rtrx from Jim Birchenoff of BMO
Questions have arisen recently regarding potential competition to Intercept's obeticholic acid (OCA) from other bile acid therapeutics, following Retrophin's acquisition Manchester Pharmaceuticals of Chenodal (chenodeoxycholic acid or CDCA a synthetic bile acid). With approval of Chenodal in the US for treatment of gallstones and use in cerebrotendinous xanthomatosis (CTX), the question is whether Chenodal could be studied successfully in primary biliary cirrhosis (PBC) and non-alcoholic steatohepatitis (NASH). Recall, that ICPT has completed two successful randomized phase 2 studies and is set to report phase 3 POISE data in 2Q14, with early stoppage of a large phase 2B study by the NIH for efficacy at improving NAFLD activity scores.
Our View:
* We see limited competitive risk from synthetic bile acids like CDCA in PBC and NASH.
* We would note that CDCA levels are normal in PBC and NASH, as opposed to a deficiency state in CTX, and use of exogenous CDCA could be limited by dose-limiting detergent effects on the liver.
* Current use of Urso in PBC is specifically designed to displace CDCA and prevent detergent toxicity that occur in conditions of cholestasis and use of CDCA in gallstones is associated with elevated liver enzymes.
* Ultimately, OCA is the most potent FXR agonist in development for PBC and NASH, and with 100x greater potency than CDCA, we expect OCA to be the bile acid therapeutic of choice for cholestatic liver disease.
