Advancing Calcitonin Gene-Related Peptide Receptor Antagonists Using Quantitative Systems Toxicology Modeling to Characterize Next-in-Class Compounds Compared to the Hepatotoxic First in Class Telcagepant

Authors: Woodhead JL, Siler SQ, Howell BA, Conway C, Watkins PB
Conference: AASLD
Keywords: hepatoxicity, QST modeling, quantitative systems toxicology (QST) analysis, telcagepant
Software: DILIsym®
Division: Quantitative Systems Pharmacology (QSP)

Introduction

While CGRP receptor antagonists have demonstrated efficacy in the acute and preventive treatment of migraine, two early CGRP signal-blocking compounds (gepants) showed liver injury signals in clinical trials. During clinical development of next-in-class gepants, confidence in compound safety was needed given the prior experience.

By Jeffrey L. Woodhead,  Scott Q. Siler,  Brett A. Howell,  Charles M. Conway, , Paul B. Watkins

Presented at AASLD The liver Meeting, November 12-15, 2021