Benralizumab (Fasenra): A Comprehensive Monograph on its Pharmacology, Clinical Efficacy, and Therapeutic Role in Eosinophil-Driven Disease

1.0 Executive Summary & Introduction

Benralizumab, marketed under the brand name Fasenra, represents a significant advancement in the targeted biological therapy of diseases driven by eosinophilic inflammation.[1] It is a humanized, afucosylated IgG1 kappa (IgG1k) monoclonal antibody engineered to act as a potent interleukin-5 receptor alpha (IL-5Rα)-directed cytolytic agent.[2] This mechanism distinguishes it from other biologics in its class, which typically target the IL-5 ligand rather than its receptor, affording Benralizumab a unique pharmacological profile characterized by rapid and profound eosinophil depletion.[4]

Developed by MedImmune and currently marketed by AstraZeneca, Benralizumab has secured regulatory approval in numerous jurisdictions, including the United States and the European Union, for two primary indications: as an add-on maintenance treatment for severe eosinophilic asthma (SEA) in adults and children, and for the treatment of adult patients with eosinophilic granulomatosis with polyangiitis (EGPA).[6] Its clinical development has been underpinned by robust Phase III trials demonstrating significant reductions in exacerbation rates, improvements in lung function, and a substantial oral corticosteroid-sparing effect.[8]

The therapeutic action of Benralizumab is multifaceted, involving both the blockade of IL-5-mediated pro-survival signaling and, more critically, the induction of eosinophil apoptosis through enhanced antibody-dependent cell-mediated cytotoxicity (ADCC).[2] This dual-action mechanism is augmented by novel, recently elucidated pathways including antibody-dependent cellular phagocytosis (ADCP) and macrophage-amplified apoptosis, further contributing to its potent anti-eosinophilic activity.[11]