A Phase 2a Study of Benralizumab for Patients with Eosinophilic Asthma in South Korea and Japan

Abstract

Background: Airway eosinophils are considered to play an important role in the pathogenesis of asthma. Interleukin-5 is believed to be a key cytokine for the development, proliferation and activation of eosinophils. Benralizumab is an anti-interleukin-5 receptor α monoclonal antibody that depletes blood and airway eosinophils. We conducted a phase 2a study in South Korea and Japan to evaluate the effect of benralizumab in an East Asian population. The primary objective was to evaluate the effect of benralizumab in adults with uncontrolled eosinophilic asthma with 2-6 incidences of exacerbations in the past year using a medium/high dose of inhaled corticosteroids and long-acting β₂-agonists. Methods: This was a multicenter, randomized, double-blind, placebo-controlled study. The subjects (n = 106) were randomized into four groups: placebo (n = 27) or benralizumab 2 mg (n = 27), 20 mg (n = 26) and 100 mg (n = 26). Benralizumab or placebo were administered subcutaneously on weeks 0 (day 1), 4, 8, 16, 24, 32 and 40. The primary endpoint was the asthma exacerbation rate at week 52. Results: The asthma exacerbation rate was reduced by 33, 45 or 36% versus the placebo group when treated with 2, 20 or 100 mg of benralizumab, respectively. The percent mean change in forced expiratory volume at 1 s increased with each of the three doses in subjects treated with benralizumab. Conclusions: Benralizumab reduced asthma exacerbation and improved lung function and asthma control in adults with uncontrolled eosinophilic asthma.

Recent Advances in Clinical Allergy and Immunology

“…Targeting eosinophils by blocking IL-5 or its receptor is a novel approach for asthma treatment. Benralizumab, an anti-IL-5 receptor antibody, has been demonstrated to significantly reduce the number of asthma exacerbations and to increase the forced expiratory volume in 1s, FEV 1 , in an Asian population [9]. Recent observations demonstrate a role for the IL-25/IL-25 receptor axis in asthma, thus also identifying this as a novel therapeutic target [10].…”

Meta-analysis of Low-versus High-dose Benralizumab in Adults with Uncontrolled Eosinophilic Asthma

“…The degree of heterogeneity measured by the I 2 statistic was not signi cant, so an analysis using a fixed-effect model was conducted. Because only one trial investigated the effects of benralizumab 20 and 100 mg on injection site reactions and pyrexia or in uenza-like illness 10 , metaanalyses for these outcomes could not be performed. Only non-inferiority tests and comparisons between low-and high-dose groups were conducted.…”

“…Several randomized controlled trials RCTs have examined the effects of benralizumab, an anti-IL-5 receptor monoclonal antibody, on uncontrolled eosinophilic asthma [10][11][12] , with the results showing that a relatively high dose of benralizumab 100 mg signi cantly reduces exacerbation rates and improves asthma symptoms and quality of life 10 12 . A relatively low dose 20 mg of benralizumab also reduces exacerbation rates in patients with uncontrolled eosinophilic asthma and has a lower incidence of adverse effects 10 , but the non-inferiority of low-versus high-dose benralizumab remains untested.…”

“…A relatively low dose 20 mg of benralizumab also reduces exacerbation rates in patients with uncontrolled eosinophilic asthma and has a lower incidence of adverse effects 10 , but the non-inferiority of low-versus high-dose benralizumab remains untested. Therefore, the aim of the present study was to perform a non-inferiority trial to compare the ef cacy and safety of low-versus high-dose benralizumab in patients with uncontrolled eosinophilic asthma through a meta-analysis of RCTs.…”

A Comparison of Adverse Effect Profiles of Two Anti-IL-5 Therapies in Adults with Uncontrolled Asthma

“…Several randomized controlled trials RCTs have examined the effects of benralizumab BRZ , an anti-IL-5 receptor monoclonal antibody, on uncontrolled asthma [7][8][9] . The results showed that a relatively low dose of benralizumab 30 mg / body significantly reduced exacerbation rates and improved both asthma symptoms and the quality of life in patients with uncontrolled asthma 10 11 .…”