Can Benralizumab Help Improve Severe, Uncontrolled Asthma?
A 4-week or 8-week benralizumab treatment can lower exacerbation rates and improve breathing in patients with asthma and high eosinophil counts, according to 2 recent studies.
The SIRROCCO1 and CALIMA2 studies both assessed the safety and efficacy of benralizumab, a monoclonal antibody against interleukin-5 receptor α that depletes eosinophils by antibody-dependent cell-mediated cytotoxicity, in patients with severe uncontrolled asthma and eosinophilia.
The SIROCCO study was a phase 3 trial conducted at 374 sites in 17 countries. The investigators recruited patients aged 12 to 75 years who were diagnosed with asthma for at least 1 year and had at least 2 exacerbations in the previous year while on high-dose inhaled corticosteroids (ICS) and long-acting β2-agonists (LABA).
In all, 1205 patients were included in the analysis. Of those, 407 patients were randomly assigned to receive placebo every 4 weeks for 48 weeks as an add-on to their standard treatment, 400 patients to benralizumab 30 mg every 4 weeks, and 398 patients to benralizumab 30 mg every 8 weeks (first 3 doses every 4 weeks).
At baseline, 809 patients had elevated eosinophil counts.
Results showed that a 4- or 8-week treatment of benralizumab lowered the annual asthma exacerbation rate over 48 weeks and improved prebronchodilator forced expiratory volume in 1 second (FEV1) compared with placebo.
In addition, asthma symptoms were improved with the 8-week dose but not with the 4-week dose vs placebo.
“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, and provide support for benralizumab to be an additional option to treat this disease in this patient population,” the investigators concluded.1
The CALIMA study was a similarly conducted phase 3 trial undertaken at 303 sites in 11 countries. The investigators recruited patients aged 12 to 75 years who had severe asthma uncontrolled by medium- to high-dosage ICS plus LABA and a history of 2 or more exacerbations in the previous year.
Of the 1306 patients included in the study, 425 patients were randomly assigned to receive benralizumab 30 mg every 4 weeks, 441 patients to benralizumab 30 mg every 8 weeks (first 3 doses 4 weeks apart), and 440 patients to placebo (all subcutaneous injection).
The investigators found that both benralizumab treatments significantly reduced annual exacerbation rates and improved prebronchodilator FEV1 compared with placebo. The 8-week treatment also improved patients’ total asthma symptom score.
“Benralizumab significantly reduced annual exacerbation rates and was generally well tolerated for patients with severe, uncontrolled asthma with blood eosinophils 300 cells per μL or greater,” the investigators concluded. “Our data further refine the patient population likely to receive the greatest benefit from benralizumab treatment.”2
- Bleecker ER, FitzGerald JM, Chanez P; SIROCCO study investigators. 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 [published online September 4, 2016]. Lancet. doi:http://dx.doi.org/10.1016/S0140-6736(16)31324-1.
- FitzGerald JM, Bleecker ER, Nair P, et al; CALIMA study investigators. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial [published online September 4, 2016]. Lancet. doi:http://dx.doi.org/10.1016/S0140-6736(16)31322-8.