New results from phase III trial for Ocaliva (obeticholic acid) in patients with primary biliary cholangitis- Intercept Pharmaceuticals

Intercept Pharmaceuticals has announced results from three new exploratory analyses of the Phase III POISE trial of Ocaliva (obeticholic acid) in patients with primary biliary cholangitis (PBC). The POISE trial evaluated the safety and efficacy of once-daily treatment with Ocaliva in PBC patients with an inadequate therapeutic response to, or who are unable to tolerate, ursodeoxycholic acid (UDCA). Of 216 patients randomized to three treatment arms—placebo, Ocaliva 5 mg titrated to 10 mg or Ocaliva 10 mg—93% continued receiving UDCA. The first POISE presentation evaluated the effects of Ocaliva on non-invasive assessments of liver fibrosis using both transient elastography (Fibroscan) and the AST to Platelet Ratio (APRI). These tests have been shown to be effective in predicting clinical outcomes in PBC, and Ocaliva-treated patients experienced improvements in both compared with those receiving placebo. In patients with transient elastography assessments at baseline and month 12 (approximately 43% of the study population), only Ocaliva-treated patients experienced a reduction in liver stiffness below 16.9 kPa, a threshold associated with the presence of cirrhosis.

The second POISE presentation evaluated the efficacy and safety of Ocaliva in the subset (17%) of patients with cirrhosis who were at the greatest risk of progression to liver-related adverse outcomes or death. At month 12, more Ocaliva-treated patients with cirrhosis achieved the primary composite study endpoint compared to placebo. Ocaliva treatment improved markers of both cholestasis (alkaline phosphatase) and hepatic impairment (bilirubin) relative to placebo in patients with cirrhosis. Consistent with previous study results, pruritus (itch) was the most common adverse event associated with Ocaliva treatment.

The third POISE presentation examined the effects of Ocaliva in PBC patients with mild and moderate renal impairment. In this exploratory analysis, Ocaliva demonstrated comparable efficacy regardless of renal status and enabled patients with renal impairment to achieve significant improvements in markers of cholestasis and hepatic damage. Ocaliva had no apparent effect on renal safety, with mild to moderate pruritus the most commonly occurring adverse event in all renal function groups. The analyses will be presented at the American Academy for the Study of Liver Diseases (AASLD) Annual Meeting.