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Clinical Trial
. 2024 Jul;41(7):2978-2990.
doi: 10.1007/s12325-024-02889-8. Epub 2024 May 27.

Efficacy of Tezepelumab in Patients with Severe, Uncontrolled Asthma Across Multiple Clinically Relevant Subgroups in the NAVIGATOR Study

Tara F Carr  1 , Wendy C Moore  2 , Monica Kraft  3 , Guy Brusselle  4 , Mario Castro  5 , Geoffrey L Chupp  6 , Michael E Wechsler  7 , Gillian Hunter  8 , Andrew W Lindsley  9 , Jean-Pierre Llanos  10 , Luke K Burke  11 , Shradha Chandarana  12 , Christopher S Ambrose  13
Affiliations
Clinical Trial

Efficacy of Tezepelumab in Patients with Severe, Uncontrolled Asthma Across Multiple Clinically Relevant Subgroups in the NAVIGATOR Study

Tara F Carr et al. Adv Ther. 2024 Jul.

Abstract

Introduction: Many patients with severe asthma continue to experience symptoms and exacerbations despite treatment with standard-of-care therapy. In the phase 3 NAVIGATOR study, tezepelumab significantly reduced exacerbations over 52 weeks compared with placebo in patients with severe, uncontrolled asthma. This analysis assessed the efficacy of tezepelumab in reducing asthma exacerbations in various clinically relevant subgroups of patients in NAVIGATOR.

Methods: NAVIGATOR was a phase 3, multicentre, randomized, double-blind, placebo-controlled study. Participants (12-80 years old) with severe, uncontrolled asthma were randomized 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Pre-specified and post hoc analyses were performed to evaluate the annualized asthma exacerbation rate (AAER) over 52 weeks in clinically relevant subgroups of patients defined by baseline patient characteristics, medical history, exacerbation triggers, medication eligibility and medication use before and during the study.

Results: Tezepelumab reduced the AAER over 52 weeks compared with placebo across a wide range of patient subgroups assessed. Reductions in exacerbations were similar across subgroups defined by baseline patient characteristics, ranging from 48% (95% confidence interval [CI]: 21, 65) to 60% (95% CI: 44, 71) in subgroups analysed by sex, smoking history and body mass index. Among the asthma-related comorbidity subgroups investigated, patients with aspirin or NSAID sensitivity had the greatest reductions in AAER with tezepelumab compared with placebo (83%; 95% CI: 66, 91). In patients eligible to receive dupilumab, tezepelumab reduced exacerbations compared with placebo by 64% (95% CI: 54, 71). Reductions in the AAER with tezepelumab compared with placebo were also observed irrespective of exacerbation trigger category and the number of asthma controller medications patients were receiving at baseline.

Conclusion: These findings further support the benefits of tezepelumab in patients with severe, uncontrolled asthma and can help to inform healthcare providers' treatment decisions.

Clinical trial registration: NAVIGATOR (NCT03347279).

Keywords: Asthma; Biologics; Comorbidities; Exacerbation; Severe asthma; Tezepelumab.

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Conflict of interest statement

Tara F. Carr has served in an advisory role or as a consultant for AstraZeneca, Genentech, GSK, Novartis and Regeneron Pharmaceuticals. Wendy C. Moore has received consultancy fees for participation in advisory boards from AstraZeneca, GSK, Regeneron Pharmaceuticals and Sanofi; her institution has received research support from AstraZeneca, Boehringer-Ingelheim, Genentech, Gossamer Bio, GSK, Regeneron Pharmaceuticals, Sanofi, Suzhou Pharmaceuticals, Teva Pharmaceuticals and the US National Heart, Lung, and Blood Institute/US National Institutes of Health. Monica Kraft has received research support from the American Lung Association, AstraZeneca, Janssen, Sanofi, Synairgen and the US National Institutes of Health, with funds paid to the University of Arizona and Mount Sinai Health System; has received personal fees from AstraZeneca, Chiesi, Genentech, Kinaset and Sanofi; and is a cofounder and Chief Medical Officer for RaeSedo, Inc. Guy Brusselle has received fees for participation in advisory boards and/or speaker fees from Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, MSD, Novartis and Sanofi. Mario Castro has received grants/research support from ALA, AstraZeneca, Gala Therapeutics, Genentech, GSK, Novartis, Patient-Centered Outcomes Research Institute, Pulmatrix, Sanofi-Aventis, Shionogi, Theravance and the US National Institutes of Health; has received consulting fees/honoraria from Allakos, Amgen, Arrowhead, AstraZeneca, Genentech, Merck, Novartis, OM Pharma, Regeneron Pharmaceuticals, Sanofi and Teva Pharmaceuticals; and has received royalties from Aer Therapeutics and Elsevier. Geoffrey L. Chupp has received speaker and consultancy fees from Amgen, AstraZeneca, Boehringer Ingelheim, Genentech, GSK, Novartis, Regeneron Pharmaceuticals, Sanofi-Genzyme and Teva Pharmaceuticals. Michael E. Wechsler is an employee of National Jewish Health and has received consultancy fees from AstraZeneca, Equillium, Genentech, GSK, Novartis, Regeneron Pharmaceuticals, resTORbio, Sanofi and Teva Pharmaceuticals. Gillian Hunter, Luke K. Burke, Shradha Chandarana and Christopher S. Ambrose are employees of AstraZeneca and may own stock or stock options in AstraZeneca. Andrew W. Lindsley and Jean-Pierre Llanos are employees of Amgen and own stock in Amgen.

Figures

Fig. 1
Fig. 1
AAER over 52 weeks in patients with severe, uncontrolled asthma grouped by baseline demographics and clinical characteristics. n is the number of patients who contributed to each analysis. aPre-specified analysis; all other analyses shown are post hoc. b< 60% is indicative of severe lung disease [30]. cPerennial aeroallergen sensitization was defined as a positive fluorescence enzyme immunoassay result for serum specific IgE against at least one common perennial aeroallergen (cat dander, dog dander, cockroach, house dust mite [Dermatophagoides farinae, D. pteronyssinus] or mould mix). AAER annualized asthma exacerbation rate; BD bronchodilator; BEC blood eosinophil count; BMI body mass index; CI confidence interval; FEV1 forced expiratory volume in 1 s; GERD gastroesophageal reflux disease; IgE immunoglobulin E; Q4W every 4 weeks
Fig. 2
Fig. 2
AAER over 52 weeks in patients with severe, uncontrolled asthma grouped by medical history and exacerbation triggers. n is the number of patients who contributed to each analysis. All analyses shown are post hoc. aOther exposure includes air pollution, fumes, exertion and stress. AAER annualized asthma exacerbation rate; AERD aspirin-exacerbated respiratory disease; CI confidence interval; GERD gastroesophageal reflux disease; N-ERD NSAID-exacerbated respiratory disease; NSAID non-steroidal anti-inflammatory drug; Q4W every 4 weeks
Fig. 3
Fig. 3
AAER over 52 weeks in patients with severe, uncontrolled asthma grouped by medication eligibility and medications received before and during the study. n is the number of patients who contributed to each analysis. aPre-specified analysis; all other analyses shown are post hoc. bOther controller medications included the following in addition to ICS: xanthine derivatives, LAMA only, LTRA only, LABA + xanthine derivatives, LABA + LTRA + xanthine derivatives, LABA + LAMA + xanthine derivatives, LAMA + LTRA + xanthine derivatives, LABA + LAMA + LTRA + xanthine derivatives, LABA + LTRA + xanthine derivatives + cromolyn. AAER annualized asthma exacerbation rate; CI confidence interval; ICS inhaled corticosteroid; LABA long-acting β2 agonist; LAMA long-acting muscarinic antagonist; LTRA leukotriene receptor antagonist; n number of patients who contributed to the analysis; OCS oral corticosteroid; Q4W every 4 weeks
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