Durable response in the markers of cholestasis through 5 years of open-label extension study of obeticholic acid in primary biliary cholangitis

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Obeticholic acid (OCA) is a selective and potent farnesoid X receptor agonist indicated for treatment of primary biliary cholangitis (PBC). POISE was a placebo-controlled, phase 3 study of the efficacy and safety of OCA in PBC, and included a 12-month double-blind phase with a 5-year open-label extension (OLE). The OLE was to assess the long-term safety of OCA and the durability of OCA effects on serum markers of cholestasis. Following the 1 year double blind phase, patients on placebo started OCA and were then pooled with OCA treated patients to evaluate the efficacy and safety of up to 6 years of OCA treatment. 146 patients (76%) completed the protocol as specified following administrative shutdown of the study. 158 patients (82%) completed 4 years of OCA treatment and 116 (60%) patients completed 5 years of OCA treatment; 52 patients who had received OCA in the double-blind phase completed 6 years on treatment. The percentage of patients meeting the primary endpoint was 46% at 12 months and 50% at 48, 60, and 72 months. Significant and durable reductions were observed for ALP, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase throughout the study (Table). Mean total bilirubin remained stable through 72 months of OCA treatment. OCA treatment resulted in sustained improvement in liver biochemistry during up to 6 years of follow-up.