Primary endpoint met early in trial of NASH treatment

The FLINT clinical trial of obeticholic acid as a therapy for patients with nonalcoholic steatohepatitis was stopped early after the primary endpoint was met, Intercept Pharmaceuticals said in a news release.

The multicenter, double blind, placebo controlled trial sought to evaluate the safety and efficacy of a daily 25-mg oral dose of obeticholic acid (OCA) over a 72-week span among patients with biopsy-proven nonalcoholic steatohepatitis (NASH). Patients also had nonalcoholic fatty liver disease (NAFLD) activity score (NAS) of 4 or greater and a score of at least 1 in each component of the NAS eight-point scale (steatosis 0-3, lobular inflammation 0-3, ballooning 0-2).

The primary histological endpoint was a decrease in NAS of at least two points coupled with no worsening of fibrosis when comparing patients from the active and placebo arms, according to the release.

The Data Safety Monitoring Board recommended the trial end early after reviewing liver biopsy data from before and after treatment in about half of the 283 randomly assigned patients and determining OCA demonstrated highly noteworthy improvement (P=.0024 on an intention-to-treat [ITT] basis), the release said.

A threshold of P<.0031 was defined ahead of time to stop the trial. Patients who had not completed the trial did not have a second biopsy and were considered to be nonresponders for the ITT analysis.

“The unexpected early stopping of FLINT due to OCA meeting the primary endpoint with such high significance is a major milestone,” Mark Pruzanski, MD, CEO of Intercept, said in the release.

Another trial comparing once-daily OCA with placebo is ongoing in Japan. It is expected to be completed this month with top-line results expected in 2015.