Phase III trial of Ocaliva (obeticholic acid) shows efficacy in primary biliary cholangitis- Intercept Pharmaceuticals

Intercept Pharmaceuticals has announced the results of two new analyses of the POISE trial, the Phase III trial of Ocaliva (obeticholic acid) for the treatment of primary biliary cirrhosis, recently renamed primary biliary cholangitis (PBC). The analyses, presented at the International Liver Congress 2016 examined a risk model to predict estimated liver transplant-free survival of patients in the POISE trial and assessed a titration strategy for managing treatment-related pruritus. Of 216 randomized patients in the POISE trial, 93% continued receiving ursodeoxycholic acid (UDCA), the current standard of care and only approved medication for PBC, upon initiating Ocaliva or placebo. The trial's primary endpoint was defined as a reduction in serum alkaline phosphatase (ALP) to below a threshold of 1.67 times upper limit normal, with a minimum of 15% reduction in ALP level from baseline, and a normal bilirubin level after 12 months of therapy. The Global PBC Study Group used data collected from more than 4,000 patients to construct and validate its risk model, with age at the beginning of UDCA therapy, total bilirubin, ALP, platelet count, and albumin following 12 months of treatment with UDCA identified as independent predictors of liver transplant-free survival. After one year, the model suggests patients treated with Ocaliva with/without UDCA had significantly improved estimated liver transplant-free survival compared to the group treated with placebo.

The second analysis utilizing the POISE study data examined the titration strategy used in the trial to address treatment-related pruritus. Despite an early increase at two weeks, patient-reported pruritus severity improved over the course of the study and by month six the Ocaliva 10 mg group and placebo with/without UDCA group were similar. Additionally, titration appeared to delay time to onset in the subset of patients who experienced pruritus, with a median of 24 days in the titration group vs. nine days in the group initiating Ocaliva treatment at 10 mg.