1. Results of a Phase 2b Trial With GB001, a Prostaglandin D2 Receptor 2 Antagonist, in Moderate to Severe Eosinophilic Asthma
- Author
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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, Institut Català de la Salut, [Moss MH] Division of Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA. [Lugogo NL] Division of Pulmonary & Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA. [Castro M] Division of Pulmonary, Critical Care & Sleep Medicine, University of Kansas, Kansas City, KS, USA. [Hanania NA] Section of Pulmonary & Critical Care Medicine, Baylor College of Medicine, Houston, TX, USA. [Ludwig-Sengpiel A] KLB Gesundheitsforschung Lübeck, Lübeck, Germany. [Saralaya D] NIHR PRC, Bradford Institute for Health Research, Bradford, England. [Ojanguren I] Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. CIBER de Enfermedades Respiratorias, Barcelona, Catalonia, Spain, and Vall d'Hebron Barcelona Hospital Campus
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Pulmonary and Respiratory Medicine ,Otros calificadores::/uso terapéutico [Otros calificadores] ,Asma - Tractament ,Respiratory Tract Diseases::Bronchial Diseases::Asthma [DISEASES] ,Critical Care and Intensive Care Medicine ,enfermedades respiratorias::enfermedades bronquiales::asma [ENFERMEDADES] ,Respiratory Tract Diseases::Lung Diseases::Pulmonary Eosinophilia [DISEASES] ,enfermedades respiratorias::enfermedades pulmonares::eosinofilia pulmonar [ENFERMEDADES] ,Other subheadings::/therapeutic use [Other subheadings] ,acciones y usos químicos::acciones farmacológicas::usos terapéuticos::fármacos del sistema respiratorio::antiasmáticos [COMPUESTOS QUÍMICOS Y DROGAS] ,Cardiology and Cardiovascular Medicine ,Eosinofília ,Medicaments antiasmàtics - Ús terapèutic ,Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Respiratory System Agents::Anti-Asthmatic Agents [CHEMICALS AND DRUGS] - Abstract
Asthma; Asthma worsening; Eosinophilic asthma Asma; Empitjorament de l'asma; Asma eosinofílica Asma; Empeoramiento del asma; Asma eosinofílica Background Prostaglandin 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 Question What is the effect of the DP2 antagonist GB001 on asthma worsening in patients 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 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. Results A 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. Interpretation Although 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. This work was supported by GB001, Inc., a wholly owned subsidiary of Gossamer Bio, Inc.
- Published
- 2022
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