POISE: Obeticholic acid reduced ALP in primary biliary cirrhosis

WASHINGTON — Patients with primary biliary cirrhosis treated with obeticholic acid showed improvements in plasma alkaline phosphatase, according to findings presented here.

Kris Kowdley, MD, of the Swedish Medical Center in Seattle, presented data on the use of the modified bile acid and Farnesoid-X-receptor agonist obeticholic acid (Intercept Pharmaceuticals) in primary biliary cirrhosis. He noted that hepatobiliary injury is reflected by increased plasma alkaline phosphatase (ALP) and bilirubin that may lead to disease progression.

Kris Kowdley

The study presented was an analysis of three studies of patients treated with obeticholic acid. One study included 23 patients treated with placebo and 20 patients treated with 10 mg obeticholic acid. The second included 38 placebo patients and 38 patients treated with 10 mg of the study drug, and all patients treated with concomitant ursodeoxycholic acid. The third study included 73 patients receiving placebo, 73 patients receiving 10 mg of the study drug and 70 patients who began with 5 mg of the study drug and then were titrated up to 10 mg.

Eligible participants had ALP at least 1.5 times the upper limit of normal.

The mean percent change in ALP served as the primary endpoint, along with a composite endpoint of ALP less than 1.67 times the upper limit of normal with a minimum 15% reduction in ALP and normal bilirubin that demonstrates a correlation with survival.

In the first study, the change in ALP was –289 U/L among patients taking obeticholic acid and –37 U/L among those in the placebo group (P < .0001). For the second study, the change was –74 U/L in the study drug group and 4 U/L in the placebo group (P < .0001). In the third study, the changes were –99 U/L in the titration group, –118 U/L in the obeticholic acid 10 mg group and –2 U/L in the placebo group (P < .0001).

The percentage of patients in the first study who reached the composite primary endpoint was 4% in the placebo group and 40% in the study drug group (P < .0001). Among patients treated with concomitant ursodeoxycholic acid, the rates were 8% for placebo and 42% for the study drug (P = .0002). Among those in monotherapy study, the primary endpoint rates were 10% for placebo and 46% for obeticholic acid (P = .0026). Findings from the pooled analysis of all studies indicated that 8% of placebo patients and 45% of study drug patients reached the primary endpoint.

“As you can see, obeticholic acid had a significantly higher proportion of subjects achieving this composite endpoint,” Kowdley said.

He reported a significant decrease in total bilirubin values across the treatment groups, along with reductions in gamma GT, ALT and AST.

“We saw a slight increase in LDL cholesterol and a decrease in HDL cholesterol across all treated patients,” Kowdley added.

Overall obeticholic acid was safe and well-tolerated with pruritus, a symptom of PBC, as the only treatment-emergent adverse event greater with obeticholic acid treatment than placebo, Kowdley told Healio Gastroenterology.

“Most treatment-related adverse events were mild or moderate,” he said. “Placebo also had a high proportion of pruritis.”

For more information:

Kowdley K, et al. Abstract 657. Presented at: Digestive Disease Week, May 16-19, 2015; Washington, D.C.

Disclosure: Kowdley reports associations with a number of device and pharmaceutical companies. Please see the DDW faculty disclosure index for all other researchers’ relevant financial disclosures.

Editor's note: This article was updated on June 15, 2015, with clarifications from the presenter.