Obeticholic Acid—From PK Model to Drug Label

Obeticholic acid (OCA) is a selective and potent farnesoid X receptor (FXR) agonist in development for the treatment of primary biliary cholangitis/cirrhosis (PBC), nonalcoholic steatohepatitis (NASH), and other liver diseases. OCA is the 6α-ethyl derivative of chenodeoxycholic acid (CDCA) and has similar pharmacokinetic (PK) properties.

The results from a hepatic impairment clinical study revealed that systemic OCA concentrations increased with moderate and severe hepatic impairment. These results are consistent with previously reported studies wherein plasma endogenous bile acids were elevated in patients with hepatic impairment, but liver concentrations were only modestly increased. Accordingly, an alternate dosing regimen was developed for OCA based on modeling and simulations for patients with moderate and severe hepatic impairment to mitigate tolerability concerns with high systemic exposures.

Watch this webinar with Jeffrey Edwards to learn how he used physiologic pharmacokinetic modeling to understand the relationship between systemic and hepatic exposure of OCA in patients with and without hepatic impairment. By watching this webinar, you will learn how pharmacokinetic modeling can support optimal dosing for patients with organ impairment and facilitate regulatory approval.