Cenicriviroc Treatment for Adults with Nonalcoholic Steatohepatitis and Fibrosis: Final Analysis of the Phase 2b CENTAUR Study.

Cenicriviroc (CVC) is a CCR2/5 dual antagonist under evaluation for treating liver fibrosis in adults with nonalcoholic steatohepatitis (NASH). Year 1 primary analysis of the 2-year CENTAUR study showed that CVC had an antifibrotic effect without impacting steatohepatitis. Herein, we report the final data from Year 2 exploratory analyses. This was a randomized, controlled study of adults with NASH, nonalcoholic fatty liver disease activity score ≥4, and NASH CRN stage 1-3 fibrosis. Participants in Arms A and C received CVC 150 mg or placebo, respectively, for 2 years; Arm B received placebo in Year 1 and switched to CVC in Year 2. Liver biopsy was performed at baseline, Year 1, and Year 2. Of 289 randomized, 242 participants entered Year 2. At Year 2, 24% of patients who switched to CVC and 17% who remained on placebo achieved ≥1-stage fibrosis improvement AND no worsening of NASH (P=0.37). Twice the proportion on CVC who achieved fibrosis response at Year 1 maintained benefit at Year 2 (60% Arm A vs. 30% Arm C), including 86% on CVC who had stage 3 fibrosis at baseline. Over 2 years, a similar proportion on CVC or placebo achieved ≥1-stage fibrosis improvement AND no worsening of NASH (15% Arm A vs. 17% Arm C). In patients with fibrosis responses, we observed consistent reductions in PRO-C3 levels and ELF scores, while increases in APRI and FIB-4 scores were consistently observed in non-responders. Safety profile was comparable across groups. Conclusions: CVC was well-tolerated, and Year 2 data corroborates antifibrotic findings from Year 1. Majority on CVC who achieved fibrosis response at Year 1 maintained it at Year 2, with greater effect in advanced fibrosis.