Depemokimab and the twice-yearly regimen: pharmacological implications and therapeutic positioning in severe eosinophilic respiratory diseases

Type 2 inflammatory diseases (T2D), notably severe eosinophilic asthma (SEA) and chronic rhinosinusitis with nasal polyps (CRSwNP), represent a significant global health burden due to their high morbidity, frequent exacerbations and reliance on systemic glucocorticoids (SGCs). Targeting Interleukin-5 (IL-5), a key driver of eosinophil production and survival, has emerged as a validated therapeutic strategy. Depemokimab is a novel, first-in-class anti-IL-5 monoclonal antibody (mAb) engineered with an extended half-life via the YTE amino acid modification of its Fc region, enabling an unprecedented twice-yearly dosing interval. This review synthesizes clinical data from the Phase III SWIFT (SEA) and ANCHOR (CRSwNP) programs, demonstrating depemokimab's sustained eosinophil depletion and significant reduction in asthma exacerbation rates (annualized asthma exacerbation rate reduction of approximately 54% versus placebo). While efficacy on secondary endpoints such as lung function (FEV1) and quality of life (QoL) was mixed, the efficacy in reducing nasal polyp size (Nasal Polyp Score and Nasal Congestion) in CRSwNP was clear. The core value proposition of depemokimab is the combination of established IL-5 inhibition efficacy with patient convenience due to its dosing. We discuss its pharmacodynamic profile, safety and pivotal role in shifting the treatment paradigm towards simplified chronic disease management, positioning depemokimab as a novel, patient-centric option in the competitive landscape of T2 biologic therapies.