Pharmacokinetic Modeling Supports the Approval of a Rare Liver Disease Treatment

Primary biliary cholangitis (PBC) is a chronic, rare disease characterized by cholestasis—the impaired flow of bile from the liver.1 The resulting increased bile acid concentrations cause cellular injury. Untreated PBC can lead to liver failure and death. The only currently approved treatment for PBC was ursodeoxycholic acid (UDCA). However, not all patients respond to UDCA. Intercept Pharmaceuticals—an emerging global biopharmaceutical company—sought to develop obeticholic acid (OCA) as an alternative treatment for PBC. OCA is a semi-synthetic analogue of the primary bile acid chenodeoxycholic acid with similar pharmacokinetic (PK) properties.2 Like other bile salts, OCA is metabolized via conjugation to glycine acid and taurine. OCA is a selective and potent farnesoid X receptor (FXR) agonist.2 FXR activation decreases the concentration of bile acids in the liver to reduce cellular injury. FGF-19 was used as a biomarker for OCA pharmacological activity.

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