. 2023 Sep 4:16:915-932.

doi: 10.2147/JAA.S413064. eCollection 2023.

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

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.

PMID: 37692126
PMCID: PMC10488831
DOI: 10.2147/JAA.S413064

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

Tanya M Laidlaw et al. J Asthma Allergy. 2023.

. 2023 Sep 4:16:915-932.

doi: 10.2147/JAA.S413064. eCollection 2023.

Authors

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.

PMID: 37692126
PMCID: PMC10488831
DOI: 10.2147/JAA.S413064

Erratum in

Erratum: Tezepelumab Efficacy in Patients with Severe, Uncontrolled Asthma with Comorbid Nasal Polyps in NAVIGATOR [Corrigendum].
[No authors listed] [No authors listed] J Asthma Allergy. 2023 Sep 27;16:1053-1054. doi: 10.2147/JAA.S441410. eCollection 2023. J Asthma Allergy. 2023. PMID: 37791042 Free PMC article.

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.

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Conflict of interest statement

Tanya M Laidlaw has served on scientific advisory boards for Amgen, GSK, Regeneron and Sanofi. Andrew Menzies-Gow is an employee of AstraZeneca and may own stock or stock options in AstraZeneca; has attended advisory board meetings for AstraZeneca, GSK, Novartis, Regeneron, Sanofi and Teva Pharmaceuticals; has received speaker fees from AstraZeneca, Novartis, Sanofi and Teva Pharmaceuticals; has participated in research with AstraZeneca, for which his institution has been remunerated; has attended international conferences with Teva Pharmaceuticals; and has consultancy agreements with AstraZeneca and Sanofi. Joseph K Han has received consultancy fees from AstraZeneca, Genentech, Gossamer Bio, GSK, Novartis, Regeneron and Sanofi-Genzyme. Elliot Israel has served as a consultant to and received personal fees from 4D Pharma, AB Science, the Allergy and Asthma Network, Amgen, AstraZeneca, Avillion, Biometry, Cowen, Equillium, Genentech, GSK, Merck, National Heart, Lung and Blood Institute, Novartis, Pneuma Respiratory, PPS Health, Regeneron Pharmaceuticals, Sanofi, Sienna Biopharmaceuticals, Teva Pharmaceuticalsand Westchester Medical Center; has received non-financial support from Circassia, Teva Pharmaceuticals and Vorso Corp; and has received clinical research grants from AstraZeneca, Avillion, Genentech, Gossamer Bio, National Institutes of Health (NIH), Novartis, Patient-Centered Outcomes Research Institute and Sanofi; royalties or licenses from UpToDate – Wolters Kluwer; stock options from Nesos Corp; study drug for NIH PrecISE trial for CSL Behring, Laurel Pharmaceuticals, Om Pharmaceuticals, Nestlé and Sun Pharmaceuticals; study drug for NIH IDEA for Sanofi-Regeneron. Jason K Lee has received research support from ALK, AstraZeneca Bausch Health, Genentech, GSK, Meda, Medexus, Miravo, Novartis, Regeneron, Roche, Sanofi-Genzyme and Takeda; has received fees for speakers’ bureau from Aralez, AstraZeneca, GSK, Medexus, Merck, Mylan, Novartis and Sanofi-Genzyme; and has received consultancy fees from and is an advisory committee member of AstraZeneca, GSK, Medexus, Novartis, Regeneron and Sanofi-Genzyme. Tobias Welte has received fees for lectures and/or advisory board meetings from AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Chiesi, GSK, MSD, Novartis, Roche, Pfizer and Sanofi Aventis; grants from the German Ministry of Research and Education, AstraZeneca and GSK. Jonathan Corren has received grants and personal fees from AstraZeneca, Genentech, RAPT, Regeneron and Vectura; and has received grants from Optinose, Pulmatrix, Sanofi and Teva Pharmaceuticals. Scott Caveney and Jean-Pierre Llanos are employees of Amgen and own stock in Amgen. Nicole Martin, Neil Martin, Ayman Megally, Bhavini Parikh and Sylvia Vong are employees of AstraZeneca and may own stock or stock options in AstraZeneca. The authors report no other conflicts of interest in this work.

Figures

**Figure 1**
AAER over 52 weeks in patients with or without nasal polyps in the 2 years before randomization in the NAVIGATOR study.

**Figure 2**
Change from baseline in SNOT-22 total score over 52 weeks in patients with nasal polyps in the 2 years before randomization in the NAVIGATOR study.

**Figure 3**
Change from baseline in SNOT-22 nasal (A), ear/facial (B), sleep (C), function (D) and emotion (E) domain scores over 52 weeks in patients with nasal polyps in the 2 years before randomization in the NAVIGATOR study.

**Figure 4**
Change from baseline in exploratory biomarkers over 52 weeks with tezepelumab compared with placebo in patients with or without NPs in the 2 years before randomization in the NAVIGATOR study.

See this image and copyright information in PMC

References

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

Affiliations

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

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

Figures

References

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