Additional Relevant Details  Although the study did not meet its primary endpoint of a two-point reduction in the NAFLD Activity Score, CENTAUR did demonstrate a clinically and statistically significant improvement in fibrosis of at least one stage without worsening of NASH, one of two key secondary endpoints, after only one year of treatment. Regulators have recently identified this endpoint for Phase 3 studies to support a marketing application. CENTAUR is the first randomized study to evaluate this as a pre-specified endpoint.

CENTAUR demonstrated that significantly more patients treated with CVC for one year saw an improvement in fibrosis by at least one stage without worsening of steatohepatitis compared to placebo (intent-to-treat population; 20% vs 10%, p=0.02). CVC showed anti-fibrotic activity across all three stages of fibrosis (F1-F3) as measured in this key secondary endpoint. The study did not meet the other key secondary endpoint, which was complete resolution of steatohepatitis. Patients remain on therapy in a blinded fashion and all endpoints will be evaluated again at year two of the study with a liver biopsy. All baseline and year one biopsies have been read in a blinded fashion as to study drug assignment by a central pathologist. The safety profile of CVC was comparable to placebo. The most commonly reported drug-related clinical adverse events of at least moderate severity in the CVC arm were fatigue (2.8%) and diarrhea (2.1%). Tobira plans to present detailed results from the CENTAUR study at a major upcoming medical conference.