GB001 recombinant peptide (Zhejiang Yingkang Biopharmaceutical)

GB001, a DP₂ antagonist, may inhibit recruitment and activation of inflammatory cells in patients with asthma, consequently reducing airway inflammation.

Explore the efficacy and safety of GB001 in adults with mild to moderate asthma.

During a 4-week run-in period, adult patients with asthma (N = 158) received medium-dose inhaled corticosteroid and placebo and were then randomized to treatment once daily with GB001 5 mg, 20 mg, or placebo for 16 weeks or until asthma worsening/exacerbation. Patients were tapered to and then discontinued from low-dose inhaled corticosteroid at randomization and at 4 weeks postrandomization, respectively. Primary end point was change in morning peak expiratory flow (AM PEF); secondary end points included measures of asthma control. Safety was also assessed.

Baseline characteristics were similar among GB001 5 mg, 20 mg, and placebo groups. Changes in AM PEF in 5 mg and 20 mg groups versus placebo showed mean differences (95% CI) of 15.2 (3.1-27.4) L/min (P = .02) and 13.7 (1.5-25.8) L/min (P = .03), respectively. The changes in forced expiratory volume in 1 second of 55 mL and 32 mL, respectively, were not significant. There was a significant difference between GB001 20 mg and placebo for the secondary end points of time to asthma worsening/exacerbation (hazard ratio, 0.29), 5-item Asthma Control Questionnaire score (-0.60 point), the percentage of days without asthma symptoms (26%), and the percentage of rescue-free days (22%). Patients with baseline eosinophil levels greater than or equal to 300/μL had larger differences between GB001 20 mg and placebo for changes in AM PEF. Similar effects were seen in a post hoc analysis for time to worsening/exacerbations and 5-item Asthma Control Questionnaire score. The most common nonserious adverse event in the GB001 groups compared with the placebo group was nasopharyngitis.

GB001 was well tolerated and although not associated with clinically meaningful changes in lung function, improvements in asthma worsening/exacerbations and markers of asthma control were demonstrated. In addition, greater treatment effects were observed in patients with high baseline blood eosinophils. Further studies are needed to confirm these findings in the context of standard of care treatment.

GB001 is an oral antagonist of the prostaglandin D2 receptor that may inhibit recruitment and activation of airway eosinophils, reducing airway inflammation.

To assess GB001 safety, efficacy and pharmacokinetics from a Phase 2 study and explore the association between type 2 biomarkers (fractional exhaled nitric oxide and blood eosinophils) and asthma control markers following GB001 administration.

A randomized, placebo‐controlled, double‐blind study evaluating 36 patients with mild‐to‐moderate atopic asthma. Patients receiving fluticasone propionate ≤500 mcg/day or equivalent were randomized (2:1) to GB001 (30 mg) or placebo once daily for 28 days. Safety, pharmacokinetics, forced expiratory volume in 1 second, asthma control questionnaire and rescue medication use were assessed. Clinical outcomes were analysed post hoc by baseline fractional exhaled nitric oxide (<35 and ≥35 ppb) and blood eosinophil (<250 and ≥250 cells/µL) subgroups.

GB001 was well tolerated and rapidly absorbed with a 14.5‐hour terminal half‐life. Overall, GB001 demonstrated greater improvement relative to placebo in forced expiratory volume in 1 second at Day 28 (102 mL [95% CI: −110, 314]). Greater effects on forced expiratory volume in 1 second were observed in the high baseline fractional exhaled nitric oxide and blood eosinophil subgroups (207 mL [95% CI: −283, 698];133 mL [95% CI: −422, 687], respectively). These effects were observed as early as Day 2 (229 mL [95% CI: −170, 628]; 163 mL [95% CI: −223, 550] for the high baseline fractional exhaled nitric oxide and blood eosinophil subgroups, respectively) and were sustained through treatment completion.

GB001 was well tolerated, with the estimated half‐life supporting once‐daily (QD) dosing. GB001 may have a rapid and sustained effect on lung function, particularly in patients with type 2 phenotype. Further studies are needed to confirm these findings.