*3.10. DP2 Antagonists*

Evidence suggests that preventing the activation of the prostaglandin D2 receptor (DP2) pathway improves symptoms of asthma and pulmonary function, and impairs any change in eosinophil shape, while indirectly inducing a reduction in the number of exacerbations in severe asthmatic patients [83].

The LEDA Phase IIb RCT [36,37] demonstrated that the DP2 antagonist GB001 given orally at 20 mg, 40 mg, and 60 mg, in addition to the standard of care therapy, induced an effect on FEV1, PEF, and ACQ5 that was comparable to PCB in moderate to severe asthmatic patients with a BEC of ≥250 cells/μL. Across all doses, GB001 numerically reduced the odds of asthma worsening vs. PCB, with no dose–response effect; subgroup analysis based on baseline BEC and/or FENO did not indicate greater treatment efficacy with higher values. GB001 20 mg and 60 mg induced a significant (*p* < 0.05) delay in the time to first asthma worsening compared to PCB (HR 0.72 (95% CI 0.52–0.995) and HR 0.70 (95% CI, 0.51–0.97), respectively), while GB001 40 mg induced a numerical delay vs. PCB. Treatment with GB001 20 mg, 40 mg, and 60 mg significantly (*p* < 0.05) reduced the annualised rate of asthma worsening vs. PCB (RR 0.56 (95% CI 0.39–0.80), RR 0.65 (95% CI 0.46–0.93), and RR 0.68 (95% CI 0.48–0.96), respectively) [36,37].

There was a numerical reduction in the annualised rate of severe asthma exacerbations compared to PCB [36,37].
