Markers of eosinophilic inflammation are associated with response to the DP2 antagonist GB001 in patients with mild atopic asthma

Abstract

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.