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Obeticholic acid decreased ALP, ALT levels in patients with primary biliary cirrhosis

Obeticholic acid effectively decreased alanine aminotransferase, gamma-glutamyl transpeptidase and alkaline phosphatase levels compared with placebo, in patients with primary biliary cirrhosis who failed previous therapy with ursodeoxycholic acid, according to data published in Gastroenterology.

“Patients with primary biliary cirrhosis presently have access to only one licensed therapy, ursodeoxycholic acid,” Gideon Hirschfield, MA, MB, PhD, of the Institute of Biomedical Research at the University of Birmingham, UK, told Healio.com/Hepatology. “In patients failing therapy, life expectancy is significantly impaired and new therapies are acutely needed. [Obeticholic acid], developed by Intercept Pharmaceuticals, has been predicted, based on animal and human studies, to have potent anti-inflammatory, anti-fibrotic and choleretic properties.”

Gideon Hirschfield

Hirschfield and colleagues randomly assigned 165 patients with primary biliary cirrhosis (PBC) to receive 10 mg, 25 mg or 50 mg of obeticholic acid (OCA, Intercept Pharmaceuticals Inc.) or placebo once a day for 3 months. Ninety-five percent of the patients were female and all maintained their regular treatment schedule for ursodeoxycholic acid therapy. The primary endpoint was the change in alkaline phosphatase (ALP) values on treatment, according to Hirschfield.   

Overall, OCA was more effective in reducing ALP levels in patients compared with placebo; mean ALP levels were greatly reduced from baseline to the end of the study for patients who received OCA (P < .0001).

“In this study, at all doses, patients given OCA met the primary endpoint of significant falls in ALP, as compared to placebo,” Hirschfield said. “Side effects were largely limited to pruritus, which appeared dose dependent.”

Eighty-two percent of patients completed the study, with 10% discontinuing due to pruritus, according to the research.

In addition, gamma-glutamyl transpeptidase levels also decreased at an average of between 43% and 63% compared with a 7% decrease in patients who received placebo from baseline to the end of the study. A greater average decrease in alanine aminotransferase (ALT) serum levels was also seen among patients who received OCA compared with patients who received placebo (21%-35% vs. 0%).   

The researchers also performed an open-label extension study, in which 78 patients were enrolled and dosed with OCA for 1 year.

“In an open-label extension of OCA use, falls in ALP values were durable over 1 year,” Hirschfield said.

Hirschfield further stated: “This study is therefore an exciting randomized controlled trial that demonstrated the potential for OCA to be used as a novel and effective therapy in PBC.  It underlies the importance of further phase 3 studies in PBC to additionally demonstrate safety and efficacy, as well as studies of OCA in other cholestatic liver diseases, and inflammatory liver disease such as non-alcoholic steatohepatitis.” – by Melinda Stevens

Disclosure: Hirschfield reports consulting for Intercept, BioTie, Lumena, Medigene and Janssen. Please see the full study for a list of all other authors’ relevant financial disclosures.