Grazoprevir / Elbasvir，默克公司的研究性慢性丙型肝炎的治疗

StephenW

www.natap.org

Grazoprevir/Elbasvir, Merck’s Investigational Chronic Hepatitis C Therapy, Granted FDA Breakthrough Therapy Designations; New Phase 2 and 3 Data in Multiple HCV Patient Types to be Presented at The International Liver CongressTM 2015

Congress Highlights Include Results from Trials in a Wide Range of HCV Patients -- Patients with Chronic Kidney Disease, HIV Co-infection, Cirrhosis, and Prior Treatment Failures

Company Remains on Track for NDA Filing with the U.S. FDA During First Half of 2015
Wednesday, April 8, 2015

KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside of the United States and Canada, today announced that grazoprevir/elbasvir, an investigational single tablet regimen for the treatment of chronic hepatitis C virus (HCV) infection, has received two new Breakthrough Therapy designations from the U.S. Food and Drug Administration (FDA) for the treatment of patients with chronic HCV genotype 4 (GT4) infection, and for the treatment of chronic HCV genotype 1 (GT1) infection in patients with end stage renal disease on hemodialysis. Additionally, the company announced presentations from the broad grazoprevir/elbasvir development program at the upcoming International Liver Congress™. A total of 14 abstracts from studies evaluating grazoprevir/elbasvir are scheduled to be presented, including three from the company’s ongoing Phase 3 pivotal C-EDGE program, one from the pivotal Phase 2b/3 C-SURFER study, and seven from ongoing or completed Phase 2 studies. The range of data to be presented underscores the company’s ongoing commitment to developing an all-oral regimen with wide application across diverse patient populations. The International Liver Congress™ 2015 – the 50th annual congress of the European Association for the Study of the Liver – is scheduled to take place at the Reed Messe Convention Center, Vienna, Austria, from April 22 – 26, 2015.

“HCV remains a global public health epidemic. At Merck, we are focused on the development of an efficacious, well-tolerated, once-daily therapy that can be used to treat multiple genotypes and a diverse population of chronic HCV patients,” said Dr. Eliav Barr, vice president, infectious diseases, Merck Research Laboratories. “Our clinical program is among the largest and most comprehensive, with studies dedicated to patient populations where significant unmet medical need still exists, such as prior treatment failures, as well as those living with co-morbid conditions, including HIV infection, chronic kidney disease and individuals on opiate substitution therapy.”

In October 2013, the FDA granted Breakthrough Therapy designation for grazoprevir/elbasvir for the treatment of patients with chronic HCV genotype 1 (GT1). In January 2015, the FDA notified Merck of its intention to rescind that Breakthrough Therapy designation. The FDA has now granted two new Breakthrough Therapy designations for grazoprevir/elbasvir; the designations are now for the treatment of patients infected with chronic HCV GT1 with end stage renal disease on hemodialysis, and patients infected with chronic HCV genotype 4 (GT4). Breakthrough Therapy designation is intended to expedite the development and review of a candidate that is planned for use, alone or in combination, to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.

At The International Liver Congress 2015™, key data presentations will include:

    Primary results from the C-EDGE program, Phase 3 clinical trials evaluating grazoprevir/elbasvir (with and without ribavirin) across multiple HCV genotypes (1, 4 and 6) and diverse patient populations, including those difficult to treat, over a 12-week treatment duration
        C-EDGE TN in treatment-naïve patients; Oral presentation, General Session 2 & Award 1, Abstract #G07, Friday, April 24, 8:30 a.m. – 8:45 a.m. CEST
        C-EDGE CO-INFXN in patients with HCV/HIV co-infection; E-poster #P0887, Thursday, April 23 at 7:30 a.m. CEST until Saturday, April 25 at 8:00 p.m. CEST
        C-EDGE TE in treatment-experienced (prior peg-interferon/ribavirin treatment failures); E-poster #P0886, Thursday, April 23 at 7:30 a.m. CEST until Saturday, April 25 at 8:00 p.m. CEST

    First results from C-SURFER, a Phase 2b/3 clinical trial evaluating grazoprevir/elbasvir (without ribavirin) in treatment-naïve and treatment-experienced patients with HCV genotype 1 infection and advanced chronic kidney disease
        Late-breaking E-poster #LP02, Thursday, April 23 at 7:30 a.m. CEST until Saturday, April 25 at 8:00 p.m. CEST
    Results from C-SALVAGE, a Phase 2 clinical trial evaluating grazoprevir/elbasvir (with and without ribavirin) for chronic HCV in genotype 1 infection after failure of direct-acting antiviral (DAA) therapy, including boceprevir, telaprevir, or simeprevir
        Oral presentation, Viral Hepatitis C Therapy session, Abstract #O001, Thursday, April 23, 4:00 p.m. – 4:15 p.m. CEST
    Results from C-SWIFT, a Phase 2 clinical trial evaluating shorter treatment durations (4, 6, 8 and 12 weeks) of grazoprevir/elbasvir plus sofosbuvir in treatment-naïve, treatment-experienced/prior treatment failure/null-response, cirrhotic and non-cirrhotic patients with genotype 1 or 3 infection
        Oral presentation, Viral Hepatitis C Therapy session, Abstract #O006, Thursday, April 23, 5:15 p.m. – 5:30 p.m. CEST
    Phase 2 efficacy and safety results from the C-SALT clinical trial, evaluating grazoprevir/elbasvir in genotype 1 infected patients with Child-Pugh class B cirrhosis
        Oral presentation, Viral Hepatitis C Therapy session, Abstract #O008, Thursday, April 23, 5:45 p.m. – 6:00 p.m. CEST
    Results from C-WORTHy, a Phase 2 clinical trial evaluating treatment with grazoprevir/elbasvir (with or without ribavirin) in genotype 1 and 3 infection, and in a variety of patient sub-populations including treatment-naïve, treatment-experienced, cirrhotic, non-cirrhotic, and HIV/HCV co-infected
        C-WORTHy Part C in treatment-naïve, non-cirrhotic patients with genotype 1b infection; E-poster #P0769, Thursday, April 23 at 7:30 a.m. CEST until Saturday, April 25 at 8:00 p.m. CEST
        C-WORTHy Part D in treatment-naïve patients with genotype 3 infection treated with ribavirin; E-poster #P0776, Thursday, April 23 at 7:30 a.m. CEST until Saturday, April 25 at 8:00 p.m. CEST
        C-WORTHy resistance analysis of virologic failures in hepatitis C genotype 1 infected patients; E-poster #P0891, Thursday, April 23 at 7:30 a.m. CEST until Saturday, April 25 at 8:00 p.m. CEST
    Results from C-SCAPE, a Phase 2 trial evaluating the efficacy and safety of 12 weeks of grazoprevir/elbasvir (with or without ribavirin) in patients with genotype 2, 4, 5 or 6 infection
        E-poster #P0771, Thursday, April 23 at 7:30 a.m. CEST until Saturday, April 25 at 8:00 p.m. CEST
    Results from a Phase 1 study to evaluate the interaction of novel nucleotide inhibitor MK-3682 (formerly IDX21437), with grazoprevir and NS5A inhibitor MK-8408 in healthy subjects
        E-poster #P0824, Thursday, April 23 at 7:30 a.m. CEST until Saturday, April 25 at 8:00 p.m. CEST

About Grazoprevir/Elbasvir

Grazoprevir/elbasvir is an investigational, once-daily single tablet regimen consisting of grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A replication complex inhibitor). As part of Merck’s broad clinical trials program, grazoprevir/elbasvir is being studied in multiple HCV genotypes and in patients with difficult-to-treat conditions such as HIV/HCV co-infection, advanced chronic kidney disease, inherited blood disorders, cirrhosis and those on opiate substitution therapy

StephenW

www.natap.org

Grazoprevir / Elbasvir，默克公司的研究性慢性丙型肝炎的治疗，授予FDA突破疗法选派;新的第2阶段和3个数据在多个HCV患者类型在国际肝病CongressTM 2015年提交

大会的亮点包括从结果试验在HCV患者一个宽范围 - 治疗慢性肾病，HIV合并感染，肝硬化，并在此之前治疗失败

公司仍有望实现NDA申报美国FDA在2015年上半年
周三，2015年4月8日

KENILWORTH，新泽西州 - （BUSINESS WIRE） - 默克（NYSE：MRK），被称为MSD美国和加拿大以外，今天宣布，grazoprevir / elbasvir，研究性单一平板电脑方案为慢性丙型肝炎病毒的治疗（ HCV）感染，已收到两个新的突破疗法名称从美国食品和药物管理局（FDA）用于治疗慢性HCV基因型4（GT4）感染的治疗，并用于治疗慢性HCV基因型1（GT1）感染的治疗患者终末期的血液透析肾脏疾病。此外，该公司宣布，从在即将举行的国际肝病会议™广大grazoprevir / elbasvir发展规划介绍。共有14文摘从研究评估grazoprevir / elbasvir预计将提交，其中包括三个来自公司正在进行三期枢纽C-EDGE方案，一是从关键阶段2B / 3 C-SURFER的研究，七从正在进行或已完成第二阶段的研究。数据将提交的范围强调了公司的持续致力于开发全口服方案横跨不同的患者人群广泛的应用。国际肝病会议™2015 - 欧洲协会为肝脏的研究第50届代表大会 - 定于发生在里德Messe会展中心，奥地利维也纳，从4月22日至26日，2015。

“HCV仍是一个全球性的公共卫生疫情。默克公司，我们专注于一种有效，耐受性良好，每日一次的治疗方法，可用于治疗多种基因型和慢性丙型肝炎患者的不同群体的发展，“Eliav巴尔博士，副总裁，传染病表示，默克研究实验室。 “我们的临床方案是专门为患者人群的地方显著未被满足的医疗需求仍然存在，如既往治疗的失败，以及那些生活在共同病态条件，包括HIV感染，慢性肾脏疾病的规模最大，最全面的，与研究中和个人对阿片类药物替代治疗。“

2013年10月，美国食品药品管理局授予的突破疗法指定为grazoprevir / elbasvir用于治疗慢性HCV基因型1（GT1）的治疗。在2015年1月，美国食品药品管理局通知，它打算默克​​公司撤销了突破性疗法指定。美国食品药物管理局已授予了两个新的突破疗法命名为grazoprevir / elbasvir;该名称是现在的患者感染的终末期肾病慢性HCV GT1血液透析治疗，并感染患者的慢性HCV基因型4（GT4）。突破治疗的指定是为了加速计划使用，单独或组合，一个候选的发展和审查，以治疗严重或威胁生命的疾病或病症时的初步临床证据表明，药物可以表现出显着改进现有治疗上的一个或多个临床显著端点。

在国际肝病会议™2015年，主要数据报告将包括：

    从C-EDGE计划初步结果，3期临床试验评估grazoprevir / elbasvir（带和不带利巴韦林）在多个HCV基因型（1,4和6）和不同的患者人群，包括那些难以治疗，超过12周治疗时间
        C-EDGE TN治疗初治患者;口头报告，全体大会2奖1项，摘要＃G07，周五，4月24日，上午8:30 - 上午8:45 CEST
        C-EDGE CO-INFXN患者HCV / HIV合并感染; E-海报＃P0887，周四，4月23日上午7:30 CEST直到周六，4月25日下午8:00 CEST
        C-EDGE TE在治疗经验的（之前PEG-干扰素/利巴韦林治疗失败）; E-海报＃P0886，周四，4月23日上午7:30 CEST直到周六，4月25日下午8:00 CEST

    从C-上网，一期2B / 3期临床试验评估grazoprevir / elbasvir（无利巴韦林）治疗初治和治疗经验的患者与感染HCV基因型1和先进的慢性肾脏病第一批成果
        近期发布的E-海报＃LP02，周四，4月23日上午07点30分CEST至星期六，4月25日下午8:00 CEST
    结果，从C-救助，一二期临床试验评估grazoprevir / elbasvir（有和没有利巴韦林）慢性HCV基因型1感染的直接作用抗病毒药（DAA）治疗失败后，用boceprevir包括，telaprevir治疗，或simeprevir
        口头介绍，丙型病毒性肝炎治疗会话，摘要＃O001，周四，4月23日，下午4:00 - 下午4:15 CEST
    结果，从C-SWIFT，一二期临床试验评估更短的治疗grazoprevir / elbasvir加sofosbuvir的持续时间（4，6，8周和12周），治疗初治，治疗经验/前治疗失败/空应答，肝硬化和非肝硬化患者的基因型1或3感染
        口头介绍，丙型病毒性肝炎治疗会话，摘要＃O006，周四，4月23日下午5时15 - 下午5时30 CEST
    第2阶段的疗效和安全性的结果从C-盐的临床试验，评价grazoprevir / elbasvir在基因型1感染患者Child-Pugh分级B级肝硬化
        口头介绍，丙型病毒性肝炎治疗会话，摘要＃O008，周四，4月23日，下午5:45 - 下午6:00 CEST
    结果从C-值得的，第2阶段的临床试验评估与grazoprevir / elbasvir治疗（有或无利巴韦林）在基因型1和3感染，并在各种患者亚群，包括治疗初治，治疗经历，肝硬化的，非肝硬化和HIV / HCV共感染
        C-值得C部分在治疗初治，非肝硬化患者的基因型1b感染; E-海报＃P0769，周四，4月23日上午7:30 CEST直到周六，4月25日下午8:00 CEST
        C-值得在治疗初治患者的基因型3感染利巴韦林治疗D部分; E-海报＃P0776，周四，4月23日上午7:30 CEST直到周六，4月25日下午8:00 CEST
        在丙型肝炎基因1型感染患者的病毒学失败C-值得耐药性分析; E-海报＃P0891，周四4月23日上午7:30 CEST至星期六，4月25日下午8:00 CEST
    结果从C-景观，阶段2试验基因型2，4，5或6个感染评估疗效和12周grazoprevir / elbasvir的安全（有或没有利巴韦林）患者
        E-海报＃P0771，周四，4月23日上午7:30 CEST直到周六，4月25日下午8:00 CEST
    结果从第1阶段研究，以评估新型核苷酸抑制剂MK-3682（原IDX21437）的相互作用，与grazoprevir和NS5A抑制剂MK-8408在健康受试者
        E-海报＃P0824，周四，4月23日上午7:30 CEST直到周六，4月25日下午8:00 CEST

关于Grazoprevir / Elbasvir

Grazoprevir / elbasvir是一种调查，每日一次单一片剂疗法选自grazoprevir（NS3 / 4A蛋白酶抑制剂）和elbasvir（NS5A复制复合抑制剂）的。由于部分默克广泛的临床试验方案，grazoprevir / elbasvir正在研究多种HCV基因型的患者难以治疗的条件，如HIV / HCV合并感染，晚期慢性肾脏病，遗传性血液疾病，肝硬化和那些对阿片类药物替代治疗