BOSTON, MA—Data from a post-hoc analysis shows no additional safety concerns with obeticholic acid in a subgroup of patients with cirrhosis, according to a presentation at The Liver Meeting® 2016.

Obeticholic acid is approved in the United States for the treatment of primary biliary cholangitis in combination with UDCA or in adults unable to tolerate UCDA.

The Phase 3 randomized, double-blind, placebo-controlled study (POISE) evaluated the efficacy of obeticholic acid 5–10mg/day in patients with primary biliary cholangitis, noted John M. Vierling, MD, professor of medicine and surgery at the Baylor College of Medicine in Houston, TX.

The study randomly assigned 216 patients to obeticholic acid 5–10mg (titrated to 10mg after 6 months based on response and tolerability; n=70), obeticholic acid 10mg (n=70), or placebo (n=73). All patients also received ursodeoxycholic acid (UDCA). The primary composite endpoint was ALP <1.67XULN with total bilirubin ≤ULN and ≥15% reduction in ALP.

For the post-hoc analysis, the investigators assessed the efficacy and safety of obeticholic acid in the subset of patients with cirrhosis documented based on biopsy, liver stiffness, and medical history. Baseline MELD scores ranges from 6.4 to 11.8, “in accordance with their compensated status,” added Dr. Vierling, who is also director of Baylor Liver Health and chief of hepatology.

The analysis found cirrhosis was present in about 17% of patients in POISE: 13 patients in the placebo group, 13 in the obeticholic acid 5–10mg group, and 10 in the obeticholic 10mg group. At Month 12, 54% of patients in the obeticholic 5–10mg (P<0.05) and 40% of patients in the obeticholic acid 10mg group achieved the primary composite endpoint vs. 8% of patients in the placebo group.

After 12 months of treatment, “total bilirubin was significantly lower in obeticholic acid-treated patients with cirrhosis compared to increases with placebo” (P<0.05), the investigators noted. Also compared with placebo, significant reductions were observed in GGT, ALT, and AST among those who received obeticholic acid.

Pruritus, the most commonly reported adverse event in patients with cirrhosis, was seen in 23% of patients in the placebo arm, 69% in the obeticholic acid 5–10mg arm, and 80% in the obeticholic acid 10mg arm. No additional safety concerns were observed in patients with cirrhosis, and all serious adverse events in the POISE trial were unrelated to the study drug, the investigators noted.

“Consistent with the total POISE population, significantly more obeticholic acid-treated patients with cirrhosis achieved the primary composite endpoint compared to placebo,” Dr. Vierling noted, adding that the treatment “also improved markers of cholestasis and hepatocellular damaged in patients with cirrhosis.”

“Obeticholic acid is a safe and effective therapy in patients with cirrhosis who have an inadequate response to UDCA or are intolerant of it,” they concluded.

The presentation was funded by Intercept Pharmaceuticals, Inc., San Diego, CA.