Tozorakimab Reduces COPD Exacerbations Across Eosinophil Levels in Phase 3 Trials

Tozorakimab (AstraZeneca), an investigational monoclonal antibody targeting interleukin-33 (IL-33), significantly reduced moderate-to-severe chronic obstructive pulmonary disease (COPD) exacerbations in the replicate phase 3 OBERON (NCT05166889) and TITANIA (NCT05158387) trials. The results support a potential biologic option for a broad population of patients who continue to experience exacerbations despite receiving inhaled maintenance therapy.^1,2

The findings were presented at the European Respiratory Society Congress 2026 and published simultaneously in The New England Journal of Medicine. The FDA has accepted a biologics license application for tozorakimab under Priority Review, with a Prescription Drug User Fee Act decision expected during the first quarter of 2027.¹

Phase 3 Trials Demonstrate Consistent Reductions

OBERON and TITANIA were randomized, double-blind, placebo-controlled trials that collectively enrolled 2306 adults with symptomatic COPD. Eligible patients had experienced at least 2 moderate exacerbations or at least 1 severe exacerbation during the previous 12 months despite receiving standard inhaled maintenance therapy for at least 3 months. Participants included current and former smokers across blood eosinophil levels and stages of lung-function impairment.^1,3

Patients received subcutaneous tozorakimab at a dose of 300 mg every 4 weeks or placebo for 52 weeks, added to their existing inhaled treatment. The primary end point was the annualized rate of moderate-to-severe COPD exacerbations among former smokers. A key secondary end point evaluated the same outcome in the overall population of current and former smokers.^2,3

Among former smokers, tozorakimab reduced moderate-to-severe exacerbations by 29% in OBERON and 34% in TITANIA compared with placebo. Reductions in the combined populations of current and former smokers were 30% and 29%, respectively.^1,2

These results are notable because the magnitude of benefit remained consistent across 2 similarly designed trials. COPD drug-development programs have previously encountered difficulty reproducing positive biologic results across pivotal studies, underscoring the importance of replication.

Benefits Extend Across Eosinophil Subgroups

Biologic treatment in airway disease has often centered on patients with elevated eosinophil counts or other evidence of type 2 inflammation. Tozorakimab demonstrated benefit across prespecified blood eosinophil subgroups, suggesting that IL-33 inhibition could apply to a broader COPD population.¹

In the pooled analysis, patients with baseline blood eosinophil counts below 150 cells/µL experienced a 23% reduction in moderate-to-severe exacerbations. Reductions reached 34% among patients with counts of at least 150 cells/µL and 43% among those with counts of at least 300 cells/µL.¹

Tozorakimab is designed to inhibit signaling by both reduced and oxidized forms of IL-33. Reduced IL-33 promotes inflammatory signaling through the ST2 receptor, whereas oxidized IL-33 contributes to epithelial dysfunction through the RAGE/EGFR pathway. By targeting both forms, tozorakimab is intended to reduce inflammation while disrupting processes associated with excessive mucus production and impaired epithelial repair.^3,4

A separate integrated analysis of OBERON and TITANIA also found that tozorakimab reduced mucus plug scores. Mucus plugging has been associated with worse clinical outcomes in COPD and represents an emerging measure of disease burden.¹

Safety and Regulatory Considerations

Tozorakimab was generally well tolerated, and its safety profile was comparable to placebo. Injection-site reaction was the only adverse drug reaction identified across the trials. More detailed data will be important for evaluating the incidence of serious adverse events, treatment discontinuations, infections, and outcomes across clinically relevant subgroups.^1,2

COPD exacerbations can accelerate disease progression and increase the likelihood of hospitalization and subsequent cardiopulmonary events. Current management relies heavily on inhaled bronchodilators and corticosteroid-containing regimens, with biologic use reserved for selected patients. The 2026 Global Initiative for Chronic Obstructive Lung Disease report emphasizes treatment optimization and exacerbation prevention as central components of COPD management.⁵

Implications for Pharmacists

If approved, tozorakimab would introduce additional responsibilities for pharmacists involved in COPD care. Patient identification would require reviewing exacerbation history, inhaler adherence, smoking status, and previous treatment optimization before initiating biologic therapy.

Pharmacists would also educate patients about subcutaneous administration, every-4-week dosing, and injection-site reactions. Continued inhaler assessment would remain necessary because tozorakimab was evaluated as add-on maintenance therapy rather than a replacement for existing COPD medications.

The consistent phase 3 findings position IL-33 inhibition as a promising strategy for patients who remain vulnerable to exacerbations. FDA review will determine whether tozorakimab becomes a new biologic option across eosinophil-defined COPD populations.

REFERENCES

1. AstraZeneca. Tozorakimab demonstrated statistically significant and highly clinically meaningful reduction in COPD exacerbations in OBERON and TITANIA phase III trials. Published September 8, 2026. Accessed September 9, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/tozorakimab-demonstrated-statistically-significant-highly-clinically-meaningful-reduction-copd-exacerbations-oberon-titania-phase-iii-trials.html

2. Sciurba FC, Watz H, Bourdin A, et al. Tozorakimab to Prevent COPD Exacerbations. New England Journal of MedicinePublished online September 8, 2026. doi:10.1056/nejmoa2606998

3. Watz H, Sciurba FC, Bonini M, et al. Phase III LUNA clinical programme: design of four randomised, double-blind, placebo-controlled studies assessing the efficacy and safety of tozorakimab in patients with symptomatic COPD and a high risk of exacerbations. BMJ Open Respir Res. 2026;13(1):e004145. Published 2026 Jul 20. doi:10.1136/bmjresp-2026-004145

4. 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(1):9825. Published 2023 Jun 17. doi:10.1038/s41598-023-36642-y

5. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease: 2026 Report. Accessed September 9, 2026. https://goldcopd.org/2026-gold-report-and-pocket-guide/