Pharmacokinetics and safety of tezepelumab in children with mild, moderate or severe asthma and adolescents with mild-to-moderate asthma.

AIM: Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin and is approved for adolescents and adults with severe asthma. This analysis assessed pharmacokinetics (PK), pharmacodynamics and safety of tezepelumab up to 85 days postdose in adolescents and children.

METHODS

The adolescent PK study (NCT02512900), in adolescents aged 12-17 years with mild-to-moderate asthma, and TRAILHEAD (NCT04673630), in children aged 5-11 years with mild, moderate or severe asthma, were both open-label, single-dose, Phase 1 studies.

RESULTS

In the adolescent PK study, 21 adolescents (median age: 14 years) received a single 140-mg subcutaneous tezepelumab dose. The mean maximum concentration (Cmax; 24.0 [SD: 6.6] μg/mL) was observed at a median time of 6 (range: 1-20) days postdose, with a mean terminal half-life of 25.3 (SD: 4.7) days. The mean area under the concentration-time curve (AUC0-infinity) was 952 (SD: 289) μg*day/mL. In TRAILHEAD, 18 children (median age: 8 years) received a single 70-mg subcutaneous tezepelumab dose. The Cmax (27.1 μg/mL [SD: 11.9]) was observed at a median time of 3.5 (range: 2-10) days postdose, with a mean terminal half-life of 25.7 (SD: 5.9) days. The mean AUC0-infinity was 974 (SD: 320) μg*day/mL. Changes from baseline in blood eosinophil count, fractional exhaled nitric oxide and serum immunoglobulin E (IgE) reflected expected pharmacodynamic effects of tezepelumab. No new safety signals were identified.

CONCLUSIONS

These results were consistent with previous studies of tezepelumab in other groups, supporting development of tezepelumab for asthma in the paediatric population.