Anti-IL-33 antibody tozorakimab cut COPD flare-ups by about 30% in two phase 3 trials, including patients with low eosinophils

Chronic obstructive pulmonary disease (COPD) flare-ups (exacerbations) damage lung function and quality of life and can lead to hospitalisation or death. The two biologics currently approved for COPD (dupilumab and mepolizumab) are limited to patients with high blood eosinophil counts. Tozorakimab, an investigational AstraZeneca antibody that blocks interleukin-33 (IL-33), works through a different pathway. The twin phase 3 trials OBERON and TITANIA appear in the 29 October 2026 print issue of NEJM (first published online on 8 September at the ERS Congress).

The trials

• Two identically designed, double-blind, placebo-controlled trials with 2,306 adults whose COPD kept flaring despite stable inhaled therapy (mostly triple therapy).
• Tozorakimab 300 mg under the skin every 4 weeks, or placebo, for 52 weeks, on top of usual treatment. Current smokers were capped at 25%.

Results

• Primary endpoint (former smokers): moderate or severe exacerbations fell by 29% (OBERON) and 34% (TITANIA) versus placebo.
• All patients: reductions of 30% and 29%.
• Pooled analysis: 23% reduction with eosinophils below 150 cells/µL, 34% at 150 or above, 43% at 300 or above.
• Overall and serious adverse events were similar to placebo; injection-site reactions were more common.

Limitations

The trials were sponsored by the drug’s developer, AstraZeneca, and lasted one year, so long-term safety is unknown. Major cardiovascular events and deaths were rare but numerically higher with tozorakimab in the pooled data, which investigators attributed partly to unusually few events in the placebo group — this needs watching. The drug is not yet approved; the FDA is reviewing it with a decision expected in Q1 2027. Patients should discuss COPD treatment with their doctor.