AstraZeneca reports positive Phase III OBERON and TITANIA results showing tozorakimab reduced COPD exacerbations and demonstrated a favourable safety profile.
Written By: Chikkula Pavan Kumar, PharmD
Reviewed By: Pharmacally Editorial Team
AstraZeneca has reported positive high-level results from the Phase III OBERON (NCT05166889) and TITANIA trials (NCT05158387), showing that its investigational biologic tozorakimab significantly reduced the annualised rate of moderate-to-severe exacerbations in patients with chronic obstructive pulmonary disease compared with placebo.
The benefit was observed both in the primary population of former smokers and in the broader study population, which included current smokers and patients across all blood eosinophil levels and stages of lung function severity. Tozorakimab was generally well tolerated, demonstrating a favourable safety profile.
Tozorakimab is a potential first-in-class monoclonal antibody targeting interleukin-33. It uniquely inhibits signalling of both reduced and oxidised forms of IL-33, addressing key drivers of disease by reducing inflammation and disrupting mucus dysfunction associated with COPD progression.
Both OBERON and TITANIA were replicate, randomised, double-blind, placebo-controlled Phase III trials enrolling a total of 2,306 patients with symptomatic COPD and a history of frequent exacerbations despite standard inhaled therapy. Patients received tozorakimab 300 mg or placebo every four weeks for 52 weeks on top of standard of care. The primary endpoint assessed the annualised rate of moderate-to-severe exacerbations in former smokers, with a key secondary endpoint evaluating the same outcome in the overall population.
COPD remains a major global health burden, affecting nearly 400 million people and ranking as the third leading cause of death worldwide. Despite existing inhaled therapies, more than half of patients continue to experience exacerbations, increasing the risk of hospitalisation, cardiopulmonary events, and mortality.
Frank Sciurba, MD, Chief Investigator of the LUNA programme, noted that targeting the IL-33 pathway demonstrated clinically meaningful benefit across a broad COPD population, independent of smoking status and eosinophil levels.
Sharon Barr, Executive Vice President of BioPharmaceuticals R&D at AstraZeneca, highlighted the results as the first confirmatory Phase III evidence for an IL-33 biologic in COPD, marking a significant scientific advancement.
The OBERON and TITANIA trials are part of the broader Phase III LUNA programme, which also includes the ongoing PROSPERO and MIRANDA studies. These trials are designed to further evaluate long-term efficacy and different dosing regimens of tozorakimab, with results expected in the first half of 2026.
Beyond COPD, tozorakimab is also being investigated in Phase III trials for severe viral lower respiratory tract disease and in a Phase II trial for asthma. The therapy has received Fast Track designation from the U.S. Food and Drug Administration for both indications.
Full detailed results from OBERON and TITANIA are expected to be presented at an upcoming scientific meeting.
References
Tozorakimab met primary endpoint in both OBERON and TITANIA Phase III trials in patients with COPD, 27 March 2026, Tozorakimab met primary endpoint in both OBERON and TITANIA Phase III trials in patients with COPD
Efficacy and Safety of Tozorakimab in Symptomatic Chronic Obstructive Pulmonary Disease with a History of Exacerbations (OBERON), ClinicalTrials.gov ID NCT05166889, https://clinicaltrials.gov/study/NCT05166889
Efficacy and Safety of Tozorakimab in Symptomatic Chronic Obstructive Pulmonary Disease with a History of Exacerbations. (TITANIA), ClinicalTrials.gov ID NCT05158387, https://clinicaltrials.gov/study/NCT05158387
About the Writer
Chikkula Pavan Kumar, PharmD is a Doctor of Pharmacy with a keen interest in clinical pharmacy, pharmacovigilance, and evidence-based practice. In his words, he is passionate about patient safety and translating complex medical information into clear, research-driven communication.