AstraZeneca’s tozorakimab has delivered statistically significant and clinically meaningful reductions in moderate and severe chronic obstructive pulmonary disease (COPD) exacerbations in two positive Phase III trials.
This marks what the company says is the first success of a biologic across a broad COPD population regardless of blood eosinophil levels or smoking status.
Full results from the OBERON and TITANIA trials showed that tozorakimab reduced moderate and severe exacerbations in patients who continued to experience flare-ups despite inhaled standard-of-care treatment. The trials included both current and former smokers, as well as patients across all blood eosinophil counts and stages of lung-function impairment.
The 300mg dose, administered once every four weeks, cut moderate and severe exacerbations by 29% in OBERON and 34% in TITANIA among former smokers, the primary population. Across current and former smokers combined, exacerbations fell by 30% in OBERON and 29% in TITANIA compared with placebo.
A pooled analysis of the two trials showed clinically meaningful reductions across all prespecified patient subgroups, including those defined by blood eosinophil count (BEC).
The reduction was particularly notable across eosinophil thresholds. Patients with a baseline BEC below 150 cells/µL experienced a 23% reduction in moderate and severe exacerbations, compared with 34% among those with BEC of 150 or higher and 43% among those with BEC of 300 or higher.
Frank Sciurba, Professor of Pulmonary and Critical Care Medicine, University of Pittsburgh, Chief Investigator of the LUNA programme, 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 favourable 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.”
The results were presented as a late-breaker oral presentation during 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 reported results from an integrated analysis of OBERON and TITANIA showing a reduction in patients’ mucus plug scores.
The company said tozorakimab is the first biologic shown to reduce mucus plugging in a broad COPD population. Mucus plug score is an emerging measure of disease severity, with mucus plugs associated with worse outcomes in COPD.
Tozorakimab was generally well tolerated and demonstrated a favourable safety profile. The only reported adverse drug reaction was an injection-site reaction.
Tozorakimab is a potential first-in-class monoclonal antibody targeting interleukin-33 (IL-33). The drug is designed to inhibit signalling from both reduced and oxidised forms of IL-33, potentially addressing inflammation as well as the cycle of mucus dysfunction that contributes to COPD worsening.
