Late Breaking Abstract - Effect of timapiprant, a DP2 antagonist, on airway inflammation in severe eosinophilic asthma

Introduction: Prostaglandin D2 acting via the DP2 receptor plays an important role in the pathogenesis of the steroid-resistant airway inflammation in severe eosinophilic asthma. We tested this hypothesis in a randomised, placebo-controlled, double-blind, parallel group proof of concept study of the effects of the DP2 antagonist timapiprant (OC459) on sputum eosinophil counts in patients with severe eosinophilic asthma. Methods: Patients meeting the ERS/ATS criteria for severe asthma, prior evidence of eosinophilic airway inflammation and screening sputum eosinophil count >3% were randomised to timapiprant 50 mg or placebo once daily for 12 weeks. Induced sputum eosinophil counts, lung function parameters, symptoms and quality of life were assessed at baseline and at 4, 8 and 12 weeks. Results: 68 patients were screened and 40 randomised. The geometric mean induced sputum eosinophil count reduced from 11.0% at baseline to 2.5% at 12 weeks with timapiprant (n=20) and from 10.7% to 6.2% with placebo (n=19). A 2.3-fold reduction (p=0.151) in sputum eosinophil level at week 12 for timapiprant compared to placebo was observed. The difference between groups for change from baseline in pre-bronchodilator FEV1 at week 12 was 127 ml (95% CI: -77 to 330 ml; p=0.214). The safety profile of timapiprant was comparable to that of placebo. Conclusions: Treatment for 12 weeks with timapiprant in severe eosinophilic asthma patients was associated with an evident reduction of airway eosinophilic inflammation and an increase in FEV1 (although not statistically significant due to the limited sample size). Studies in larger population are needed to confirm these effects.