Ocaliva obeticholic acid regulatory update

FDA’s Gastrointestinal Drugs Advisory Committee voted 17-0 that there is substantial evidence to support accelerated approval of Ocaliva obeticholic acid from Intercept to treat primary biliary cholangitis (PBC). Panelists also thought there were sufficient data to support Ocaliva’s use in combination with ursodeoxycholic acid (UDCA) and as monotherapy in patients who cannot tolerate UDCA. However, they were concerned there may be insufficient safety and efficacy data for patients with moderate or advanced PBC, who were underrepresented in the NDA’s sole Phase III trial and who could be at risk for hepatic toxicity due to hepatic impairment. The oral farnesoid X receptor (FXR; NR1H4) agonist is under Priority Review with a May 29 PDUFA date.

Panelists mostly agreed that alkaline phosphatase (ALP) is a biomarker likely to predict benefit in early stage PBC. FDA had preferred that Intercept show Ocaliva’s efficacy on a composite endpoint using both ALP and total bilirubin, but few patients in the lone pivotal study in Ocaliva’s NDA had total bilirubin levels outside the normal range. ...