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Intercept Pharmaceuticals Announces Results of Phase 2 Trial of OCA in NASH Patients in Japan

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NEW YORK, Oct. 28, 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 the results of a 72-week Phase 2 dose ranging trial of obeticholic acid (OCA), Intercept's lead FXR agonist, in adult patients with nonalcoholic steatohepatitis (NASH) in Japan. The trial was conducted by Intercept's collaborator, Sumitomo Dainippon Pharma.

This trial is the first to evaluate the safety and efficacy of OCA in Japanese NASH patients. The primary efficacy analysis was conducted on an intention to treat (ITT) basis, testing the dose dependent effects of once daily OCA (10mg, 20mg and 40mg) versus placebo on the primary endpoint of a two point improvement in the NAFLD Activity Score (NAS) with no worsening of fibrosis. The ITT analysis included all randomized patients who received treatment (50 per group), and patients who discontinued or did not have a repeat biopsy were treated as non-responders. A pre-specified completer analysis was conducted on the patients who had biopsies at both baseline and 72 weeks (45, 44, 44 and 37 patients in the placebo, 10mg, 20mg and 40mg OCA groups, respectively).

The ITT results in the table below show a dose dependent increase in the percentage of OCA treated patients compared to placebo who achieved the primary endpoint (p=0.053, not significant). The 40mg OCA dose group achieved statistical significance on the primary endpoint compared to placebo (p=0.0496). Dose-dependent trends not reaching statistical significance were also observed for several other pre-specified histologic endpoints, including the proportion of patients with steatosis and inflammation improvement, ballooning resolution and NASH resolution. No difference was seen in fibrosis improvement in the OCA groups compared to placebo.

  placebo 10mg 20mg 40mg  
ITT results N=50 N=50 N=50 N=50  
NAS improvement ≥2 points
with no worsening of fibrosis
10 (20%)
 
11 (22%)
p=0.8070**
 14 (28%)
 p=0.3378**
 
19 (38%)
p=0.0496**
p=0.053* 
 

* Primary efficacy analysis is a stratified Cochran-Armitage test with multiple contrast coefficients. Statistical significance is based on a p-value < 0.05.

** The secondary efficacy analysis is a CMH (Cochran-Mantel-Haenszel) test stratified by baseline fibrosis stage for pairwise comparison of each OCA group vs. placebo group. The multiplicity was not adjusted.

In the completer analysis, similar dose dependent effects were observed, with 51% of patients in the 40mg dose group compared to 22% in the placebo group meeting the primary endpoint (p=0.0061).

With the exception of dose dependent pruritus, OCA appeared to be generally safe and well tolerated. The number of pruritus associated discontinuations were 0, 0, 2 and 5 patients in the placebo, 10mg, 20mg and 40mg OCA groups, respectively. Changes in lipid parameters, including LDL-C, HDL-C and triglycerides, appeared to be consistent with previously reported lipid changes in Western NASH patients. No other meaningful differences in the rate of adverse events between the OCA and placebo groups were noted.  

"This study provides the first data on safety, efficacy and dose effects for OCA in Japanese NASH patients and we look forward to continuing to work with our partner Sumitomo Dainippon Pharma to understand the results further," said Mark Pruzanski, MD, Chief Executive Officer and President of Intercept. "There were distinct differences in baseline characteristics in this study population when compared to the Western patients in the previously conducted FLINT trial. We are currently actively enrolling our Phase 3 REGENERATE trial, which was designed based on the robust FLINT results to evaluate OCA's safety and efficacy in a similar Western patient population."

Conference Call on October 28th at 8:00 am ET

Intercept will hold a conference and webcast on Wednesday, October 28th at 8:00 am ET to discuss the results. The live event will be available on the investor page of Intercept's website at http://ir.interceptpharma.com or by calling (855) 232-3919 (toll-free domestic) or (315) 625-6894 (international) five minutes prior to the start time (no passcode is required). A replay of the call will be available on Intercept's website approximately two hours after the completion of the call and will be archived for two weeks.

About the Phase 2 NASH Trial Conducted by Sumitomo Dainippon Pharma

In this dose-ranging study, 202 Japanese biopsy-proven NASH patients (NAS 5-8) were randomized into one of four arms to receive either a 10mg, 20mg or 40mg dose of OCA, or placebo, and 200 of these patients – 50 per group – initiated treatment for a 72-week double-blind treatment phase, followed by a 24-week off treatment phase which is still ongoing. The primary endpoint was histologic improvement defined as at least a two point improvement in NAFLD activity score (NAS) with no worsening of fibrosis. The primary efficacy analysis tested the dose dependent effects of OCA versus placebo on the primary endpoint.

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 adult biopsy proven NASH patients at eight U.S. centers comprising the NIDDK's NASH clinical research network (CRN). Patients were randomized to receive either a 25mg 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 serum lipid changes, including average increases in total cholesterol and LDL-C and an average decrease in HDL-C, that developed within 12 weeks of treatment initiation, then began reversing through the end of treatment and returned to baseline during the 24-week post-treatment follow-up phase. OCA was generally well tolerated in the FLINT trial. Adverse events were generally mild to moderate in severity and the incidence in the OCA and placebo treatment groups was similar for all symptoms except pruritus. Pruritus in the OCA treatment group occurred more frequently (23% versus 6%, p<0.0001), at a higher grade (predominantly moderate pruritus) but resulted in only one patient discontinuation.   

About the Phase 3 REGENERATE Trial

In September 2015, Intercept initiated its international Phase 3 trial studying OCA in NASH. The trial, known as REGENERATE, is expected to enroll approximately 2,000 NASH patients with advanced liver fibrosis at up to 300 qualified centers worldwide. OCA is the first investigative therapy in NASH to have shown reversal of liver fibrosis with a significantly greater therapeutic response versus placebo in patients at higher risk of progression to cirrhosis. The U.S. Food and Drug Administration (FDA) has designated OCA as a breakthrough therapy in NASH patients with fibrosis and REGENERATE was designed in accordance with advice from the FDA and European Medicines Agency (EMA).

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 Intercept

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 a nuclear receptor 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), 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 Intercept's plans to continue its development program for OCA in NASH as currently designed, Intercept's ability to seek marketing approval for OCA in NASH with liver fibrosis on the basis of a pre-planned interim analysis, the clinical relevance and utility of the endpoints to be studied in the REGENERATE trial, the link between fibrosis and outcomes in NASH, the ability of past results to predict future results, the prevalence of NASH and the potential size of the NASH market, the potential phenotypic and other differences in NASH across patient populations, 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.

CONTACT: For more information about Intercept Pharmaceuticals, please contact: Intercept Pharmaceuticals: Mark Vignola +1-646-747-1000 investors@interceptpharma.com Media inquiries: media@interceptpharma.com Investor inquiries: investors@interceptpharma.com

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