Mechanistic Modeling And Hepatic Biomarker Data From Ggf2 (Cimaglermin Alfa)-Treated Subjects In Phase 1 Clincial Trials Suggest Low Likelihood Of Progressive Liver Injury

Authors: Longo DM, Generaux GT, Howell BA, Siler SQ, Antoine DJ, Button D, Caggiano A, Eisen A, Iaci J, Stanulis R, Watkins PB
Conference: ASCPT
Keywords: clinical trials, hepatic biomarker, liver injury, mechanistic modeling
Software: DILIsym®
Division: Quantitative Systems Pharmacology (QSP)

Background

GGF2 (USAN cimaglermin alfa) is an investigational drug for the treatment of heart failure. During Phase 1 clinical trials, concomitant, transient elevations in serum aminotransferases (ALT/AST) and bilirubin meeting FDA DILI Guidance stopping criteria (Hy’s Law) were observed in two treated subjects but resolved within 2 weeks, with no further LFT abnormalities over the following 1-3 years. GGF2 has no direct toxic effect on human hepatocytes in vitro, so further exploration of these cases was undertaken.

American Society for Clinical Pharmacology & Therapeutics (ASCPT) 2017 Annual Meeting, March 15-18, 2017,  Washington, DC

By Diane M. Longo, Grant T. Generaux, Brett A. Howell, Scott Q. Siler, Daniel J. Antoine, Donald Button, Anthony Caggiano, Andrew Eisen, Jennifer Iaci, Ric Stanulis, Paul B. Watkins