José Maria Cendrós 1, Núria Folguera Blasco 1, Diansong Zhou 2, Susanne Prothon 3, Lubna Abuqayyas 4, Anna Lundahl 3, David Boulton 5, Jacob Leander 3
1 Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences, R&D AstraZeneca (Barcelona, Spain), 2 Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences, R&D AstraZeneca (Waltham, USA), 3 Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences, R&D AstraZeneca (Gothenburg, Sweden), 4 Clinical Pharmacology, Modeling and Simulation, Amgen (Cambridge, USA), 5 Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences, R&D AstraZeneca (Gaithersburg, USA)
Introduction/Objectives: Tezepelumab (210 mg subcutaneously [SC] every 4 weeks [Q4W]) is approved in several markets worldwide as an add-on maintenance treatment for adult and paediatric patients (≥ 12 years) with severe, uncontrolled asthma. It is the only biologic approved for severe asthma without phenotypic (e.g. eosinophilic or allergic) or biomarker limitations [1]. The phase 3 WAYPOINT study (NCT04851964) aimed to evaluate the effect of tezepelumab in adult patients with chronic rhinosinusitis with nasal polyposis (CRSwNP).
This analysis aimed to extend the population pharmacokinetic (popPK) model of tezepelumab in asthma to patients with CRSwNP to support regulatory approval in adults and adolescents.
Methods: To develop a popPK model for tezepelumab in patients with CRSwNP, we first explored pharmacokinetic (PK) variability across indications. Then, the previously established asthma popPK model for tezepelumab [2] was updated to confirm its applicability in CRSwNP. The covariate analysis followed a structured process: previously established covariates (e.g. body weight [BW], inhaled corticosteroid [ICS] dose level, race, formulation and age) were first assessed for continued significance using backward elimination from the full covariate model to obtain a statistically parsimonious model; then, pre-planned new covariates of interest were tested via stepwise addition to evaluate incremental predictive value and clinical relevance. The analysis used a pooled population comprising adult healthy volunteers, adult and adolescent patients (12–17 years) with asthma and adult patients with CRSwNP. The integrated dataset combined eight clinical studies across phases 1–3 and the WAYPOINT study, totalling 1571 evaluable patients, 203 of whom were adults with CRSwNP.
Additionally, since WAYPOINT did not include adolescents, a model-based extrapolation to the CRSwNP adolescent population was performed based on (a) similar tezepelumab PK for adults with asthma and adults with CRSwNP and (b) ability of the popPK model to integrate PK data for adults and adolescents with asthma. The model-based simulations for adolescents used a non-Asian virtual population with age and weight distributions derived from National Health and Nutrition Examination Survey (NHANES) database [3], in which the covariate describing the use of ICS (categorised as no/low vs medium/high) was added for simulations.
Results: The resulting popPK model after the inclusion of the WAYPOINT data retained the same structure as the previously established popPK model used for asthma indications, with parameter estimates differing by < 10% from the previous estimates. Therefore, tezepelumab in patients with CRSwNP also follows a two-compartment linear disposition model with first-order absorption and elimination, including BW, ICS dose level and race on clearance from the central compartment (CL); BW, ICS dose level and age on volume of distribution from the central compartment (Vc); and BW on intercompartmental clearance (Q) and volume of distribution from the peripheral compartment (Vp), as statistically significant covariates. However, these covariates were not deemed to be clinically meaningful as their impact was < 20%. Among the new covariates tested in the forward selection step, none showed statistical significance; therefore, they were not added to the model. Disease condition (healthy vs asthma vs CRSwNP patients) on CL was one among those tested without statistical significance, indicating similar PK behaviour across disease indications. With the paediatric extrapolation, the PK behaviour of tezepelumab was concluded to be similar between virtual adolescents and adults with CRSwNP. The recommended dosage of 210 mg SC Q4W for adolescents with CRSwNP showed no meaningful differences in tezepelumab exposure compared to that in adults with CRSwNP, suggesting that similar efficacy and safety profiles can be expected in adolescents. Therefore, the similarity in PK via exploratory analysis, popPK modelling and exposure simulations supported the use of the approved asthma regimen (210 mg SC Q4W) for both adults and adolescents with CRSwNP. Conclusions: The PK of tezepelumab is similar in patients with CRSwNP and asthma, as shown by the popPK model developed. No meaningful difference in tezepelumab exposure has been identified between patients with asthma and those with CRSwNP. Adolescents with CRSwNP are expected to reach a systemic exposure that has proven to be efficacious in adults with CRSwNP; as a result, the same dosing scheme (210 mg SC Q4W) is recommended. This study was funded by AstraZeneca and Amgen Inc. References: [1] AstraZeneca. Tezepelumab-ekko (TEZSPIRE™) US Prescribing Information, 2021. Available from: http://www.azpicentral.com/pi.html?product=tezspire (Accessed 23 January 2026). [2] Zheng Y et al. J Clin Pharmacol 2024;64:908–21. [3] Centers for Disease Control and Prevention (CDC). National Center for Health Statistics (NCHS). National Health and Nutrition Examination Survey Data 2017–2023. Available from: https://www.cdc.gov/nchs/nhanes/ (Accessed 23 January 2026). Acknowledgements Medical writing support was provided by Priyanka Narang, PhD, of PharmaGenesis London, London, UK, with funding provided by AstraZeneca and Amgen Inc. Disclosures José-Maria Cendrós, Núria Folguera-Blasco, Diansong Zhou, Susanne Prothon, Anna Lundahl, David Boulton and Jacob Leander are employees of AstraZeneca and may own stock or stock options in AstraZeneca. Lubna Abuqayyas is an employee of Amgen and owns stock in Amgen.
Reference: PAGE 34 (2026) Abstr 12260 [www.page-meeting.org/?abstract=12260]
Poster: Clinical Applications