Efficacy of tezepelumab in patients with severe, uncontrolled asthma and perennial aeroallergen sensitization: a pooled analysis of the phase 2b PATHWAY and phase 3 NAVIGATOR studies
A. Menzies-Gow1; J. Corren2; CS. Ambrose3; B. Cook3; Å. Hellqvist4; SL. Roseti5; N. Martin6, 7; AW. Lindsley8; G. Colice5
1Royal Brompton and Harefield Hospitals, London, United Kingdom; 2David Geffen School of Medicine, UCLA, Los Angeles, United States of America; 3Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, United States of America; 4Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden; 5Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, United States of America; 6Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK, Cambridge, United Kingdom; 7University of Leicester, Leicester, United Kingdom; 8US Medical Affairs, Amgen, Thousand Oaks, United States of America
Background

Allergic asthma is the most common asthma phenotype and approximately 60% of adult patients with severe asthma have allergic asthma. Tezepelumab, a human monoclonal antibody, blocks the activity of the epithelial cytokine thymic stromal lymphopoietin (TSLP). This post hoc analysis was designed to evaluate the efficacy of tezepelumab with increased statistical precision in patients with severe, uncontrolled asthma and perennial aeroallergen sensitization using pooled data from the phase 2b PATHWAY and phase 3 NAVIGATOR studies.

Method

PATHWAY (NCT02054130) and NAVIGATOR (NCT03347279) were multicentre, randomized, double-blind, placebo-controlled studies with similar designs. Patients with severe, uncontrolled asthma who received tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks and had a positive or negative fluorescence enzyme immunoassay test for serum-specific immunoglobulin E against at least one perennial aeroallergen were included in this analysis. The annualized asthma exacerbation rate (AAER) over 52 weeks (primary endpoint in both trials) and the annualized rate of exacerbations that required hospitalization or an emergency department (ED) visit over 52 weeks were assessed in patients grouped by perennial allergic status.

Results

Overall, 1299 patients were included; 815 (63%) had perennial aeroallergen sensitization and 484 (37%) did not. Tezepelumab reduced the AAER over 52 weeks compared with placebo by 62% (95% CI: 53–70) in patients with perennial aeroallergen sensitization and by 54% (95% CI: 38–66) in those without (Figure). The annualized rate of exacerbations that required hospitalization or an ED visit was reduced with tezepelumab compared with placebo by 80% (95% CI: 61–90) in patients with perennial aeroallergen sensitization and by 74% (95% CI: 41–88) in those without (Figure). For exacerbations that required hospitalization, reductions with tezepelumab compared with placebo were 85% (95% CI: 62–94) and 79% (95% CI: 42–93) in patients with and without perennial aeroallergen sensitization, respectively.

Conclusion

Tezepelumab reduced exacerbations compared with placebo, including those that required hospitalization or an ED visit, in patients with severe, uncontrolled asthma with or without perennial aeroallergen sensitization. These findings further support the benefits of tezepelumab in a broad population of patients with severe, uncontrolled asthma, including those with allergic and non-allergic asthma.