Longitudinal Modeling of Prebronchodilator FEV1 Response to Benralizumab for Patients with Severe Asthma

Introduction: Benralizumab is an anti-eosinophil monoclonal antibody. In the randomized, controlled Phase III SIROCCO ( Lancet . 2016;388:2115 – 27) and CALIMA ( Lancet . 2016;388:2128 – 41) trials, benralizumab 30 mg every 4 weeks (Q4W) and 30 mg every 8 weeks (Q8W; first three doses Q4W) significantly increased FEV 1 for patients with severe asthma receiving inhaled corticosteroids/high-dosage long-acting β 2 -agonists (ICS/LABA) with baseline blood eosinophils ≥300 cells/µL. We aimed to characterize change of prebronchodilator FEV 1 from baseline in placebo- and benralizumab-treated patients with severe asthma receiving high-dosage ICS/LABA by using population modeling. Methods: Pooled FEV 1 data (N = 2,244) were modeled sequentially to characterize effects of placebo and benralizumab. A likelihood ratio test evaluated effects of demographic and disease covariates on FEV 1 changes from baseline. Results: Height and age were identified as covariates for baseline FEV 1 and placebo effect. Benralizumab was associated with more rapid improvement of FEV 1 (estimated half-maximum time: 7.6 d) than placebo (estimated half-life: 18 d). Estimated typical placebo and benralizumab treatment effects were 184 mL and 96 mL, respectively. Benralizumab efficacy was greater in patients with greater baseline eosinophil counts, with a trend toward improved efficacy in patients with more exacerbations in the past year. Benralizumab dosages, steady-state exposure, anti-drug antibody (ADA), body weight, and concomitant medications did not significantly affect efficacy. Conclusions: The efficacy plateau for prebronchodilator FEV 1 was reached with benralizumab Q8W. This regimen minimized the impact of pharmacokinetic variability associated with ADA or heavy body weight on efficacy.