Results of a Phase 2b Trial With GB001, aProstaglandin D2Receptor 2 Antagonist, inModerate to Severe Eosinophilic Asthma

BACKGROUND: Prostaglandin D2receptor 2 (DP2) antagonists inhibit prostaglandin D2-induced effects, including recruitment and activation of cells driving asthma pathogenesis.However, challenges identifying target population and end points persist. RESEARCH QUESTION: What is the effect of the DP2antagonist GB001 on asthma worsening inpatients with moderate to severe eosinophilic asthma? STUDY DESIGN AND METHODS: In this phase IIb, randomized, double-blind, placebo-controlled, dose-ranging, parallel-group, multicenter study, GB001 or placebo was added to standard-of-care treatment in patients with moderate to severe asthma with a blood eosin-ophil count$250 cells/mL. Patients aged$18 years to < 75 years received one of four once-daily treatments (GB001 20 mg, 40 mg, or 60 mg or placebo). The primary end point was the proportion of patients who experienced asthma worsening by 24 weeks. Efficacy analyses were performed for the intention-to-treat population and safety analyses for patients who received at least one dose of study treatment. RESULTS:A total of 480 patients were treated. The ORs for asthma worsening for GB00120 mg, 40 mg, and 60 mg vs placebo were 0.674 (95% CI, 0.398-1.142), 0.677 (95% CI, 0.399-1.149), and 0.651 (95% CI, 0.385-1.100), respectively. Analysis according to baseline blood eosinophil levels and/or fractional exhaled nitric oxide did not show greater treatment effects with higher values. Elevated liver aminotransferase levels and adverse events leading to discontinuation were more frequent for GB001 60 mg than with placebo, GB001 20 mg, andGB001 40 mg. INTERPRETATION: Although GB001 did not significantly reduce the odds of asthma worsening, reductions favoring GB001 were observed. Treatment effects were consistent regard-less of high/low type 2 phenotype. The overall safety profile was acceptable, although GB00160 mg was associated with risk of liver injury.

Automated summary

This study aimed to investigate the effect of DP2 antagonist GB001 on asthma worsening in patients with moderate to severe eosinophilic asthma. The results showed that GB001 did not significantly reduce the odds of asthma worsening, but reductions favoring GB001 were observed. Treatment effects were consistent regardless of the type 2 phenotype. However, the use of high-dose GB001 may be associated with the risk of liver injury compared to placebo and low-dose GB001.