Intercept Pharmaceuticals announced that Ocaliva met its phase 3 study primary endpoint of fibrosis improvement by 1 stage or more with no worsening of nonalcoholic steatohepatitis, according to a press release and investor call.
“Fibrosis is currently the only NASH histology endpoint that predicts liver-related adverse clinical outcomes and all-cause mortality,” Mark Pruzanski, MD, president and CEO of Intercept, said during the investor call. “We believe today’s results represent a historic milestone in the development of novel treatments for patients with progressive fibrosis due to NASH, an indication for which there are no approved therapies.”
The primary efficacy analysis at 18 months included 931 patients with stage 2 or stage 3 fibrosis due to NASH who received once-daily Ocaliva (obeticholic acid or OCA). Fibrosis improved by 1 stage or more with no worsening of NASH in both the OCA 25 mg group (23.1%; P = .0002) and the OCA 10 mg group (17.6%; P = .0446), compared with placebo.
A higher proportion of patients in the OCA 25 mg group (11.7%) and those in the OCA 10 mg group (11.2%) achieved NASH resolution with no worsening of fibrosis compared with placebo (8%), although this did not reach statistical significance.
“The additional data we’ve so far had the opportunity to analyze from REGENERATE on NASH resolution show OCA’s effect on key underlying histopathologic features of the disease,” Pruzanski said during the investor call. “These data will provide an important edition to our growing understand of this evolving endpoint.”
Researchers noted similar discontinuation rates between the placebo groups, patients who received OCA 10 mg, and patients who received OCA 25 mg.
The safety and tolerability analysis comprised 1,968 patients who received at least one dose of OCA or placebo. Adverse events were generally mild to moderate. The frequency of serious adverse events was similar across all three groups and occurred in less than 1% of treated patients. Of the three recorded deaths, none were considered related to treatment.
The ongoing phase 3 REGENERATE study is targeted to enroll more than 2,000 adults with NASH and stage 2 or stage 3 fibrosis from international centers. The end-of-study analyses will evaluate the effect of OCA on mortality, liver-related outcomes, and long-term safety.
“Patients with significant fibrosis due to NASH are at the greatest risk of progression to severe liver-related complications, such as liver failure and death, and fibrosis is considered the strongest predictor of liver-related mortality in this population,” Zobair M. Younossi, MD, chairman of the department of medicine at Inova Fairfax Hospital in Virginia and chair of the study’s steering committee, said in a press release. “As the first successful pivotal trial in NASH, REGENERATE is an important advancement for the liver community.”
Intercept intends to file for approval in the U.S. and Europe in the second half of 2019. Additionally, the company will present study results at The International Liver Congress 2019.