Depemokimab: a new long-acting anti-IL5 treatment for severe asthma and chronic rhinosinusitis with nasal polyps

Purpose of review Clinical data are reviewed pertaining to depemokimab, the first extended life anti-IL5 mAb, for treating severe eosinophilic asthma. This molecule was engineered through amino acid modification (YTE mutation) of the Fc region. This modification increases Fc receptor affinity and enables antibody recycling, thereby greatly extending serum half-life and will allow a dosing duration of 26 weeks. Recent findings Phase 1 and 3 clinical studies have demonstrated that depemokimab maintains drug concentrations and reduces peripheral eosinophils over a single 26-week dosing interval. A 52-week double-blinded, placebo-controlled (DBPC) Phase 3 study of patients with severe eosinophilic asthma demonstrated that depemokimab reduced annualized asthma exacerbations by 54% compared with placebo, the primary efficacy outcome. No significant differences between active and placebo arms were detected for secondary endpoints (e.g., symptoms, FEV1 and quality of life). Results of a noninferiority study comparing depemokimab, benralizumab and mepolizumab are pending. In a DBPC trial of chronic rhinosinusitis with nasal polyps (CRSwNP), depemokimab was also effective in reducing nasal polyp endoscopy scores and nasal obstruction. Summary Depemokimab could offer patients with severe persistent asthma a more convenient add-on treatment option than existing shorter acting biologics and thereby improve overall adherence.