Tozorakimab Reduces COPD Exacerbations in Phase III Trials

Full results from the positive Phase III OBERON and TITANIA trials showed that tozorakimab is the first biologic to demonstrate statistically significant and highly clinically meaningful efficacy in reducing moderate and severe exacerbations in a broad population of patients with chronic obstructive pulmonary disease (COPD) still experiencing exacerbations while on inhaled standard of care.^1,2 The trials included former and current smokers, and patients across all blood eosinophil counts (BEC) and all stages of lung function severity.^1,2

Tozorakimab 300mg, administered once every four weeks, demonstrated a reduction in moderate and severe COPD exacerbations in the primary population of former smokers by 29% (OBERON) and 34% (TITANIA), and in the overall population of current and former smokers by 30% (OBERON) and 29% (TITANIA) compared with placebo while on inhaled standard of care.^1,2 In a pooled analysis of OBERON and TITANIA, tozorakimab also demonstrated clinically meaningful reductions in moderate and severe exacerbations in all prespecified patient subgroups including those defined by BEC in the overall population.^1,2 In addition, patients on tozorakimab with a baseline BEC of less than 150 achieved a 23% reduction in moderate and severe exacerbations; patients at or above 150 achieved a 34% reduction; and patients at or above 300 achieved a 43% reduction.^1,2 See Table 1.

Frank Sciurba, MD, FCCP, Professor of Pulmonary and Critical Care Medicine, University of Pittsburgh, Chief Investigator of the LUNA program, said: “The OBERON and TITANIA trials mark the first time we have seen a biologic in COPD achieve efficacy in a broad population across blood eosinophil thresholds, including in patients with baseline eosinophils below 150, and irrespective of smoking status. These unprecedented results, along with its favorable safety profile, underscore tozorakimab’s potential as an innovative treatment for the millions of people living with COPD who remain at risk despite treatment with inhaled standard of care.”

Sharon Barr, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “Today’s groundbreaking tozorakimab results, from two replicate trials, set a new standard for COPD treatment outcomes in a broad population of patients. AstraZeneca has clinically validated the novel approach of targeting the signalling of the two forms of IL-33 to both decrease inflammation and disrupt the cycle of mucus dysfunction. With our FDA Priority Review, we look forward to bringing this treatment to patients as quickly as possible.”

These data were presented today as a late-breaker oral presentation in the ALERT-2 plenary session at the European Respiratory Society Congress and were simultaneously published in the New England Journal of Medicine.

In a separate poster presentation at the ERS Congress 2026, AstraZeneca presented results from an integrated analysis of OBERON and TITANIA that demonstrated a reduction in patients’ mucus plug score.³ Tozorakimab is the first biologic to reduce mucus plugging in a broad population of COPD patients.³ Mucus plug score is an important emerging outcome measure, as mucus plugs have been associated with worse outcomes in COPD.⁴

Tozorakimab was generally well tolerated with a favorable safety profile. The only adverse drug reaction was injection-site reaction.^1,2

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.^5-9

The Biologics License Application for tozorakimab 300mg, administered once every four weeks, has been accepted for Priority Review by the US Food and Drug Administration as an add-on maintenance treatment for adult patients with COPD. The Prescription Drug User Fee Act date is anticipated during the first quarter of 2027 following use of a Priority Review voucher. Tozorakimab is currently under regulatory review for the treatment of COPD in major markets, including the EU and China. It is also being studied in a Phase II trial in severe asthma and a Phase III trial in severe viral lower respiratory tract disease.^10,11

Table 1. Tozorakimab impact on annualized rate of moderate and severe COPD exacerbations^1,2

Notes

COPD

COPD, the third leading cause of death (excluding COVID-19) worldwide, is a progressive respiratory condition characterized by persistent airflow limitation and chronic inflammation of the airways.^12,13 Common symptoms include breathlessness, chronic cough and excess mucus production.¹³ These symptoms can worsen over time and contribute to ongoing inflammation and bronchoconstriction, making it difficult to breathe and increasing the risk of COPD exacerbations.¹³ These COPD exacerbations have a profound impact on the lives of those with the disease, accelerating disease progression, increasing hospitalizations, and increasing the risk of future cardiopulmonary events – including heart attacks, all of which can be life-threatening.^13,14 In the US, exacerbations cause more than 2,500 emergency department visits per day.¹⁵ Only 50% of COPD patients live more than 3.5 years after their first severe exacerbation.¹⁶

OBERON and TITANIA

OBERON and TITANIA were replicate Phase III double-blind, placebo-controlled trials investigating the efficacy and safety of tozorakimab in adults with symptomatic COPD with a history of ≥ 2 moderate or ≥ 1 severe COPD exacerbations in the 12 months prior to enrollment. A total of 2,306 patients were randomized in both trials, including former and current smokers, and patients across all blood eosinophil counts and all stages of lung function severity.^17,18 Patients were placed on a regimen of tozorakimab 300mg once every four weeks, or placebo over the course of 52 weeks, on top of inhaled therapy.

Prior to enrollment, patients received standard-of-care inhaled maintenance therapy for at least three months. The primary endpoint was annualized rate of moderate-to-severe COPD exacerbations in former smokers with COPD. A key secondary endpoint measured the annualized rate of moderate-to-severe COPD exacerbations in the overall population of former and current smokers.^17,18

AstraZeneca announced positive high-level results from these trials in March.¹⁹

Tozorakimab

Tozorakimab is being developed by AstraZeneca as a first-in-class potent human immunoglobulin monoclonal antibody that binds to interleukin-33 (IL-33). Tozorakimab targets the top of the inflammatory cascade uniquely inhibiting IL-33 signalling in two ways, thereby suppressing inflammation and disrupting the cycle of mucus dysfunction.^5-9 Tozorakimab is currently being investigated in a Phase III clinical trial for severe viral lower respiratory tract disease and a Phase II trial for asthma.^10,11 Tozorakimab was granted Fast Track Designation by the US Food and Drug Administration for the treatment of severe viral lower respiratory tract disease in November 2023 and for COPD in December 2024.²⁰

AstraZeneca in Respiratory & Immunology

Respiratory & Immunology, part of AstraZeneca BioPharmaceuticals, is a key disease area and growth driver to the Company.

AstraZeneca is an established leader in respiratory care with a 50-year heritage and a growing portfolio of medicines in immune-mediated diseases. The Company is committed to addressing the vast unmet needs of these chronic, often debilitating, diseases with a pipeline and portfolio of inhaled medicines, biologics and new modalities aimed at previously unreachable biologic targets. Our ambition is to deliver life-changing medicines that help eliminate COPD as a leading cause of death, eliminate asthma attacks and achieve clinical remission in immune-mediated diseases.

AstraZeneca

AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Disease, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Social Media @AstraZeneca.

References

1. Sciurba FC, Watz H, Bourdin A, et al. Tozorakimab to prevent COPD exacerbations: results from the replicate OBERON and TITANIA phase 3 studies. [Oral Presentation: 6571]. Presented at: the European Respiratory Society (ERS) Congress 2026; September 5-9, 2026; Barcelona, Spain.

2. Sciurba FC, Watz H, Bourdin A, et al. Tozorakimab to Prevent COPD Exacerbations. N Engl J Med. DOI: 10.1056/NEJMoa2606998.

3. Washko G, Sciurba F, Watz H, et al. Tozorakimab reduces the number of lung segments with mucus plugs in patients with COPD at high risk of exacerbations: integrated analysis of the replicate OBERON and TITANIA phase 3 studies. [Poster Presentation, Abstract: 131612]. Presented at: the European Respiratory Society (ERS) Congress 2026; September 5-9, 2026; Barcelona, Spain.

4. Lin L, Li T, Zhang P, et al. Airway mucus plugs in COPD clinical phenotypes and prognosis across stable and exacerbation states. Sci Rep. 2026;16:8178.

5. 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.

6. 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.

7. 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.

8. Cohen S, Strickson S, Scott IC, et al. Distinct Pharmacological Profiles of IL-33 Antibodies. Am J Resp Crit Care Medicine. 2024;209(1):A3294.

9. Strickson S, Konstantinidi R, Wyatt O, et al. Tozorakimab exerts distinct dual pharmacology to reduce COPD epithelial remodeling. Eur Respir J. 2025;66:Suppl. 69, OA6527.

10. Clinicaltrials.gov. Efficacy and Safety of Tozorakimab in Patients Hospitalized for Viral Lung Infection Requiring Supplemental Oxygen (TILIA). Available at: https://clinicaltrials.gov/study/NCT05624450. [Last accessed: September 2026].

11. 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). Available at: https://clinicaltrials.gov/study/NCT06932263. [Last accessed: September 2026].

12. World Health Organization (WHO). The top 10 causes of death. 2024. Available at: https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death. [Last accessed: September 2026].

13. GOLD. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease: 2026 Report. Available at: https://goldcopd.org/2026-gold-report-and-pocket-guide/. [Last accessed: September 2026].

14. 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.

15. American Lung Association. COPD Trends Brief: Burden. Available at: https://www.lung.org/research/trends-in-lung-disease/copd-trends-brief/copd-burden. [Last accessed: September 2026].

16. Suissa S, Dell’Aniello S, Ernst P. Long-term natural history of chronic obstructive pulmonary disease: severe exacerbations and mortality. Thorax. 2012;67:957–963.

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

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

19. AstraZeneca. Tozorakimab met primary endpoint in both OBERON and TITANIA Phase III trials in patients with COPD. Available at: https://www.astrazeneca.com/media-centre/press-releases/2026/tozorakimab-met-primary-endpoint-in-oberon-titania-phase-iii-trials-in-patients-with-copd.html. [Last accessed: September 2026].

20. AstraZeneca. Clinical Trials Appendix Q1 2026 Results Update. Available at: https://www.astrazeneca.com/content/dam/az/PDF/2026/eq1/Q1-2026-results-clinical-trials-appendix.pdf. [Last accessed: September 2026].

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