Tozorakimab Reduces COPD Exacerbations vs Placebo in Former Smokers
Key Highlights
- Tozorakimab reduced moderate or severe chronic obstructive pulmonary disease exacerbation rates by 29% in OBERON and 34% in TITANIA among former smokers.
- Significant reductions were also observed in the overall populations, which included current and former smokers.
- Patients were enrolled without blood eosinophil count eligibility criteria.
- Overall adverse event rates were similar, although injection-site reactions were more frequent with tozorakimab.
Tozorakimab significantly reduced annualized moderate or severe exacerbation rates among patients with chronic obstructive pulmonary disease (COPD) and a history of exacerbations despite maintenance inhaler therapy, according to results from 2 replicate phase 3 trials published in The New England Journal of Medicine. The benefit was observed among former smokers—the primary analysis population—and among the overall population of current and former smokers.
OBERON and TITANIA were randomized, double-blind, placebo-controlled trials enrolling adults aged 40 years or older with COPD, at least 10 pack-years of smoking exposure, and recent exacerbations despite stable dual or triple inhaled maintenance therapy. Eligibility was not based on blood eosinophil count.
Patients received subcutaneous tozorakimab 300 mg or placebo every 4 weeks for 52 weeks in addition to standard care. OBERON included 446 patients assigned to tozorakimab and 431 assigned to placebo; TITANIA included 438 and 435 patients, respectively. The primary end point was the annualized rate of moderate or severe exacerbations among former smokers.
Study Findings
Among former smokers in OBERON, annualized moderate or severe exacerbation rates were 1.34 with tozorakimab and 1.90 with placebo, representing a 29% reduction (rate ratio [RR], 0.71; 95% CI, 0.57-0.88; P=.002). Corresponding rates in TITANIA were 1.37 and 2.07, respectively, representing a 34% reduction (RR, 0.66; 95% CI, 0.55-0.80; P<.001).
In the overall OBERON population, annualized exacerbation rates were 1.41 with tozorakimab and 2.00 with placebo (RR, 0.70; 95% CI, 0.58-0.85; P<.001). Rates in the overall TITANIA population were 1.44 and 2.03, respectively (RR, 0.71; 95% CI, 0.59-0.84; P<.001).
Changes in St. George’s Respiratory Questionnaire total scores did not differ significantly between groups in either trial. Under the hierarchical testing procedure, no further statistical testing of key secondary end points was performed.
Overall and serious adverse event rates appeared similar between groups. Injection-site reactions were more frequent with tozorakimab, while rare major adverse cardiovascular events and serious adverse events resulting in death occurred more frequently with tozorakimab than placebo; the investigators reported no apparent patterns in event components or causes.
Clinical Implications
According to the study authors, consistent findings across the replicate trials confirm the efficacy of tozorakimab for reducing moderate or severe exacerbations in a broad COPD population receiving standard care. The results across blood eosinophil count thresholds support further evaluation of interleukin-33 as a therapeutic target beyond populations defined by elevated eosinophil counts.
Limitations included a lack of systematic monitoring of maintenance-therapy adherence and insufficient follow-up and sample sizes to evaluate rare safety events. Some racial groups were underrepresented, and the trials were not designed to evaluate patients who had never smoked or determine tozorakimab’s mechanism of action.
Expert Commentary
“In a broad population of patients with COPD who had a history of exacerbations and were receiving standard care, add-on tozorakimab therapy resulted in a lower rate of moderate or severe exacerbations than placebo,” the researchers concluded.
Reference
Sciurba FC, Watz H, Bourdin A, et al. Tozorakimab to prevent COPD exacerbations. N Engl J Med. Published online September 8, 2026. doi:10.1056/NEJMoa260699