NEW YORK, May 6, 2014 (GLOBE NEWSWIRE) -- Intercept Pharmaceuticals, Inc. (Nasdaq:ICPT) (Intercept) today announced new OBADIAH trial results showing potential clinical benefits of obeticholic acid (OCA) for patients with bile acid diarrhea. 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 primary biliary cirrhosis (PBC), nonalcoholic steatohepatitis (NASH) and other liver and intestinal diseases, including bile acid diarrhea. The new OBADIAH trial results were presented today at Digestive Disease Week® 2014 (DDW) in Chicago. OBADIAH is an investigator-initiated and sponsored open label Phase 2 trial conducted by Professor Julian Walters and colleagues at Imperial College, London in the United Kingdom. The trial evaluated once daily administration of 25 mg OCA for two weeks in 32 patients with diarrhea. Initial results from the OBADIAH trial in primary bile acid diarrhea were presented in 2013.
Primary Bile Acid Diarrhea
Primary bile acid diarrhea (PBAD) is estimated to affect approximately one percent of the general population and about one-third of patients diagnosed with diarrhea-predominant irritable bowel syndrome. Prior studies have shown these patients have low levels of fibroblast growth factor 19 (FGF19), a hormonal regulator of hepatic bile acid synthesis, with resulting persistently high levels of bile acids that cause their diarrhea. Intercept's previously completed Phase 2 trials that assessed FGF19 have shown that OCA markedly and dose dependently stimulates the release of FGF19 in several patient populations.
The first of two posters from the OBADIAH trial presented at DDW (poster #Tu1262) demonstrates that two weeks of OCA therapy in ten PBAD patients produced an increase in fasting FGF19, the primary outcome measure, along with an improvement in clinical symptoms. Significant correlations were observed between reductions in serum bile acid levels, on the one hand, and reductions in stool frequency (p=0.004) and increases in fasting FGF19 (p = 0.02), on the other. A reduction in fasting C4, a measure of new bile acid synthesis, was significantly associated with a reduced 'urgency' score (p=0.04) and with the change in FGF19 six-hour response (p=0.05). OCA was well tolerated in patients with PBAD and no adverse events were reported during or following the two week treatment period.
"While often unrecognized by clinicians, excess fecal bile acid loss can be the cause of chronic diarrhea," said Professor Walters. "There is a very large number of patients with primary bile acid diarrhea who, for reasons we don't yet understand, do not produce adequate FGF19 to turn off their bile acid production. Our data show that the improvement in clinical symptoms with OCA treatment is related to an increase in FGF19 with a resulting reduction in bile acid synthesis. This is consistent with the anticipated FXR mediated effects of OCA therapy and represents a rational approach to treating patients with bile acid diarrhea that should be further studied in larger well-controlled clinical trials."
Secondary Bile Acid Diarrhea
Secondary bile acid diarrhea (SBAD) is common in Crohn's disease patients with ileal inflammation and/or surgical resection. Since FGF19 is normally produced in the ileum (the final segment of the small intestine), its production in such patients is compromised, leading to excessive bile acid synthesis and chronic diarrhea.
In the second OBADIAH poster presented at DDW (poster #Tu1263), over a two week OCA treatment period seven of eight Crohn's patients with SBAD showed positive changes in stool form and stool index (p=0.03 and p=0.07, respectively), with both pain frequency (p=0.03) and severity (p=0.04) improving. Clinical improvements were more pronounced in patients with shorter ileal resections (i.e., those with more intact ileum). Ileal resection length correlated with the change in stool frequency (p=0.01), stool index (p=0.05), urgency (p=0.03), post-prandial bile acid response (p=0.03), fasting and peak bile acid values. OCA was well tolerated in patients with SBAD and only one adverse event was reported during or following the two week treatment period.
Further supporting OCA's selective mechanism of action in patients with PBAD and SBAD, control patients with chronic diarrhea not related FGF19 deficiency and excess bile acids did not show any significant clinical response to OCA treatment.
"We believe the discovery of reduced levels of FGF19 in patients with bile acid diarrhea is a turning point in what for many years was a poorly understood and often misdiagnosed condition," said David Shapiro, M.D., Chief Medical Officer of Intercept. "Because FGF19 is synthesized in the small intestine under the direct regulation of FXR, it is not surprising that OCA produced such a rapid clinical benefit. We believe these results will stimulate further research in this area and we look forward to working with the gastroenterology community to advance a new treatment strategy for these patients whose symptoms frequently restrict their lifestyle."
About Digestive Disease Week (DDW)
DDW is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract, DDW takes place May 3-6, 2014 at McCormick Place in Chicago. The meeting showcases more than 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology. For more information, visit www.ddw.org.
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.
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 potential effect of OCA in bile acid diarrhea such as its impact on serum biomarkers and clinical symptoms, clinical and regulatory developments for OCA, and the timing of the anticipated enrollment and availability of results, 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.
CONTACT: For more information about Intercept Pharmaceuticals, please contact: Intercept Pharmaceuticals: Barbara Duncan or Senthil Sundaram +1-646-747-1000 firstname.lastname@example.org Media inquiries: Chantal Beaudry or Christopher Frates Lazar Partners + 1-212-867-1762 Intercept@lazarpartners.com
Source:Intercept Pharmaceuticals, Inc.