Intercept Announces Positive Pivotal Phase 3 POISE Trial Results
-OCA Meets Primary Endpoint With High Statistical Significance of p < 0.0001
-Company to Conduct Conference Call and Webcast March 17, 2014 at 8:30 a.m. ET
NEW YORK, March 16, 2014 (GLOBE NEWSWIRE) -- Intercept Pharmaceuticals, Inc. (Nasdaq:ICPT) (Intercept) today announced that its international Phase 3 POISE trial of obeticholic acid (OCA) for the treatment of primary biliary cirrhosis (PBC) demonstrated that OCA, at both a 10 mg dose and a 5 mg dose titrated to 10 mg, met the trial's primary endpoint of achieving a reduction in serum alkaline phosphatase (ALP) to < 1.67x ULN with a = 15% reduction from baseline and a normal bilirubin level after 12 months of therapy. The proportion of patients meeting the POISE primary endpoint was: 10% in the placebo group, 47% in the 10 mg OCA group and 46% in the 5-10 mg OCA group (both dose groups p < 0.0001 vs placebo) in an intention to treat analysis. The placebo group experienced a mean decrease in ALP from baseline of 5%, compared to a significant mean decrease of 39% in the 10 mg OCA dose group and 33% in the 5-10 mg OCA titration group (both dose groups p < 0.0001 vs placebo). In addition, both OCA dose groups met pre-specified secondary endpoints of improvements in other liver function parameters, including GGT, ALT, AST and total bilirubin (both dose groups p < 0.0005 vs placebo).
OCA, Intercept's lead product candidate, is a bile acid analog and first-in-class agonist of the farnesoid X receptor (FXR) in development for PBC, nonalcoholic steatohepatitis (NASH) and other liver and intestinal diseases.
"These POISE trial results indicate that OCA clearly produced clinically meaningful improvements, not only in the primary endpoint but also across a broad range of biochemical liver function parameters," said Professor Frederik Nevens, M.D. Ph.D., Chairman of the Department of Hepatology at the University of Leuven, Belgium and the lead investigator in POISE. "While ursodiol has been the mainstay of PBC therapy for the past 20 years, a significant proportion of patients fail to get an adequate response with this drug and we need new therapies to prevent their disease progressing to cirrhosis and liver failure. I believe that the POISE data indicate OCA will provide a meaningful clinical improvement in these patients."
"POISE is Intercept's third successful international, placebo controlled trial of OCA in PBC patients conducted over the past seven years, setting the stage for our anticipated filing for approval of OCA in the U.S., Europe and other countries," said David Shapiro, M.D., Chief Medical Officer of Intercept. "With the results of POISE and our ongoing long-term study of PBC patients on therapy for more than four years, we have shown that OCA produces a significant durable response and believe this will result in better clinical outcomes for many patients. We would like to thank the many investigators and patients who participated in POISE and our other PBC trials."
Primary Endpoint & Clinical Outcomes
In order to evaluate the clinical relevance of the POISE primary endpoint, Intercept sponsored an independent study conducted by the Global PBC Study Group (the 'PBC Supergroup'), consisting of 15 leading PBC centers in eight countries that contributed to a clinical outcomes database of more than 6,000 PBC patients. In this study, patients who did not achieve the POISE endpoint after one year were shown to have a greatly increased risk of liver transplant or death compared to those who achieved the endpoint (Hazard Ratio 2.83, p=1x10-34). The PBC Supergroup has also previously confirmed that higher ALP levels in patients correlate with increased risk of liver transplant and death.
Safety and Tolerability
Pruritus, generally mild to moderate, was the most frequently reported adverse event associated with OCA treatment (placebo: 38%, OCA 10 mg: 68%, OCA 5-10 mg titration: 56%). Eight patients discontinued due to pruritus: none in the placebo group, seven (10%) of the patients in the 10 mg OCA group, and only one (1%) of the patients in the OCA 5-10 mg titration group. Apart from pruritus, the incidence of adverse events was generally similar across both OCA and placebo groups (placebo: 90%, OCA 10 mg: 86%, OCA 5-10 mg: 89%). Overall, serious adverse events (SAEs) occurred in 22 (10%) of the patients and, although there were more SAEs in the OCA treatment groups, none were considered drug-related and there were no apparent patterns in the SAEs. PBC patients typically have significantly elevated HDL cholesterol levels and modest decreases in HDL were observed in both OCA dose groups, similar to those seen in the prior PBC clinical trials. In addition, slight decreases in triglycerides but no change in LDL cholesterol were observed in the OCA dose groups.
The POISE trial results will be presented in greater detail at the upcoming International Liver Congress of the European Association for the Study of the Liver (EASL) in April 2014.
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