Synergy Between Two Mechanisms of Action Contributes to Species Differences in the Liver Safety Profile for PF-04895162

Authors: Lakhani VV, Generaux GT, Yang Y, Nadanaciva S, Qiu L, Riccardi K, Di L, Howell BA, Siler SQ, Watkins PB, Barton HA, Aleo MD, Shoda LKM
Conference: SOT
Keywords: DILI, hepatotoxicity, in vitro, live stream learning, liver safety
Software: DILIsym®
Division: Quantitative Systems Pharmacology (QSP)

Introduction

PF-04895162 (ICA-105665), a drug in development for the treatment of epilepsy, was terminated after transaminase elevations (up to grade 3) were observed in healthy volunteers (NCT01691274). The human hepatotoxicity was unexpected because liver safety concerns had not been raised in preclinical safety studies (Aleo et al. 2019).

By Vinal V. Lakhani, Grant Generaux, Yuching Yang, Sashi Nadanaciva, Luping Qiu, Keith Riccardi, Li Di, Brett A. Howell, Scott Q. Siler, Paul B. Watkins, Hugh A. Barton, Michael D. Aleo, Lisl K. M. Shoda

Canceled: SOT 59th Annual Meeting & ToxExpo March 15-19. 2020 in Anaheim, California