Intercept Presents New Data Analyses on Non-Invasive Liver Testing From FLINT Trial of Obeticholic Acid in Nonalcoholic Steatohepatitis at AASLD 2015
NEW YORK, Nov. 14, 2015 (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 underserved liver diseases, today announced new results from the first non-invasive evaluation of liver fibrosis in patients from the FLINT trial of obeticholic acid (OCA) for the treatment of nonalcoholic steatohepatitis (NASH). The data will be presented on November 17 at the American Academy for the Study of Liver Diseases (AASLD) Annual Meeting (The Liver Meeting®) in an oral presentation entitled, "Longitudinal changes in FIB-4 and improvement in fibrosis stage with obeticholic acid: A secondary analysis of FLINT Trial" at 12:15 p.m. PT in the Moscone Center, Room 2016.
In the FLINT trial, treatment with once daily 25 mg OCA was shown to reverse fibrosis in a significant proportion of biopsy-proven NASH patients, as observed by repeat liver biopsy at the end of the double-blind treatment phase (week 72). The post-hoc analysis to be presented at AASLD evaluated the early predictive value of three known non-invasive fibrosis tests in identifying patients who experienced improvement in fibrosis: FIB-4, APRI and NFS. Each was assessed at baseline and over the course of treatment in the study population and then correlated with histologic changes observed in the 200 OCA and placebo patients who completed the trial with a repeat liver biopsy.
The analysis demonstrated that OCA treatment of NASH patients in FLINT led to a statistically significant decrease in FIB-4 from baseline as compared to placebo (-0.246 OCA vs -0.047 placebo; p=0.0076). Further, a decline in FIB-4 of 10% after 24 weeks of treatment predicted improvement in fibrosis by at least one stage as assessed by biopsy at 72 weeks (p=0.0448). Similarly, OCA-treated patients experienced a significant decrease in APRI as compared to placebo (-0.243 OCA vs. –0.082 placebo; p=0.0009) and a 34% reduction in APRI at 24 weeks predicted improvement in fibrosis by at least one stage at 72 weeks (p=0.0346). On average, OCA treatment reduced the FIB-4 score to <1.3 and the APRI score to <0.5, the respective cut-off values associated with advanced fibrosis, while placebo patients remained above these cut-offs. While NFS declined in the OCA-treated patients and increased in the placebo patients, it did not appear to be sensitive to changes in fibrosis.
Advanced liver fibrosis has been shown to be the best predictor of liver-related mortality in patients with NASH, and the current standard for staging fibrosis is liver biopsy. The FLINT results provide support for the use of both the FIB-4 and APRI scores as potential non-invasive alternative means for monitoring fibrosis changes in response to treatment through simple blood tests. FIB-4 is calculated using an algorithm based on aspartate aminotransferase (AST), alanine aminotransferase (ALT), platelet count and age, while APRI is based on AST and platelet count alone.
"This is an exciting finding from FLINT for members of the medical community who are looking for reliable, non-invasive tests to evaluate changes in fibrosis in patients with NASH soon after initiation of treatment," said Arun Sanyal, M.D., Professor of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, Virginia Commonwealth University. "It provides proof of concept that noninvasive biomarkers can be sensitive to changes in fibrosis and future studies with greater refinement may allow non-invasive assessment of the benefits of treatment of NASH in terms of fibrosis regression."
In September 2015, Intercept initiated the REGENERATE international Phase 3 trial of OCA in NASH patients with liver fibrosis. The U.S. Food and Drug Administration (FDA) has designated OCA as a breakthrough therapy in this patient population. REGENERATE will initially target enrollment of 1,400 biopsy-proven NASH patients with stage 2 and 3 fibrosis at up to 300 sites worldwide.
About Nonalcoholic Steatohepatitis
NASH is a serious chronic liver disease caused by excessive fat accumulation in the liver that induces chronic inflammation, resulting in progressive fibrosis (scarring) that can lead to cirrhosis, eventual liver failure, cancer and death. There are currently no drug therapies approved for the treatment of NASH. Patients with early disease but with risk factors such as diabetes, obesity or elevated ALT are at increased risk of progression to cirrhosis. The proportion of liver transplants attributable to NASH has increased rapidly in past years and by 2020 the disease is projected to become the leading indication for liver transplant ahead of chronic hepatitis C and alcoholic liver disease.
About the Phase 2b FLINT Trial
The FLINT trial was sponsored by the National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) and the results were published online in The Lancet in November 2014. FLINT enrolled 283 biopsy-proven adult NASH patients at eight U.S. centers comprising the NIDDK's NASH Clinical Research Network. Patients were randomized to receive either a once daily 25 mg dose of OCA or placebo for 72 weeks. FLINT was stopped early primarily due to the demonstrated efficacy of OCA in a pre-planned interim analysis based on achieving the primary endpoint of at least a two point improvement in NAFLD Activity Score (NAS) with no worsening of fibrosis (p=0.0024 vs. placebo). OCA treatment for 72 weeks also resulted in the improvement of fibrosis by at least one stage and resolution of NASH (among those with definite NASH at baseline) in a significant proportion of patients versus placebo. OCA treatment was associated with an increase in average total cholesterol and LDL-C and a decrease in average HDL-C, developing soon after treatment initiation, then gradually reversing through the end of treatment and returning to baseline during the post-treatment follow-up phase. OCA was generally well tolerated in the FLINT trial with the incidence of adverse events in the OCA and placebo treatment groups similar for all symptoms except for pruritus (23% vs. 6%, p<0.0001), resulting in one patient discontinuation. The incidence of severe or life threatening events was not different between the two treatment groups.
Intercept is a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat chronic underserved liver diseases. The Company's lead product candidate, obeticholic acid (OCA), is an agonist of the farnesoid X receptor (FXR). OCA is being developed for a variety of chronic liver diseases, including primary biliary cirrhosis, recently renamed primary biliary cholangitis (PBC), nonalcoholic steatohepatitis (NASH), primary sclerosing cholangitis (PSC) and biliary atresia. The FDA has granted OCA breakthrough therapy designation for the treatment of NASH with liver fibrosis and granted OCA fast track designation for the treatment of patients with PBC. OCA has also 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, 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, preclinical and regulatory developments for Intercept's product candidates, the anticipated results of Intercept's clinical trials and preclinical studies and other development activities and the timing thereof, Intercept's potential development and regulatory milestones and the timeframes under which it anticipates such milestones may be achieved, Intercept's plans to continue its development program for OCA in NASH as currently designed, the ability of past results to predict future results, the clinical utility of our selected endpoint and any potential consensus relating thereto, 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 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, 2014 filed on March 2, 2015 as well as any updates to these risk factors filed from time to time in 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.