WILMINGTON, DE — AstraZeneca’s experimental COPD drug tozorakimab reduced moderate and severe exacerbations by as much as 34% in two Phase III trials across a broad patient population, supporting a U.S. regulatory application now under Priority Review with an FDA decision anticipated in the first quarter of 2027.
The results from the OBERON and TITANIA trials showed statistically significant reductions in exacerbations among former smokers, the studies’ primary population, of 29% and 34%, respectively, compared with placebo when added to inhaled standard-of-care therapy.
Among the broader population of current and former smokers, exacerbations declined 30% in OBERON and 29% in TITANIA.
A pooled analysis also showed reductions across prespecified blood eosinophil count subgroups. Patients with baseline counts below 150 had a 23% reduction in moderate and severe exacerbations, compared with 34% for those with counts of at least 150 and 43% for patients with counts of at least 300.
The findings could broaden the population potentially addressed by biologic treatment for chronic obstructive pulmonary disease because the trials enrolled patients across blood eosinophil levels, smoking status and stages of lung-function severity.
“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,” said Frank Sciurba, professor of pulmonary and critical care medicine at the University of Pittsburgh and chief investigator of the LUNA program.
AstraZeneca presented the results at the European Respiratory Society Congress 2026, with the findings simultaneously published in the New England Journal of Medicine.
A separate integrated analysis presented at the congress found tozorakimab reduced mucus plug scores. Mucus plugging has been associated with worse outcomes in COPD.
Tozorakimab was generally well tolerated in the trials, according to AstraZeneca. The company identified injection-site reaction as the only adverse drug reaction.
The monoclonal antibody targets interleukin-33, or IL-33, and is designed to inhibit signaling from both reduced and oxidized forms of the protein, targeting inflammation and mucus dysfunction associated with COPD.
The FDA has accepted AstraZeneca’s Biologics License Application for Priority Review for tozorakimab at a 300-milligram dose administered once every four weeks as an add-on maintenance treatment for adults with COPD.
A Prescription Drug User Fee Act decision date is anticipated during the first quarter of 2027 following the use of a Priority Review voucher. The drug is also under regulatory review for COPD in the European Union and China.
OBERON and TITANIA were replicate, double-blind, placebo-controlled Phase III trials involving a combined 2,306 adults with symptomatic COPD. Participants had experienced at least two moderate or one severe exacerbation during the 12 months before enrollment.
Patients received either 300 milligrams of tozorakimab once every four weeks or placebo for 52 weeks in addition to inhaled therapy. Before enrollment, participants had received standard inhaled maintenance treatment for at least three months.
The primary endpoint measured the annualized rate of moderate-to-severe exacerbations among former smokers. A key secondary endpoint measured the same outcome across current and former smokers.
AstraZeneca previously reported positive high-level findings from the trials in March.
Beyond COPD, the company is studying tozorakimab in a Phase II severe-asthma trial and a Phase III trial involving severe viral lower respiratory tract disease. The FDA granted the drug Fast Track designation for severe viral lower respiratory tract disease in November 2023 and for COPD in December 2024.
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