Emricasan (DB05408): A Comprehensive Monograph on a Pan-Caspase Inhibitor from Preclinical Promise to Clinical Discontinuation in Liver Disease

Executive Summary

Emricasan (DB05408) is an investigational, first-in-class, orally active, irreversible pan-caspase inhibitor. It was developed with the primary therapeutic goal of treating chronic liver diseases, particularly non-alcoholic steatohepatitis (NASH), by targeting the fundamental pathological processes of apoptosis and inflammation. The scientific rationale for Emricasan was compelling: by broadly inhibiting caspases—a family of enzymes central to programmed cell death and inflammatory signaling—the drug was designed to protect hepatocytes from excessive apoptosis, thereby reducing liver injury, inflammation, and the subsequent progression to fibrosis and cirrhosis.

This hypothesis was strongly supported by a robust body of preclinical evidence across various animal models of liver disease, where Emricasan consistently demonstrated potent anti-apoptotic, anti-inflammatory, and anti-fibrotic effects. Its unique pharmacokinetic profile, characterized by high first-pass hepatic uptake, positioned it as a "liver-targeted" agent, intended to maximize efficacy in the target organ while minimizing systemic exposure. These promising data propelled the drug into extensive clinical development and attracted a landmark collaboration between Conatus Pharmaceuticals and Novartis, signaling significant confidence in its potential.