Benralizumab in children with severe eosinophilic asthma: Pharmacokinetics and long-term safety (TATE study)

H. James Wedner, Takao Fujisawa, Theresa W. Guilbert, Masanori Ikeda, Vinay Mehta, Jonathan S. Tam, Pradeep B. Lukka, Sara Asimus, Tomasz Durżyński, James Johnston, Wendy I. White, Mihir Shah, Viktoria Werkström, Maria L. Jison

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Abstract

Background: Benralizumab is an anti-interleukin-5 receptor α monoclonal antibody approved as an add-on maintenance treatment for patients with uncontrolled severe asthma. Prior Phase 3 studies have evaluated benralizumab in patients aged ≥12 years with severe uncontrolled asthma. The TATE study evaluated the pharmacokinetics (PK), pharmacodynamics (PD), and safety of benralizumab treatment in children. Methods: TATE was an open-label, Phase 3 study of benralizumab in children aged 6–11 years from the United States and Japan (plus participants aged 12–14 years from Japan) with severe eosinophilic asthma. Participants received benralizumab 10/30 mg according to weight (<35/≥35 kg). Primary endpoints included maximum serum concentration (Cmax), clearance, half-life (t1/2), and blood eosinophil count. Clearance and t1/2 were derived from a population PK (popPK) analysis. Safety and tolerability were also assessed. Results: Twenty-eight children aged 6–11 years were included, with an additional two participants from Japan aged 12–14 years also included in the popPK analysis. Mean Cmax was 1901.2 and 3118.7 ng/mL in the 10 mg/<35 kg and 30 mg/≥35 kg groups, respectively. Clearance was 0.257, and mean t1/2 was 14.5 days. Near-complete depletion of blood eosinophils was shown across dose/weight groups. Exploratory efficacy analyses found numerical improvements in mean FEV1, mean ACQ-IA, patient/clinician global impression of change, and exacerbation rates. Adverse events occurred in 22/28 (78.6%) of participants; none led to discontinuation/death. Conclusion: PK, PD, and safety data support long-term benralizumab in children with severe eosinophilic asthma, and were similar to findings in adolescents and adults. Trial Registration: ClinicalTrials.gov-ID: NCT04305405.

Original languageEnglish
Article numbere14092
JournalPediatric Allergy and Immunology
Volume35
Issue number3
DOIs
StatePublished - Mar 2024

Keywords

  • asthma
  • eosinophils
  • inflammation
  • interleukin-5
  • pharmacokinetics
  • safety
  • symptom exacerbation

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