Long-term safety and pharmacodynamics of mepolizumab in children with severe asthma with an eosinophilic phenotype

Abstract

Mepolizumab is approved for patients with severe asthma with an eosinophilic phenotype aged 12 or more (United States) or 6 or more (European Union) years, but its long-term use in children aged 6 to 11years has not yet been assessed. We sought to assess the long-term safety, efficacy, and pharmacodynamics of mepolizumab in children aged 6 to 11years with severe asthma with an eosinophilic phenotype. In this open-label, uncontrolled, repeat-dose extension study (NCT02377427), children aged 6 to 11years with severe asthma with an eosinophilic phenotype (blood eosinophil counts ≥150cells/μL at screening or ≥300cells/μL in the previous year) received a body weight-dependent dose of subcutaneous mepolizumab of 40mg (<40kg) or 100mg (≥40kg) over 52weeks. End points included the incidence of adverse events (AEs) and immunogenicity (primary), absolute blood eosinophil counts (cells per microliter; secondary), and annualized exacerbation rates and asthma control questionnaire/childhood asthma control test scores (exploratory). Over 52weeks, 30 children received mepolizumab; 27 (90%) and 7 (23%) experienced on-treatment AEs and serious AEs, respectively. No serious AEs were treatment related. There were no fatal AEs. No specific patterns of AEs were evident, and no anti-drug antibody or neutralizing antibody responses were reported. Compared with baseline values, mepolizumab treatment reduced blood eosinophil counts and asthma exacerbations and improved asthma control across all treatment groups. Long-term safety, pharmacodynamic, and efficacy data from this study support a positive benefit-risk profile for mepolizumab in children with severe asthma with an eosinophilic phenotype and were similar to data in studies inadults and adolescents.