NAVIGATOR Data Presented at ATS 2022 Show Improved Clinical Responses to Treatment with Tezepelumab vs Placebo

A greater proportion of patients with severe, uncontrolled asthma had more significant clinical responses to tezepelumab than placebo, according to new research presented at the American Thoracic Society’s (ATS) International Conference 2022, held May 13-18 live in San Francisco and online.

Findings showed that nearly half of the tezepelumab-treated participants experienced a complete response to treatment across measures of exacerbation reduction, asthma control, lung function, and clinician assessment. The results were published simultaneously in the American Journal of Respiratory and Critical Care Medicine.

The study is a prespecified on-treatment analysis of responses to tezepelumab using data from the phase 3 NAVIGATOR clinical trial, the results of which were presented at ATS 2021.

“Overall, these results align with the NAVIGATOR results reported at ATS 2021 and add an important patient-level perspective to the primary study results,” said presenting author Njira Lugogo, MD, director, Asthma Program, Division of Pulmonary and Critical Care Medicine, University of Michigan, in a press release. “Across each measure, tezepelumab recipients were more likely to have a response; the greatest difference observed was for exacerbation reduction.”

A total of 471 patients receiving tezepelumab and 449 patients receiving placebo completed the on-treatment period and were included in the analysis. Endpoint responses were defined as:

• ≥50% reduction in asthma exacerbations on-treatment compared with the previous year.
• An improvement from baseline in Asthma Control Questionnaire (ACQ)-6 total score of ≥0.5.
• An improvement from baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV1) of ≥100 mL or ≥5%.
• A Clinical Global Impression of Change (CGI-C) score defined as minimally, much, or very much improved.

Across the response criteria, Lugogo and colleagues found that the proportion of responders was higher in the tezepelumab cohort than in the placebo cohort for exacerbations (85.4% vs 67.5%; odds ratio [OR], 2.82; 95% confidence interval [CI], 2.04-3.90); ACQ-6 total score (86.9% vs 76.6%; OR, 2.05; 95% CI, 1.42-2.97); pre-bronchodilator FEV1(60.3% vs 49.9%; OR, 1.52; 95% CI, 1.15-2.02); and CGI-C score (81.5% vs 67.7%; OR, 2.21; 95% CI, 1.58-3.08).

The proportion of on-treatment complete responders—patients who met all 4 response criteria—was higher in the tezepelumab group than in the placebo cohort (48.2% vs 25.3%; OR, 2.78; 95% CI, 2.05-3.77), according to the study abstract.

Lugogo noted in the press statement that these results can be used in shared decision making when clinicians discuss initiating tezepelumab therapy with patients.

“Patients are always interested in understanding the potential outcomes following therapy initiation and our results can guide clinicians in informing patients about the likelihood of both individual and complete response to therapy,” said Lugogo.

Tezepelumab (Tezpire, AstraZeneca/Amgen), a first-in-class a thymic stromal lymphopoietin inhibitor, was approved by the US Food and Drug Administration in December 2021 as add-on maintenance treatment for adult and pediatric patients aged ≥12 years with severe asthma.

Lugogo presented the study, “Clinical responses to treatment with tezepelumab among patients with severe, uncontrolled asthma in the phase 3 NAVIGATOR study,” on Monday, May 16, at 3:25 pm PDT / 6:25 pm ET in Room 3006/3008 (West Building, Level 3), Moscone Center.