Depemokimab

Depemokimab is an interleukin-5 (IL-5) antagonist monoclonal antibody (humanized Immunoglobulin G1 [IgG1] kappa) engineered with high potency and enhanced binding affinity for IL-5. It binds to IL-5, inhibiting its bioactivity by blocking its interaction with the alpha chain of the IL-5 receptor complex expressed on the eosinophil cell surface. IL-5 is the major cytokine responsible for the growth, differentiation, recruitment, activation, and survival of eosinophils. By inhibiting IL-5 signalling, depemokimab reduces the production and survival of eosinophils; however, the mechanism of depemokimab action in asthma has not been definitively established. Uniquely, depemokimab contains a triple amino acid substitution (YTE) in the fragment crystallizable (Fc) region which increases binding to the neonatal Fc receptor (FcRn) at acidic pH, thereby preventing intracellular degradation and extending the elimination half-life to enable twice-yearly dosing.