S91 Tozorakimab (anti-IL-33 mAb) reduces mucus plugging in COPD: an imaging sub-study in the FRONTIER-4 phase 2a COPD trial

Introduction

Mucus plugging in COPD is associated with airflow obstruction, poor health-related quality of life and high all-cause mortality. Preclinical studies have shown that tozorakimab reduces mucus hypersecretion in cultured COPD epithelial cells.

Objective

Assess the impact of tozorakimab on mucus plugs using computed tomography (CT) imaging.

Methods

The FRONTIER-4 phase 2 study (NCT04631016) investigated tozorakimab in COPD patients with chronic bronchitis on dual- or triple-inhaled maintenance therapy. Patients were randomized 1:1 to receive tozorakimab 600 mg or placebo s.c. Q4W. In an exploratory sub-study, mucus plugging was assessed in lung segments by CT imaging at baseline and week 28, in patients receiving tozorakimab (n=18) or placebo (n=21).

Results

Mucus plug score was reduced in patients receiving tozorakimab versus placebo (LS mean difference: –1.5; 80% CI: –3.0, 0.0; p=0.097). This result was further supported in a post-hoc non-parametric analysis stratified by baseline score (p=0.0312; figure 1).

Conclusion

This exploratory study offers the first insights into the effect of tozorakimab on mucus plugging in COPD, using CT imaging. Ongoing phase 3 studies (NCT05166889, NCT05158387, NCT06040086) provide further opportunity to investigate the effect of tozorakimab on mucus plugging and the impact on symptoms, quality of life and lung function.