Full Phase III results from the previously announced positive OBERON and TITANIA trials show that AstraZeneca's IL-33 antibody tozorakimab reduced moderate-to-severe COPD exacerbations by 29–34% in former smokers, with efficacy extending across blood eosinophil strata. Data published simultaneously in the New England Journal of Medicine and presented at the European Respiratory Society Congress 2026 show that tozorakimab reduced COPD exacerbations by 29–30% in the overall population, which included current smokers and patients across all blood eosinophil counts (BEC) and all stages of lung function severity. The data underpin a Biologics License Application (BLA) accepted by the US FDA under Priority Review, with a Prescription Drug User Fee Act (PDUFA) date anticipated in Q1 2027.
Notably, the two approved biologics in COPD — Sanofi/Regeneron's Dupixent (dupilumab), cleared by the FDA in September 2024, and GSK's Nucala (mepolizumab), approved in May 2025 — both require evidence of an eosinophilic phenotype for prescribing, restricting their use to patients with elevated BEC. Tozorakimab was studied without any eosinophil threshold restriction. In a pooled analysis, patients with BEC below 150 cells/µL achieved a 23% reduction in exacerbations; those at or above 300 cells/µL achieved a 43% reduction. The efficacy gradient across eosinophil strata, including a statistically significant result in the low-eosinophil group, could extend biologic treatment to patients with lower eosinophil counts who are not covered by current COPD biologic labels.
Tozorakimab is a monoclonal antibody that binds interleukin-33 (IL-33), an epithelial alarmin released by tissue injury from viral infection, cigarette smoke, and other insults. AstraZeneca describes it as uniquely inhibiting both the reduced form of IL-33 — which signals via the ST2 receptor to drive type 2 inflammation — and the oxidized form, which signals through a RAGE/EGFR complex to promote mucus dysfunction. This dual mechanism places tozorakimab upstream of the pathways targeted by dupilumab and mepolizumab, which act on downstream effectors of eosinophilic inflammation. A separate integrated analysis presented at the ERS Congress reported that tozorakimab also reduced mucus plug scores in a broad COPD population, an emerging outcome measure associated with worse prognosis.
The OBERON and TITANIA trials together randomized 2,306 adults with symptomatic COPD and a history of at least two moderate or one severe exacerbation in the prior 12 months. Patients received tozorakimab 300 mg or placebo subcutaneously every four weeks for 52 weeks, on top of inhaled maintenance therapy. The primary endpoint was the annualized rate of moderate-to-severe exacerbations in former smokers. Safety was favorable; the only reported adverse drug reaction was injection-site reaction.