The association between blood eosinophil count and benralizumab efficacy for patients with severe, uncontrolled asthma: subanalyses of the Phase III SIROCCO and CALIMA studies

Objective: Benralizumab, an anti-eosinophilic monoclonal antibody, in combination with high-dosage inhaled corticosteroids and long-acting beta(2)-agonists (ICS/LABA), significantly reduced asthma exacerbations, improved lung function, and reduced symptoms for patients with severe, uncontrolled asthma with blood eosinophil counts 300 cells/L in the Phase III SIROCCO and CALIMA studies. To understand the efficacy and safety of benralizumab for patients with eosinophil-driven disease with blood eosinophil counts lower than 300 cells/mu L, we evaluated the effect of applying an eosinophil cutoff of >= 150 cells mu L. Methods: Adult patients with uncontrolled asthma despite high-dosage ICS/LABAadditional asthma controller(s) received subcutaneous benralizumab 30mg every 8 weeks (Q8W; first three doses every 4 weeks) or placebo for 48 (SIROCCO) or 56 (CALIMA) weeks. Efficacy measures including annual exacerbation rate, prebronchodilator FEV1, and total asthma symptom score were analyzed by baseline blood eosinophil counts >= 150 vs. <150 cells/mu L. Results: Benralizumab reduced asthma exacerbation rates by 42% in SIROCCO (rate ratio=0.58; 95% CI=0.46-0.74; p<0.001; n=325) and 36% in CALIMA (rate ratio=0.64; 95% CI=0.50-0.81; p<0.001; n=300) vs. placebo (n=306 for SIROCCO, n=315 for CALIMA) for patients with blood eosinophil counts >= 150 cells/mu L. Benralizumab increased prebronchodilator FEV1 (both studies, p <= 0.002) and improved total asthma symptom score in SIROCCO (p=0.009) at end of treatment vs. placebo for patients with blood eosinophil counts >= 150 cells/mu L. The overall adverse events frequency was similar between treatment groups and eosinophil count cohorts. Conclusion: These results support the efficacy and safety of benralizumab for patients with severe asthma and blood eosinophil counts >= 150 cells/mu L.