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.

Keywords:

• Benralizumab
• Asthma
• Exacerbations
• Eosinophils
• Interleukin-5 receptor
• Monoclonal antibody

Transparency

Declaration of funding

Funding for the SIROCCO and CALIMA studies was provided by AstraZeneca and Kyowa Hakko Kirin. Funding for the analyses was provided by AstraZeneca.

Declaration of financial and other interests

MG, IH, JGZ, PN, and XX are full-time employees of AstraZeneca/MedImmune LLC. Peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no other relevant financial relationships to disclose.

Author contributions

All authors conceived and designed the study, acquired the data, and accessed, analyzed, and interpreted the data. All authors participated in the development and critical review of the manuscript. All authors provided final approval for publication submission and are accountable for the accuracy and integrity of the work.

Acknowledgments

The authors would like to thank the investigators, health care providers, research staff, and patients who participated in the SIROCCO and CALIMA studies. Writing and editing support, including preparation of the draft manuscript under the direction and guidance of the authors, incorporating author feedback, and manuscript submission, was provided by Alan Saltzman, PhD, of Endpoint Medical Communications, Conshohocken, PA, USA, and Michael A. Nissen, ELS, of AstraZeneca (Gaithersburg, MD, USA). This support was funded by AstraZeneca.