Effect of Tezepelumab on Lung Function in Patients With Severe, Uncontrolled Asthma in the Phase 3 NAVIGATOR Study

Introduction: Severe asthma is associated with airway inflammation and airway obstruction. In the phase 3 NAVIGATOR study, tezepelumab treatment significantly improved pre-bronchodilator forced expiratory volume in 1 s (FEV₁) compared with placebo in patients with severe, uncontrolled asthma. This analysis assessed the effect of tezepelumab versus placebo on additional lung function parameters in patients from NAVIGATOR.

Methods: NAVIGATOR was a multicenter, randomized, double-blind, placebo-controlled study. Patients (12-80 years old) receiving medium- or high-dose inhaled corticosteroids and at least one additional controller medication, with or without oral corticosteroids, were randomized 1:1 to tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Changes from baseline to week 52 in pre-bronchodilator FEV₁, post-bronchodilator FEV₁, forced vital capacity (FVC), pre-bronchodilator FEV₁/FVC ratio, pre-bronchodilator forced expiratory flow between 25 and 75% of vital capacity (FEF_25-75), and morning and evening peak expiratory flow (PEF) were assessed.

Results: Tezepelumab treatment improved all evaluated lung function parameters over 52 weeks compared with placebo [least-squares mean difference (95% confidence interval): pre-bronchodilator FEV₁, 0.13 (0.08, 0.18) L; post-bronchodilator FEV₁, 0.12 (0.07, 0.16) L; FVC, 0.13 (0.07, 0.19) L; FEV₁/FVC ratio, 2.06% (1.22%, 2.90%); FEF_25-75, 0.13 (0.07, 0.19) L/s; morning PEF, 16.6 (8.1, 25.1) L/min; and evening PEF, 14.9 (6.3, 23.4) L/min]. Improvements were observed as early as weeks 1-2 and were maintained over 52 weeks. Greater improvements in lung function compared with placebo were observed in patients with a disease duration of less than 20 years, those with baseline post-bronchodilator FEV₁ reversibility of at least 20%, and in patients with a baseline post-bronchodilator FEV₁/FVC ratio of less than 0.7.

Conclusion: These findings further support the benefits of tezepelumab treatment in improving airflow limitation in patients with severe, uncontrolled asthma.

Clinical trial registration: NAVIGATOR (NCT03347279).