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默沙东doravirine用于初治HIV疗效显著

来源:生物谷 2014-03-07 09:04

2014年3月7日讯 /生物谷BIOON/ --3月6日,默沙东(Merck & Co)在第21届逆转录病毒和机会性感染大会(CROI 2014)上公布了实验性HIV药物doravirine IIb期临床试验的积极数据。该项随机、双盲、剂量探索研究,在初治HIV成人感染者中开展,调查了4种剂量doravirine(25mg、50mg,75mg,100mg;每日一次)联合替诺福韦/恩曲他滨(tenofovir/emtricitabine;每日一次)相对于依非韦伦(efavirenz,600mg)的疗效、安全性和耐受性。主要疗效分析是达到病毒学应答(<40拷贝/毫升)的患者百分比。

中期数据表明,4种剂量doravirine联合替诺福韦/恩曲他滨用于初治HIV成人感染者时具有强劲的疗效。在24周时,doravirine 4个剂量组均表现出了与依非韦伦组相一致的病毒学反应率。研究中,所有治疗组CD4细胞计数均表现增加。药物相关不良事件发生率在doravirine各剂量组相当。根据24周数据,100mg剂量doravirine已被选择用于该项研究的剩余部分试验,直至96周。

基于这些发现,以及doravirine临床项目的其他数据,默沙东计划于2014年下半年启动一项III期项目,调查doravirine与抗逆转录病毒疗法(ARV)的联合用药。

关于doravirine

doravirine又名MK-1439,是一种实验性、新一代、非核苷类逆转录酶抑制剂(NMRTI),目前正调查用于HIV-1感染的治疗。在临床前研究中,doravirine针对HIV-1表现出强劲的抗病毒活性。在早期临床研究中,doravirine表现出的药代动力学特性支持每日一次给药,同时并未表现出显著的食物影响。

英文原文:Merck’s Investigational HIV Therapy, Doravirine (MK-1439), Demonstrates Antiviral Activity in Phase 2B Study of Treatment-Na?ve Adults

Merck Plans to Initiate Phase 3 Clinical Development Program in Second Half of 2014

BOSTON--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today presented data from the dose-ranging portion of an ongoing Phase 2B clinical trial of doravirine, the company’s investigational next-generation, non-nucleoside reverse transcriptase inhibitor (NNRTI), at the 21st Conference on Retroviruses and Opportunistic Infections (CROI). Interim data demonstrating potent antiretroviral (ARV) activity for four doses (25, 50, 100 and 200 mg) of once-daily, oral doravirine in combination with tenofovir/emtricitabine in treatment-na?ve, HIV-1 infected adults after 24 weeks of treatment were presented during a late-breaker oral session. Based on these findings as well as other data from the doravirine clinical program, Merck plans to initiate a Phase 3 clinical trial program for doravirine in combination with ARV therapy in the second half of 2014.

“Building on our long-standing commitment to the HIV community, Merck continues to evaluate new candidates we believe have the potential to make a meaningful difference in the lives of HIV patients,” said Daria Hazuda, Ph.D., vice president, Infectious Diseases, Merck Research Laboratories. “We look forward to advancing doravirine into Phase 3 clinical trials in the second half of 2014.”

Doravirine Clinical Data

This randomized, double-blind clinical trial examined the safety, tolerability and efficacy of once-daily doravirine (25, 50, 100 and 200 mg) in combination with once-daily tenofovir/emtricitabine versus efavirenz (600 mg), in treatment-na?ve, HIV-1 infected patients. The primary efficacy analysis was percentage of patients achieving virologic response (< 40 copies/mL).

At 24 weeks, doravirine doses of 25, 50, 100, and 200 mg showed virologic response rates consistent with those observed for efavirenz at a dose of 600 mg. All treatment groups showed increased CD4 cell counts.

The incidence of drug-related adverse events was comparable among the doravirine-treated groups. The overall incidence of drug-related adverse events was lower in the doravirine-treated groups (n=166) than the efavirenz-treated group (n=42), 35 percent and 57 percent, respectively. The most common central nervous system (CNS) adverse events at week 8, the primary time point for evaluation of CNS adverse experiences, were dizziness [3.0% doravirine (overall) and 23.8% efavirenz], nightmare [1.2% doravirine (overall) and 9.5% efavirenz], abnormal dreams [9.0% doravirine (overall) and 7.1% efavirenz], and insomnia [5.4% doravirine (overall) and 7.1% efavirenz].

Based on the 24-week data from this dose-finding study, a single dose of 100 mg doravirine was chosen to be studied for the remainder of this study, up to 96 weeks.

About Doravirine

Doravirine, also known as MK-1439, is an investigational next-generation, NNRTI being evaluated by Merck for the treatment of HIV-1 infection. In preclinical studies, doravirine demonstrated potent antiviral activity against HIV-1 with a characteristic profile of resistance mutations selected in vitro compared with currently available NNRTIs. In early clinical studies, doravirine demonstrated a pharmacokinetic profile supportive of once-daily dosing and did not show a significant food effect.

Merck’s Commitment to HIV

For more than 25 years, Merck has been at the forefront of the response to the HIV epidemic, and has helped to make a difference through our proud legacy of commitment to innovation, collaborating with the community, and expanding global access to medicines. Merck is dedicated to applying our scientific expertise, resources and global reach to deliver healthcare solutions that support people living with HIV worldwide.

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