benralizumab + mepolizumab

Benralizumab + mepolizumab is a combination of two monoclonal antibody drugs, each targeting the interleukin-5 (IL-5) pathway but via different mechanisms. Both are used as add-on therapies for severe eosinophilic asthma and have also been studied in eosinophilic granulomatosis with polyangiitis (EGPA). Benralizumab is a humanized IgG1k monoclonal antibody that binds to the alpha subunit of the IL-5 receptor on eosinophils and basophils, blocking IL-5 signaling and inducing antibody-dependent cell-mediated cytotoxicity (ADCC), leading to rapid depletion of eosinophils. Mepolizumab is a humanized IgG1 kappa monoclonal antibody that binds directly to IL-5, preventing it from interacting with its receptor on the surface of eosinophils, thereby reducing their survival and activity. The combination would theoretically provide dual blockade at both ligand (IL-5) and receptor levels; however, there is limited clinical evidence supporting combined use in practice as most studies compare these agents head-to-head rather than together[1][2][4].