- Largest Analysis of Data from Patients with Primary Biliary Cirrhosis
- Alkaline Phosphatase (ALP) and Bilirubin Shown to Significantly Predict Clinical Outcomes
NEW YORK, Dec. 5, 2014 (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 and intestinal diseases, announced today the publication of the meta-analysis performed by the Global Primary Biliary Cirrhosis Study Group (Global PBC Study Group) in the December issue of Gastroenterology. In the largest meta-analysis of individual PBC patient data conducted to date, researchers confirmed that levels of ALP and bilirubin predicted clinical outcomes of patients with PBC.
Of the 4,845 patients included in the analysis, 1,118 reached a clinical outcome defined as liver transplantation or death. For the first time, the researchers reported a log-linear association between ALP values and liver transplant-free survival. At one year after study enrollment, an ALP level of two times upper limit of normal (ULN) best predicted patient outcome (C statistic, 0.71) but not significantly better than other lower ALP thresholds such as 1.67 times ULN. Of patients with ALP levels less than or equal to two times ULN, 84% survived for over a ten year follow-up period compared with 62% of those with levels exceeding two times ULN (p < 0.0001). Elevated bilirubin levels were strongly predictive of a worse prognosis and only 41% of such patients had not had a liver transplant or died over the subsequent 10 years compared with 86% of patients with normal bilirubin levels (p < 0.0001).
The Global PBC Study Group analysis also showed that ALP and bilirubin were correlated with clinical outcomes consistently over time and in all the patient subgroups evaluated. Specifically, ALP was predictive of transplant-free survival in PBC patients both on and off standard of care treatment, those with histologically advanced or early stage disease, patients 45 years or younger or over 45 years at the time of diagnosis, female or male, and irrespective of the year of diagnosis.
"This study represents the largest international collaboration in PBC and provided us with a wealth of data supporting the use of this biochemical endpoint for therapeutic clinical trials," said senior author Bettina Hansen, Ph.D., Department of Gastroenterology and Hepatology, Erasmus University Medical Centre in Rotterdam. "But the key takeaway from this analysis for everyday clinical practice is that the lower a patient's ALP level and having a normal bilirubin level correlate with an improved prognosis for patients with PBC."
The Global PBC Study Group consists of 15 leading PBC centers in eight countries that contributed to a clinical outcomes database of more than 6,000 patients with PBC. Data were analyzed under the direction of Dr. Bettina Hansen, Dr. Willem J. Lammers, Dr. Henk van Buuren and colleagues at Erasmus University Medical Centre in Rotterdam, the Netherlands. Intercept was a sponsor of this independent academic research program but was not involved in the study design, data collection, analysis or publication.
"We believe the Global PBC Study Group's research supports the clinical relevance of a primary endpoint based on ALP and bilirubin in clinical trials of patients with PBC," said David Shapiro, M.D., Chief Medical Officer of Intercept. "More broadly, it should enhance monitoring of disease progression and lead to better dialogue between clinicians and patients."
"The work done by the Global PBC Study Group exemplifies the value of such cooperative initiatives in generating large clinical datasets that may provide evidence for the utility of proposed surrogate endpoints and a better understanding of the natural history of diseases such as PBC," said Mark Pruzanski, M.D., CEO of Intercept. "We hope the Global PBC Study Group's work continues in the future and would like to thank all of the researchers and patients involved in making such an invaluable contribution to the medical community's understanding of this rare disease."
About Primary Biliary Cirrhosis
PBC is an autoimmune liver disease that may progress to cirrhosis and liver failure, and it is currently the second leading indication for liver transplant among women in the United States. It is primarily a disease of women, afflicting approximately one in 1,000 women over the age of 40. Ursodiol is the only approved drug treatment for PBC and studies have shown that up to 50% of PBC patients may have an inadequate response, thereby remaining at risk of adverse outcomes.
About Intercept
Intercept is a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat orphan and more prevalent chronic 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 including primary biliary cirrhosis (PBC), nonalcoholic steatohepatitis (NASH), and primary sclerosing cholangitis (PSC). OCA has received Fast Track Designation in the United States and orphan drug designation in both the United States and Europe for the treatment of PBC and PSC. Several large, randomized, controlled studies of OCA in the treatment of chronic liver disease have been completed. These include Intercept's Phase 3 POISE trial for the treatment of patients with PBC and the NIDDK-sponsored FLINT trial for the treatment of patients with NASH. The detailed results of POISE were previously reported in April 2014 and the primary endpoint was based on the achievement of both a reduction in ALP level to below a threshold of 1.67 times ULN, with a minimum of 15% reduction in ALP level from baseline, and a normal bilirubin level. Intercept owns worldwide rights to OCA outside of Japan, China and Korea, where it has out-licensed the product candidate to Sumitomo Dainippon 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 clinical relevance of the Global PBC Study Group data and the applicability thereof to OCA in PBC, the potential relationship between ALP and bilirubin and adverse clinical outcomes, the clinical utility of the POISE trial selected endpoints and any potential consensus relating thereto, clinical, preclinical and regulatory developments for our product candidates, the anticipated timetable for our clinical, regulatory and 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 our development activities, preclinical studies and clinical trials; the timing of and our ability to obtain and maintain regulatory approval of OCA and any other product candidates we 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; our plans to research, develop and commercialize our product candidates; the election by our collaborators to pursue research, development and commercialization activities; our ability to attract collaborators with development, regulatory and commercialization expertise; our ability to obtain and maintain intellectual property protection for its product candidates; our ability to successfully commercialize our product candidates; the size and growth of the markets for our product candidates and our 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; our need for and ability to obtain additional financing; our estimates regarding expenses, future revenues and capital requirements and the accuracy thereof; our ability to retain key scientific or management personnel; and other factors discussed under the heading "Risk Factors" contained in our 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 our 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.