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Intercept Announces New Data Analyses From FLINT Trial of Obeticholic Acid in NASH

--Histologic improvements shown in OCA-treated patients regardless of fibrosis stage and in those at increased risk of rapid disease progression

--OCA-treated patients who initiated statins rapidly reversed LDL increases to below baseline levels

NEW YORK, March 20, 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 neglected chronic liver diseases, announced today new subgroup analyses from the Phase 2b FLINT trial of obeticholic acid (OCA) in patients with nonalcoholic steatohepatitis (NASH). Intercept is presenting the data in two posters during today's poster session at the American Association for the Study of Liver Disease (AASLD) and Industry Colloquium: Novel Targets and Therapies in Liver Disease.

Obeticholic acid (OCA) is a first-in-class farnesoid X receptor (FXR) agonist being developed for primary biliary cirrhosis (PBC), NASH and other chronic liver indications. Intercept has initiated a rolling New Drug Application with the FDA for PBC, and expects to complete the NDA and MAA submission in 2Q 2015. The commercial launch of OCA in the U.S. and Europe is planned in 2016. OCA was also recently granted breakthrough therapy designation by FDA for the treatment of NASH with liver fibrosis.

OCA Histological Effects in High-Risk NASH Patients

Established fibrosis is currently the best predictor of liver-related mortality in patients with NASH (Younossi, Hepatology 2011), and patients with early disease but with risk factors such as diabetes, obesity or elevated ALT are at risk of rapid progression to cirrhosis (Adams, J Hepatology 2005; Ekstedt, Hepatology 2006). The efficacy of OCA was evaluated in a high-risk subset of NASH patients in the FLINT trial more likely to experience liver-related clinical outcomes, defined as patients with a NAFLD activity score (NAS) of 4 or more and (i) advanced fibrosis (stage 2 or 3), or (ii) those with both early fibrosis (stage 1) and concomitant diabetes, obesity or elevated ALT. In this post hoc analysis of the high-risk subgroup (n=160; OCA=84; placebo=76), OCA-treated patients experienced improvements in NASH resolution (18% OCA vs 5% placebo, p=0.014), NAS by ≥2 points (60% OCA vs 30% placebo, p=0.0004), and liver fibrosis by at least one stage (39% OCA vs 21% placebo, p=0.007). Further analysis of the observed fibrosis improvement in NASH patient subgroups with the greatest risk of progression demonstrated that OCA treatment resulted in at least one stage fibrosis improvement in obese patients (39% OCA vs 18% placebo, p=0.003) and patients with diabetes (43% OCA vs 18% placebo, p=0.009). In addition, fewer OCA-treated patients experienced fibrosis progression (17% OCA vs 29% placebo, p=0.047). The histologic benefits observed in OCA-treated patients occurred across all baseline fibrosis stages, supporting the potential for long-term OCA treatment to prevent progression to cirrhosis.

OCA Effects on Cardiometabolic Parameters

Patients with NASH generally experience cardiometabolic abnormalities that correspond to a relatively high cardiovascular disease risk and mortality. In the FLINT trial, OCA treatment for 72 weeks resulted in improvements in liver fibrosis (the hepatic feature most correlated with both cardiovascular and liver-related mortality) and other markers of cardiovascular risk, such as body weight (median: -1.7 kg OCA vs +0.6 kg placebo, p=0.001) systolic blood pressure (mean: -4.0 mmHg OCA vs -0.8 mmHg placebo, p=0.0331) and triglyceride/HDL ratio, a marker of cardiovascular risk and mortality (mean: -0.6 OCA vs 0.1 placebo, not significant). OCA treatment was not associated with changes in the Framingham Risk Score, a long-term measure of cardiovascular risk.

This post hoc analysis also evaluated the effect of statin use during FLINT. OCA-treated patients who initiated statins during the FLINT trial (n=26) experienced a rapid reversal of their observed mean LDL increase to below baseline levels, with a mean decrease after 72 weeks of treatment of -18.9 mg/dL. In contrast, other OCA-treated patients with no reported initiation or change in statin therapy experienced an increase in LDL that peaked at week 12 and was sustained over the 72 week treatment period. Patients treated with statins at baseline who maintained statin treatment over the duration of the study (n=50) experienced a mean LDL increase of 8.7 mg/dL at 72 weeks. Patients not treated with statins during the study (n=65) experienced a mean LDL increase of 16.0 mg/dL. Treatment related LDL increases in all groups reversed with treatment discontinuation. This post hoc analysis suggests that the OCA associated LDL increase reaches a maximum peak and plateaus soon after initiation of therapy and that concomitant statin use in NASH patients receiving OCA may ameliorate any treatment-related LDL increases.

Further, another new finding in this analysis was that statin use appeared to have an additive effect to OCA-related improvements in liver biochemistry parameters, while not impacting liver histology.

"Given the relatively high risk of progression to cirrhosis and mortality in this population of NASH patients with liver fibrosis and other co-morbidities, the findings being presented at the AASLD Colloquium add important new insights into the potential for OCA as a novel therapy to address a major unmet medical need," said David Shapiro, M.D., Chief Medical Officer of Intercept. "In addition to the histologic improvements in fibrosis and steatohepatitis seen in patients most at risk of progressing to cirrhosis, we are encouraged by the observation that OCA improved several important cardiometabolic parameters. Furthermore, the data support the potential for statins to effectively manage LDL and further improve liver enzymes, providing additional support for their use in NASH patients as currently recommended in the AASLD and EASL practice guidelines."

Previously Reported Safety and Tolerability Information

As previously reported in the primary analysis of FLINT, OCA was generally well tolerated. 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% vs 6%, p<0.0001), at a higher grade (predominantly moderate pruritus) and resulted in one patient discontinuation. The incidence of severe or life threatening events was not different between the two treatment groups and most of the events in both groups were deemed to be unrelated to treatment, including all severe or life threatening cardiovascular events. As previously disclosed, two deaths occurred in the OCA treatment group, but neither was considered related to OCA treatment.

Research Analyst and Investor Event on March 20, 2015

Intercept management will host an event for research analysts and investors after the market close on Friday, March 20, 2015 with a presentation starting at 6:00 p.m. ET to discuss the data presented in the two posters. A live webcast of the presentation 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 required. A replay will also be available on the Intercept website approximately two hours after the completion of the event and will be archived for two weeks.

About FLINT

The Farnesoid X Receptor Ligand Obeticholic Acid in Nonalcoholic Steatohepatitis Treatment (FLINT) trial was sponsored by the National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK). FLINT enrolled 283 adult NASH patients at eight U.S. centers comprising the NIDDK's NASH clinical research network (CRN). Patients were randomized to receive either a 25-mg dose of OCA or placebo for 72 weeks. Patients enrolled in the trial were qualified based on a diagnosis determined by liver biopsy at the start of the trial with a NAFLD Activity Score (NAS) of four or greater and with a score of at least one in each component of the NAS eight point scale (steatosis 0-3, lobular inflammation 0-3, ballooning 0-2). End of trial biopsies were conducted in patients after the 72-week treatment period, with all biopsies centrally scored in a blinded fashion. Further details can be found at http://clinicaltrial.gov/ct2/show/NCT01265498. The results from the FLINT trial were published online in The Lancet in November 2014.

About Nonalcoholic Steatohepatitis

NASH is a serious chronic liver disease caused by excessive fat accumulation in the liver that induces chronic inflammation which leads to progressive fibrosis (scarring) that can lead to cirrhosis, eventual liver failure and death. There are currently no drugs approved for the treatment of NASH. Studies have shown that 21-26% of NASH patients will develop cirrhosis over 8.2 years of follow-up and that liver-related mortality due to this disease is ten-fold that of the general population. According to recent epidemiological studies, it is estimated that more than 10% of the U.S. adult population has NASH with more than 60% of patients (potentially more than 14 million in total) believed to have liver fibrosis or cirrhosis due to progression of the disease. 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. NASH patients with fibrosis are at greater risk of progressing to cirrhosis, liver failure and cancer.

About Intercept and Obeticholic Acid

Intercept is a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat neglected chronic liver diseases. The company's lead product candidate, obeticholic acid (OCA), is a 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), primary sclerosing cholangitis (PSC) and biliary atresia. The FDA has granted OCA breakthrough therapy designation for the treatment of NASH with fibrosis and granted OCA fast track designation for the treatment of patients with PBC who have an inadequate response to or are intolerant of ursodiol. 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 potential utility of the histological primary and secondary endpoints used in FLINT; the potential acceptance by regulatory authorities of the endpoints and data from FLINT; the potential of OCA to treat patients with NASH; the potential that statin use may ameliorate LDL increases resulting from OCA treatment; the anticipated clinical, regulatory and commercial milestones for OCA, including the anticipated completion of the NDA for OCA in PBC in 2Q 2015 and the anticipated commercial launch of OCA in PBC in 2016; 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, INT-767 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, 2014 filed on March 2, 2015 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.

This press release contains the results of retrospective analyses presented at a scientific congress. Retrospective analyses after the unblinding of results can potentially introduce bias and regulatory authorities typically give greatest weight to results from pre-specified analyses as compared to retrospective analyses.

CONTACT: For more information about Intercept, please contact Barbara Duncan or Senthil Sundaram, both of Intercept Pharmaceuticals at 1-646-747-1000. Media inquiries: media@interceptpharma.com Investor inquiries: investors@interceptpharma.com

Source:Intercept Pharmaceuticals, Inc.