Investigational DP2 antagonist strikes out in eosinophilic asthma

The prostaglandin D₂ receptor 2 (DP₂) antagonist GB001 does not appear to significantly lower the risk of disease worsening in patients with moderate-to-severe eosinophilic asthma, according to data from a phase IIb trial.

A total of 480 adult patients with blood eosinophil count of ≥250 cells/μL were randomized to receive GB001 20 mg (n=120), 40 mg (n=118), 60 mg (n=122), or placebo (n=120) once daily in addition to standard-of-care treatment. 

Mean blood eosinophil count at baseline was 464 cells/µL. Of the patients, 56 (11.7 percent) discontinued study treatment, with discontinuation rates higher among patients who received higher GB001 doses (60 mg: 18.9 percent and 40 mg: 15.3 percent) than among those given placebo (5.8 percent) or GB001 20 mg (6.7 percent).

Compared with placebo, GB001 had no significant effect on the primary endpoint of asthma worsening by 24 weeks. In multivariable logistic regression models, the odds ratios for asthma worsening were 0.674 (95 percent confidence interval [CI], 0.398–1.142) with GB001 20 mg, 0.677 (95 percent CI, 0.399–1.149) with the 40-mg dose, and 0.651 (95 percent CI, 0.385–1.100) with the 60-mg dose.

Treatment effects were consistent, with analysis by baseline blood eosinophils and/or fractional exhaled nitric oxide showing no greater treatment effects with higher values.

While the overall safety profile of GB001 was acceptable, elevated liver aminotransferases and adverse events leading to discontinuation occurred more frequently with the highest GB001 dose vs placebo and the 20- and 40-mg doses.