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GSK启动mepolizumab III期COPD项目

2014年5月1日讯 /生物谷BIOON/ --葛兰素史克(GSK)4月29日宣布,启动一项III期临床项目,评估美泊利单抗(mepolizumab)作为一种辅助疗法,用于重度慢性阻塞性肺病(COPD)治疗的疗效和安全性。该项目将招募约1500例尽管接受标准背景疗法(standard background therapy)但仍存在高风险COPD病情加重(exacerbation)的患者。

对COPD患者表型的检查表明,主导表型存在的一种白细胞——嗜酸性粒细胞,与增加的COPD病情加重风险相关。mepolizumab是一种实验性全人源化IgG1单克隆抗体,特异靶向于白细胞介素-5(IL-5)。mepolizumab靶向结合IL-5,从而阻止IL-5与嗜酸性粒细胞表明的受体结合。据了解,抑制IL-5的结合作用,能够降低血液、组织和痰液中嗜酸性粒细胞的水平。

该III期项目包括2个关键研究(117113和117106),2个研究均采用52周、多中心、随机、安慰剂对照、双盲、平行组设计。主要终点均为中度/重度病情加重的频率。

COPD治疗的一个重要目标是预防和减少未来病情加重及之后健康的恶化。该III期项目的启动,标志着为那些尽管接受标准背景疗法但仍存在高风险病情加重的患者群体,提供一种靶向疗法方向迈进的的重要里程碑。

目前,葛兰素史克正在评估mepolizumab用于慢性阻塞性肺病、重度嗜酸粒细胞性哮喘、嗜酸粒细胞性肉芽肿性多血管炎(EGPA)的治疗。

关于美泊利单抗(mepolizumab):

Mepolizumab是一种实验性全人源化单克隆抗体,特异靶向白细胞介素5(IL-5)。IL-5是一种细胞因子,能够调节嗜酸性粒细胞(白细胞)的生长、活化、存活,并能够为嗜酸性粒细胞从骨髓迁移至肺部及其他器官提供重要的信号。mepolizumab与人IL-5结合,阻断IL-5与嗜酸性粒细胞表面受体的结合。以这种方式抑制IL-5对受体的结合作用,能够降低血液、组织、痰液中的嗜酸性粒细胞水平,这反过来又能够降低嗜酸性粒细胞所介导的炎症。目前mepolizumab还未获任何监管批准。(生物谷bioon.com)

英文原文:GSK announces start of phase III programme for mepolizumab in patients with COPD

Issued: Tuesday 29 April 2014, London UK

GlaxoSmithKline plc (LSE/NYSE: GSK) today announced the start of a phase III programme to evaluate the efficacy and safety of mepolizumab as an adjunctive therapy for adults who have severe chronic obstructive pulmonary disease (COPD). The programme will enrol approximately 1500 patients who are at high risk of COPD exacerbations despite the use of standard background therapy.

Examination of COPD patient phenotypes has shown that an eosinophil (a type of white blood cell) predominant phenotype exists that is associated with an increased risk of exacerbations. Mepolizumab is an investigational fully humanised IgG1 monoclonal antibody specific for interleukin-5 (IL-5). Mepolizumab prevents IL-5 from binding to its receptor on the surface of eosinophils. It is understood that inhibiting IL-5 binding reduces blood, tissue and sputum eosinophil levels.

The phase III programme consists of two pivotal studies (117113 and 117106) that together will integrate dose-ranging and long-term efficacy and safety evaluations.  Each study uses a 52-week multi-centre, randomised, placebo controlled, double-blind, parallel group design. The primary endpoint in both is the frequency of moderate / severe exacerbations.

Study 117113, will randomise patients to either mepolizumab 100mg subcutaneous (SC), mepolizumab 300mg SC or placebo, administered every four weeks. All patients will be required to have a blood eosinophil count above a pre-specified threshold to be eligible for this study. Study 117106 will randomise patients to mepolizumab 100mg SC or placebo administered every four weeks. Patients in both studies will continue on baseline standard of care COPD medications throughout the entire duration of the study.

“An important goal of COPD therapy is the prevention and reduction of future exacerbations and subsequent deterioration in patients’ health,” explained Dave Allen, Head, Respiratory Therapy Area Unit, R&D. “The initiation of this study programme is an important milestone in our work to provide a targeted treatment for patients who still have exacerbations despite being on standard background therapy.”

Mepolizumab is in development for COPD, severe eosinophilic asthma and Eosinophilic Granulomatosis with Polyangiitis (EGPA). Mepolizumab is not approved anywhere in the world.

关键词:美泊利单抗,葛兰素史克,单抗,mepolizumab,慢性阻塞性肺病,COPD,IL-5

信息来源:生物谷