Mepolizumab (Nucala): A Comprehensive Monograph on a Foundational Anti-Interleukin-5 Therapy

Executive Summary

Mepolizumab is a humanized IgG1 kappa monoclonal antibody that represents a cornerstone in the targeted treatment of diseases driven by eosinophilic inflammation. Marketed by GlaxoSmithKline under the brand name Nucala, it functions as a high-affinity antagonist of Interleukin-5 (IL-5), the principal cytokine governing the maturation, activation, and survival of eosinophils. By selectively neutralizing IL-5, mepolizumab induces a profound and sustained reduction in circulating and tissue eosinophil levels, thereby mitigating the inflammatory cascade central to a spectrum of pathologies.

Initially approved for severe eosinophilic asthma, mepolizumab's clinical utility has expanded significantly, securing indications for eosinophilic granulomatosis with polyangiitis (EGPA), hypereosinophilic syndrome (HES), chronic rhinosinusitis with nasal polyps (CRSwNP), and, most recently, chronic obstructive pulmonary disease (COPD) with an eosinophilic phenotype. This expansion reflects a paradigm shift in medicine, moving from organ-centric disease definitions toward a biomarker-driven, mechanism-based approach to therapy. Across these indications, pivotal Phase 3 clinical trials have consistently demonstrated its efficacy in reducing disease exacerbations, decreasing reliance on oral corticosteroids (OCS), and improving clinical outcomes and quality of life.