Clinical response and on-treatment clinical remission with tezepelumab in a broad population of patients with severe, uncontrolled asthma: results over 2 years from the NAVIGATOR and DESTINATION studies

Michael E Wechsler; Guy Brusselle; J Christian Virchow; Arnaud Bourdin; Konstantinos Kostikas; Jean-Pierre Llanos; Stephanie L Roseti; Christopher S Ambrose; Gillian Hunter; David J Jackson; Mario Castro; Njira Lugogo; Ian D Pavord; Neil Martin; Christopher E Brightling

doi:10.1183/13993003.00316-2024

Clinical response and on-treatment clinical remission with tezepelumab in a broad population of patients with severe, uncontrolled asthma: results over 2 years from the NAVIGATOR and DESTINATION studies

Eur Respir J. 2024 Sep 26:2400316. doi: 10.1183/13993003.00316-2024. Online ahead of print.

Authors

Michael E Wechsler¹, Guy Brusselle², J Christian Virchow³, Arnaud Bourdin⁴, Konstantinos Kostikas⁵, Jean-Pierre Llanos⁶, Stephanie L Roseti⁷, Christopher S Ambrose⁸, Gillian Hunter⁹, David J Jackson^{10

11}, Mario Castro¹², Njira Lugogo¹³, Ian D Pavord¹⁴, Neil Martin^{15

16}, Christopher E Brightling¹⁷

Affiliations

¹ National Jewish Health, Denver, CO, USA.
² Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
³ Department of Pneumology and Department of Intensive Care Medicine, University of Rostock, Rostock, Germany.
⁴ PhyMedExp, University of Montpellier, CNRS, INSERM, CHU Montpellier, Montpellier, France.
⁵ Respiratory Medicine Department, University of Ioannina, Ioannina, Greece.
⁶ Global Medical Affairs, Amgen, Thousand Oaks, CA, USA.
⁷ Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
⁸ Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA.
⁹ Biometrics, Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
¹⁰ Guy's Severe Asthma Centre, Guy's and St Thomas' NHS Foundation Trust, London, UK.
¹¹ School of Immunology & Microbial Sciences, King's College London, London, UK.
¹² Division of Pulmonary, Critical Care and Sleep Medicine, University of Kansas School of Medicine, Kansas City, KS, USA.
¹³ Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI, USA.
¹⁴ Respiratory Medicine, National Institute for Health and Care Research, Oxford Biomedical Research Centre, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
¹⁵ Institute for Lung Health, National Institute for Health and Care Research, Leicester Biomedical Research Centre, University of Leicester, Leicester, UK.
¹⁶ Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK.
¹⁷ Institute for Lung Health, National Institute for Health and Care Research, Leicester Biomedical Research Centre, University of Leicester, Leicester, UK [email protected].

PMID: 39326921
DOI: 10.1183/13993003.00316-2024

Abstract

Background: In asthma, clinical response is characterized by disease improvement with treatment, whereas clinical remission is characterized by long-term disease stabilization with or without ongoing treatment. The proportion of patients receiving tezepelumab who responded to treatment and those who achieved on-treatment clinical remission was assessed in the NAVIGATOR (NCT03347279) and DESTINATION (NCT03706079) studies of severe, uncontrolled asthma.

Methods: NAVIGATOR and DESTINATION were phase 3, randomized, double-blind, placebo-controlled studies; DESTINATION was an extension of NAVIGATOR. Complete clinical response was defined as achieving all of the following: ≥50% reduction in exacerbations versus the previous year, improvements in pre-bronchodilator (BD) forced expiratory volume in 1 s (FEV₁) of ≥100 mL or ≥5%, improvements in Asthma Control Questionnaire (ACQ)-6 score of ≥0.5 and physicians' assessment of asthma improvement. On-treatment clinical remission was defined as an ACQ-6 total score ≤1.5, stable lung function (pre-BD FEV₁ >95% of baseline) and no exacerbations or use of oral corticosteroids during the time periods assessed.

Results: Higher proportions of tezepelumab than placebo recipients achieved complete clinical response over weeks 0-52 (46% versus 24%; OR: 2.83 [95% CI: 2.10-3.82]), and on-treatment clinical remission over weeks 0-52 (28.5% versus 21.9%; OR: 1.44 [95% CI: 0.95-2.19]) and weeks >52-104 (33.5% versus 26.7%; OR: 1.44 [95% CI: 0.97-2.14]). Tezepelumab recipients who achieved on-treatment clinical remission versus complete clinical response at week 52 had better preserved lung function and lower inflammatory biomarkers at baseline, and fewer exacerbations in the 12 months before the study.

Conclusions: Among patients with severe, uncontrolled asthma, tezepelumab treatment was associated with an increased likelihood of achieving complete clinical response and on-treatment clinical remission compared with placebo. Both are clinically important outcomes but may be driven by different patient characteristics.

Associated data

ClinicalTrials.gov/NCT03706079