Tezepelumab for Severe Asthma: One Drug Targeting Multiple Disease Pathways and Patient Types

Figures & data

Figure 1 Epithelial cytokines and other inflammatory mediators and cell types involved in asthma pathogenesis.^4,16–19

Note: Adapted from Thymic stromal lymphopoietin: its role and potential as a therapeutic target in asthma, by Gail M. Gauvreau, Roma Sehmi, Christopher S. Ambrose & Janet M. Griffiths © 2020 The Author(s) taken from Expert Opinion on Therapeutic Targets © 2020, 24:8 © 2020 Taylor & Francis Ltd, adapted by permission of the publisher, Taylor & Francis Ltd http://www.tandfonline.com.⁴

Abbreviations: Ig, immunoglobulin; IL, interleukin; ILC2, innate lymphoid cell type 2; T2, type 2; Th, T helper; TSLP, thymic stromal lymphopoietin.⁴

Figure 2 Histopathological staining for TSLP (yellow) in asthmatic bronchiolar epithelial and stromal cells.

Note: Image source: AstraZeneca, in-house data.

Abbreviation: TSLP, thymic stromal lymphopoietin.

Figure 3 Summary of mechanisms and efficacy of tezepelumab in severe asthma, by asthma subtype.

Note: AAER reductions cited are based primarily on pooled PATHWAY/NAVIGATOR results but with inclusion of additional subgroup results, when relevant, from NAVIGATOR, as described in the text.

Abbreviations: AAER, annualized asthma exacerbation rate; ASMC, airway smooth muscle cell; ED, emergency department; FeNO, fractional exhaled nitric oxide; IgE, immunoglobulin E; IL, interleukin; T2, type 2; TSLP, thymic stromal lymphopoietin.

Figure 4 Mean percentage changes from baseline to Week 52 in BEC (A), FeNO levels (B), and total serum IgE levels (C), in patients receiving tezepelumab 210 mg Q4W or placebo, grouped by baseline level of the respective biomarker. A post hoc analysis of the NAVIGATOR Phase 3 study. Adapted from Effect of tezepelumab on asthma inflammatory biomarker levels varies by baseline biomarker levels. J Corren J, J Spahn, C Ambrose, N Martin, G Colice, N Molfino, B Cook. Ann Allergy Asthma Immunol 129(5)(Suppl):S36. Copyright 2022, with permission from Elsevier.³⁸

Abbreviations: BEC, blood eosinophil count; CI, confidence interval; FeNO, fractional exhaled nitric oxide; IgE, immunoglobulin E; Q4W, every 4 weeks.

Figure 5 Micrograph images of airway eosinophils (brown staining) from CASCADE, before and after treatment with tezepelumab.

Note: Image source: AstraZeneca, in-house data.

Figure 6 AAER during each season in patients with any seasonal aeroallergen sensitization/allergy overall (A), with baseline BEC <300 cells/μL (B), and with baseline BEC ≥300 cells/μL (C), receiving tezepelumab 210 mg Q4W or placebo. A post hoc analysis of the NAVIGATOR Phase 3 study.

Notes: Calendar seasons were defined as winter (January to March), spring (April to June), summer (July to September), and fall (October to December).

Abbreviations: AAER, annualized asthma exacerbation rate; BEC, blood eosinophil count; FEIA+, fluorescence enzyme immunoassay positive; Q4W, every 4 weeks.

Figure 7 Proportional representation of patients by baseline BEC and allergy to perennial aeroallergens in the pooled PATHWAY and NAVIGATOR populations.

Note: Excludes 35 patients with no allergy testing results.

Abbreviation: BEC, blood eosinophil count.

Gauvreau GM, Sehmi R, Ambrose CS, Griffiths JM. Thymic stromal lymphopoietin: its role and potential as a therapeutic target in asthma. Expert Opin Ther Targets. 2020;24(8):777–792. doi:10.1080/14728222.2020.1783242

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Corren J, Spahn JD, Ambrose CS, et al. Effect of tezepelumab on asthma inflammatory biomarker levels varies by baseline biomarker levels. Presented at: American College of Allergy, Asthma and Immunology (ACAAI) Annual Scientific Meeting. Louisville, KY, USA; 2022.

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