Obeticholic acid prevents liver fibrosis from NASH

Obeticholic acid (OCA) 25 mg significantly improved fibrosis and key components of disease activity among patients with non-alcoholic steatohepatitis (NASH). The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit.

Dr Isabel Graupera (Institut d'Investigacions Biomediques August Pi I Sunyer, Barcelona, Spain) reported the positive results from the prespecified 18-month interim analysis of the phase 3, randomised, double-blind, placebo-controlled, multicentre study REGENERATE study of OCA in patients with liver fibrosis due to NASH [1], which was conducted to assess the effect of OCA on liver histology comparing baseline biopsies with biopsies taken at month 18. The intention-to-treat population for the interim analysis included 931 patients with stage 2 and 3 fibrosis (placebo, n=311; OCA 10 mg, n=312; OCA 25 mg, n=308). REGENERATE has completed target enrolment for the clinical outcomes cohort, with 2,480 adult NASH patients randomised, and will continue through clinical outcomes for verification and description of clinical benefit.

The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the OCA 10 mg group (P=0.045), and 71 (23%) in the OCA 25 mg group (P=0.0002). The NASH resolution endpoint was not met (8% of patients in the placebo group, 11% in the OCA 10 mg group [P=0.18], and 12% in the OCA 25 mg group [P=0.13])

The safety population of the interim analysis included 1,968 randomised patients who received at least one dose of study drug (OCA or placebo). Adverse events were generally mild to moderate in severity and the most common were consistent with the known profile of OCA. The frequency of serious adverse events was similar across treatment arms (11% in placebo, 11% in OCA 10 mg, and 14% in OCA 25 mg). The most common adverse event reported was dose-dependent pruritus (placebo, 19%; OCA 10 mg, 28%; OCA 25 mg, 51%). The large majority of pruritus events were mild to moderate.

Dr Graupera concluded, “The antifibrotic efficacy observed with just 18 months of OCA treatment in REGENERATE is particularly meaningful because fibrosis is the most important histological predictor of liver failure and death in patients with NASH.”

1. Graupera I et al. UEG Week 2019, Abstract OP196.

Posted on 23 October 201918 March 2021