D96-08 Tozorakimab Improves Quantitative Mucus Plugging Metrics in Patients With Moderate-to-Severe COPD

Abstract Rationale Mucus plugging is a clinically meaningful feature of chronic obstructive pulmonary disease (COPD), linked to airflow obstruction, increased exacerbation risk and higher mortality. Prior studies have shown that tozorakimab reduces visually assessed mucus scores in patients with COPD.1 However, conventional mucus scoring captures the presence of at least one plug within individual lung segments. This study evaluates the impact of tozorakimab on mucus plugging using an expanded set of quantitative imaging metrics. Methods FRONTIER-4 (NCT04631016) was a phase 2a, randomized, double-blind, placebo-controlled study evaluating the efficacy, safety and tolerability of tozorakimab in adults aged 40-80 years with moderate-to-severe COPD and chronic bronchitis, receiving standard-of-care dual or triple inhaled maintenance therapy. Participants were randomized 1:1 to receive tozorakimab 600 mg or placebo subcutaneously every 4 weeks. An exploratory substudy collected standardized high-resolution computed tomography (CT) scans at baseline and end of treatment. In this post hoc analysis, quantitative imaging metrics included the number, volume, and mass, as well as mucus-obstructed airway diameters and areas. Changes in these metrics were compared between treatment arms. Relative change from baseline to week 28 was calculated as: (week 28 mean - baseline mean)/(baseline mean). Results Of the 135 randomized participants, 38 provided evaluable quantitative CT mucus metrics at both baseline and week 28 (tozorakimab, n = 18; placebo, n = 20). The tozorakimab arm demonstrated numerically greater reductions than placebo across all quantitative mucus metrics (Table). In participants receiving tozorakimab, mucus mass, mucus volume and mucus-obstructed area showed changes from baseline of −0.045 g (−22.5% relative to baseline), −0.023 mL (-9.3%), and −4.070 mm2 (−15.7%), respectively, versus increases of + 0.050 g (+58.1%), +0.059 mL (+44.0%), and +0.915 mm2 (+6.1%) in the placebo group. Conclusions Tozorakimab consistently reduced airway mucus plugging and obstruction compared with placebo in adults with moderate-to-severe COPD. 1Singh D et al. Eur Respir J. 2025;66. This abstract is funded by: AstraZeneca