Relationship Between Benralizumab Exposure and Efficacy for Patients With Severe Eosinophilic Asthma

Abstract

We evaluated the relationship between benralizumab (30 mg every 4 and 8 weeks (Q4W, Q8W)) pharmacokinetic ( PK) exposure and end points of asthma exacerbation rates ( AERs) and change from baseline in prebronchodilator forced expiratory volume in 1 second ( FEV ₁) for patients with severe, uncontrolled eosinophilic asthma in the SIROCCO/ CALIMA phase III trials. In empirical assessment, AER ratios in SIROCCO were similar across PK quartiles. However, the lowest PK quartile in CALIMA had reduced efficacy; low CALIMA placebo AER possibly confounded this result. In population modeling, estimated benralizumab 90% effective concentration for AER reduction was 927 ng/ mL, below the Q8W dosage steady‐state average PK concentration (1,066 ng/ mL). Benralizumab treatment resulted in more rapid FEV ₁ improvement vs. placebo (estimated half‐maximum time: 7.6 vs. 18 days); this response was greater for patients with greater baseline eosinophil counts. These results confirmed 30 mg Q8W is the optimal benralizumab dosage for patients with severe eosinophilic asthma.