The proportions of tezepelumab-treated patients with severe, uncontrolled asthma who achieved twice the minimum clinically important difference in patient-reported outcome measures in the phase 3 NAVIGATOR study
D. Jackson1, 2; B. Cook3; N. Martin4, 5; N. Clarke6; G. Hunter7; JP. Llanos-Ackert8; S. Ponnarambil7
1Guy's and St Thomas' NHS Foundation Trust, London, UK, London, United Kingdom; 2King's College London, London, United Kingdom; 3Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, United States of America; 4Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Cambridge, United Kingdom; 5University of Leicester, Leicester, United Kingdom; 6Patient-centered Science, Respiratory and Immunology, AstraZeneca, Gaithersburg, United States of America; 7Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom; 8Global Medical Affairs, Amgen, Thousand Oaks, United States of America
Background

Patients with severe, uncontrolled asthma experience poor symptom control and health-related quality of life (HRQoL). Tezepelumab is a human monoclonal antibody that blocks the activity of thymic stromal lymphopoietin (TSLP). In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab significantly reduced exacerbations and improved lung function, asthma control and HRQoL versus placebo in patients with severe, uncontrolled asthma. This analysis assessed the proportion of patients in NAVIGATOR who achieved a ‘super response’ in patient-reported outcome (PRO) measures of asthma control, asthma symptoms and HRQoL, and who achieved well-controlled or partially controlled symptoms.

Method

NAVIGATOR was a multicentre, randomized, double-blind, placebo-controlled study. Patients (12–80 years old) receiving medium- or high-dose inhaled corticosteroids and ≥ 1 additional controller medication with or without oral corticosteroids were randomized 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. The proportions of patients who achieved super-responses in PROs, defined as a change from baseline of at least twice the minimum clinically important difference (MCID) for Asthma Control Questionnaire 6 (ACQ-6; twice MCID, 1.0), Asthma Quality of Life Questionnaire (standardized) for patients aged 12 years and older (AQLQ[S]+12; 1.0), Asthma Symptom Diary (ASD; 1.0) and St George's Respiratory Questionnaire (SGRQ; 8) scores were assessed. ACQ-6 score was used to assess the proportion of patients who achieved well-controlled (≤ 0.75) or partially controlled (> 0.75 to < 1.5) asthma symptoms.

Results

Overall, 528 patients received tezepelumab and 531 received placebo. A higher proportion of tezepelumab-treated patients than placebo-treated patients achieved twice the MCID at week 52 for ACQ-6 score (72.6% vs 59.7%), AQLQ(S)+12 score (64.2% vs 52.5%), weekly mean ASD score (31.8% vs 26.6%) and SGRQ total score (75.3% vs 62.5%), and at the first post-treatment timepoint assessed (Table). Over 52 weeks, a higher proportion of tezepelumab recipients than placebo recipients had well-controlled or partially controlled asthma symptoms (Figure). 

Conclusion

Tezepelumab treatment resulted in a greater proportion of patients achieving early and sustained clinically meaningful improvements in PRO measures of asthma control, asthma symptoms and HRQoL, further demonstrating the efficacy of tezepelumab in patients with severe, uncontrolled asthma.