阿斯利康将于 2023 年 9 月 9 日至 13 日在意大利米兰召开的 2023 年欧洲呼吸学会(ERS)国际大会上展示其领先的吸入剂、生物制剂和早期呼吸领域相关产品组合的最新真实临床研究数据。会上，阿斯利康将公布 93 篇摘要，其中包括 18 场口头报告，重点关注重度哮喘、慢性阻塞性肺疾病 (COPD)和其他急性呼吸系统疾病未被满足的需求。

阿斯利康全球执行副总裁，生物制药事业部负责人Ruud Dobber 表示：“与许多其他免疫介导性的疾病不同，‘缓解’并不是哮喘治疗的既定目标。ERS上展示的关键数据展示了Fasenra（通用名：benralizumab）和Tezspire（通用名：tezepelumab）在缓解哮喘、提高医疗水平以及进一步改善患者生活的巨大潜力。基于这些数据，我们可以看到阿斯利康在改善哮喘、慢性阻塞性肺疾病和其它呼吸系统疾病治疗方面取得了哪些重要进展。”

benralizumab是一种单克隆抗体，可直接与嗜酸性粒细胞上的IL-5Rα结合，并吸引NK细胞，通过凋亡（程序性细胞死亡）导致嗜酸性粒细胞几乎完全耗竭，且耗尽过程迅速。benralizumab是阿斯利康的首个呼吸系统生物制剂，目前在美国、欧盟、日本和其他几个地区被批准作为嗜酸粒细胞性重度哮喘的联合维持治疗。基于MIRACLE III 期试验的出色结果，中国国家药品监督管理局 (NMPA) 正式受理benralizumab用于治疗重度哮喘的新药上市申请。

临床缓解是重度哮喘的更高治疗目标，通常包括：无急性加重；未接受口服糖皮质激素(OCS)维持治疗；肺功能稳定；长期无明显哮喘症状。

多项临床研究表明，生物制剂benralizumab是治疗嗜酸粒细胞性重度哮喘(SEA)生物制剂的领先疗法

• SHAMAL IV 期试验：这项突破性临床试验首次报道了生物制剂可以显著降低重度哮喘患者背景用药（吸入性糖皮质激素ICS）剂量。
• BORA III 期扩展试验和XALOC(RWE)项目：这两项研究中的SEA患者接受超过2年的benralizumab治疗，研究结果为临床缓解作为可实现且可持续的治疗目标提供了证据支持。
• MIRACLE III 期试验：这项研究的最新数据评估了benralizumab在中国及其他亚洲国家中病情未得到控制的 SEA 患者中的疗效和安全性。该试验的研究结果表明，benralizumab治疗后，重度哮喘患者的急性发作率在临床上和统计学意义上均显著降低。

多项临床研究显示，tezepelumab或可为广大重度哮喘患者提供持续缓解

• DESTINATION III 期事后探索分析显示，相较于安慰剂，在广大无表型或生物标志物限制的重度哮喘患者群体中，tezepelumab能够为患者带来超过2年的持续临床缓解。
• 治疗结束后DESTINATION III 期扩展研究分析显示，tezepelumab的治疗效果在停药后有所下降。但在最后一次用药后9个月内，患者的生物标记物水平和临床效果均仍优于基线水平。这一结果表明了长期使用tezepelumab的重要性。

强调通过新的心肺风险真实世界数据预防慢性阻塞性肺疾病恶化的紧迫性

• EXACOS-CV 多国回顾性队列研究：来自超过30万例慢性阻塞性肺疾病患者的最新真实世界数据表明，经历过急性加重的患者在前6个月内严重心血管事件的风险增加，而且这种风险在一年内仍居高不下。这些数据强调了预防COPD急性加重对降低心肺风险和死亡率的重要性。

早期管线的科学进展

• 细胞因子、白介素 33 (IL-33) 研究：来自ACCORD-2 IIa 期试验的最新疗效和安全性数据证实，托唑拉基单抗（一种 IL-33 中和单克隆抗体）可作为因新冠肺炎住院患者的潜在治疗选择。
• 将分享探索性研究成果，以展示新平台研究 IL-33 生物学和筛选新型疗法的潜力。
• 早期慢性阻塞性肺疾病研究：识别早期慢性阻塞性肺疾病的生物驱动因素的新方法，以改善早期诊断。

参考文献：

1，Menzies-Gow A, et al. An expert consensus framework for asthma remission as a treatment goal. J Allergy Clin Immunol. 2020;145(3):757-765. 

2，AstraZeneca plc. H1 and Q2 2023 Results Presentation. Available at: https://www.astrazeneca.com/content/dam/az/PDF/2023/h1/H1-and-Q2-2023-results-announcement.pdf. [Last accessed: August 2023].

3，Jackson D, et al. SHAMAL: Reduction of Maintenance Inhaled Corticosteroids in Patients with Severe Eosinophilic Asthma Treated with Benralizumab: A Randomised Phase 4 Study. [Oral Presentation]. Presented at the European Respiratory Society (ERS) International Congress 2023 (9-13 September).

4，Lommatzsch, M, et al. Durability of Benralizumab-induced remission in severe asthma: an analysis of the BORA study [Oral Presentation]. Presented at the European Respiratory Society (ERS) International Congress 2023 (9-13 September).

5，Pelaia, G, et al. Patients with severe eosinophilic asthma achieved remission over 2 years with benralizumab: Integrated analysis of the >1000-patient, multinational, real-world XALOC-1 study [Poster Session]. Presented at the European Respiratory Society (ERS) International Congress 2023 (9-13 September).

6，Lai, K, et al. Efficacy and safety of benralizumab in patients with severe uncontrolled asthma despite ICS-LABA: a randomised, double-blind, placebo-controlled phase 3 trial in Asia (MIRACLE) [Poster Session]. Presented at the European Respiratory Society (ERS) International Congress 2023 (9-13 September).

7，Huang K, et al. Prevalence, risk factors, and management of asthma in China: a national cross-sectional study. Lancet. 2019; 394: 407-418. 

8，AstraZeneca plc. H1 and Q2 2023 Results Clinical Trials Appendix. Available at: https://www.astrazeneca.com/content/dam/az/PDF/2023/h1/H1-and-Q2-2023-results-clinical-trials-appendix.pdf. [Last accessed: August 2023].

9，Wechsler, ME, et al. On-treatment clinical remission with tezepelumab in patients with severe, uncontrolled asthma in the phase 3 DESTINATION study [Poster Session]. Presented at the European Respiratory Society (ERS) International Congress 2023 (9-13 September).

10，Brightling, C, et al. Biomarkers and clinical outcomes after cessation of tezepelumab after 2 years of treatment (DESTINATION) [Oral Presentation]. Presented at the European Respiratory Society (ERS) International Congress 2023 (9-13 September).

11，Vogelmeier, C, et al. Increased risk of severe cardiovascular events following exacerbations of COPD: a multi-database cohort study [Poster Session]. Presented at the European Respiratory Society (ERS) International Congress 2023 (9-13 September).

12，GOLD. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD), 2023. [Online]. Available at: http://goldcopd.org. [Last accessed: August 2023]

13，Wilkinson, T, et al. Tozorakimab in patients hospitalised with COVID-19: a phase 2, randomised adaptive platform study (ACCORD-2) [Poster Session]. Presented at the European Respiratory Society (ERS) International Congress 2023 (9-13 September).

14，England E, et al. Tozorakimab (MEDI3506): an anti-IL-33 antibody that inhibits IL-33 signalling via ST2 and RAGE/EGFR to reduce inflammation and epithelial dysfunction. Sci Rep. 2023 Jun 17;13(1):9825.

15，Stephenson, K, et al. Development of a huPCLS platform to explore IL-33 biology and test novel therapies [Poster Session]. Presented at the European Respiratory Society (ERS) International Congress 2023 (9-13 September).

16，Ritchie, AI, et al. Characterising radiological abnormalities in Early COPD [Poster Session]. Presented at the European Respiratory Society (ERS) International Congress 2023 (9-13 September).

17，Chung, KF, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014 Feb;43(2):343-73.

18，The Global Asthma Network. The Global Asthma Report 2022. Available at: http://globalasthmareport.org/resources/Global_Asthma_Report_2022.pdf. [Last accessed: August 2023.]

19，Wenzel S. Severe asthma in adults. Am J Respir Crit Care Med. 2005;172:149-60.

20，Fernandes AG, et al. Risk factors for death in patients with severe asthma. J Bras Pneumol. 2014; 40: 364-372.

21，Peters SP, et al. Uncontrolled asthma: a review of the prevalence, disease burden and options for treatment. Respir Med 2006;100(7):1139-51.

22，World Health Organization. The Top 10 Causes of Death. Accessible at: https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death. [Last accessed: August 2023].

23，Adeloye D, et al. Global, regional, and national prevalence of, and risk factors for, chronic obstructive pulmonary disease (COPD) in 2019: a systematic review and modelling analysis. Lancet Respir Med. (2022) Vol 10(5); 447-458.

24，AstraZeneca. Fasenra Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/fasenra-epar-product-information_en.pdf. [Last accessed: August 2023].

25，Corren J, et al. Tezepelumab in adults with uncontrolled asthma [supplementary appendix; updated April 18, 2019]. N Engl J Med. 2017;377:936-946.

26，Varricchi G, et al. Thymic Stromal Lymphopoietin Isoforms, Inflammatory Disorders, and Cancer. Front Immunol. 2018;9:1595.

27，AstraZeneca plc. Tezspire (tezepelumab) approved in the US for severe asthma. Available at: https://www.astrazeneca.com/media-centre/press-releases/2021/tezspire-tezepelumab-approved-in-the-us-for-severe-asthma.html. [Last accessed: August 2023]. 

28，AstraZeneca plc. Tezspire approved in the EU for the treatment of severe asthma. 2022. Available at: https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2022/tezspire-approved-in-the-eu-for-the-treatment-of-severe-asthma.html. [Last accessed: August 2023]. 

29，AstraZeneca plc. Tezspire approved in Japan for the treatment of severe asthma. Available at: https://www.astrazeneca.com/media-centre/press-releases/2022/tezspire-approved-in-japan-for-severe-asthma.html. [Last accessed: August 2023].

Tags： 2023ERS多项临床结果公布，慢阻肺病急性加重将增加心肺风险