This announcement contains inside information
2020年11月10日07:00 GMT
Trial also met the primary endpoint in patients with low levels of eosinophils
澳门在线赌城娱乐 and Amgen today announced positive results from the NAVIGATOR Phase III trial for the potential new medicine tezepelumab in patients with severe, 不受控制的哮喘.
NAVIGATOR met the primary endpoint with tezepelumab added to standard of care (SoC) demonstrating a statistically significant and clinically meaningful1 在整个患者人群中，52周的年化哮喘加重率(AAER)降低, compared to placebo when added to SoC. SoC was medium- or high-dose inhaled corticosteroids (ICS) plus at least one additional controller medication with or without oral corticosteroids (OCS).
In the subgroup of patients with baseline eosinophil counts less than 300 cells per microlitre the trial also met the primary endpoint, tezepelumab显示具有统计学意义和临床意义的aer降低. Similar reductions in AAER were observed in the subgroup of patients with baseline eosinophil counts less than 150 cells per microlitre.
Tezepelumab was very well tolerated in patients with severe asthma. Preliminary analyses show no clinically meaningful differences in safety results between the tezepelumab and placebo groups. NAVIGATOR试验的结果将在即将召开的医学会议上公布.
严重哮喘是一种使人衰弱的疾病，影响着全世界约3400万人.2.3 Many severe asthma patients continue to experience symptoms and frequent exacerbations despite the use of high-dose asthma controller medicines, currently available biologic therapies and OCS.3-5
Andrew Menzies-Gow教授, Director of the Lung Division, 皇家布朗普顿医院, 伦敦, UK, and principal investigator of the NAVIGATOR Phase III trial, said: “Due to the complex nature of severe asthma, many patients continue to face debilitating symptoms despite receiving standard of care inhaled medicines and currently approved biologics. Today’s ground-breaking results show that tezepelumab has the potential to transform care for a broad population of severe asthma patients who are underserved today, including those without an 嗜酸性 phenotype.”
Mene Pangalos, Executive Vice President, 澳门第一赌城在线娱乐 R&D, said: “Tezepelumab works differently from any other asthma biologic medicine and targets multiple inflammatory pathways that contribute to asthma symptoms and exacerbations. Building on the broad efficacy previously seen with tezepelumab, 这些令人兴奋的数据使澳门第一赌城在线娱乐离给严重哮喘患者提供药物又近了一步, including those with low eosinophil counts.”
Tezepelumab是一种潜在的一流药物，可阻断胸腺基质淋巴生成素(TSLP)的作用。, 一种在哮喘炎症谱中起关键作用的上皮细胞因子.6,7 NAVIGATOR是首个通过靶向TSLP治疗严重哮喘的III期临床试验.
The statistically significant and clinically meaningful exacerbation rate reductions demonstrated with tezepelumab in patients with baseline eosinophil counts less than 300 cells per microlitre support the US Food and Drug Administration Breakthrough Therapy Designation granted to tezepelumab in September 2018 for patients with severe asthma, without an 嗜酸性 phenotype. Tezepelumab is being developed by 澳门在线赌城娱乐 in collaboration with Amgen (see 澳门在线赌城娱乐 and Amgen collaboration below).
严重的哮喘
哮喘是一种异质性疾病，影响全世界约3.39亿人.2,3 Approximately 10% of asthma patients have severe asthma.3,4 Despite the use of inhaled asthma controller medicine, currently available biologic therapies and OCS, many severe asthma patients remain uncontrolled.3-5 Due to the complexity of severe asthma, many patients have unclear or multiple drivers of inflammation and may not qualify for or respond well to a current biologic medicine.4,8,9
严重的, 不受控制的哮喘会使患者衰弱，患者会经历频繁的病情恶化, significant limitations on lung function and a reduced quality of life.3,5,10 Patients with severe asthma are at an increased risk of mortality and account for twice as many asthma-related hospitalisations.11-13 T在这里 is also a significant socio-economic burden, with these patients accounting for 50% of asthma-related costs.14
NAVIGATOR and the PATHFINDER clinical trial programme
Building on the Phase IIb PATHWAY trial, the Phase III PATHFINDER programme included two trials, NAVIGATOR和SOURCE.15,16 该方案包括额外计划的机械和长期安全性试验.
NAVIGATOR是III期试验, 随机, 双盲, 安慰剂对照试验在成人(18-80岁)和青少年(12-17岁)严重, 不受控制的哮喘, who were receiving treatment with medium- or high-dose ICS plus at least one additional controller medication with or without OCS. The trial population included approximately equal proportions of patients with high (≥ 300 cells/µL) and low (< 300 cells/µL) blood eosinophil counts. The trial comprised a five to six week screening period, a 52-week treatment period and a 12-week post-treatment follow-up period. 在整个试验过程中，所有患者都接受了处方的对照药物治疗，没有变化.15,17
主要疗效终点是52周治疗期间哮喘年化加重率. Key secondary endpoints included the effect of tezepelumab on lung function, asthma control and health-related quality of life.15,17
SOURCE is a Phase III 多中心, 随机, 双盲, 与这些相应平行的组织, 安慰剂对照 trial for 48 weeks in adult patients with severe asthma who require continuous treatment with ICS plus long-acting beta2-agonists (LABA), and chronic treatment with maintenance OCS therapy. 主要终点是每日OCS剂量从基线减少的分类百分比, while not losing asthma control.16,18
参加NAVIGATOR和SOURCE试验的患者有资格继续DESTINATION试验, a Phase III extension trial assessing long term safety and efficacy.19
Tezepelumab
Tezepelumab是一种潜在的一流人单克隆抗体，可抑制TSLP的作用, a key epithelial cytokine that sits at the top of multiple inflammatory cascades and is critical in the initiation and persistence of allergic, 嗜酸性粒细胞和其他类型的气道炎症与严重哮喘相关.6,7 TSLP是对与哮喘恶化相关的多种触发因素的反应, 包括过敏原, viruses and other airborne particles.6,7 Expression of TSLP is increased in the airways of patients with asthma and has been correlated with disease severity.7,20 阻断TSLP可阻止免疫细胞释放促炎细胞因子, resulting in the prevention of asthma exacerbations and improved asthma control.7,20 Tezepelumab acts at the top of the inflammation cascade and has the potential to treat a broad population of severe asthma patients regardless of their type of inflammation.7,20
澳门在线赌城娱乐 and Amgen collaboration
Earlier in 2020, Amgen and 澳门在线赌城娱乐 updated the 2012年合作协议 对于tezepelumab. Both companies will continue to share costs and profits equally after payment by 澳门在线赌城娱乐 of a mid single-digit royalty to Amgen. 澳门在线赌城娱乐继续引领研发，安进继续引领生产. 合作的所有方面都在联合理事机构的监督之下. Under the amended agreement in North America, Amgen and 澳门在线赌城娱乐 will jointly commercialise tezepelumab; Amgen will record sales in the US and 澳门在线赌城娱乐 will record sales in Canada. 澳门在线赌城娱乐在美国从tezepelumab获得的毛利润份额将被确认为合作收入. 在美国和加拿大以外的所有国家，澳门在线赌城娱乐将单独商业化tezepelumab. 澳门在线赌城娱乐 will record all sales outside of the US as product sales and recognise Amgen’s share of gross profit as cost of sales.
澳门在线赌城娱乐在呼吸系统 & 免疫学
呼吸 & 免疫学是澳门在线赌城娱乐三大治疗领域之一，也是公司的主要增长动力.
澳门在线赌城娱乐 is an established leader in respiratory care, 2019年，其吸入和生物药物惠及5300多万患者. Building on a 50-year heritage, 该公司旨在通过专注于早期生物学主导的治疗来改变哮喘和COPD的治疗, eliminating preventable asthma attacks, and removing COPD as a top-three leading cause of death. 公司早期的呼吸系统研究重点是涉及免疫机制的新兴科学, 疾病和神经元功能障碍中的肺损伤和异常细胞修复过程.
呼吸道和免疫学的共同途径和潜在疾病驱动因素, 澳门在线赌城娱乐正在跟踪从慢性肺部疾病到免疫驱动疾病领域的科学. The Company’s growing presence in immunology is focused on five mid- to late-stage franchises with multi-disease potential, in areas including rheumatology (including Systemic Lupus Erythematosus), 皮肤病学, 胃肠病学, and systemic 嗜酸性-driven diseases. 澳门在线赌城娱乐’s ambition in 呼吸 & 免疫学是实现疾病的改变和持久缓解数以百万计的世界各地的患者.
澳门在线赌城娱乐
澳门在线赌城娱乐 (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - 肿瘤学, 心血管, 肾 & 新陈代谢和呼吸 & 免疫学. 总部设在剑桥, UK, 澳门在线赌城娱乐在100多个国家开展业务，其创新药物被全球数百万患者使用. 请访问 澳门在线赌城娱乐.com and follow the Company on 推特 @澳门在线赌城娱乐.
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参考文献
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15. 临床试验.政府. Study to Evaluate Tezepelumab in Adults & Adolescents With 严重的 Uncontrolled Asthma (NAVIGATOR) (在线). 可以在: http://clinicaltrials.gov/ct2/show/NCT03347279. [Last accessed: November 2020].
16. 临床试验.政府. Study to Evaluate the Efficacy and Safety of Tezepelumab in Reducing Oral Corticosteroid Use in Adults With Oral Corticosteroid Dependent Asthma (SOURCE) (在线). 可以在: http://clinicaltrials.gov/ct2/show/NCT03406078. [Last accessed: November 2020].
17. Menzies-Gow A, Colice G, Griffiths JM 等. NAVIGATOR: a phase 3 多中心, 随机, 双盲, 安慰剂对照, 平行组试验评估tezepelumab在成人和青少年重症糖尿病中的有效性和安全性, 不受控制的哮喘. 和物. 2020; 21(1): 266.
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20. 李勇，王伟，吕铮等. Elevated Expression of IL-33 and TSLP in the Airways of Human Asthmatics In Vivo: A Potential Biomarker of 严重的 Refractory Disease. 免疫学杂志. 2018; 200: 2253–2262.
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