Tezepelumab Efficacy in Patients with Severe, Uncontrolled Asthma with Comorbid Nasal Polyps in NAVIGATOR

Tanya M Laidlaw; Andrew Menzies-Gow; Scott Caveney; Joseph K Han; Nicole Martin; Elliot Israel; Jason K Lee; Jean-Pierre Llanos; Neil Martin; Ayman Megally; Bhavini Parikh; Sylvia Vong; Tobias Welte; Jonathan Corren

doi:10.2147/JAA.S413064

Tezepelumab Efficacy in Patients with Severe, Uncontrolled Asthma with Comorbid Nasal Polyps in NAVIGATOR

J Asthma Allergy. 2023 Sep 4:16:915-932. doi: 10.2147/JAA.S413064. eCollection 2023.

Authors

Tanya M Laidlaw^#^{1

2}, Andrew Menzies-Gow^#³, Scott Caveney⁴, Joseph K Han⁵, Nicole Martin^{6

7}, Elliot Israel⁸, Jason K Lee^{9

10}, Jean-Pierre Llanos¹¹, Neil Martin^{12

13}, Ayman Megally¹⁴, Bhavini Parikh¹⁴, Sylvia Vong¹⁵, Tobias Welte¹⁶, Jonathan Corren¹⁷

Affiliations

¹ Jeff and Penny Vinik Center for Allergic Diseases Research, Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, MA, USA.
² Department of Medicine, Harvard Medical School, Boston, MA, USA.
³ Royal Brompton and Harefield Hospitals, School of Immunology and Microbial Sciences, King's College London, London, UK.
⁴ Global Development, Inflammation, R&D, Amgen, Thousand Oaks, CA, USA.
⁵ Department of Otolaryngology, Head and Neck Surgery, Eastern Virginia Medical School, Norfolk, VA, USA.
⁶ Biometrics, Late-Stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Waltham, MA, USA.
⁷ Cytel Inc, Waltham, MA, USA.
⁸ Divisions of Pulmonary and Critical Care Medicine and Allergy and Clinical Immunology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁹ Evidence Based Medical Educator Inc., Toronto, ON, Canada.
¹⁰ Toronto Allergy and Asthma Clinic, Toronto, ON, Canada.
¹¹ Global Medical Affairs, Amgen, Thousand Oaks, CA, USA.
¹² Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK.
¹³ University of Leicester, Leicester, UK.
¹⁴ Late-Stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
¹⁵ Translational Science and Experimental Medicine, Early Respiratory and Immunology, AstraZeneca, Gaithersburg, MD, USA.
¹⁶ Department of Respiratory Medicine and German Center for Lung Research, Hannover Medical School, Hannover, Germany.
¹⁷ David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.

^# Contributed equally.

Abstract

Purpose: Tezepelumab, a human monoclonal antibody, blocks thymic stromal lymphopoietin. In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab reduced annualized asthma exacerbation rates (AAERs) versus placebo, irrespective of baseline disease characteristics, and improved lung function and symptom control versus placebo in adults and adolescents with severe, uncontrolled asthma. We assessed the efficacy of tezepelumab in patients with severe asthma with or without nasal polyps (NPs) in the 2 years before randomization in NAVIGATOR.

Methods: Patients with severe asthma (N=1059) were randomized (1:1) and received tezepelumab 210 mg or placebo every 4 weeks subcutaneously for 52 weeks. Prespecified exploratory analyses included: AAER over 52 weeks and changes from baseline to week 52 in pre-bronchodilator forced expiratory volume in 1 second, Sino-Nasal Outcome Test (SNOT)-22 scores, and asthma control and health-related quality life (HRQoL) outcomes in NP subgroups. Changes from baseline in fractional exhaled nitric oxide (FeNO), blood eosinophil counts, total immunoglobulin E (IgE), eosinophil-derived neurotoxin (EDN), matrix metalloproteinase-10 (MMP-10), and serum interleukin (IL)-5, IL-6, IL-8 and IL-13 were assessed (post hoc).

Results: Tezepelumab reduced the AAER over 52 weeks versus placebo by 85% (95% confidence interval [CI]: 72, 92; n=118) and 51% (95% CI: 40, 60; n=941) in patients with and without NPs, respectively. At week 52, tezepelumab improved lung function, asthma control and HRQoL versus placebo in patients with and without NPs. Tezepelumab reduced SNOT-22 total scores (least-squares mean difference versus placebo [95% CI]) in patients with NPs at 28 weeks (-12.57 points [-19.40, -5.73]) and 52 weeks (-10.58 points [-17.75, -3.41]). At week 52, tezepelumab reduced blood eosinophil counts and FeNO, IgE, IL-5, IL-13, EDN and MMP-10 levels versus placebo, irrespective of NP status.

Conclusion: Tezepelumab resulted in clinically meaningful improvements in sino-nasal symptoms and asthma outcomes in patients with severe asthma with comorbid NPs.

Keywords: SNOT-22; chronic rhinosinusitis; nasal polyps; thymic stromal lymphopoietin.

Grants and funding

This study was funded by AstraZeneca and Amgen Inc.