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Intercept Pharmaceuticals Announces Initiation of Prospective Trial to Explore Effect of Combined OCA and Statin Therapy on Lipid Metabolism in NASH Patients

NEW YORK, Dec. 7, 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 initiation of the Combination OCA aNd sTatins for monitoRing Of Lipids (CONTROL) Phase 2 clinical trial to evaluate the effect of obeticholic acid (OCA), the company's lead FXR agonist, in combination with statin therapy on lipid metabolism in patients with nonalcoholic steatohepatitis (NASH).

"We are committed to a broad and comprehensive clinical development program in NASH, given the significant unmet need for this serious condition," said Mark Pruzanski, M.D., Chief Executive Officer and President of Intercept. "Practice guidelines support statin use to treat dyslipidemia in NASH patients and we believe CONTROL will provide valuable information about OCA's impact on lipid metabolism, as well as the ability of co-administered statins to manage LDL in this patient population, adding to the findings from our FLINT study."

CONTROL has been designed as a randomized, double-blind, placebo-controlled Phase 2 clinical trial. The trial is expected to enroll 80 NASH patients who are naïve to statin therapy or have undergone a statin washout, and will include a 16-week double-blind phase followed by an optional two-year long-term safety extension phase.

CONTROL will assess lipid and subfraction changes every four weeks over the course of the study as follows:

  • The first four weeks will evaluate three doses of OCA (5 mg, 10 mg, 25 mg) or placebo with no concomitant statin therapy
  • At week four, all patients will receive the lowest approved dose of atorvastatin (10 mg) and will titrate to the next highest prescribed dose of atorvastatin (20 mg) at week eight
  • At week 12, physicians will be free to titrate the dose of atorvastatin at their discretion through to the end of study

In the Phase 2b FLINT trial, OCA became the first investigative therapy studied in NASH patients to achieve reversal of liver fibrosis with a significantly greater therapeutic response versus placebo. OCA treatment was associated with an increase in average total cholesterol and LDL and a decrease in average HDL. A post-hoc analysis showed OCA-treated patients who initiated statins during the FLINT trial experienced a rapid reversal of their observed mean LDL increase to below baseline levels. 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. Treatment-related LDL increases in all groups reversed with treatment discontinuation. This 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.

The U.S. Food and Drug Administration (FDA) has designated OCA as a breakthrough therapy in NASH patients with fibrosis, and in September 2015, Intercept announced the initiation of REGENERATE, its international Phase 3 trial studying OCA in NASH patients with advanced fibrosis.

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 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.

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. 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 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 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. Intercept's pipeline of product candidates includes other novel bile acid analogs such as INT-767, which is in clinical development. 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 of statin co-administration to manage LDL increases in NASH patients, the results of the CONTROL trial providing insight into our clinical development program for OCA in NASH, our plans and 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 our various NASH trials, the link and significance 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, 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.

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

Source:Intercept Pharmaceuticals, Inc.