美国制药巨头默沙东（Merck &Co）近日收获“苦涩”的幸福，曾经被FDA取消突破性药物（BTD）资格的丙肝全口服鸡尾酒Grazoprevir/Elbasvir(MK-5172/MK-8742)再次获得了FDA的2个新的突破性药物（BTD）资格，分别为：（1）治疗基因型4慢性丙型肝炎病毒（HCV GT4）感染者的BTD资格；（2）治疗伴有终末期肾病正在进行血液透析治疗的基因型1 HCV（HCV GT1）感染者的BTD资格。
默沙东表示，该药的监管计划仍按原计划进行，将在2015年上半年向FDA提交新药申请（NDA）。业界认为，该鸡尾酒有望在今年第三季度获得批准，成为市面上第3个丙肝鸡尾酒，而其竞争对手为吉利德的丙肝鸡尾酒Harvoni及艾伯维的丙肝鸡尾酒Viekira Pak，这2个药物目前已获美欧2大市场批准上市。
慢性丙型肝炎（HCV）一直是默沙东研发的重心，丙肝鸡尾酒Grazoprevir/Elbasvir对该公司而言意义重大。之前，FDA曾在2013年10月授予丙肝鸡尾酒Grazoprevir/Elbasvir治疗基因型1 HCV（HCV GT1）感染者的BTD资格，但在2015年2月初却撤销了，一同被取消BTD资格的还有百时美施贵宝的丙肝药物Daclatasvir。FDA表示，撤销这2个丙肝药物BTD资格是因为当前丙肝治疗领域的迅速发展。而FDA这一决定，对默沙东而言无疑是个重大打击。
FDA的突破性疗法认定（BTD）旨在加速开发及审查治疗严重的或威胁生命的疾病的新药。获得BTD资格的药物，在研发时能得到包括FDA高层官员在内的更加密切的指导，保障在最短时间内为患者提供新的治疗选择。此次，FDA重新授予默沙东丙肝鸡尾酒Grazoprevir/Elbasvir 2个新的BTD资格，反映了HCV GT1和HCV GT4治疗领域迫切的医疗需求，同时也是对该鸡尾酒在丙肝临床治疗中相对现有疗法取得实质性改善作用的积极肯定。
Grazoprevir/Elbasvir是一种实验性、每日一次的复方单片，由grazoprevir（一种NS3/4A蛋白酶抑制剂）和elbasvir（一种NS5A复制复合体抑制剂）组成。作为默沙东广泛临床试验项目的一部分，Grazoprevir/Elbasvir目前正被调查用于数个基因型HCV感染及难治性丙肝群体的治疗，包括HIV/HCV合并感染、晚期慢性肾脏病、遗传性血液疾病、肝硬化以及正在接受阿片类药物替代治疗的丙肝群体。
英文原文：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
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.
“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.
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.
Merck’s Commitment to HCV
For nearly 30 years, Merck has been at the forefront of the response to the HCV epidemic. Merck employees are dedicated to applying their scientific expertise, resources and global reach to deliver innovative healthcare solutions that support people living with HCV worldwide.
