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 B, Conway C, Watkins PB
Conference: AASLD
Keywords: clinical trial, liver injury, migraine
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