Benralizumab

The pathology of severe asthma with eosinophilic phenotype is called the TH2-high phenotype. Patients with this phenotype are characterized by the expression of IL-5 and IL-13, airway hyperresponsiveness, responsiveness to inhaled corticosteroids, high serum IgE, and eosinophilia in the blood and airways. In the TH2-high phenotype, IL-5 plays a critical role as it is responsible for eosinophil differentiation, survival, activation, and migration to the lungs. It induces an eosinophil-mediated inflammatory response by binding to the IL-5 receptor (IL-5R) expressed in eosinophils, basophils, and some mast cells.

Benralizumab binds with high affinity to the domain I of the α-chain of IL-5R and blocks its signaling and the proliferation of IL-5-dependent signaling cascades. In addition, benralizumab is an afucosylated antibody in the CH2 region which gives it a high affinity for the FcγRIIIa on natural killer cells, macrophages, and neutrophils. This binding triggers a magnified apoptosis response in eosinophils via antibody-dependent cell-mediated cytotoxicity.