Population Pharmacokinetic Modeling and Exposure–Efficacy and Body Weight–Response Analyses for Tezepelumab in Patients With Severe, Uncontrolled Asthma

• DOI: 10.1002/jcph.2433
• Publication Date: 2024-04-18T04:59:47Z
• Authors: Yanan Zheng; Lubna Abuqayyas; Angelica Quartino; Ye Guan; Yuying Gao; Lu Liu; Åsa Hellqvist; Gene Colice; Alexander MacDonald
• Keywords: Regimen; Concomitant

Abstract Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin. This analysis assessed suitability fixed‐dose regimen tezepelumab 210 mg every 4 weeks (Q4W) in adults and adolescents with severe, uncontrolled asthma. A population pharmacokinetic model was developed using data from 1368 patients asthma or healthy participants enrolled 8 clinical studies (phases 1‐3). exposure‐efficacy relationships were analyzed phase 3 NAVIGATOR study (NCT03347279), exacerbation rates over 52 changes pre‐bronchodilator forced expiratory volume 1 s at week 52. pharmacokinetics well characterized by 2‐compartment linear disposition first‐order absorption elimination following subcutaneous intravenous administration 2.1‐420 210‐700 mg, respectively. There no clinically relevant effects on age (≥12 years), sex, race/ethnicity, renal hepatic function, disease severity (inhaled corticosteroid dose level), concomitant medication use, smoking history, anti‐drug antibodies. Body weight most influential covariate exposure, but meaningful differences efficacy safety observed across body quartiles who received subcutaneously Q4W. apparent relationship between exposure this regimen, suggesting it plateau exposure‐response curve tezepelumab. In conclusion, Q4W appropriate for eligible