Efficacy and Safety of Benralizumab for Patients With Severe Asthma Uncontrolled With High-Dosage Inhaled Corticosteroids and Long-acting β2-agonists (SIROCCO): A Randomised, Multicentre, Placebo-Controlled Phase 3 Trial
PURPOSE OF THE STUDY.
To assess the safety and efficacy of benralizumab, a monoclonal antibody against the interleukin-5 (IL-5) receptor α that depletes eosinophils for patients with severe, uncontrolled asthma with eosinophilia.
Between 2013–2015, 2681 patients were enrolled in this randomized, double-blind, parallel-group, placebo-controlled phase 3 study in 17 countries. Inclusion criteria were being 12–75 years old, having a physician-based diagnosis of asthma for at least 1 year, and having at least 2 exacerbations while on high-dose inhaled corticosteroids and long-acting β2-agonists in the previous year.
Patients were randomly assigned (1:1:1) to subcutaneous benralizumab 30 mg either every 4 weeks (Q4W) or every 8 weeks (Q8W) or a placebo Q4W for 48 weeks as add-on therapy. Patients were stratified 2:1 based on blood eosinophil counts of greater or less than 300 cells per μL. The primary end point was the annual exacerbation rate ratio.
Compared with the placebo, Q4W and Q8W benralizumab reduced the annual asthma exacerbation rate by up to 51% over 48 weeks and significantly improved prebronchodilator FEV1 at week 48. Compared with the placebo, Q8W benralizumab significantly improved asthma symptoms. The most common adverse events were worsening asthma and nasopharyngitis.
These results confirm the efficacy and safety of benralizumab for patients with severe asthma and elevated eosinophils, which are uncontrolled by high-dosage ICS plus LABA.
This is the first phase 3 study of benralizumab, which acts against interleukin-5 (IL-5) receptor α and induces direct, rapid, and near-complete depletion of eosinophils. Because it acts differently than mepolizumab and reslizumab and is effective with Q8W dosing, benralizumab may be an additional option in this asthma population.
- Copyright © 2017 by the American Academy of Pediatrics