Note: Since the publication of this article, the US Food and Drug Administration has approved mepolizumab for the treatment of severe eosinophilic asthma in children aged 6 to 11 years.
Long-term use of mepolizumab has a positive benefit-risk profile for children aged 6 to 11 years with severe asthma of an eosinophilic phenotype, according to a study published in the Journal of Allergy and Clinical Immunology.
The researchers made this determination using pharmacodynamics, safety, and efficacy data similar to findings reported for adults and adolescents. Mepolizumab has been approved for children with severe asthma of an eosinophilic phenotype who are 12 and older in the United States and 6 and older in the European Union, and following this study, the US Food and Drug Administration approved mepolizumab in children aged 6 to 11 years. This uncontrolled, open-label, repeat-dose extension to a phase 2 study was designed to evaluate the long-term efficacy, safety, and pharmacodynamics of mepolizumab in that population.
Severe asthma with an eosinophilic phenotype was defined by blood eosinophil counts ≥150 cells/μL at screening or ≥300 cells/μL in the previous year. Participants were given body weight-dependent doses of subcutaneous mepolizumab (40 mg for <40 kg or 100 mg for ≥40 kg) over a period of 12 weeks and were then given the option of continuing through part B of the study, for which they received another 13 rounds of 4-weekly doses. The primary end points included changes in vital measurements and laboratory parameters, frequency of positive antimepolizumab binding and neutralizing antibodies, and the incidence of adverse events. The secondary end point was the absolute blood eosinophil count (cells/µL), and the exploratory end points were annualized exacerbation rates and results from asthma control questionnaires and childhood asthma control test scores.
Over 52 weeks, 30 children were treated with mepolizumab. On-treatment adverse events were seen in 90% (n=27) of participants, and of these, 8 (27%) were considered to be related to mepolizumab. On-treatment serious adverse events were seen in 23% (n=7) participants, and all resolved without interrupting mepolizumab treatment. The only on-treatment serious adverse event reported in >1 child was asthma exacerbation (5 participants), and 1 participant each reported on-treatment serious adverse events of epistaxis, anaphylactic shock, and pneumonia. No antidrug antibody or neutralizing antibody responses were reported and, of the 2 participants with positive antidrug antibody responses in the first 12 weeks of the study, one did not proceed to part B and the other showed negative antidrug antibody responses throughout the remaining 13 weeks of the study.
Geometric mean blood eosinophil counts across all 30 patients decreased from 336 cells/µL at baseline to approximately 50 to 60 cells/µL preceding the fourth dose in part B. This reduction was sustained through the remaining weeks of the study. In children who were followed through the 80th week, blood eosinophil counts increased toward baseline values, but did not reach them. Before receiving mepolizumab, the mean scores for the 7-item and 5-item Asthma Control Questionnaires (ACQ-7 and ACQ-5) and the Childhood Asthma Control Test (C-ACT) were 1.79 (95% CI, 1.39-2.19), 1.87 (95% CI, 1.44-2.31), and 17.6 (95% CI, 15.8-19.4), respectively. The greatest improvements were seen at week 36, with mean scores of 0.79 (95% CI, 0.51-1.06), 0.79 (95% CI, 0.51-1.07), and 22.0 (95% CI, 20.7-23.3), respectively. Four weeks after the last dose at week 52, mean scores were 1.14 (95% CI, 0.79-1.49), 1.08 (95% CI, 0.64-1.52), and 20.5 (95% CI, 18.8-22.2), respectively.
The study was limited by its open-label design, although a placebo-controlled, double-blind, randomized trial would be difficult to perform in this population owing to the rarity of this asthma phenotype in the age group studied. Other study limitations included the small sample size and short follow-up period.
Study investigators concluded, “Although limited, the uncontrolled efficacy data in children 6–11 years of age appeared to be consistent with adult/adolescent efficacy data. The PK in Part A and the pharmacodynamic and safety profiles of mepolizumab in both parts of this study appear to be similar to those found in adults and adolescents, supporting the extrapolation of mepolizumab treatment efficacy data from adults and adolescents to children.”
Disclosure: This clinical trial was supported by GlaxoSmithKline. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Gupta A, Ikeda M, Geng B, et al. Long-term safety and pharmacodynamics of mepolizumab in children with severe asthma with an eosinophilic phenotype [published online August 16, 2019]. J Allergy Clin Immunol. doi:10.1016/j.jaci.2019.08.005