新闻稿 obeticholic酸（ OCA）的非酒精性脂肪性肝炎高度显着改

StephenW

PRESS RELEASE

Jan. 9, 2014, 7:33 a.m. EST
Intercept Announces NASH Primary Endpoint Met: FLINT Trial Stopped Early for Efficacy Based on Highly Statistically Significant Improvement in Liver Histology

NEW YORK, Jan 09, 2014 (GLOBE NEWSWIRE via COMTEX) -- Intercept Pharmaceuticals, Inc.ICPT +273.81% (Intercept) today announced that the FLINT trial of obeticholic acid (OCA) for the treatment of nonalcoholic steatohepatitis (NASH) has been stopped early for efficacy based on a planned interim analysis showing that the primary endpoint of the trial has been met. FLINT is a multi-center, double-blind, placebo-controlled clinical trial assessing the safety and efficacy of a 25 mg oral dose of OCA administered daily to biopsy-proven adult NASH patients over a 72-week treatment period. The trial has been sponsored and conducted by the National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK), a part of theNational Institutes of Health, at eight leading US academic hepatology centers comprising the NIDDK's NASH clinical research network (CRN).

The decision to stop FLINT has been based on the recommendation of the Data Safety Monitoring Board (DSMB) which reviewed liver biopsy data from before and at the end of the treatment period in approximately half of the 283 randomized patients, in accordance with a planned interim efficacy analysis. This analysis demonstrated that OCA treatment resulted in a highly statistically significant improvement (p=0.0024 on an intention-to-treat [ITT] basis) in the primary histological endpoint, defined as a decrease in the NAFLD Activity Score (NAS) of at least two points with no worsening of fibrosis, as compared to placebo. Those patients who had not yet completed the trial and therefore did not have a second biopsy were treated as non-responders in the ITT analysis. The pre-defined threshold of statistical significance for stopping FLINT was p < 0.0031.

"The unexpected early stopping of FLINT due to OCA meeting the primary endpoint with such high significance is a major milestone," said Mark Pruzanski, M.D., Chief Executive Officer of Intercept. "NASH has grown to epidemic proportions worldwide, having become a leading cause of cirrhosis and liver failure. On its current trajectory, the disease is projected to become the leading indication for liver transplant. We are deeply grateful to the NIDDK and the NASH CRN for their longstanding commitment both to improving our understanding of the disease and to sponsoring ambitious trials like FLINT in their quest to identify novel treatments for patients suffering from NASH."

Intercept will discuss NASH and the FLINT trial during the previously announced conference call and audio webcast scheduled to take place today at 4:30 p.m. ET. The live event will be available on the investor page of the Intercept website athttp://ir.interceptpharma.com or by calling (855) 232-3919 (domestic) or (315) 625-6894(international) five minutes prior to the start time. A replay of the call will be available on the Intercept website approximately two hours after the completion of the call and will be archived for two weeks.

About FLINT

The Farnesoid X Receptor Ligand Obeticholic Acid in Nonalcoholic Steatohepatitis Treatment (FLINT) trial has been sponsored and conducted by the National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK). FLINT enrolled 283 adult NASH patients at eight US centers comprising the NIDDK's NASH clinical research network. 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 study 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 .

Intercept's collaborator Dainippon Sumitomo Pharma is currently conducting a NASH trial in Japan. This trial is evaluating the safety and efficacy of a once-daily dose of OCA as compared to placebo, with a targeted enrollment of 200 patients. Enrollment is projected to be completed by the end of January 2014 with top-line results expected by the end of 2015.

About NASH

NASH is a serious chronic liver disease caused by excessive fat accumulation in the liver that, for reasons that are still incompletely understood, 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 over a ten year period at least 10% of NASH patients will develop cirrhosis, and liver-related mortality due to this disease is ten-fold that of the general population. According to recent epidemiological studies, it is estimated that approximately 12% of the U.S. adult population has NASH, while 2.7% (potentially more than six million patients) are believed to have advanced 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 over the next decade 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 orphan and more prevalent liver 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 NASH, primary biliary cirrhosis (PBC), portal hypertension and bile acid diarrhea. OCA has received orphan drug designation in both the United States and Europe for the treatment of PBC. Intercept owns worldwide rights to OCA outside of Japan and China, where it has out-licensed the product candidate to Dainippon Sumitomo Pharma. For more information about Intercept, please visit the Company's website at:www.interceptpharma.com .

StephenW

新闻稿

2014年1月9日，上午07时33 EST
拦截宣布纳什主要终点满足：火石试验提前终止的功效基础上高度显着改善肝脏组织学

纽约， 2014年1月9日（ GLOBE通过COMTEX电讯） - 拦截制药， Inc.ICPT 273.81 ％ （截取）今天宣布， obeticholic酸（ OCA）的非酒精性脂肪性肝炎（NASH）的治疗火石试验已早期的基础上有计划的中期分析显示，试验的主要终点已经达到疗效停止。 FLINT是一个多中心，双盲，安慰剂对照的临床试验评估25毫克口服剂量亚奥理事会的日常管理，以活检证实的成人NASH患者超过72周的治疗期的安全性和有效性。该试验已经赞助，糖尿病与消化及肾脏疾病研究所（ NIDDK ） ，卫生theNational研究院的一部分，在八个主要包括美国的NIDDK的NASH临床研究网络（ CRN）学术肝病中心进行。

停止火石的决定是基于对数据安全监督委员会（DSMB ），它由前，在大约一半的283例患者随机分为治疗期结束时审阅肝活检数据，按照中期计划的建议疗效分析。这一分析表明，亚奥理事会治疗导致高度统计学显著改善（ P = 0.0024的意向性治疗[ ITT ]基准）的主要组织学终点，定义为至少在NAFLD活动积分下降（ NAS ）两个点没有恶化纤维化，与安慰剂比较。谁尚未完成试验，因此没有一个第二次活检的患者被视为无应答者在ITT分析。具有统计意义的停止FLINT预先定义的阈值为P < 0.0031 。

“火石由于亚奥理事会会议上如此高的意义主要终点的意外提前终止是一个重要的里程碑， ”马克Pruzanski拦截，医学博士，行政总裁。 “纳什已经发展到流行病的程度世界各地，已成为肝硬化和肝功能衰竭的主要原因。在目前的轨道，这种疾病预计将成为肝移植的主要指征，我们深表感谢NIDDK和NASH CRN的他们长期致力于既能提高我们对疾病的认识，并赞助如坚石雄心勃勃的试验在他们的搜寻，以确定新的治疗患者NASH的痛苦。 “

拦截将讨论纳什和此前公布的电话会议，并定于今日东部时间下午4:30录音网络直播期间，火石审判。现场活动将可在截取网站网址为:/ / ir.interceptpharma.com的投资者页面，或致电（ 855 ） 232-3919 （国内）或（ 315 ） 625-6894 （国际）前5分钟的开始时间。电话会议的重播将在网站拦截在完成通话大约两小时后，将被归档了两个星期。

关于FLINT

该法尼醇X受体配体Obeticholic酸在非酒精性脂肪性肝炎的治疗（火石）试验已经赞助，糖尿病与消化及肾脏疾病研究所（ NIDDK ）进行。火石招收283成人NASH患者在包括NIDDK的NASH临床研究网络八美中心。患者被随机分配接受25毫克剂量的亚奥理事会或安慰剂治疗72周。患者参加了试验基础上通过肝活检有四个或以上的NAFLD活动评分（ NAS）和具有至少一个在NAS 8点规模的各部分得分的审判开始确定的诊断为合格（ 0-3脂肪变性，小叶内炎症0-3 ，气球0-2） 。研究活检的结束是在72周的治疗期后的患者进行，集中刻划在双盲的方式都活检。详情可http://clinicaltrial.gov/ct2/show/NCT01265498找到。

拦截的合作者大日本住友制药目前正在进行一项试验纳什在日本。这项试验是评估每日一次剂量亚奥理事会作为安慰剂相比，在安全性和有效性，有200例患者有针对性的招生。注册预计将于2014年1月月底预计到2015年年底顶线结果完成。

关于NASH

NASH是过度引起的脂肪蓄积在肝脏的是，对于那些仍然不完全了解的原因，引起慢性炎症导致进行性纤维化（瘢痕形成） ，可导致肝硬化，最终肝衰竭和死亡的严重慢性肝病。目前还没有批准用于NASH的治疗药物。研究表明，在十年期间NASH患者中的至少10％将发展为肝硬化和肝相关的死亡率是由于这种疾病是10倍的总人口。根据最近的流行病学研究中，据估计，在美国成人人口的约12 ％有NASH ，而2.7 ％ （可能超过600万患者）被认为是晚期肝纤维化或肝硬化，由于该疾病的进展。归属于NASH肝移植的比例在过去几年中迅速增长，在未来十年的疾病预计将成为肝移植的主要指标提前慢性丙型肝炎和酒精性肝病。

关于Intercept

Intercept是一家生物制药公司专注于创新疗法，治疗孤儿和利用其在胆汁酸的化学专业知识更为普遍的肝脏疾病的发展和商业化。公司的主导产品候选人， obeticholic酸（ OCA ） ，是胆汁酸的模拟和先入类激动剂的法尼醇X受体（ FXR ）的。亚奥理事会正在开发适用于各种慢性肝脏疾病，包括纳什，原发性胆汁性肝硬化（PBC ） ，门静脉高压及胆汁酸腹泻。亚奥理事会已收到孤儿药同时在美国和欧洲对PBC的治疗。拦截在全球拥有权利亚奥日本和中国，它已超出许可的候选产品，以大日本住友制药之外。有关拦截的更多信息，请访问公司网站： www.interceptpharma.com 。