OBERON 与 TITANIA 两项Ⅲ期临床试验显示，Tozorakimab显著降低慢阻肺病急性加重率，且总体耐受性和安全性良好

针对慢性阻塞性肺病（COPD，简称慢阻肺病）患者的OBERON和TITANIA两项Ⅲ期试验的初步阳性结果显示，在主要研究人群（既往吸烟者）以及总体人群（包括既往和当前吸烟者，且涵盖所有血嗜酸性粒细胞*水平和所有肺功能严重程度分级的患者）中，与安慰剂组相比，tozorakimab降低了慢阻肺病年中重度急性加重率。Tozorakimab总体耐受性和安全性良好。

Tozorakimab有望成为“全球首创”、靶向白细胞介素-33 (IL-33)的单克隆抗体，其独特之处在于能同时抑制还原型与氧化型IL-33的信号传导，兼具减轻炎症和打破黏液失调病理循环的潜力，二者是导致慢阻肺病恶化的重要原因^1-4。OBERON和TITANIA试验在接受标准吸入治疗后仍出现急性加重的慢阻肺病患者中，对tozorakimab进行了评估^5,6。患者在标准治疗基础上，每四周接受一次300mg tozorakimab治疗或安慰剂治疗。

慢阻肺病是一种异质性、进展性疾病，也是全球第三大致死病因，当前全球共有近4亿确诊的慢阻肺病患者^7,8。即使接受标准吸入治疗，仍有超过50%的患者会出现急性加重，这些患者面临更高的心肺事件风险和死亡风险^9-12。

美国胸科医师学会院士，匹兹堡大学肺病与危重症医学教授，LUNA项目首席研究员Frank Sciurba博士表示：“这些试验结果表明，靶向IL-33通路的tozorakimab能为广泛慢阻肺病患者（无论吸烟状态及嗜酸性粒细胞水平）带来重要临床获益。慢阻肺病长期以来都是一种难以治疗的疾病，存在高异质性和巨大未满足需求，全球多达一半的患者面临急性加重、住院、心肺事件和死亡风险——这凸显了此次阳性结果对于推动慢阻肺病科学进步的重要性。”

阿斯利康全球执行副总裁、生物制药研发负责人Sharon Barr表示：“今天公布的 tozorakimab 研究结果，是靶向IL-33生物制剂取得的首批两项验证性Ⅲ期临床试验的积极结果，标志着在全球第三大致死病因——慢阻肺领域取得重要研发进展。Tozorakimab的作用方式与其他生物制剂存在本质不同，它通过抑制还原型和氧化型IL-33的信号传导，同时减少炎症并打破作为慢阻肺病关键驱动因素的黏液失调病理循环。”

OBERON和TITANIA两项临床试验的完整结果将在后续召开的医学会议上向学界公布。

Tozorakimab针对慢阻肺病的另外两项Ⅲ期临床试验 PROSPERO 和 MIRANDA 正在进行中^13,14。Tozorakimab针对重度病毒性下呼吸道疾病的Ⅲ期临床试验和针对哮喘的Ⅱ期临床试验也在进行中^15,16。

*嗜酸性粒细胞：一种白细胞，其水平升高可能促进呼吸道疾病炎症¹⁷。

参考文献

1. England E, Rees DG, Scott IC, 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;13:9825.       

2. Singh D, Guller P, Reid F, et al. A Phase 2a trial of the IL-33 mAb tozorakimab in patients with COPD: FRONTIER-4. Eur Respir J 2025;doi 10.1183/13993003.02231-2024.

3. Strickson S, Houslay KF, Negri VA, et al. Oxidised IL-33 drives COPD epithelial pathogenesis via ST2-independent RAGE/EGFR signalling complex. Eur Respir J 2023;62:2202210.

4. Strickson S, et al. Distinct Pharmacological Profiles of IL-33 Antibodies. [Poster Presentation]. Presented at the American Thoracic Society (ATS) 2024. May 2024.

5. Clinicaltrials.gov. Efficacy and Safety of Tozorakimab in Symptomatic Chronic Obstructive Pulmonary Disease With a History of Exacerbations (OBERON). [Online]. Available at: https://clinicaltrials.gov/study/NCT05166889. Accessed March 2026.     

6. Clinicaltrials.gov. Efficacy and Safety of Tozorakimab in Symptomatic Chronic Obstructive Pulmonary Disease With a History of Exacerbations. (TITANIA). [Online]. Available at: https://clinicaltrials.gov/study/NCT05158387. Accessed March 2026.

7. Montes de Oca M, Perez-Padilla R, Celli B, et al. The global burden of COPD: epidemiology and effect of prevention strategies. Global Epidemiology of Chronic Respiratory Disease. 2025; 13(18):709-724.

8. World Health Organization (WHO). The top 10 causes of death. 2024. Available from: https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death Accessed March 2026.

9. Chen S, Small M, Lindner L, Xu X. Symptomatic burden of COPD for patients receiving dual or triple therapy. Int J Chron Obstruct Pulmon Dis 2018;13:1365–1376. 

10. Chen S, Miravitlles M, Rhee CK, et al. Patients with chronic obstructive pulmonary disease and evidence of eosinophilic inflammation experience exacerbations despite receiving maximal inhaled maintenance therapy. Int J Chron Obstruct Pulmon Dis 2022;17:2187–2200. 

11. Nordon C, Carstens D, Fageras M, et al. Exacerbation and mortality in COPD patients on triple inhaler and at high exacerbation risk. Eur Respir J 2024;64(Suppl. 68):PA1287 (Abstract). 

12. Singh D, Han MK, Hawkins NM, et al. Implications of cardiopulmonary risk for the management of COPD: a narrative review. Adv Ther. 2024;41:2151–2167. 

13. Clinicaltrials.gov. Long-term Efficacy and Safety of Tozorakimab in Participants With Chronic Obstructive Pulmonary Disease With a History of Exacerbations (PROSPERO). [Online]. Available at: https://clinicaltrials.gov/study/NCT05742802. Accessed March 2026.

14. Clinicaltrials.gov. Efficacy and Safety of Tozorakimab in Symptomatic Chronic Obstructive Pulmonary Disease With a History of Exacerbations (MIRANDA). [Online]. Available at: https://clinicaltrials.gov/study/NCT06040086. Accessed March 2026.

15. Clinicaltrials.gov. Efficacy and Safety of Tozorakimab in Patients Hospitalised for Viral Lung Infection Requiring Supplemental Oxygen (TILIA). [Online]. Available at: https://clinicaltrials.gov/study/NCT05624450 Accessed March 2026.

16. Clinicaltrials.gov Dose Range Finding Study to Assess Efficacy and Safety of Tozorakimab in Adults With Uncontrolled Asthma on Medium-to-High Dose Inhaled Corticosteroids (UMBRIEL). [Online]. Available at: https://clinicaltrials.gov/study/NCT06932263 Accessed March 2026.

17. Jackson D, Akuthota P, Roufosse F, Eosinophils and eosinophilic immune dysfunction in health and disease. Eur Respir Rev 2022 31(163):210150.