Additional data reported for phase III REGENERATE trial of Ocaliva in NASH

Intercept Pharmaceuticals announced additional supportive data from its pivotal Phase III REGENERATE study of Ocaliva (obeticholic acid or OCA) in patients with liver fibrosis due to nonalcoholic steatohepatitis (NASH). The new data based on additional analyses show that OCA demonstrated robust efficacy across a range of additional histologic and biochemical parameters.

The primary efficacy analysis (Intent-to-Treat or ITT) assessed efficacy at 18 months in 931 patients with stage 2 or 3 liver fibrosis due to NASH. Approximately three-fold more patients in the OCA 25 mg group achieved an improvement of fibrosis by at least 2 stages compared to placebo (13.3% vs 4.5%; p=0.0008). In an analysis of changes in fibrosis by at least 1 stage, approximately three-fold more patients in the OCA 25 mg group improved versus worsened (38.0% vs 13.1%); in contrast, in the placebo group, a similar proportion of patients improved versus worsened (23.2% vs 20.9%). Substantially more patients in the OCA 25 mg group achieved improvements in the key underlying features of NASH, including hepatocellular ballooning (where an improvement of at least 1 point was seen in 43.6% of patients receiving OCA 25 mg, as compared to 28.6% of patients receiving placebo [p=0.0008]) and lobular inflammation (where an improvement of at least 1 point was seen in 52.3% of patients receiving OCA 25 mg, as compared to 42.0% of patients receiving placebo [p=0.03]).

Rapid and sustained reductions in key liver biochemistry parameters, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were observed in the OCA treatment groups. These data from REGENERATE are being presented at the International Liver Congress 2019.

Comment: Nonalcoholic steatohepatitis (NASH) is a serious progressive liver disease caused by excessive fat accumulation in the liver that induces chronic inflammation, resulting in progressive fibrosis that can lead to cirrhosis, eventual liver failure, cancer and death. Advanced fibrosis is associated with a substantially higher risk of liver-related morbidity and mortality in patients with NASH, and as early as 2020, the disease is projected to become the leading cause of liver transplants in the United States. There are currently no medications approved for the treatment of NASH.