TY - JOUR T1 - ARRY-502, a potent, selective, oral CRTh2 antagonist reduces Th2 mediators in patients with mild to moderate Th2-driven asthma JF - European Respiratory Journal JO - Eur Respir J VL - 44 IS - Suppl 58 SP - 4836 AU - Sally Wenzel AU - David Chantry AU - Christine Eberhardt AU - Robert Hopkins AU - Michael Saunders AU - Lisa Anderson AU - Roger Aitchinson AU - Stacie Bell AU - Kenji Izuhara AU - Junya Ono AU - Laurence Burgess Y1 - 2014/09/01 UR - http://erj.ersjournals.com/content/44/Suppl_58/4836.abstract N2 - Asthma and other allergic diseases are associated with mast cell activation and prostaglandin D2 (PGD2) generation. PGD2 exerts pro-inflammatory activity via chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTh2). The safety and efficacy of CRTh2 antagonist ARRY-502 was studied in mild atopic asthmatic adults in a double-blind, placebo-controlled 4 week phase 2a study. Enrolled patients were free of inhaled corticosteroids with an FEV1% predicted of 60-85%. Potential participants were screened and randomized to receive 200 mg BID ARRY-502 (n = 93) or matching placebo (n = 91). In patients with elevated Th2 associated biomarkers at baseline there were significant improvements in spirometric outcomes, measures of asthma control and quality of life. In addition, there was a significant reduction in markers of Th2 driven inflammation in these patients. For example, patients that exhibited FENO levels at or above the median value of 48 ppb at baseline experienced a reduction in FENO of 27.0 ppb (p<0.0001) at week 4 in the ARRY-502 group versus placebo group. This indicates significant anti-inflammatory activity of ARRY-502 via CRTh2 antagonism. Other markers of Th2 inflammation were also reduced including serum periostin, serum squamous cell carcinoma antigens 1 & 2, serum TARC (CCL17), and blood CRTh2+ eosinophils. These results imply that ARRY-502 controls multiple Th2 inflammatory pathways and could be beneficial in patients that suffer from other Th2-driven allergic diseases like atopic dermatitis and allergic rhinitis. ER -