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Late-Stage Trial Supports Efficacy of Obeticholic Acid in Patients With Biliary Cirrhosis

Data expected to be submitted to FDA at end of 2014

Positive efficacy and safety results from the phase III POISE trial of obeticholic acid (OCA) for the treatment of primary biliary cirrhosis (PBC) were presented April 12 at the International Liver Congress of the European Association for the Study of the Liver (EASL), held in London.

OCA is a bile acid analog and first-in-class agonist of the farnesoid X receptor in development for the treatment of PBC, nonalcoholic steatohepatitis, and other liver and intestinal diseases.

In a previous report, the POISE study met its primary endpoint with high statistical significance (P < 0.0001), demonstrating the drug’s efficacy on a composite liver biochemical endpoint, which has been shown to strongly correlate with improved clinical outcomes. The proportions of patients meeting the POISE primary endpoint were 47% in the OCA 10-mg group, 46% in the OCA 5-mg to 10-mg group, and 10% in the placebo group (both dose groups, P < 0.0001 vs. placebo).

New data presented at the EASL meeting showed that OCA-treated patients achieved a statistically significant reduction in alkaline phosphatase as early as 2 weeks after the start of treatment, with a peak effect achieved by 6 months.

Generally mild-to-moderate pruritus was the most frequently reported adverse event in the POISE trial. However, only one (1%) of the patients in the OCA 5-mg to 10-mg titration group discontinued therapy because of pruritus after moving up to the 10-mg dose, compared with seven (10%) of the patients in the OCA 10-mg group. Additional data showed that the incidence and severity of OCA-related pruritus diminished with time on therapy. Specifically, pruritus scores were no different from placebo in both OCA treatment groups during the second half of the trial.

In a separate poster presentation, researchers described a retrospective analysis of two phase II trials of OCA for the treatment of PBC in 224 patients. Pooled results from these studies were evaluated using the endpoint of the phase III POISE trial. The analysis showed that, overall, 43% of patients receiving 10 mg, 25 mg, or 50 mg of OCA met the POISE primary endpoint compared with 8% of those given placebo (P < 0.0001), corroborating the phase III results. Moreover, a strong OCA treatment effect was observed regardless of whether OCA was administered as monotherapy or as an add-on to ursodiol (ursodeoxycholic acid). Treatment with OCA was generally well-tolerated, with pruritus (primarily mild or moderate) being the most common adverse event.

Data from the phase III POISE trial and from the two phase II studies of OCA for the treatment of PBC are expected to be submitted to the FDA at the end of 2014 as part of a new drug application.

Source: Intercept Pharmaceuticals; April 12, 2014.

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