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Background Many subjects with asthma exhibit sputum eosinophilia associated with exacerbations. Benralizumab targets eosinophils by binding interleukin-5 receptor alpha, inducing apoptosis via antibody-dependent cell-mediated cytotoxicity. Objectives To evaluate the safety of benralizumab in adults with eosinophilic asthma, and its effects on eosinophil counts in airway mucosal/submucosal biopsies, sputum, bone marrow, and peripheral blood. Methods In this multicenter, double-blind, placebo-controlled Phase I study, 13 subjects were randomized to single intravenous placebo or benralizumab 1 mg/kg (day 0) [Cohort 1], and 14 subjects were randomized to three monthly subcutaneous doses of placebo or benralizumab 100 or 200 mg (days 0, 28, and 56) [Cohort 2]. Cohorts 1 and 2 were consecutive. Results The incidence of adverse events was similar between groups. No serious adverse events related to benralizumab occurred. Cohort 1: intravenous benralizumab produced a median decrease from baseline of 61.9% in airway mucosal eosinophils (day 28; placebo: +19.6%; P = .28), 18.7% (day 21) in sputum and 100% (day 28) in blood. Eosinophils were not detectable in bone marrow of benralizumab-treated subjects (day 28, n=4). Cohort 2: subcutaneous benralizumab demonstrated a combined (100 + 200 mg) median reduction of 95.8% in airway eosinophils (day 84; placebo −46.7%; P = .06), 89.9% (day 28) in sputum and 100% (day 84) in blood. Conclusion Single-dose intravenous and multiple-dose subcutaneous benralizumab reduced eosinophil counts in airway mucosa/submucosa and sputum, and suppressed eosinophils in bone marrow and peripheral blood. The safety profile supports further development. Additional studies are needed to assess clinical benefit in asthma.

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