Positive high‑level results from the phase 3 OBERON and TITANIA trials indicate that tozorakimab achieved statistically significant and clinically meaningful reductions in the annualised rate of moderate to severe COPD exacerbations compared with placebo.
The findings applied both to the primary population of former smokers and to the overall population, which included former and current smokers, with patients spanning all blood eosinophil counts and all stages of lung function severity. According to the data, tozorakimab was generally well tolerated with a favourable safety profile.
Tozorakimab is described as a potential first‑in‑class monoclonal antibody targeting interleukin‑33, uniquely inhibiting signalling of both the reduced and oxidised forms of IL‑33. The approach aims to reduce inflammation and disrupt the cycle of mucus dysfunction that contributes to COPD worsening.
In both trials, patients continued to experience exacerbations despite inhaled standard of care and received either tozorakimab 300mg or placebo once every four weeks on top of their existing treatment.
COPD affects nearly 400 million people worldwide and remains the third leading cause of death globally. Even with inhaled standard of care, more than half of patients continue to experience exacerbations, increasing the risk of cardiopulmonary events and mortality.
Frank Sciurba, Professor of Pulmonary and Critical Care Medicine at the University of Pittsburgh and Chief Investigator of the LUNA programme, said: “These trial results suggest that targeting the IL‑33 pathway with tozorakimab delivers meaningful clinical benefit in a trial representing a broad COPD population, independent of smoking status and eosinophilic levels.
“COPD has long been a difficult‑to‑treat disease with inherent heterogeneity and significant unmet need, with up to half of patients worldwide at risk of exacerbations, hospitalisations, cardiopulmonary events, and death — underscoring the importance of these results for advancing COPD science.”
Sharon Barr, Executive Vice President, BioPharmaceuticals R&D at AstraZeneca, said: “Today’s tozorakimab results deliver the first two confirmatory phase 3 trials for an IL‑33 biologic, which is a major scientific advancement in COPD, the world’s third leading cause of death.”
She added: “Tozorakimab works in a fundamentally different way from other biologics, inhibiting the signalling of the reduced and oxidised forms of IL‑33 to both decrease inflammation and disrupt the cycle of mucus dysfunction that are key disease drivers in COPD.”
Full results will be presented at an upcoming medical meeting. Additional phase 3 trials, PROSPERO and MIRANDA, are ongoing, and tozorakimab is also being studied in severe viral lower respiratory tract disease and in asthma.
