209-bib-0030-20240114","doi-asserted-by":"crossref","first-page":"e105930","DOI":"10.1371\/journal.pone.0105930","article-title":"Genome\u2010wide binding and transcriptome analysis of human farnesoid X receptor in primary human hepatocytes","volume":"9","year":"2014","journal-title":"PLoS One"},{"key":"hep41209-bib-0031-20240114","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1056\/NEJMc071467","article-title":"Hypercholesterolemia in primary biliary cirrhosis","volume":"357","year":"2007","journal-title":"N Engl J Med"},{"key":"hep41209-bib-0032-20240114","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1136\/gut.2005.079814","article-title":"Hypercholesterolaemia is not associated with early atherosclerotic lesions in primary biliary cirrhosis","volume":"55","year":"2006","journal-title":"Gut"},{"key":"hep41209-bib-0033-20240114","first-page":"399","article-title":"The challenge of cholestatic pruritus","volume":"75","year":"2012","journal-title":"Acta Gastroenterol Belg"},{"key":"hep41209-bib-0034-20240114","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1002\/hep.26909","article-title":"Pruritus in cholestasis: facts and fiction","volume":"60","year":"2014","journal-title":"Hepatology"}],"container-title":["Hepatology Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep4.1209","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hep4.1209","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/hep4.1209","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/02009842-201809000-00006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,14]],"date-time":"2024-01-14T17:06:29Z","timestamp":1705251989000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/02009842-201809000-00006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,30]]},"references-count":33,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2018]]}},"URL":"https:\/\/doi.org\/10.1002\/hep4.1209","relation":{},"ISSN":["2471-254X","2471-254X"],"issn-type":[{"value":"2471-254X","type":"print"},{"value":"2471-254X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,30]]}}}