Predicting the Efficacy of Obeticholic Acid Treatment for Non-Alcoholic Steatohepatitis (NASH) Using NAFLDsym, a Quantitative Systems Pharmacology Model of Non-Alcoholic Fatty Liver Disease

Authors: Woodhead JL, Yang K, Singh FA, Schmidt BJ, Siler SQ, Generaux GT
Conference: AAPS
Keywords: farnesoid X receptor (FXR), FGF19, NAFLDsym, NASH, Non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), obeticholic acid (OCA), PBPK modeling, quantitative systems pharmacology (QSP)
Software: NAFLDsym®
Division: Quantitative Systems Pharmacology (QSP)

Purpose

Obeticholicacid (OCA), a bile acid analog and agonist of the farnesoidX receptor (FXR), is currently in clinical trials for the treatment of non-alcoholic steatohepatitis (NASH). Decreases in plasma transaminases and liver fat content have been reported after 72 weeks of OCA treatment in Phase 3 studies (1,2). Other FXR agonists have indicated that they are targeting intestinal FXR (and subsequent hepatic effects of increased FGF19), whereas OCA may have the ability to target both intestinal and hepatic FXR. The purpose of this work was to represent OCA using quantitative systems pharmacology (QSP) modeling and to understand whether OCA’s effects are primarily due to liver or gut FXR.

By Jeffrey L. Woodhead, Kyunghee Yang, Fulya Akpinar Singh, Brian J. Schmidt, Scott Q. Siler, and Grant Generaux

Displayed at American Association of Pharmaceutical Scientists (AAPS)’s PharmSci 360, October 17-20, 2021