Tozorakimab has met its primary endpoint in two replicate Phase 3 trials in chronic obstructive pulmonary disease (COPD), marking a potential first for an IL-33-targeting biologic in the indication, according to high-level results from the OBERON and TITANIA studies.

The monoclonal antibody, developed by AstraZeneca, significantly reduced the annualised rate of moderate-to-severe COPD exacerbations compared with placebo in patients receiving standard inhaled therapy. Benefits were observed in both former smokers and the broader study population, including current smokers and patients across eosinophil levels and disease severity.

COPD is a progressive inflammatory lung disease affecting hundreds of millions globally and remains a leading cause of death. Despite standard inhaled therapies, more than half of patients continue to experience exacerbations, which are associated with accelerated lung decline, hospitalisation and increased mortality.

Tozorakimab is a first-in-class monoclonal antibody targeting interleukin-33 (IL-33), a cytokine involved in airway inflammation and mucus dysfunction. It is designed to inhibit both reduced and oxidised forms of IL-33, aiming to interrupt multiple inflammatory pathways implicated in COPD worsening.

Tozorakimab was generally well tolerated across both studies, with a safety profile described as favourable. The trials evaluated a 300mg dose administered every four weeks on top of standard of care inhaled treatment.

Frank Sciurba, professor of pulmonary and critical care medicine at the University of Pittsburgh and chief investigator of the LUNA programme, said the results support IL-33 pathway inhibition as a clinically meaningful approach across a broad COPD population, independent of smoking status or eosinophilic profile.

Sharon Barr, executive vice president of biopharmaceuticals R&D at AstraZeneca, said the findings represent a major step forward in COPD biology.

She said the data from two confirmatory Phase 3 trials demonstrated that targeting IL-33 offers a differentiated mechanism compared with existing biologics, addressing both inflammation and mucus dysfunction that drive disease progression.

The OBERON and TITANIA results will be presented in full at an upcoming scientific meeting. Additional Phase 3 studies in COPD, PROSPERO and MIRANDA, are ongoing, alongside investigations in severe viral lower respiratory tract disease and asthma.

COPD remains a major area of unmet need, driven by heterogeneous inflammatory mechanisms that limit the effectiveness of current therapies. The consistent efficacy across broad patient subgroups in two replicate Phase 3 trials is likely to be closely watched as the programme progresses toward regulatory evaluation.