Tezepelumab May Improve Peak Expiratory Flow in Patients with Severe Asthma, Suggests Analysis of NAVIGATOR Trial

In a secondary analysis of the phase 3 NAVIGATOR clinical trial, the novel thymic stromal lymphopoietin inhibitor tezepelumab was shown to rapidly improve morning and evening peak expiratory flow (PEF) in patients with severe, uncontrolled asthma.

The findings will be presented at the upcoming annual meeting of the American College of Chest Physicians (CHEST 2021), held virtually between October 17-20, 2021.

The phase 3 NAVIGATOR trial randomized 1059 patients aged 12 to 80 years in a 1:1 fashion to receive treatment with tezepelumab 210 mg (n=528) or placebo (n=531) subcutaneously every 4 weeks for 52 weeks. Participants had severe, uncontrolled asthma, and were receiving medium- or high-dose inhaled corticosteroids and at least 1 additional controller medication with or without oral corticosteroids.

The results—published in the May 2021 issue of NEJMshowed tezepelumab significantly reduced exacerbations in adults and adolescents, including those with baseline blood eosinophil counts below 300 cells/µL.

A secondary objective of NAVIGATOR was the examine the effect of tezepelumab on morning and evening PEF, which was reported in the current study. A repeated measures model was used to estimate least-squares (LS) mean changes from baseline in weekly mean morning and evening PEF, as well as the difference between treatment groups, according to the study abstract.

Results

At baseline, the weekly mean morning PEF was 261.7 L/min and 262.5 L/min for the tezepelumab and placebo arms, respectively, and the weekly mean evening PEF was 276.9 L/min and 278.2 L/min, respectively. Greater improvements from baseline in weekly mean morning and evening PEF were found with tezepelumab than with placebo over 52 weeks, according to the abstract.

For weekly mean morning PEF, the LS mean difference for the tezepelumab group versus placebo was 7.4 L/min (95% confidence interval [CI]: 3.4-11.4) at week 1, 13.9 L/min (95% CI: 9.2-18.7) at week 2, 16.6 L/min (95% CI: 8.9-24.3) at week 26, and 16.6 L/min (95% CI: 8.1-25.1) at week 52.

For weekly mean evening PEF, the LS mean difference versus placebo was 5.4 L/min (95% CI: 1.7-9.2) at week 1, 12.5 L/min (95% CI: 7.7-17.2) at week 2, 16.4 L/min (95% CI: 8.7-24.2) at week 26, and 14.9 L/min (95% CI: 6.3-23.4) at week 52.

“Treatment with tezepelumab resulted in rapid improvement in both morning and evening PEF versus placebo, with effects observed as early as week 1 and continued improvements seen throughout the 52-week treatment period,” concluded researchers. “This analysis demonstrates that tezepelumab rapidly and sustainedly improves lung function in a broad range of patients with severe, uncontrolled asthma.”

In July 2021, tezepelumab was granted FDA Priority Review in response to a May 2021 submission of a Biological License Application for the treatment of severe asthma.


Reference: Israel E, Ambrose C, Hunter G, et al. Rapid improvement in morning and evening peak expiratory flow in patients with severe, uncontrolled asthma treated with tezepelumab. CHEST. 2021:160:A34-36.