On January 9, 2014, Intercept Pharmaceuticals, Inc. announced that the Phase 2b clinical trial of OCA for the treatment of NASH (FLINT) has been stopped early for efficacy based on a planned interim analysis showing that the primary endpoint of the trial has been met. The decision to stop FLINT has been based on the recommendation of the Data Safety Monitoring Board of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), which reviewed liver biopsy data from before and at the end of the treatment period in approximately half of the 283 randomized patients in accordance with a planned interim efficacy analysis. This analysis demonstrated that OCA treatment resulted in a highly statistically significant improvement (p=0.0024 on an intention-to-treat basis) in the primary histological endpoint, defined as a decrease in the NAFLD Activity Score, a system of scoring the histopathological features in the liver ("NAS"), of at least two points with no worsening of fibrosis, as compared to placebo.

Those patients who had not yet completed the trial and therefore did not have a second biopsy were treated as non-responders in the intention-to-treat analysis. The pre-defined threshold of statistical significance for stopping FLINT was p<0.0031. FLINT is a multi-center, double-blind, placebo-controlled, Phase 2b clinical trial assessing the safety and efficacy of a 25 mg oral dose of OCA administered daily to adult NASH patients.

FLINT enrolled 283 patients at eight academic hepatology centers in the United States comprising the NASH clinical research network. Patients were randomized to receive either a 25 mg dose of OCA or placebo for 72 weeks. Patients enrolled in the trial were qualified based on a diagnosis determined by liver biopsy at the start of the trial with a NAS of four or greater and with a score of at least one in each component of the NAS eight point scale (steatosis 0-3, lobular inflammation 0-3, ballooning 0-2).

The primary endpoint in the FLINT trial is defined as an improvement of two or more points in the NAS with no worsening of liver fibrosis, as compared to placebo. End of study biopsies were conducted in patients after the 72-week treatment period, with all biopsies centrally scored in a blinded fashion. The trial has been sponsored and conducted by the NIDDK, a part of the National Institutes of Health, which submitted an IND to the FDA for OCA for the treatment of NASH in 2010.

NASH is a serious chronic liver disease caused by excessive fat accumulation in the liver that, for reasons that are still incompletely understood, induces chronic inflammation which leads to progressive fibrosis (scarring) that can lead to cirrhosis, eventual liver failure and death. There are currently no drugs approved for the treatment of NASH. Studies have shown that over a ten year period at least 10% of NASH patients will develop cirrhosis, and liver-related mortality due to this disease is ten-fold that of the general population.

According to recent epidemiological studies, it is estimated that approximately 12% of the U.S. adult population has NASH, while 2.7% (potentially more than six million patients) are believed to have advanced liver fibrosis or cirrhosis due to progression of the disease. The proportion of liver transplants attributable to NASH has increased rapidly in past years, and over the next decade the disease is projected to become the leading indication for liver transplant ahead of chronic hepatitis C and alcoholic liver disease.