Quantitative Systems Pharmacology (QSP) Model Predicts Lack of Efficacy for Cenicriviroc, a CCR2/5 Antagonist, in NAFLD/NASH Patients

Conference: AASLD
Software: NAFLDsym®
Division: DILIsym Services

Introduction

A phase 3 clinical trial (AURORA) for cenicriviroc (CVC), a CC chemokine receptor 2 and 5 (CCR2/5) antagonist, was recently terminated due to lack of efficacy. CVC was thought to suppress the inflammatory response and decrease collagen deposition by reducing recruitment of macrophages and activation of hepatic stellate cells,respectively.2,3 CVC exposure and its effects were implemented within a quantitative systems pharmacology (QSP) model, NAFLDsym (Figure 1), to see if simulations captured the lack of efficacy observed in the AURORA study and to explore if efficacy was limited by the potency of CVC in NAFLD/NASH patients.

By Christina Battista, Lisl KM Shoda, Grant T Generaux, Scott Q Siler

Presented at American Association for the Study of Liver Diseases (AASLD) Liver Meeting, November 12-16, 2021