AstraZeneca (LSE/STO/NYSE: AZN) reported that tozorakimab met its primary endpoint in the Phase III MIRANDA trial, reducing the annualized rate of moderate-to-severe COPD exacerbations in former smokers and in the overall population — the third consecutive positive pivotal readout for the IL-33-targeting antibody and the one that most directly tests whether the drug's biology extends across the full spectrum of COPD patients, regardless of eosinophil count.
MIRANDA is a Phase III double-blind, placebo-controlled trial that randomised 1,454 adults with symptomatic COPD and a history of at least two moderate or one severe exacerbation in the prior 12 months to tozorakimab 300mg or placebo every two weeks on top of inhaled standard of care for 52 weeks.
AstraZeneca did not disclose numerical effect sizes in the top-line release. The company said the reduction in exacerbation rate was statistically significant and clinically meaningful in both the primary population of former smokers and in the overall population, which included current smokers and patients across all blood eosinophil counts and all stages of lung function severity. A key secondary endpoint — exacerbation rate in the overall former-and-current-smoker population — also met its threshold. Tozorakimab was described as generally well tolerated, with a safety profile consistent with prior trials.
MIRANDA follows the Phase III OBERON and TITANIA trials, which together randomised 2,306 patients at a four-week dosing interval and produced positive high-level results announced in March 2026. The LUNA programme also includes PROSPERO, a long-term extension study in 1,713 patients from OBERON and TITANIA, with a primary endpoint focused on severe exacerbations — hospitalisations and death — over 104 weeks.
The mechanistic rationale for tozorakimab in COPD centres on IL-33, an epithelial alarmin released in response to injury, infection, and cigarette smoke. Unlike approved biologics in COPD, which target downstream effectors of eosinophilic inflammation, tozorakimab neutralises IL-33 itself, blocking signalling through both the canonical ST2 receptor and a RAGE/EGFR-associated pathway activated by the oxidised form of the cytokine. AstraZeneca has argued that the oxidised IL-33 axis drives mucus dysfunction and epithelial pathology in a manner independent of eosinophil biology — a claim supported by published mechanistic work but not yet confirmed in a head-to-head clinical setting.
That mechanistic distinction carries commercial weight. The two approved biologics in COPD — dupilumab (Dupixent, Sanofi/Regeneron), cleared by the FDA in September 2024, and mepolizumab (Nucala, GSK), approved in May 2025 — both require evidence of an eosinophilic phenotype for prescribing. Dupilumab's pivotal data were drawn from patients with blood eosinophil counts of at least 300 cells per microlitre; mepolizumab's label extends to counts of at least 150 cells per microlitre. A substantial proportion of COPD patients who continue to exacerbate on maximal inhaled therapy fall below those thresholds and currently have no biologic option.