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

Abstract

Objective: Benralizumab, an anti-eosinophilic monoclonal antibody, in combination with high-dosage inhaled corticosteroids and long-acting β2-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/μL 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/μL, we evaluated the effect of applying an eosinophil cutoff of ≥150 cells/μL. Methods: Adult patients with uncontrolled asthma despite high-dosage ICS/LABA ± additional asthma controller(s) received subcutaneous benralizumab 30 mg 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/μL. 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/μL. 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/μL. 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/μL.