-Notable Improvements on Key Endpoints as Early as Two Weeks After OCA Treatment Initiation
-Titration Regimen Well Tolerated With Pruritus Incidence and Severity Diminishing Over Course of Treatment
NEW YORK, April 12, 2014 (GLOBE NEWSWIRE) -- Intercept Pharmaceuticals, Inc. (Nasdaq: ICPT ) (Intercept) today announced efficacy and safety results from the Phase 3 POISE trial of obeticholic acid (OCA) for the treatment of primary biliary cirrhosis (PBC) to be presented in a late-breaker session at the International Liver Congress of the European Association for the Study of the Liver (EASL). 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.
As previously reported, the POISE trial met its primary endpoint with high statistical significance (p < 0.0001), demonstrating OCA's efficacy on a composite liver biochemical endpoint which has been shown to strongly correlate with improved clinical outcomes. 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). New data in today's presentation show that OCA treated patients achieved a highly statistically significant reduction in alkaline phosphatase (ALP) as early as two weeks, with a peak effect achieved by six months.
Pruritus, generally mild to moderate, was the most frequently reported adverse event in the POISE trial. However, only one (1%) of the patients in the OCA 5-10 mg titration group discontinued therapy due to pruritus after moving up to the 10 mg dose, as compared to seven (10%) of the patients in the 10 mg OCA group. Additional data presented today show that the incidence and severity of OCA related pruritus diminishes with time on therapy. Specifically, pruritus scores were no different from placebo in both OCA treatment groups during the second half of the trial.
"After many years without any new developments in the treatment of PBC, we have finally reached a turning point," said Frederik Nevens, M.D., Ph.D., Chairman of the Department of Hepatology at the University of Leuven, Belgium and the POISE trial's lead investigator. "These data clearly demonstrate that OCA is effective in reducing ALP and other liver enzymes in patients who failed to respond adequately to standard therapy for many years. In addition and importantly, we were able to find a dosing approach that markedly increased tolerability for patients. Patients starting with a 5 mg dose and the option to titrate up to 10 mg experienced less pruritus, but achieved similar rates of ALP and other liver enzyme reduction compared to patients who were treated with a 10 mg dose."
Collette Thain, M.B.E., founder of The United Kingdom PBC Foundation and a PBC patient, said, "At the time of my diagnosis, little was known about this rare autoimmune disease, and diagnosis was a long and stressful process. Since then, awareness has increased significantly, but there remains only one approved treatment for PBC: ursodiol (UDCA), to which not all patients have an adequate response. The Foundation and I are delighted to see research being conducted to provide the medical community with new options for treating patients with PBC."
Separately, in a poster presentation at the International Liver Congress, researchers presented a retrospective analysis of two Phase 2 trials of OCA for the treatment of PBC in a total of 224 patients. Pooled results from these trials were evaluated using the Phase 3 POISE trial endpoint. This analysis showed that overall 43% of patients receiving 10 mg, 25 mg or 50 mg of OCA met the POISE primary endpoint, compared with 8% who received placebo (p < 0.0001), corroborating the Phase 3 results. Moreover, a strong OCA treatment effect was observed regardless of whether OCA was administered as monotherapy or as an add-on to existing ursodiol. OCA treatment was generally well-tolerated, with pruritus, primarily mild or moderate, being the most common adverse event.
"We believe OCA can fill a major gap in the treatment of PBC by providing an effective second-line therapy for the up to 50% of patients who do not achieve an adequate response with ursodiol, the current standard of care," said Mark Pruzanski, M.D., chief executive officer of Intercept. "The POISE trial represents the culmination of more than a decade of work and this important milestone would not be possible without the dedication of researchers, clinicians and patients around the globe."
Intercept plans to submit data from the Phase 3 POISE trial and the two Phase 2 trials of OCA for the treatment of PBC as part of a New Drug Application to the U.S. Food and Drug Administration and a Marketing Authorization Application to the European Medicines Agency. These regulatory filings are currently anticipated at the end of 2014.
POISE Clinical Results
As previously reported, 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 ALP to < 1.67x ULN with a ≥ 15% reduction from baseline and a normal bilirubin level after 12 months of therapy. 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 OCA dose groups p < 0.0001 vs placebo).
In addition to a reduction in ALP levels, treatment with OCA met pre-specified secondary endpoints. Intercept's presentation today provides additional details on reductions in gamma-glutamyl transferase (GGT) of 64% and 50%, alanine transaminase (ALT) of 42% and 36%, aspartate transaminase (AST) of 24% and 22%, in each case for the 10 mg and 5-10 mg OCA dose groups, respectively (both OCA dose groups p < 0.0005 vs placebo). The company's presentation today also provides additional details on lipid observations in the POISE trial, including modest but significant decreases in triglycerides, VLDL cholesterol and HDL cholesterol in both OCA dose groups. No change in LDL cholesterol was observed.
As previously reported, the incidence of adverse events was generally similar across both OCA and placebo groups (placebo: 90%, OCA 10 mg: 86%, OCA 5-10 mg titration: 89%). 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. 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.
About Intercept
Intercept is a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat orphan and more prevalent liver and intestinal diseases utilizing its expertise in bile acid chemistry. The company's lead product candidate, obeticholic acid (OCA), is a bile acid analog and first-in-class agonist of the farnesoid X receptor (FXR). OCA is being developed for a variety of chronic liver diseases and patient populations including primary biliary cirrhosis (PBC), nonalcoholic steatohepatitis (NASH), cirrhosis, portal hypertension, alcoholic hepatitis, primary sclerosing cholangitis (PSC) and bile acid diarrhea. OCA has received orphan drug designation in both the United States and Europe for the treatment of PBC and PSC. Intercept owns worldwide rights to OCA outside of Japan and China, where it has out-licensed the product candidate to Dainippon Sumitomo Pharma. For more information about Intercept, please visit the Company's website at: www.interceptpharma.com .
About Primary Biliary Cirrhosis
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 disease of women, 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% of PBC patients fail to respond adequately, thereby remaining at risk of adverse outcomes.
Safe Harbor Statements
This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the utility of the selected endpoint for POISE; the acceptance by regulatory authorities of the POISE trial endpoint or results; clinical and regulatory developments for OCA; the anticipated timeframe for the commencement, completion and receipt of results from the clinical trials in OCA and for the making of regulatory submissions; the anticipated results of our clinical and preclinical trials and other development activities; and our strategic directives under the caption "About Intercept." These "forward-looking statements" are based on management's current expectations of future events and are subject to a number of important risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: the initiation, cost, timing, progress and results of Intercept's development activities, preclinical studies and clinical trials; the timing of and Intercept's ability to obtain and maintain regulatory approval of OCA, INT-767 and any other product candidates it may develop, particularly the possibility that regulatory authorities may require clinical outcomes data (and not just results based on achievement of a surrogate endpoint) as a condition to any marketing approval for OCA, and any related restrictions, limitations, and/or warnings in the label of any approved product candidates; Intercept's plans to research, develop and commercialize its product candidates; the election by Intercept's collaborators to pursue research, development and commercialization activities; Intercept's ability to attract collaborators with development, regulatory and commercialization expertise; Intercept's ability to obtain and maintain intellectual property protection for its product candidates; Intercept's ability to successfully commercialize its product candidates; the size and growth of the markets for Intercept's product candidates and its ability to serve those markets; the rate and degree of market acceptance of any future products; the success of competing drugs that are or become available; regulatory developments in the United States and other countries; the performance of third-party suppliers and manufacturers; Intercept's need for and ability to obtain additional financing; Intercept's estimates regarding expenses, future revenues and capital requirements and the accuracy thereof; Intercept's ability to retain key scientific or management personnel; and other factors discussed under the heading "Risk Factors" contained in Intercept's annual report on Form 10-K for the year ended December 31, 2013 filed on March 14, 2014 as well as any updates to these risk factors filed from time to time in Intercept's other filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Intercept undertakes no duty to update this information unless required by law.
For more information about Intercept Pharmaceuticals, please contact: Intercept Pharmaceuticals: Barbara Duncan or Senthil Sundaram +1-646-747-1000 Media inquiries: In Europe Instinctif Partners Katherine Lynch +44 (0)7500 027 181 or Gemma Howe +44 (0)7814 907 932 In the USA Chantal Beaudry or Christopher Frates Lazar Partners + 1-212-867-1762
