Evaluating the Therapeutic Potential of Cenicriviroc in the Treatment of Nonalcoholic Steatohepatitis with Fibrosis: A Brief Report on Emerging Data

Abstract

Non-alcoholic steatohepatitis (NASH) is associated with significant morbidity and mortality due to liver cirrhosis, liver failure, and hepatocellular carcinoma, and represents a leading indication for liver transplantation in the United States (U.S.). A growing spectrum of novel therapies are currently in clinical development and target several mechanisms of action which address hepatic steatosis, steatohepatitis, and hepatic fibrosis. Cenicriviroc (Allergan, Dublin, Ireland) is a novel oral antagonist of CC-motif chemokine receptors 2 and 5 (CCR2/5) which have demonstrated expression on circulating monocytes and Kupffer cells. Preclinical models have confirmed that CCR2/5 antagonism may block fat accumulation and Kupffer cell activation and disrupt monocyte/macrophage recruitment and hepatic stellate cell activation responsible for fibrogenesis. Herein we review results from the phase 2b CENTAUR trial and study designs for the phase 2b TANDEM and phase 3 AURORA trials and discuss the potential role of cenicriviroc in future pharmacotherapy for NASH fibrosis.

Keywords: antifibrotic therapy; cenicriviroc; clinical trials; fatty liver; liver fibrosis; non-alcoholic steatohepatitis.

Figure 1

Cenicriviroc mechanism of action. Abbreviations: CCL-2, chemokine (C-C motif) ligand 2; CCR2, C-C chemokine receptor 2; TFGB, transforming growth factor β; PDGF, platelet-derived growth factor.