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
澳门葡京网赌游戏(澳门葡京网赌游戏)和安进(Amgen)今天宣布，潜在新药tezepelumab用于重度糖尿病患者的NAVIGATOR III期试验取得积极结果, 不受控制的哮喘.
NAVIGATOR达到了tezepelumab加入标准护理(SoC)的主要终点，显示出统计学意义和临床意义1 reduction in the annualised asthma exacerbation rate (AAER) over 52 weeks in the overall patient population, compared to placebo when added to SoC. SoC是中剂量或高剂量吸入皮质类固醇(ICS)加上至少一种额外的控制药物，有或没有口服皮质类固醇(OCS)。.
在基线嗜酸性粒细胞计数低于每微升300个细胞的患者亚组中，试验也达到了主要终点, with tezepelumab demonstrating a statistically significant and clinically meaningful reduction in AAER. 在基线嗜酸性粒细胞计数低于每微升150个细胞的患者亚组中，也观察到AAER的类似减少.
Tezepelumab was very well tolerated in patients with severe asthma. 初步分析显示tezepelumab组和安慰剂组在安全性结果上没有临床意义上的差异. Results from the NAVIGATOR trial will be presented at a forthcoming medical meeting.
严重的哮喘 is a debilitating condition affecting approximately 34 million people worldwide.2.3 尽管使用了高剂量哮喘控制药物，许多严重哮喘患者仍然出现症状并频繁加重, 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, 尽管接受了标准治疗的吸入药物和目前批准的生物制剂，许多患者仍然面临衰弱症状. 今天的突破性结果表明，tezepelumab有可能改变目前服务不足的广大严重哮喘患者的护理, including those without an 嗜酸性 phenotype.”
Mene Pangalos, Executive Vice President, 澳门葡京赌博游戏 R&D, 他说:“Tezepelumab的作用不同于任何其他哮喘生物药物，它针对导致哮喘症状和恶化的多种炎症途径. Building on the broad efficacy previously seen with tezepelumab, these are exciting data that bring us one step closer to delivering a medicine to severe asthma patients, including those with low eosinophil counts.”
Tezepelumab is a potential first-in-class medicine that blocks the action of thymic stromal lymphopoietin (TSLP), an epithelial cytokine that plays a key role across the spectrum of asthma inflammation.6,7 NAVIGATOR is the first Phase III trial to show benefit in severe asthma by targeting TSLP.
tezepelumab在基线嗜酸性粒细胞计数低于每微升300个细胞的患者中显示的具有统计学意义和临床意义的恶化率降低支持了这一观点 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由澳门葡京网赌游戏与安进合作开发(见下文澳门葡京网赌游戏与安进合作)。.
严重的哮喘
Asthma is a heterogeneous disease affecting an estimated 339 million people worldwide.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, 许多患者有不清楚的或多种炎症驱动因素，可能不符合当前生物药物的资格或对其反应良好.4,8,9
严重的, 不受控制的哮喘 is debilitating with patients experiencing frequent exacerbations, significant limitations on lung function and a reduced quality of life.3,5,10 严重哮喘患者的死亡风险增加，与哮喘相关的住院人数是后者的两倍.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 The programme includes additional planned mechanistic and long-term safety trials.
NAVIGATOR是III期试验, 随机, 双盲, 安慰剂对照 trial in adults (18–80 years old) and adolescents (12–17 years old) with severe, 不受控制的哮喘, 谁正在接受中剂量或高剂量ICS加至少一种额外的对照药物治疗，有或没有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. All patients received their prescribed controller medications without change throughout the trial.15,17
The primary efficacy endpoint was the annualised asthma exacerbation rate during the 52-week treatment period. 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, 需要持续使用ICS加长效β 2激动剂(LABA)治疗的成年严重哮喘患者48周的安慰剂对照试验, and chronic treatment with maintenance OCS therapy. The primary endpoint is the categorised percentage reduction from baseline in the daily OCS dose, while not losing asthma control.16,18
Patients who participated in the NAVIGATOR和SOURCE trials were eligible to continue in DESTINATION, a Phase III extension trial assessing long term safety and efficacy.19
Tezepelumab
Tezepelumab is a potential first-in-class human monoclonal antibody that inhibits the action of TSLP, 一个关键的上皮细胞因子，位于多个炎症级联反应的顶端，在过敏的开始和持续中起关键作用, 嗜酸性 and other types of airway inflammation associated with severe asthma.6,7 TSLP is released in response to multiple triggers associated with asthma exacerbations, 包括过敏原, viruses and other airborne particles.6,7 TSLP在哮喘患者气道中的表达增加，并与疾病严重程度相关.7,20 Blocking TSLP may prevent the release of pro-inflammatory cytokines by immune cells, resulting in the prevention of asthma exacerbations and improved asthma control.7,20 Tezepelumab作用于炎症级联反应的顶端，无论其炎症类型如何，都有可能治疗广泛的严重哮喘患者.7,20
澳门葡京网赌游戏 and Amgen collaboration
Earlier in 2020, Amgen and 澳门葡京网赌游戏 updated the 2012年合作协议 对于tezepelumab. 在澳门葡京网赌游戏向安进支付个位数的专利使用费后，两家公司将继续平均分担成本和利润. 澳门葡京网赌游戏 continues to lead development and Amgen continues to lead manufacturing. All aspects of the collaboration are under the oversight of joint 政府erning bodies. Under the amended agreement in North America, Amgen and 澳门葡京网赌游戏 will jointly commercialise tezepelumab; Amgen will record sales in the US and 澳门葡京网赌游戏 will record sales in Canada. 澳门葡京网赌游戏’s share of gross profits from tezepelumab in the US will be recognised as collaboration revenue. In all countries outside the US and Canada, 澳门葡京网赌游戏 will solely commercialise tezepelumab. 澳门葡京网赌游戏将把美国以外的所有销售记录为产品销售，并将安进在毛利润中的份额计入销售成本.
澳门葡京网赌游戏在呼吸系统 & 免疫学
呼吸 & 免疫学 is one of 澳门葡京网赌游戏’s three therapy areas and is a key growth driver for the Company.
澳门葡京网赌游戏 is an established leader in respiratory care, and its inhaled and biologic medicines reached more than 53 million patients in 2019. Building on a 50-year heritage, the Company aims to transform the treatment of asthma and COPD by focusing on earlier biology-led treatment, eliminating preventable asthma attacks, and removing COPD as a top-three leading cause of death. The Company’s early respiratory research is focused on emerging science involving immune mechanisms, lung damage and abnormal cell-repair processes in disease and neuronal dysfunction.
With common pathways and underlying disease drivers across respiratory and immunology, 澳门葡京网赌游戏 is following the science from chronic lung diseases to immunology-driven disease areas. 该公司在免疫学领域的业务日益增长，主要集中在五个具有多疾病潜力的中后期特许经营权, in areas including rheumatology (including Systemic Lupus Erythematosus), 皮肤病学, 胃肠病学, and systemic 嗜酸性-driven diseases. 澳门葡京网赌游戏’s ambition in 呼吸 & 免疫学 is to achieve disease modification and durable remission for millions of patients worldwide.
澳门葡京网赌游戏
澳门葡京网赌游戏 (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, 澳门葡京网赌游戏 operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. 请访问 澳门葡京网赌游戏.com and follow the Company on 推特 @澳门葡京网赌游戏.
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参考文献
1. Bonini M, Di Paolo M, Bagnasco D, 等. Minimal clinically important difference for asthma endpoints: an expert consensus report. 欧元呼吸机. 2020; 29: 190137.
2. 全球哮喘网络. The Global Asthma Report 2018. (在线). 可以在: http://www.globalasthmareport.org/Global%20Asthma%20Report%202018.pdf. [Last accessed: November 2020].
3. Chung KF, 文策尔年代E, Brozek JL, 等. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur呼吸器. 2014; 43: 343–73.
4. 文策尔年代. 成人严重哮喘. 我是急救医生吗. 2005; 172; 149–60.
5. Peters SP, Ferguson G, Deniz Y, 等. Uncontrolled asthma: a review of the prevalence, disease burden and options for treatment. 和地中海. 2006; 100 (7): 1139-51.
6. Varricchi G, Pecoraro A, Marone G, 等. Thymic Stromal Lymphopoietin Isoforms, Inflammatory Disorders, and Cancer. 前面Immunol. 2018; 9: 1595.
7. Corren J, Parnes JR, Wang L， 等. Tezepelumab in Adults with Uncontrolled Asthma [published correction appears in [英]医学. 2019年5月23日;380(21):2082]. [英]医学. 2017; 377 (10): 936-946.
8. Hyland ME, Masoli M, Lanario JW, 等. A Possible Explanation for Non-responders, Responders and Super-responders to Biologics in 严重的 Asthma. 探索性假说医学. 2019; 4:35–38.
9. Tran TN, Zeiger RS, Peters SP, 等. 异位重叠, 嗜酸性, and TH2-high asthma phenotypes in a general population with current asthma. 安过敏哮喘免疫. 2016; 116:37–42.
10. Fernandes AG, Souza-Machado C, Coelho RC, 等. Risk factors for death in patients with severe asthma. [J]. 2014; 40 (4): 364-372.
11. Chastek B，等. Economic Burden of Illness Among Patients with 严重的 Asthma in a Managed Care Setting. J管理护理规范药房. 2016; 22: 848–861.
12. Hartert TV, Speroff T, Togias A, 等. Risk factors for recurrent asthma hospital visits and death among a population of indigent older adults with asthma. 安过敏哮喘免疫. 2002; 89: 467–73.
13. Price D, Fletcher M, van der Molen T. Asthma control and management in 8,000 European patients: the REcognise Asthma and LInk to Symptoms and Experience (REALISE) survey. NPJ整洁护理呼吸医学. 2014; 12; 24: 14009.
14. World Allergy Organization (WAO). The management of severe asthma: economic analysis of the cost of treatments for severe asthma. 可以从: http://www.worldallergy.org/educational_programs/world_allergy_forum/anaheim2005/blaiss.php [Last accessed: November 2020].
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. Tezepelumab减少成人口服皮质类固醇依赖性哮喘患者口服皮质类固醇使用的有效性和安全性研究(来源)[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, 与这些相应平行的组织 trial to evaluate the efficacy and safety of tezepelumab in adults and adolescents with severe, 不受控制的哮喘. 和物. 2020; 21(1): 266.
18. Weschler ME, Colice G, Griffiths JM 等. 来源:A阶段3, 多中心, 随机, 双盲, 安慰剂对照, 平行组试验，以评估Tezepelumab减少口服皮质类固醇依赖性哮喘成人患者口服皮质类固醇使用的有效性和安全性. 和物. 2020; 21(1), 264.
19. 临床试验.政府. Extension Study to Evaluate the Safety and Tolerability of Tezepelumab in Adults and Adolescents With 严重的, Uncontrolled Asthma (DESTINATION) (在线). 可以在: http://clinicaltrials.gov/ct2/show/NCT03706079. [Last accessed: November 2020].
20. 李勇，王伟，吕铮等. 体内人类哮喘患者气道中IL-33和TSLP表达升高:严重难治性疾病的潜在生物标志物. 免疫学杂志. 2018; 200: 2253–2262.
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