Intercept Pharmaceuticals, Inc., a clinical stage biopharmaceutical company focused on the development and commercialisation of novel bile acid therapeutics to treat chronic liver diseases, has completed enrollment in POISE, its pivotal phase III clinical trial of obeticholic acid (OCA) in primary biliary cirrhosis (PBC). Results from the 12-month double-blind portion of POISE are anticipated to be available in the second quarter of 2014 and, if successful, will be used to seek regulatory approval of OCA, a first-in-class FXR agonist, as a second line treatment in PBC.
By enrolling 218 patients at 59 centres in 13 countries, Intercept exceeded its targeted number of patients and completed enrollment in POISE faster than originally projected.
"We are delighted that POISE is fully enrolled ahead of schedule and believe this reflects the enthusiasm of both the investigators and patients for a new treatment option," commented David Shapiro, MD, Intercept's chief medical officer.
PBC is an 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. It is primarily a female disease, afflicting approximately one in 1,000 women over the age of 40. Clinically, the progress of the disease is assessed by measuring the blood levels of alkaline phosphatase (ALP) and bilirubin, which have been shown to correlate with risk of adverse outcomes. Ursodiol is the only approved drug treatment for PBC and studies have shown that up to 50 per cent of PBC patients fail to respond adequately, thereby remaining at risk of adverse outcomes.
The POISE trial is studying the safety and efficacy of a once daily dose of OCA in PBC patients with an inadequate therapeutic response to, or who are unable to tolerate, ursodiol. Patients were randomized to one of three groups in the study: 5mg, 10mg or placebo. The primary endpoint of the 12-month double—blind portion of the trial is the achievement of both an ALP level of less than 1.67 times upper limit normal (with at least a 15 per cent reduction from baseline) and a normal bilirubin level, as compared to placebo. Patients with ALP and bilirubin levels below these thresholds have been shown in long-term clinical studies to have a significantly lower risk of progressing to liver transplant and death. All of the patients will be allowed to participate in a long-term extension of the trial during which patients are expected to be treated with OCA for five years.