Reductions in eosinophil biomarkers by benralizumab in patients with asthma.

Abstract Background Eosinophilic inflammation is frequently associated with increased asthma severity. Benralizumab is a humanized, afucosylated, anti–interleukin-5Rα monoclonal antibody that selectively depletes eosinophils and basophils through enhanced antibody-dependent cell-mediated cytotoxicity. Objective To study effects of benralizumab on eosinophil counts and activity following administration to asthma patients. Methods Sera were collected from asthma patients enrolled in two clinical studies. Placebo or benralizumab was subcutaneously administered to patients in Phase I (100 or 200 mg, multiple doses; N  = 14; NCT00659659) and Phase IIa (25, 100, or 200 mg every 4 weeks; N  = 24; NCT00783289) studies. Sera were also collected from healthy volunteers ( N  = 20) for comparison. Blood eosinophils, IL-5, eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), eotaxin/chemokine (C–C motif) 11 (CCL11), eotaxin-2/CCL24, tumor necrosis factor (TNF), and interferon-γ (IFN-γ) were measured at baseline and post-treatment. Results Increased EDN concentrations were observed in sera of patients from both studies relative to healthy volunteers ( p s  = 0.5; p p p Conclusions In two independent studies, serum IL-5, EDN, and ECP were modulated following benralizumab. Eosinophil depletion after benralizumab also resulted in significant reductions in EDN and ECP concentrations, suggesting that cytotoxic granule proteins were not released after eosinophil reduction.