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. Schmidt2, Scott Q. Siler, Grant Generaux
Presented at American Association of Pharmaceutical Scientists (AAPS) PharmSci 360, October 17-20, 2021