RT Journal Article
SR Electronic
T1 Markers of eosinophilic inflammation are associated with response to the DP2 antagonist GB001 in patients with mild atopic asthma
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP PA3713
DO 10.1183/13993003.congress-2019.PA3713
VO 54
IS suppl 63
A1 Hector Ortega
A1 Mary Fitzgerald
A1 Kartik Raghupathi
A1 Cindyann Tompinks
A1 Dave Singh
YR 2019
UL http://erj.ersjournals.com/content/54/suppl_63/PA3713.abstract
AB Background: GB001 is an oral antagonist of the prostaglandin D2 receptor 2 (DP2). DP2 is expressed on a variety of cells including Th2 and eosinophils. DP2 antagonists may inhibit recruitment of airway eosinophils, with consequent reduction in airway inflammation.Objectives: Characterize the effect of GB001 on markers of asthma control including FEV1 using baseline fractional exhaled nitric oxide (FeNO) and blood eosinophil (Eos) thresholds in post-hoc analysis.Methods: In this study 36 subjects with mild atopic asthma were randomized (2:1) to 30 mg of GB001 or placebo once daily for 28 days. Subjects received a total daily dose of FP ≤500 mcg or equivalent. FEV1 was measured at visits including baseline and on Days 2, 7, 14 and 28. Outcomes were analyzed by baseline FeNO (<35 & ≥35ppb) and Eos (<250 & ≥250/µL) subgroups. Safety was also assessed.Results: Mean age was 34.6 years, 92% male, and 92% Caucasian. Mean baseline FEV1 was 3,789 ml. In the overall population, GB001 had a numeric effect on FEV1 at Day 28 (difference in mean change for GB001 vs placebo of 102 ml, n=35). Greater effects on FEV1 were observed in the high baseline FeNO and Eos subgroups (differences of 207 ml, n=13 and 133 ml, n=11, respectively). These effects were observed as early as Day 2 (difference of 229 and 163 ml for high baseline FeNO and Eos subgroups, respectively) and were sustained through completion of treatment on Day 28. No safety signals were identified.Conclusions: These results suggest that GB001 may have a rapid and sustained effect on lung function in subjects with markers of eosinophilic inflammation. Prospective studies are needed to confirm these findings.FootnotesCite this article as: European Respiratory Journal 2019; 54: Suppl. 63, PA3713.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).