STUDY DESIGN

Chronic obstructive pulmonary disease (COPD) exacerbations accelerate lung function decline, impair quality of life, and increase the risks of hospitalization and death.¹ Despite standard-of-care (SoC) inhaled maintenance therapy, many patients remain at high risk of exacerbations, while approved biologics are limited to patients with an eosinophilic phenotype.¹ Tozorakimab is a monoclonal antibody that inhibits both reduced and oxidized interleukin-33 (IL-33), which contribute to inflammation, mucus hypersecretion, and epithelial remodeling.¹ The replicate phase 3 OBERON and TITANIA trials evaluated the efficacy and safety of tozorakimab compared with placebo when added to SoC in patients with COPD and a history of exacerbations.¹

OBERON and TITANIA were randomized, double-blind, placebo-controlled studies that enrolled patients aged ≥40 years who were current or former smokers with moderate to very severe COPD, ≥2 moderate or ≥1 severe exacerbations in the preceding 12 months, on stable inhaled maintenance therapy, post-bronchodilator forced expiratory volume in 1 second (FEV₁) >20% predicted, and a COPD Assessment Test (CAT) total score ≥10.¹ Eligibility was not restricted by baseline blood eosinophil count (BEC).¹ Patients were randomized 1:1:1 to tozorakimab 300mg subcutaneously every 4 weeks (Q4W), tozorakimab 300mg every 8 weeks (Q8W), or placebo, all added to SoC, and were followed for 52 weeks.¹ The Q8W arm was halted following a protocol amendment.¹ Baseline characteristics were balanced between treatment groups and across trials.¹

The primary endpoint was the annualized rate of moderate/severe exacerbations in former smokers.¹ The key secondary endpoint reported was the annualized rate of moderate/severe exacerbations in the overall population of current and former smokers.¹

FINDINGS

“Tozorakimab is a first-in-class biologic that has demonstrated replicated efficacy in a broad population of COPD patients with a history of exacerbations”

Professor Frank C. Sciurba
University of Pittsburgh School of Medicine, United States