Conatus Pharmaceuticals Inc. announced aggregate top-line results from three pharmacokinetic and pharmacodynamic clinical trials in organ-impaired patients, which include a Phase 2 clinical trial in patients with acute-on-chronic liver failure (ACLF), a Phase 1 clinical trial in patients with mild, moderate and severe hepatic impairment and a Phase 1 clinical trial in patients with severe renal impairment. All three trials provided important information on the effects of renal and hepatic impairment on the pharmacokinetics and pharmacodynamics of emricasan, and provided support for emricasan's continued development in patients with liver cirrhosis. While more severe forms of cirrhosis may be associated with concomitant renal impairment, emricasan pharmacokinetics were only modestly affected by severe renal impairment.

A separate trial assessed the effect of stable mild, moderate or severe hepatic impairment upon the pharmacokinetics of emricasan. Emricasan pharmacokinetics were not affected by stable mild hepatic impairment while systemic drug exposures were progressively increased in patients with both moderate and severe hepatic impairment. In the ACLF trial, which assessed patients with acutely decompensated severe hepatic impairment, emricasan exposure after the first dose was more than twice the exposure in patients with stable severe hepatic impairment.

The ACLF trial was designed to assess the pharmacokinetics of emricasan, as well as biomarker and clinical responses, following twice daily (BID) oral dosing of emricasan or placebo for 28 days. As expected, alanine aminotransferase (ALT) levels were not increased in the ACLF patient population. By contrast, levels of key mechanism-specific biomarkers of caspase activity and inflammation caspase-cleaved cytokeratin 18 (cCK18"), Caspase 3/7, and Interleukin-18 (IL-18") and a biomarker of more generalized cell death full-length cytokeratin 18 (flCK18") were all elevated at baseline, demonstrating their important role in the ACLF disease process.

These biomarkers also showed increasing elevations at baseline as a function of worsening hepatic impairment.