• Mark H Moss, Njira L Lugogo, Mario Castro, Nicola A Hanania, Andrea Ludwig-Sengpiel, Dinesh Saralaya, Rafal Dobek, Iñigo Ojanguren, Ivan Vyshnyvetskyy, Jean-Marie Bruey, Robin Osterhout, Cindy-Ann Tompkins, Karen Dittrich, Kartik Raghupathi, Hector Ortega, and LEDA Investigators.
• Division of Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI.
• Chest. 2022 Aug 1; 162 (2): 297-308.

BackgroundProstaglandin D2 receptor 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 QuestionWhat is the effect of the DP2 antagonist GB001 on asthma worsening in patients with moderate to severe eosinophilic asthma?Study Design And MethodsIn 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 eosinophil count ≥ 250 cells/μL. 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.ResultsA total of 480 patients were treated. The ORs for asthma worsening for GB001 20 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, and GB001 40 mg.InterpretationAlthough GB001 did not significantly reduce the odds of asthma worsening, reductions favoring GB001 were observed. Treatment effects were consistent regardless of high/low type 2 phenotype. The overall safety profile was acceptable, although GB001 60 mg was associated with risk of liver injury.Clinical Trial RegistrationClinicalTrials.gov; No.: NCT03683576; URL: www.Clinicaltrialsgov.Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

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