Pharmacokinetics, pharmacodynamics and safety of tezepelumab in children with asthma

<bold>Background:</bold> Tezepelumab is approved for the treatment of patients aged ≥12 years with severe asthma. <bold>Objective:</bold> TRAILHEAD (<ext-link>NCT04673630</ext-link>) evaluated the pharmacokinetics (PK), pharmacodynamics (PD) and safety of tezepelumab in children with asthma. <bold>Methods:</bold> TRAILHEAD was a phase 1, multicentre, open-label study in children (5–11 years) with mild, moderate or severe asthma requiring daily controller medication use. PK (primary outcome), PD (exploratory outcome) and safety were evaluated for up to 85 days after a single subcutaneous dose of tezepelumab 70 mg. <bold>Results:</bold> Of 23 children enrolled, 18 received treatment and completed the study (median age, 8 years; 61% male). Max geometric mean serum concentration of tezepelumab (24.6 μg/mL) was observed at a median time of 3.5 days post dose, followed by exponential decline with a mean terminal half-life of 25.7 days (<bold>Figure</bold>). Mean area under the concentration–time curve was 974 μg*day/mL. Changes in biomarkers from baseline (blood eosinophil count, serum total IgE and FeNO) reflected the expected PD effects of tezepelumab. Seven patients (39%) reported adverse events; all were mild or moderate intensity and considered by the investigator to be unrelated to treatment. <bold>Conclusion:</bold> The PK, PD and safety after a single 70 mg dose of tezepelumab in children were as expected from previous studies in other age groups, supporting further development of tezepelumab for children with asthma. <fig><object-id>erj;64/suppl_68/PA3562/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>