NEW YORK, Nov. 8, 2012 (GLOBE NEWSWIRE) -- Intercept Pharmaceuticals, Inc. (Nasdaq:ICPT) (Intercept), a clinical stage biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat chronic liver diseases, today announced initial results from PESTO, an open-label Phase 2a trial evaluating the effects of obeticholic acid (OCA) for the treatment of portal hypertension. Twelve patients with established alcoholic cirrhosis and portal hypertension were administered a 10mg daily dose of OCA for seven days. The drug was well tolerated in all twelve patients and, of the eight patients assessed for changes in portal pressure, five met the primary efficacy endpoint with a clinically significant improvement in hepatic venous pressure gradient (HVPG), the standard measurement of portal pressure in such patients.
The initial results from PESTO will be presented at the American Association for the Study of Liver Disease (AASLD)'s annual Liver Meeting in Boston as a late-breaking poster on Monday, November 12, 2012. The abstract is available at www.aasld.org.
PESTO Trial Results
The rationale for the PESTO trial is based on previously obtained results in an animal model of cirrhosis, demonstrating that five days of OCA therapy can reverse portal hypertension via a local nitric oxide induced mechanism with no concomitant change in systemic blood pressure [Hepatology 2009, Vol 50, 74A]. PESTO is designed to evaluate OCA's ability to reduce hepatic portal venous pressure in patients with liver cirrhosis, first testing a 10mg dose and then proceeding with a 25mg dose (still ongoing). The first four patients enrolled were assessed for drug safety alone; the subsequent eight patients were then assessed for efficacy as well by measuring HVPG.
The primary efficacy endpoint of the trial is to lower HVPG after seven days of treatment by 15% or more, or to less than 12 mm Hg, a level at which the risk of adverse clinical outcomes has been shown to be significantly reduced. Five of the eight patients in the efficacy cohort met at least one of these endpoint criteria, while a sixth patient experienced slightly more than a 14% reduction in HVPG. Among these six patients who experienced a reduction in HVPG, the mean baseline HVPG was 16 mm Hg which decreased to 12 mm Hg at the end of therapy, reflecting a mean 24% reduction (range: 14% to 38%). Systemic mean arterial blood pressure (MAP) increased slightly in the six patients, with the mean baseline MAP at 84 mm Hg rising to 97 mm Hg at the end of therapy. All patients tolerated OCA therapy and no significant changes were seen in aminotransferases, creatinine, bilirubin or coagulation.
"The available results so far from the PESTO trial are encouraging," commented Dr. Raj Mookerjee from University College London, the investigator conducting the trial. "It is believed that portal hypertension is caused at least to some degree by a reduction in available intra-hepatic nitric oxide, and we have previously shown in an animal model that OCA can significantly increase nitric oxide in the liver. The aim of PESTO is to assess the ability of OCA to similarly reduce portal hypertension in patients acutely, after only a week of treatment, via a mechanism independent of any longer term anti-fibrotic effects. Indeed, the data from the 10mg dose cohort suggest that OCA may rapidly improve portal hypertension in patients without reducing systemic blood pressure. These results merit further study of OCA in longer term, controlled trials as a potential novel portal hypertension treatment."
About Portal Hypertension
Portal hypertension results from increased pressure in the portal vein, which feeds most of the blood supply to the liver. Clinically significant portal hypertension is defined as an HVPG >10 mm Hg (1 mm to 5 mm HVPG is normal). It is a common cause of morbidity and mortality in patients with cirrhosis, seen at the end stage of all chronic liver diseases. One manifestation of portal hypertension is the development of esophageal varices, which are distended and weakened veins in the lower part of the esophagus that can burst and cause catastrophic bleeding. More than 40% of patients with cirrhosis have varices at the time of diagnosis. Patients with an HVPG ≥12 mm Hg are at particularly high risk of variceal bleeding, with each episode carrying an approximate 20% mortality risk, and a goal of therapeutic intervention is therefore to lower portal pressure ideally below this threshold. There are no approved therapies for the treatment of portal hypertension, although beta blockers are commonly used. However, they are effective in only approximately one third of portal hypertension patients and present significant safety issues in advanced disease. One challenge with beta blockers is that they lower systemic blood pressure in these patients who already tend to have low blood pressure (hypotension) and therefore are at risk of fainting and reduced perfusion of critical organs.
About Intercept
Intercept is a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat orphan and more prevalent liver diseases utilizing its expertise in bile acid chemistry. The company's lead product candidate, obeticholic acid, or OCA, 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 (PBC) in patients with an inadequate response to, or who are unable to tolerate, ursodiol, the only approved therapy for this indication. PBC 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. 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 outlicensed the product candidate to Dainippon Sumitomo Pharma (DSP). For more information about Intercept, please visit the Company's website at: www.interceptpharma.com.
Safe Harbor Statement
This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to OCA's potential to treat portal hypertension, the utility of the endpoints of the PESTO trial and Intercept's 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 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 success and timing of Intercept's preclinical studies and clinical trials; Intercept's ability to obtain and maintain regulatory approval of OCA and any other product candidates it may develop, and the labeling under any approval it may obtain; regulatory developments in the United States and other countries; the performance of third-party manufacturers; Intercept's plans to develop and commercialize its product candidates; Intercept's ability to obtain and maintain intellectual property protection for its product candidates; the successful development of Intercept's sales and marketing capabilities; the potential 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; the loss of key scientific or management personnel; Intercept's ability to obtain additional financing; the accuracy of Intercept's estimates regarding expenses, future revenues and capital requirements; and other factors discussed under the heading "Risk Factors" contained in Intercept's prospectus dated October 10, 2012 filed with the Securities and Exchange Commission pursuant to Rule 424(b) of the Securities Act of 1933, as amended, as well as any updates to these risk factors filed from time to time in Intercept's Quarterly Reports on Form 10-Q or Current Reports on Form 8-K and 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, please contact Mark Pruzanski, M.D., or Barbara Duncan, both of Intercept Pharmaceuticals, at 1-646-747-1000.