Benralizumab is a humanised monoclonal antibody specific for the alpha subunit of the interleukin-5 receptor. It recruits natural killer cells to induce rapid depletion of eosinophils via antibody-dependent cell-mediated cytotoxicity, reducing the eosinophilic inflammation seen in about half of patients with severe asthma.
SIROCCO and CALIMA were two randomised, double-blind, placebo-controlled phase III trials that evaluated the safety and efficacy of benralizumab in 2510 patients with severe asthma inadequately controlled by medium to high doses of inhaled corticosteroids and long-acting β-agonists. Patients also had a history of two or more exacerbations in the previous year.
Participants were randomly assigned to receive 30mg benralizumab every 4 or 8 weeks (with the first three doses given every 4 weeks) or matching placebo, for a total of 48 weeks in the SIROCCO trial and 56 weeks in the CALIMA trial. The primary endpoint was the annual exacerbation rate in patients with baseline blood eosinophil counts of ≥300 cells per μL who were taking high-dose inhaled corticosteroids plus long-acting β-agonists.
In both trials, patients receiving benralizumab experienced significant reductions in exacerbations compared with placebo. Benralizumab reduced the annual exacerbation rate by 51% compared with placebo in SIROCCO (rate ratio 0.49 [95% CI 0.37—0.64], p<0.001) and by 28% in CALIMA (rate ratio 0.72 [95% CI 0.54—0.95], p=0.019).
Improvement in pre-bronchodilator FEV1 was also significantly greater in patients receiving benralizumab than in those receiving placebo, at 0.398L versus 0.239L in SIROCCO (p=0.001) and 0.330L versus 0.215L in CALIMA (p=0.01).
Reduced corticosteroid dose
ZONDA, a 28-week phase III trial, evaluated the effects of benralizumab 30mg every 4 or 8 weeks (with the first three doses given every 4 weeks) versus placebo on oral corticosteroid doses in adults with severe asthma. The primary endpoint was the percentage change in the oral corticosteroid dose from baseline to week 28 while asthma control was maintained.
Benralizumab significantly reduced the median oral corticosteroid dose from baseline by 75%, compared with a 25% reduction in the placebo group (p< 0.001 for both doses). Patients treated with benralizumab were more than four times as likely to have their oral corticosteroid dose reduced as those in the placebo group.
The most commonly reported adverse reactions during benralizumab treatment were headache, pharyngitis, fever, injection site reactions and hypersensitivity.
Treatment should be reviewed at least annually with regard to disease severity, level of exacerbation control and blood eosinophil counts.