In order to censor out deaths due to causes other than PBC-associated liver failure, the Study Group, among other things, analyzed a younger subgroup of patients who were under 60 years old (n=666) at the time they initiated ursodiol therapy. In this subgroup, 61.3% of patients (n=408/666) failed to meet the POISE endpoint after one year of ursodiol therapy and 26.2% of these patients went on to require a liver transplant or die (n=107/408), as compared to 7.4% of patients in the responder group (n=19/258), reflecting a 3.6-fold higher event rate for the non-responders (p=1x10E-7).
The event rate among the responders in this subgroup was 41.3% lower than the event rate of the responder group in the overall patient cohort that included older patients. We believe that this difference is likely due to the greater exclusion of mortality unrelated to PBC in the younger patient subgroups, resulting in even greater differentiation of the responder and non-responder groups.
About The Global Primary Biliary Cirrhosis Study Group
The Global Primary Biliary Cirrhosis Study Group is currently comprised of a group of 15 academic medical centers from eight countries that are pooling their data to investigate the relationship between biochemical assessments of liver function and adverse clinical outcomes in primary biliary cirrhosis. Intercept is sponsoring this independent academic research program but is not involved in the data collection and analysis, which are being conducted by Dr. Henk van Buuren and Dr. Bettina Hansen of Erasmus University Medical Centre in Rotterdam, The Netherlands. The data demonstrate that the primary endpoint being used in Intercept's Phase 3 POISE trial is highly statistically predictive of liver transplant-free survival in primary biliary cirrhosis patients. Intercept anticipates final data from at least 4,000 patients will be collected and analyzed as part of the study.
About Obeticholic Acid (OCA) and the POISE Trial
Intercept's lead product candidate, obeticholic acid, is a bile acid analog and first-in-class agonist of the farnesoid X receptor (FXR). OCA is initially being developed for the second line treatment of primary biliary cirrhosis in patients with an inadequate response to, or who are unable to tolerate, ursodiol (ursodeoxycholic acid), the only approved therapy for this indication. Primary biliary cirrhosis is a chronic autoimmune liver disease that may progress to cirrhosis and liver failure, and it is currently the fifth leading indication for liver transplant in the United States. Intercept is currently conducting a Phase 3 clinical trial of OCA in primary biliary cirrhosis, called the POISE trial, which is anticipated to serve as the basis for seeking regulatory approval in the United States and Europe. Intercept completed enrollment of 217 patients in the POISE trial in December 2012 and expects results to be available in the second quarter of 2014. OCA has orphan drug designation in both the United States and Europe for the treatment of PBC. Intercept owns worldwide rights to OCA outside of Japan and China, where it has out-licensed the product candidate to Dainippon Sumitomo Pharma.