The new Back to Basics section: emerging concepts in basic and translational medicine.

Abstract

RATIONALE: Benralizumab is a humanized, afucosylated, anti-interleukin-5 receptor alpha (IL-5Ra) monoclonal antibody with enhanced antibody-dependent cell cytotoxicity that has been shown to reduce blood and airway eosinophils in early-phase clinical investigations. Basophils express IL-5Ra, are associated with asthma, and could be a potential target for benralizumab. The aim of this analysis was to determine whether benralizumab reduced the number of blood basophils in asthma. METHODS: MI-CP220 (NCT01238861) was a 52 week, double-blind, placebo controlled phase 2 study to evaluate the efficacy and safety of benralizumab (2, 20 and 100mg administered subcutaneously on weeks 1, 4, 8, 16, 24, 32, and 40) in 606 adults with uncontrolled asthma. In an exploratory analysis, blood basophils were assessed by flow cytometry using FCeR1 expression paired with CRTH2, CD123, and CCR3 at week -1 (baseline) and week 52. RESULTS: The mean baseline absolute basophil counts (N = 549 subjects) were 45.2 (placebo), 51.2 (2mg), 54.7 (20mg) and 48.7 (100mg) cells/mm 3 . Mean basophil counts (N = 451 subjects) decreased following 20 or 100mg benralizumab at week 52 relative to baseline- percent change from baseline was: placebo (+16.3%), 2mg (-4.17%, p = 0.152), 20mg (-46.97%, p = 0.039), and 100mg (-60.3%, p 1 . CONCLUSIONS: In adults with uncontrolled asthma, benralizumab reduced blood basophil counts. Benralizumab holds promise as a novel therapy for asthma by removing two key cell types, eosinophils and basophils, associated with asthma pathobiology and warrants continued investigation.