Phase 2b CENTAUR NASH trial meets secondary, not primary endpoint

Tobira Therapeutics announced its lead candidate for treatment of nonalcoholic steatohepatitis, cenicriviroc, did not meet its primary endpoint after 1 year in a phase 2b trial, but it did meet a secondary endpoint, according to a press release.

Laurent Fischer

Further, because the study’s primary endpoint is not required in the phase 3 application, Laurent Fischer, MD, chief executive officer at Tobira, expects this medication to advance to phase 3.

“We designed the CENTAUR trial to explore a number of registrational and non-registrational endpoints and achieved statistical significance of the most clinically relevant — regression in fibrosis after only one year of treatment,” Fisher said in the release. “These data exceeded our expectations and we plan to meet with regulators later this year to discuss the phase 3 study design.”

Cenicriviroc (CVC) is a daily oral medication that blocks the chemokine receptors CCR2 and CCR5, which are involved in the inflammatory pathways of NASH leading to liver damage, according to the release.

CENTAUR — a phase 2b trial of CVC comprising 289 patients — is the first randomized study to evaluate fibrosis improvement without NASH worsening as an endpoint, according to the release. This secondary endpoint of the phase 2b trial was recently named a registrational endpoint for phase 3 studies, whereas the study’s primary endpoint of achieving a two-point reduction in NAFLD activity score was not. CVC also did not show a complete resolution of steatohepatitis, which was the other secondary endpoint and a registrational endpoint. However, its safety profile was comparable to placebo.

“The very favorable safety profile of CVC combined with the efficacy data underscore the potential of CVC to emerge as a treatment of fibrosis associated with NASH, at a time when there are no approved therapies yet for this growing epidemic,” Scott L. Friedman, MD, of the division of liver diseases at Icahn School of Medicine at Mount Sinai and CENTAUR study chairman, said in the release. “The CENTAUR patient population is similar to the anticipated phase 3 population, and we expect to initiate a global pivotal study in 2017 to confirm CVC’s anti-fibrotic activity to address this high unmet need.” – by Will Offit

Disclosures: Fischer is an employee of Tobira. Healio.com/Hepatology was unable to confirm Friedman’s relevant financial disclosures at the time of publication.