阿斯利康启动单抗药benralizumab III期项目

2013年10月31日讯 /生物谷BIOON/ --阿斯利康（AstraZeneca）10月30日宣布启动实验性单抗药物benralizumab的III期Windoward项目，该项目的首个III期研究CALIMA将确定benralizumab是否能减少经高剂量吸入性皮质类固醇及长效β激动剂治疗后病情仍无法控制的严重哮喘患者病情加重（exacerbation）的次数。

CALIMA研究将评估benralizumab用于病情不受控制的哮喘患者的安全性及疗效，同时将评估benralizumab对肺功能、哮喘症状、以及其他哮喘控制措施、哮喘住院率的影响。该项研究中，benralizumab将通过一个预冲式注射器皮下下注射（subcutaneous）给药。

benralizumab是一种单克隆抗体，能够与白细胞介素5受体的α亚基（IL-5Rα）结合，消耗嗜酸性粒细胞。嗜酸性粒细胞是一种白细胞，在引发哮喘、哮喘严重程度及哮喘发作中发挥了关键作用。越来越多的证据表明，对于嗜酸性粒细胞计数升高的哮喘患者，除基于指南的治疗策略外，利用一种IL-5抑制剂可能改善患者的哮喘控制并降低哮喘发作的频率。

benralizumab由阿斯利康从协和发酵麒麟（Kyowa Hakko Kirin）全资子公司BioWa授权获得。根据独家协议，协和发酵麒麟/BioWa拥有benralizumab在日本及一些特定亚洲国家的独家开发和商业化权利。阿斯利康则拥有benralizumab在包括美国和欧洲在内的其余所有国家的开发和商业化权利。（生物谷Bioon.com）

英文原文：AstraZeneca advances MedImmune’s benralizumab to Phase III in severe asthma

Wednesday, 30 October 2013

AstraZeneca today announced the start of the Phase III Windward programme for benralizumab, a potential treatment for severe uncontrolled asthma developed by MedImmune, the company’s global biologics research and development arm. The goal of CALIMA, the first study in the Windward programme, is to determine whether benralizumab reduces the number of exacerbations in patients with severe asthma that remains uncontrolled, despite receiving high doses of inhaled corticosteroids in combination with a second controller such as a long-acting beta agonist.

Benralizumab is a monoclonal antibody binding to the interleukin-5 receptor (IL-5Rα) that depletes eosinophils, a type of white blood cell, which play a critical role in the cause and severity of asthma and asthma exacerbations. Emerging evidence shows that for patients with elevated eosinophil counts, treatment with an IL-5 inhibitor in addition to guideline-based strategies may improve their asthma control and decrease the frequency of asthma attacks.

“We are pleased to begin the Phase III trial programme for benralizumab and advance innovative research in respiratory disease, a core therapy area for AstraZeneca,” said William Mezzanotte, Vice President and Head of Respiratory & Inflammation and Neuroscience in AstraZeneca’s Global Medicines Development unit. “The development of benralizumab underscores our commitment to addressing and ultimately changing the course of chronic respiratory diseases through targeted and personalised treatment. Benralizumab has the potential to address an important area of unmet medical need as there are currently limited treatment options available for patients with severe uncontrolled asthma.”

The CALIMA trial will evaluate the safety and effectiveness of benralizumab in actively reducing exacerbations in patients with uncontrolled asthma. The study will also assess the effect of benralizumab on lung function, asthma symptoms and other asthma control measures, as well as emergency room and hospitalisation rates due to asthma. Trial participants will be classified in the trial based on blood eosinophils measured through a simple blood test. They will be administered benralizumab subcutaneously via a pre-filled syringe.

Initiation of this trial is based on results from the Phase IIb asthma study, conducted by MedImmune, which showed that patients with elevated eosinophils on benralizumab had a statistically significant reduction in exacerbation rate compared to placebo, as well as improvements in lung function and asthma symptoms. The efficacy and safety data from this trial supported the progression of benralizumab into our Phase III programme. These results are expected to be shared at a scientific conference in the first half of 2014.

In addition to CALIMA, the Windward programme will include two pivotal exacerbation trials for benralizumab added to high- (SIROCCO) or medium- (PAMPERO) dose inhaled corticosteroids plus a long-acting beta agonist; an oral corticosteroid-reducing trial (ZONDA); and a long-term safety trial (BORA). These trials are designed to provide additional information about benralizumab in patients with severe uncontrolled asthma.

Benralizumab is in-licensed from BioWa, Inc., a wholly-owned subsidiary of Kyowa Hakko Kirin Co., Ltd. Under the exclusive license agreement, Kyowa Hakko Kirin/BioWa have exclusive development and commercialisation rights for benralizumab in Japan and certain countries in Asia. AstraZeneca has exclusive rights for benralizumab in all other countries including the US and Europe. BioWa is eligible for milestone payments and royalties related to the development and commercialisation of benralizumab in those countries.

NOTES TO EDITORS

About Benralizumab

Benralizumab is a monoclonal antibody directed at the alpha subunit of the interleukin-5 receptor (IL-5Rα) that depletes eosinophils, a key target cell in inflammatory respiratory disease. Scientific literature supports that eosinophil count is associated with exacerbations and increased eosinophils are associated with frequent exacerbations.

An estimated 5 to 10 per cent of the 300 million people worldwide who suffer from asthma have a severe form, and people with eosinophilic airway inflammation represent approximately 40 to 60 per cent of the severe asthmatic population.