Third positive pivotal Phase III clinical trial of AstraZeneca plc (LON:AZN) IL-33-targeting biologic further demonstrates its benefits in COPD
Positive high-level results from the pivotal Phase III MIRANDA trial showed potential first-in-class tozorakimab demonstrated a statistically significant and clinically meaningful reduction in the annualised rate of moderate-to-severe COPD exacerbations in the primary population of former smokers and in the overall population, which included former and current smokers, and patients across all blood eosinophil* counts and all stages of lung function severity.
In MIRANDA, patients received tozorakimab 300mg or placebo on top of standard of care once every two weeks.1 The trial enrolled patients with COPD still experiencing moderate-to-severe exacerbations while on inhaled standard of care.1 These results follow an announcement in March of the positive high-level results from the pivotal Phase III OBERON and TITANIA trials studying tozorakimab at a four-week dosing interval.
Frank Sciurba, MD, FCCP, Professor of Pulmonary and Critical Care Medicine, University of Pittsburgh, Chief Investigator of LUNA programme said: “These results add to the growing body of evidence that indicates tozorakimab delivered meaningful clinical benefits for COPD patients who urgently need new treatment options. Up to half of patients today still experience exacerbations even when taking standard-of-care inhaled therapies, putting them at risk of serious health consequences including hospitalisation and even death.”
Sharon Barr, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “These data further demonstrate tozorakimab’s exciting potential as a first-in-class biologic with a truly differentiated mechanism of action that inhibits the signalling of the reduced and oxidised forms of IL-33 to address underlying drivers of COPD. We look forward to sharing the data with regulators and the scientific community as soon as possible.”
Tozorakimab was generally well tolerated with a favourable safety profile consistent with previous trials. The data will be submitted to regulatory authorities and shared with the scientific community at an upcoming medical meeting.
Nearly 400 million people are diagnosed with COPD, a heterogenous and progressive disease and the 3rd leading cause of death globally.2,3 Even when on inhaled standard of care, more than 50% of patients experience exacerbations, putting them at an increased risk of cardiopulmonary events and mortality.4-7
Tozorakimab is a potential first-in-class monoclonal antibody targeting interleukin-33 (IL-33), that uniquely inhibits the signalling of the reduced and oxidised forms of IL-33, offering the potential to both reduce inflammation and disrupt the cycle of mucus dysfunction that contribute to COPD worsening.8-11
Tozorakimab is also being studied in a Phase III trial for severe viral lower respiratory tract disease and in a Phase II trial in asthma.12,13
*eosinophil: a type of white blood cell, which at increased levels may contribute to inflammation in respiratory diseases.14
References
1. 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. [Last accessed: April 2026]
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8. 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.
9. 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.
10. 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.
11. Strickson S, et al. Distinct Pharmacological Profiles of IL-33 Antibodies. [Poster Presentation]. Presented at the American Thoracic Society (ATS) 2024. May 2024.
12. 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 [Last accessed: April 2026]
13. 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 [Last accessed: April 2026]
14. Jackson D, Akuthota P, Roufosse F. Eosinophils and eosinophilic immune dysfunction in health and disease. Eur Respir Rev 2022 31(163):210150.
