LATE-BREAKING ABSTRACT: Effect of QAW039, an oral prostaglandin D2 receptor (DP2/CRTh2) antagonist, upon bronchial epithelial integrity in treatment-resistant asthma in a randomized, placebo controlled study

The bronchial epithelium contributes to airway remodeling in asthma. DP2/CRTh2 is expressed by intact bronchial epithelium, and its stimulation in vitro increases bronchial epithelial cell migration and metaplasia which are inhibited by CRTh2 antagonism. This study investigated the effects of QAW039, an oral CRTh2 antagonist on bronchial epithelial cell integrity in asthmatics with treatment-resistant sputum eosinophilia. Asthmatic subjects (GINA II-V) with a ≥2% baseline sputum eosinophil count were randomized to QAW039 225mg BID or placebo in addition to their standard-of-care treatment for 12 weeks following a 2-week placebo run-in. Bronchial biopsies were obtained at the end of run-in and after the treatment period. Subjects were stratified at randomization so that background oral corticosteroid (OCS) usage was balanced between QAW039 and placebo patients undergoing biopsy. The analysis presented is unadjusted for baseline variability and OCS treatment. Subjects treated with QAW039 demonstrated both an increase in the percentage of their epithelium that was intact (27.8±12.1%, p=0.030) and a significant decrease in the percentage of denuded epithelium (-26.6±8.9%,p=0.006) compared with their placebo-treated counterparts. Epithelial thickness increased by 15.4μm following QAW039 compared to placebo, but this did not reach statistical significance. While further studies are required to confirm these findings, these data suggest that QAW039 acts directly or indirectly on bronchial epithelial cells to promote epithelial cellular integrity and may reduce remodeling of the airway epithelium in asthma.