Luketic, Victor Vargas, Catherine Vincent, Bettina E. Hansen Obeticholic acid (OCA, 6-ethyl chenodeoxycholic acid) is a highly potent FXR agonist being developed for the treatment of primary biliary cirrhosis. Efficacy and safety of OCA, given as monotherapy, was evaluated in a 12-week,

Phase 2, double-blind placebo controlled trial and showed significant improvement in alkaline phosphatase (ALP), bilirubin and other indices of cholestasis, inflammation and hepatic function. This was followed by an open-label long-term extension period in which patients either continued OCA or switched from placebo to OCA. This analysis evaluated the safety and efficacy of OCA selleck chemical through 3.5 and 4 years of treatment. During the ongoing open label extension period, subjects initiated find more OCA at 10mg once daily and

titrated to 50mg based on response and tolerability. Ursodeoxycholic acid (UDCA) was added in 11 subjects. Subjects (N=28): mean age 58yrs; female: 78%; Caucasian: 96%. Baseline: ALP: 442±275U/L; bilirubin: 4.6±3.2mmol/L; GGT: 460±318U/L; ALT: 91±61U/L; AST: 72±39 U/L. Median exposure was 3.8 (2.6-4.2yrs). Nine subjects terminated early overall; 6 due to AEs, 4 of which were pruritus. The majority of patients received OCA doses ≤ 25mg. Improvement in serum liver biochemical tests through 4 years of treatment was observed. Pruritus, the most common AE, improved with long-term treatment; The incidence of new onset pruritus declined after the 1st year and severity tended to decrease with continued treatment. PBC is a chronic cholestatic liver disease with persistent significant unmet need. Long-term OCA treatment in this study maintained a durable improvement in ALP and other hepatic biochemistry analytes with no new safety findings and improved tolerability. Data are mean(SE). *p≤0.05 change from baseline Disclosures: Kris V. Kowdley 上海皓元 – Advisory Committees or Review Panels: AbbVie, Gilead, Merck, Novartis, Trio Health, Boeringer Ingelheim, Ikaria, Janssen; Grant/Research Support: AbbVie, Beckman, Boeringer Ingelheim, BMS, Gilead Sciences, Ikaria, Janssen, Merck, Mochida,

Vertex Richard Pencek – Employment: Intercept Pharmaceuticals; Stock Shareholder: Intercept Pharmaceuticals Tonya Marmon – Employment: Intercept Pharmaceuticals, Inc; Stock Shareholder: Intercept Pharmaceuticals, Inc David Shapiro – Employment: Inttercept Pharmaceuticals Roya Hooshmand-Rad – Employment: Intercept pharmaceuticals Inc. Secondary sclerosing cholangitis in critically ill patients (SSC-CIP) is a relatively new previously unrecognized entity which may lead to severe biliary disease with rapid progression to cirrhosis. It is possibly mediated by ischemic damage of the biliary tree, followed by bacterial colonization and progressive destruction of biliary ducts. SSC-CIP is described very rarely in patients following major burn.