Late-breaking abstract: Phase 2a randomized placebo-controlled trial of the oral prostaglandin D2 receptor (DP2/ CRTh2) antagonist QAW039 in eosinophilic asthma

Introduction There is a high unmet need for safe, effective and convenient therapies to control symptoms and reduce the impact of exacerbations in severe asthma. Eosinophilic inflammation is common in asthma and attenuation of sputum eosinophilia is strongly associated with reduced exacerbation frequency. Methods In this single-center, double-blind, randomized controlled study, asthmatics (GINA II-V), with a sputum eosinophil count ≥2% at baseline, were randomised to QAW039 225mg BID or placebo for 12 weeks after a 2-week placebo run-in. The primary endpoint was the reduction of sputum eosinophils. Secondary, exploratory and post-hoc outcomes included changes in Asthma Control Questionnaire score (ACQ7), Asthma Quality of Life score (AQLQ) and FEV1. Results 61 patients were randomized (30 to QAW039 and 31 to placebo); 90% were ≥GINA IV; and 25% were GINA V requiring up to 10 mg prednisolone daily. The primary endpoint was met, with QAW039 reducing sputum eosinophils 3.5-fold over placebo (95% CI: 1.7-7.0, p=0.001). The AQLQ improved in those treated with QAW039 compared to placebo (0.59 points; p=0.008) with non-significant improvements in ACQ7 in the group as a whole (0.40 points; p=0.084), which was greater in those with poor asthma control (ACQ≥1.5) at baseline (0.56 points; p=0.046). FEV1 improved in those receiving QAW039 versus placebo (0.074L; p=0.408; pre-bronchodilator (BD), 0.163L; p=0.022; post-BD). AEs were mild/moderate, balanced between both groups with no SAEs or deaths. Conclusion QAW039 is effective at attenuating eosinophilic airway inflammation, improves health status and lung function and has a favourable safety profile.