Obeticholic acid: Phase III data

The double-blind, international Phase III POISE trial in 217 patients who inadequately responded to or were unable to tolerate ursodiol showed that once-daily 5 mg (titrated up to 10 mg) and 10 mg oral obeticholic acid each met the primary endpoint of a greater proportion of patients achieving a composite of a reduction in alkaline phosphatase levels to <1.67 times the upper limit of normal with a >=15% reduction from baseline in alkaline phosphatase levels and a total bilirubin level within normal limits at 12 months vs. placebo (46% and 47%, respectively, vs. 10%, p<0.0001 for both). Additionally, mean alkaline phosphatase levels were reduced from baseline to 12 months by 33% with the low-dose obeticholic acid regimen and by 39% with high-dose obeticholic acid vs. 5% with placebo (p<0.0001 for both). Both dose groups of obeticholic acid also met the secondary endpoints of improving GGT, ALT, AST and total bilirubin levels vs. placebo (p<0.0005 for all).

The most common reported treatment-related adverse event was pruritus. There were 8 discontinuations in the obeticholic acid treatment arms due to pruritus vs. 0 in the placebo arm. Intercept said that although there were more serious adverse events in the obeticholic acid treatment arms compared to the placebo arm, none were considered treatment-related. Patients who completed the double-blind portion of POISE were eligible to continue obeticholic acid treatment in a 5-year, open-label extension study. Data will be presented at the European Association for the Study of the Liver meeting in London in April. ...