RT Journal Article
SR Electronic
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
FD European Respiratory Society
SP 4836
VO 44
IS Suppl 58
A1 Sally Wenzel
A1 David Chantry
A1 Christine Eberhardt
A1 Robert Hopkins
A1 Michael Saunders
A1 Lisa Anderson
A1 Roger Aitchinson
A1 Stacie Bell
A1 Kenji Izuhara
A1 Junya Ono
A1 Laurence Burgess
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/4836.abstract
AB 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.