The International Liver Congress 2019

Abstract

Interim results from the REGENERATE study, a phase 3 trial of obeticholic acid for patients with biopsy-proven non-alcoholic steatohepatitis (NASH), were presented by Zobair Younossi (Falls Church, VA, USA). Patients with NASH and fibrosis stage F2–3 were randomly assigned to receive placebo (n=311), obeticholic acid 10 mg (n=312), or obeticholic acid 25 mg (n=308) once daily. Two primary endpoints were assessed at the prespecified 18-month interim analysis: fibrosis improvement (of one stage or more) with no worsening of NASH, and NASH resolution with no worsening of liver fibrosis per liver biopsy. 11·9% of patients in the placebo group had an improvement of one fibrosis stage or more with no worsening of NASH, as did 17·6% of those in the 10 mg group (p=0·04 vs placebo) and 23·1% of those in the 25 mg group (p=0·0002 vs placebo, meeting the US Food and Drug Administration mandated level of significance). 8·0% of patients in the placebo group achieved NASH resolution with no worsening of fibrosis, as did 11·2% of those in the 10 mg group and 11·7% of those in the 25 mg group (neither group was significantly different vs placebo). The most common adverse event was pruritus (19% of patients on placebo, 28% of those in the 10 mg group, and 51% of those in the 25 mg group). Serious adverse events occurred in 11% of patients in both the placebo and 10 mg group, and in 14% of those in the 25 mg group. Three deaths occurred, none of which were deemed treatment-related. The study remains in follow-up for clinically important outcomes.