Biological functions and clinical efficacy of IL-5/IL-5Rα-targeted therapies across eosinophilia-associated diseases

Interleukin-5 (IL-5) is a central regulator of eosinophil differentiation, maturation, survival, activation, and mobilization, and it contributes to eosinophil recruitment to inflamed tissues. These biological functions have made the IL-5/IL-5 receptor alpha (IL-5Rα) pathway a key therapeutic target in eosinophil-associated diseases.

Four biologics currently target this pathway in clinical practice: mepolizumab, reslizumab, and depemokimab bind soluble IL-5, whereas benralizumab targets IL-5Rα and induces antibody-dependent cellular cytotoxicity. Clinical development has been successful in severe eosinophilic asthma (SEA), where targeting the IL-5/IL-5Rα pathway reduces exacerbation risk and can lower the need for long-term oral corticosteroid use.

The therapeutic scope has since expanded to chronic rhinosinusitis with nasal polyps (CRSwNP), eosinophilic granulomatosis with polyangiitis (EGPA), and idiopathic hypereosinophilic syndrome (iHES). Mepolizumab has shown efficacy across these eosinophilia-associated diseases, reducing asthma exacerbations, nasal polyp burden, EGPA relapse activity, HES flares, and eosinophils in peripheral blood.

Mepolizumab is approved by both FDA and EMA for SEA, CRSwNP, EGPA, and HES. Reslizumab improves exacerbation rates and lung function in SEA and is approved by FDA and EMA for this indication.