Abstract Rationale Benralizumab, a humanized afucosylated monoclonal antibody, targeting the interleukin-5 receptor α subunit on eosinophils and basophils, induces near-complete eosinophil depletion via natural killer cell recruitment and antibody-dependent cellular cytotoxicity. Phase 3 studies show that benralizumab significantly reduces exacerbations and improves lung function, symptoms, and health-related quality of life (HRQoL) in patients with severe eosinophilic asthma uncontrolled on medium- to high-dose ICS-LABA therapy. In patients with uncontrolled eosinophilic asthma, escalation from medium- to high-dose ICS often provides limited clinical benefit and may increase systemic side effects. Earlier treatment intervention with benralizumab (initiating at medium-dose ICS-LABA rather than stepping up to high-dose) may improve outcomes, reduce corticosteroid exposure, and address GINA concerns about high-dose ICS risks. BRISOTE is a Phase 3b, multicenter, double-blind, double-dummy, parallel-group, active-controlled study evaluating the efficacy and safety of benralizumab as add-on therapy in patients with eosinophilic asthma uncontrolled on medium-dose ICS-LABA versus escalation to high-dose ICS-LABA. Methods Patients aged 12─75 years with eosinophilic asthma (bEOS count ≥150 cells/μL) receiving at least medium-dose ICS-LABA for ≥12 months and ≥2 exacerbations in the past 12 months are being enrolled. Eligible patients are randomized 1:1 (stratified by bEOS 150─300 or ≥ 300 cells/μL) to medium-dose ICS-LABA plus benralizumab 30 mg subcutaneously (SC) Q4W for first 3 doses and Q8W thereafter, or high-dose ICS-LABA plus placebo (SC) on the same schedule for 48 Weeks (Figure). The primary endpoint is annual asthma exacerbation rate (AAER) over 48 weeks. The key secondary endpoint is change in HRQoL (St. George’s Respiratory Questionnaire SGRQ total score) from baseline to Week 48. Additional secondary endpoints include lung function (pre-BD FEV1), proportion of SGRQ responders (≥4-point improvement), ACQ-6 (change from baseline, proportion of responders ≥0.5-point improvement, proportion achieving asthma control ACQ-6 1.5), time to first exacerbation, AAER associated with emergency/hospital visits, clinical remission as defined by GINA 2024 (assessed using 3- and 4-component remission criteria), rescue medication use, productivity loss, and patient-reported severity (Patient Global Assessment of Severity). Exploratory endpoints include biomarkers (bEOS count, FeNO). Safety is assessed throughout the study. Results BRISOTE is recruiting, with the aim of randomizing 400 patients across 120 centers in 12 countries; study completion anticipated as November 2027. Conclusions BRISOTE is the first study to assess whether adding benralizumab to medium-dose ICS-LABA, rather than escalating to high-dose therapy, can reduce AAER and improve clinical outcomes in uncontrolled eosinophilic asthma, potentially redefining treatment strategies through earlier, more targeted intervention to improve asthma trajectory. This abstract is funded by: AstraZeneca
Bourdin et al. (Fri,) studied this question.
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