ArticlesBenralizumab, an anti-interleukin 5 receptor α monoclonal antibody, versus placebo for uncontrolled eosinophilic asthma: a phase 2b randomised dose-ranging study
Introduction
Persistent eosinophilic airway inflammation in asthma increases the risk of subsequent exacerbations.1, 2, 3 Monoclonal antibodies against interleukin 5 (eg, mepolizumab and reslizumab) reduce blood and sputum eosinophils in patients with asthma.4, 5 However, findings from an early study of mepolizumab in an unselected population of patients with asthma did not show clinical benefit,5 suggesting that anti-interleukin 5 therapy might be effective only in a targeted subgroup with an eosinophilic phenotype.6 In three randomised, placebo-controlled studies, mepolizumab significantly reduced exacerbations in participants with asthma and evidence of eosinophilic inflammation.7, 8, 9 Thus, selection of patients with asthma and an eosinophilic phenotype might be a more useful approach to investigate the efficacy of anti-interleukin 5 therapies. Benralizumab (MedImmune, Gaithersburg, MD, USA) is a humanised, afucosylated IgG-1κ monoclonal antibody that targets human interleukin 5 receptor α (IL5Rα)10 expressed on eosinophils and basophils.11, 12, 13 In vitro, benralizumab exhibits enhanced antibody-dependent cell-mediated cytotoxicity and induces apoptosis of target cells.10 Findings from two studies in participants with atopic or eosinophilic asthma have shown that benralizumab depletes eosinophils in blood,14, 15 airway mucosa, and sputum.15
In a phase 2b randomised dose-ranging study, we aimed to assess the efficacy and safety of repeated doses of subcutaneous benralizumab in adults with uncontrolled asthma to determine whether this biological product should undergo further phase 3 development.
Section snippets
Study design and participants
We did a phase 2b, randomised, double-blind, placebo-controlled, dose-ranging study at 33 sites in the USA, Canada, Bulgaria, Brazil, Peru, Mexico, Poland, Russia, Argentina, and Colombia.
We enrolled adults aged 18–75 years who had asthma and were treated with medium-dose to high-dose inhaled corticosteroids in combination with longacting β agonist therapy16 for at least 1 year; criteria for medium and high daily doses of inhaled corticosteroids are provided in the appendix (p 5). Eligible
Results
We screened 964 patients and randomly assigned 609 between Jan 3, 2011 and March 6, 2012. The trial started screening in December 2010 (first participant enrolled Jan 3, 2011) and the first participant was dosed on Jan 3, 2011. The study was completed in August 2013 after the last protocol-specified visit or assessment was done (including telephone contact) for the last participant in the study.
We randomly assigned 324 patients in the eosinophilic cohort (81 in the 2 mg benralizumab group, 81
Discussion
In this phase 2 dose-ranging study in participants with uncontrolled eosinophilic asthma, benralizumab 100 mg seemed to reduce exacerbations and improve lung function and quality of life in participants with a protocol-defined eosinophilic phenotype (and also in a prespecified subgroup analysis in participants with baseline blood eosinophils ≥300 cells per μL), with a predetermined α of 0·169. These potentially promising results are important in the early development of a drug but are not
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