葛兰素史克（GSK）2月14日宣布，启动关键性III期研究MEA115921，评估实验性IL-5拮抗剂——美泊利单抗（mepolizumab）用于治疗嗜酸细胞性肉芽肿性多血管炎（EGPA）的疗效和安全性。
EPGA即Churg-Strauss综合征，是一种罕见的全身性炎症性疾病，特征是小血管内壁广泛的炎症（血管炎，vasculitis），该病可累及多个器官，包括心脏、肺、皮肤、胃肠道、肾脏及神经系统。EGPA临床治疗的主要目标是诱导和维持缓解，同时减少糖皮质激素等免疫疗法的使用。
MEA115921是在EGPA患者中开展的有史以来首个随机、双盲、安慰剂对照研究，将在正接受标准护理治疗（包括背景皮质类固醇疗法或无免疫抑制疗法）的复发性或难治性EGPA患者中开展，目的是在52周的研究治疗期，调查300mg剂量mepolizumab（每4周皮下注射）相对于安慰剂的疗效和安全性。
关于
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），目前正开发用于下列疾病：EGPA、嗜酸性粒细胞炎症相关重度哮喘、嗜酸性细胞增多综合征、嗜酸性粒细胞性食管炎及鼻息肉。GSK于2012年10月启动了一项III期项目，调查mepolizumab用于嗜酸性粒细胞炎症相关重症哮喘患者的疗效和安全性。
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。
英文原文：
Issued: Friday 14 February 2014
GlaxoSmithKline (GSK) today announced the start of a Phase III study to evaluate the efficacy and safety of mepolizumab, an investigational IL-5 antagonist, in patients with Eosinophilic Granulomatosis with Polyangiitis (EGPA).
EGPA, previously known as Churg-Strauss syndrome, is a rare disease which is characterised by widespread inflammation in the walls of small blood vessels (vasculitis). It can affect multiple organs, including the heart, lungs, skin, gastrointestinal tract, kidneys, and nervous system, with varying symptoms, depending on which organs are affected, and to what extent. The disease can be life-threatening for some patients. A key goal in the treatment of EGPA is to induce and maintain remission while reducing the use of corticosteroids and other immunosuppressive therapies.
The pivotal Phase III study, MEA115921, is a randomised, double-blind study with the purpose to investigate the efficacy and safety of a 300mg dose of mepolizumab (administered subcutaneously every 4 weeks) compared with placebo over a 52-week study treatment period in patients with relapsing or refractory EGPA receiving standard of care therapy including background corticosteroid therapy with or without immunosuppressive therapy.
The study is being conducted as part of an agreement between GSK and the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health, demonstrating an example of industry – public body collaboration in the field of rare disease drug development. Through this collaboration the mechanisms that underlie EGPA will also be investigated, with potential future benefits for patients.
“This is the first ever double-blind, placebo-controlled study to be conducted in patients with Eosinophilic Granulomatosis with Polyangiitis marking a significant milestone in our efforts to help patients with this rare systemic inflammatory disease.” commented Richard Philipson, Disease Area Head, GSK Rare Diseases. “There are currently limited treatment options for patients with EGPA and our plan to start this Phase III study was achieved in collaboration with the NIAID.”
About Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome)
EGPA is one of the rarest systemic vasculitic (inflammation of blood vessel walls) diseases with an approximate prevalence of 4,300 patients in the United States and five European countries, respectively. The mean age of diagnosis is 48 years. While symptoms vary from one patient to another, almost all have asthma and/or nasal sinus polyps and blood eosinophilia.
The current approach to disease management is primarily based on reduction of active inflammation and suppression of the immune response through the use of corticosteroid therapy with concomitant immunosuppressive therapy (e.g., methotrexate, azathioprine, mycophenolate mofetil) and/or cytotoxic agents (e.g., cyclophosphamide). Although the use of these treatments can be effective for establishing remission, patients remain vulnerable to either the complications of the long-term use of these therapies, or to the risk of relapse, particularly if the dose of corticosteroid is reduced.
About mepolizumab
Mepolizumab is an investigational fully humanised IgG monoclonal antibody specific for interleukin 5 (IL-5) which is in development for the following diseases: EGPA, severe asthma with eosinophilic inflammation, hypereosinophilic syndrome, eosinophilic esophagitis and nasal polyposis. The start of the Phase III programme investigating mepolizumab in patients with severe asthma with eosinophilic inflammation was announced in October 2012. Mepolizumab is not approved for use anywhere in the world.
IL-5 is a cytokine which regulates the growth, activation and survival of eosinophils (white blood cells) and provides an essential signal for the movement of eosinophils from the bone marrow into the lung and other organs. Mepolizumab binds to human IL-5, stopping it from binding to its receptor on the surface of eosinophils. Inhibiting IL-5 binding in this manner reduces blood, tissue and sputum eosinophil levels, which in turn reduces eosinophil-mediated inflammation.
关键词： GSK 美泊利单抗 mepolizumab III期 EPGA 试验
免责声明：
本文仅供专业人士学术交流探讨，不作为诊疗及用药依据。
如有侵权，请联系我们删除