AstraZeneca has reported full results from the Phase 3 OBERON and TITANIA trials evaluating tozorakimab in patients with Chronic Obstructive Pulmonary Disease (COPD) who continued to experience exacerbations despite inhaled standard-of-care treatment.

Tozorakimab 300 mg, administered once every four weeks, reduced moderate-to-severe COPD exacerbations by 29 percent in OBERON and 34 percent in TITANIA among the primary population of former smokers, compared with placebo. In the overall population of current and former smokers, exacerbations were reduced by 30 percent and 29 percent, respectively.

A pooled analysis of the two trials showed clinically meaningful reductions across all prespecified patient subgroups, including those defined by Blood Eosinophil Count (BEC). Patients with a baseline BEC below 150 cells/µL experienced a 23 percent reduction in moderate-to-severe exacerbations, while reductions were 34 percent among those with BEC of at least 150 cells/µL and 43 percent among those with BEC of at least 300 cells/µL.

The trials enrolled a total of 2,306 patients and evaluated tozorakimab 300 mg or placebo administered every four weeks for 52 weeks alongside inhaled maintenance therapy. The replicate, double-blind, placebo-controlled Phase 3 studies included former and current smokers across blood eosinophil counts and stages of lung function severity.

An integrated analysis also showed a reduction in mucus plug scores among patients receiving tozorakimab. AstraZeneca said the findings represent the first evidence of a biologic reducing mucus plugging in a broad COPD population. Mucus plugs have been associated with poorer outcomes in people with COPD.

Tozorakimab was generally well tolerated, with injection-site reactions reported as the only adverse drug reaction in the trials.

Tozorakimab is an investigational monoclonal antibody targeting interleukin-33 (IL-33). It is designed to inhibit signalling from both reduced and oxidised forms of IL-33, with the aim of reducing inflammation and disrupting mucus dysfunction associated with COPD.

The US Food and Drug Administration has accepted AstraZeneca’s Biologics License Application for tozorakimab 300 mg under Priority Review as an add-on maintenance treatment for adults with COPD. The Prescription Drug User Fee Act date is anticipated in the first quarter of 2027. The candidate is also under regulatory review in the European Union and China and is being evaluated in Phase II asthma and Phase 3 severe viral lower respiratory tract disease trials.