默沙东丙肝鸡尾酒MK-5172/MK-8742初治群体治愈率近100%

snow

2014年4月11日讯--默沙东（Merck & Co）4月10日公布了一项正在开展的II期研究（C-WORTHY Study）的额外数据。对初治非肝硬化患者组开展的一项中期分析表明，接受为期12周的MK-5127/MK-8742方案（联合利巴韦林RBV及无RBV）治疗后，MK-5127/MK-8742（无RBV）治疗组有98%（42/43）的患者取得持续病毒学应答（SVR），MK-5127/MK-8742+RBV治疗组为94%（75/80）。这些数据连同8周方案的数据已提交至第49届欧洲肝脏研究协会年会（EASL 2014-49th）。

MK-5172和MK-8742均属于非常有前途的新一类抗病毒药物。MK-5172是一种实验性HCV NS3/4A蛋白酶抑制剂，MK-8742则是一种实验性HCV NS5A复制复合体抑制剂。此前，FDA于2013年10月授予MK-5172/MK-8742全口服方案突破性疗法认定。
慢性丙型肝炎是默沙东研发的优先重点。目前，该公司正在一个广泛的临床项目中评价MK-5172和MK-8742，包括多种HCV基因型感染初治患者、治疗失败的患者、以及其他重要的HCV亚群，如肝硬化和HCV/HIV合并感染。（生物谷Bioon.com）
英文原文：Merck Announces Results from Studies Evaluating Investigational Hepatitis C Treatments, MK-5172 and MK-8742, in Treatment-Naïve Patients with Genotype 1 Infection
WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside of the United States and Canada, today announced additional data from the ongoing C-WORTHy study, a multi-arm Phase 2 clinical trial evaluating the efficacy and safety of a once-daily, all-oral regimen combining MK-5172, an investigational hepatitis C virus (HCV) NS3/4A protease inhibitor, and MK-8742, an investigational HCV NS5A replication complex inhibitor, among patients with chronic HCV Genotype 1 infection (GT1). In an interim analysis of treatment-naïve, non-cirrhotic patients administered a 12-week regimen of MK-5172/MK-8742, with and without ribavirin (RBV), a sustained viral response1 (SVR) was observed in 98 percent (42/43) of patients administered MK-5172/MK-8742 alone and 94 percent (75/80) in those administered MK-5172/MK-8742 plus RBV. These data were presented, along with data on an 8-week regimen, at the 49th Annual Meeting of the European Association for the Study of the Liver (EASL), also known as The International Liver Congress™ 2014, in London, UK.
“These Phase 2 results add to growing evidence for the potential efficacy of MK-5172 and MK-8742 for treatment of chronic HCV infection,” said Dr. Eliav Barr, vice president, Infectious Diseases, Merck Research Laboratories. “These findings are integral to advancing our research of these investigational candidates into C-EDGE, the Phase 3 clinical program that will seek to more broadly evaluate the potential of MK-5172/MK-8742 in diverse patient populations.”
C-WORTHy Study Design
C-WORTHy is a two-part, parallel-group, randomized (within group) clinical trial evaluating a range of subpopulations of patients with HCV GT1 infection. The study evaluated different treatment durations of MK-5172 (100 mg once daily) plus MK-8742 (50 mg once daily), with or without RBV. A total of 471 patients with HCV GT1 RNA levels of ≥10,000 IU/mL were enrolled in C-WORTHy across 16 arms.
Key Findings for MK-5172/MK-8742
The interim results presented were from treatment-naïve, non-cirrhotic patients who received one of 3 regimens: A) MK-5172/MK-8742 + RBV for 8 weeks (N=30), B) MK-5172/MK-8742 + RBV for 12 weeks (N=85), and C) MK-5172/MK-8742 (without RBV) for 12 weeks (N=44).
PN038 Study Design and Findings
Additionally, new data from PN038, a Phase 2 dose-ranging clinical trial evaluating MK-5172 once-daily with peginterferon alfa-2b and ribavirin (PR, weekly), were presented, evaluating SVR24 in treatment-naïve, non-cirrhotic patients with GT1 infection. PN038 is a Phase 2 clinical trial investigating the efficacy and safety of MK-5172 doses (25 mg, 50 mg, and 100 mg) once-daily with PR over a 12-week treatment cycle in GT1 treatment-naïve, non-cirrhotic patients (n=87). The analysis presented was ITT, in which all patients who did not achieve SVR (including those who dropped out for non-virologic reasons), were recorded as failures.
MK-5172 at doses of 50 mg and 100 mg with PR for 12 weeks of treatment achieved SVR24 rates of 75.0 percent (21/28) and 83.3 percent (25/30), respectively, supporting use of MK-5172 below 100 mg dose (see table 2).
About Merck’s Phase 3 HCV Program: C-EDGE
Based on the results of the Phase 2 clinical program, Merck has initiated Phase 3 clinical trials for MK-5172/MK-8742. The Phase 3 program, called C-EDGE, will evaluate the safety and efficacy of MK-5172/MK-8742 with and without ribavirin in various genotypes and across a broad range of patient populations with chronic HCV. Study cohorts will include: C-EDGE TN (GT1, GT4-6; treatment-naive ± cirrhosis), C-EDGE CO-INFXN (GT1, GT4-6; treatment-naive ± cirrhosis with HIV/HCV co-infection), C-EDGE RECOVERY (GT1, GT4-6; treatment-naive ± cirrhosis; ± HIV/HCV co-infection on opiate substitution therapy), and C-EDGE TE (GT1, GT4-6; prior failed treatment with peginterferon/ribavirin; ± HIV/HCV co-infection).

Merck’s Commitment to HCV
For more than 25 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 healthcare solutions that support people living with HCV worldwide.