S92 FRONTIER-4: a phase 2a study to investigate tozorakimab (anti-IL-33 mAb) in COPD

Introduction

FRONTIER-4 (NCT04631016) examined the effect of tozorakimab on lung function in COPD patients with chronic bronchitis on dual- or triple-inhaled maintenance therapy.

Methods

Patients were randomized 1:1 to receive tozorakimab 600 mg or placebo (PBO) s.c. Q4W. The primary endpoint was change in pre-BD FEV₁ from baseline to week 12. Secondary outcomes included post-BD FEV₁, time-to-first COPDCompEx event and safety.

Results

The ITT population included 135 patients (tozorakimab, n=67; PBO, n=68). Baseline mean (SD)% predicted pre-BD FEV₁ was 44.0% (15.2) for tozorakimab; 45.2% (12.9) for PBO. Former smokers comprised 64.2% (n=43) for tozorakimab; 52.9% (n=36) for PBO. Most patients (>88%) had baseline blood eosinophil counts (BEC) <300 cells/μL. Although the primary endpoint was not met, at week 12 tozorakimab numerically improved pre-BD FEV₁ vs PBO (LS mean: 24mL [80% CI −15, 63] p=0.216). Greater effects were observed in patients with ≥2 exacerbations in the prior 12 months (LS mean: 69mL [80% CI 9, 130] n=59) and in those with BEC ≥150 cells/μL (LS mean: 82mL [80% CI 26, 138] n=62). Tozorakimab improved post-BD FEV₁ vs PBO at week 12 (LS mean: 67mL [80% CI 17, 116] p=0.044). In a time-to-event analysis, tozorakimab numerically reduced risk of COPDCompEx events vs PBO at week 28 (HR=0.79 [80% CI 0.57, 1.11] p=0.186), with greater effect in patients with ≥2 exacerbations in the prior 12 months (HR=0.61 [80% CI 0.37, 1.00]). Numerical improvements in all endpoints presented here were seen in both former and current smokers. Tozorakimab was well tolerated.

Conclusion

Tozorakimab may improve lung function and reduce COPD exacerbations, especially in patients with frequent exacerbation history.