Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Mar 19:17:219-236.
doi: 10.2147/JAA.S342391. eCollection 2024.

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

Reynold Panettieri Jr  1 , Njira Lugogo  2 , Jonathan Corren  3 , Christopher S Ambrose  4
Affiliations
Review

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

Reynold Panettieri Jr et al. J Asthma Allergy. .

Abstract

Asthma is a heterogeneous inflammatory disease of the airways, affecting many children, adolescents, and adults worldwide. Up to 10% of people with asthma have severe disease, associated with a higher risk of hospitalizations, greater healthcare costs, and poorer outcomes. Patients with severe asthma generally require high-dose inhaled corticosteroids and additional controller medications to achieve disease control; however, many patients remain uncontrolled despite this intensive treatment. The treatment of severe uncontrolled asthma has improved with greater understanding of asthma pathways and phenotypes as well as the advent of targeted biologic therapies. Tezepelumab, a monoclonal antibody, blocks thymic stromal lymphopoietin, an epithelial cytokine that has multifaceted effects on the initiation and persistence of asthma inflammation and pathophysiology. Unlike other biologic treatments, tezepelumab has demonstrated efficacy across severe asthma phenotypes, with the magnitude of effects varying by phenotype. Here we describe the anti-inflammatory effects and efficacy of tezepelumab across the most relevant phenotypes of severe asthma. Across clinical studies, tezepelumab reduced annualized asthma exacerbation rates versus placebo by 63-71% in eosinophilic severe asthma, by 58-68% in allergic severe asthma, by 67-71% in allergic and eosinophilic severe asthma, by 34-49% in type 2-low asthma, and by 31-41% in oral corticosteroid-dependent asthma. Furthermore, in all these asthma phenotypes, tezepelumab demonstrated higher efficacy in reducing exacerbations requiring hospitalizations or emergency department visits versus placebo. In patients with severe uncontrolled asthma, who commonly have multiple drivers of inflammation and disease, tezepelumab may modulate airway inflammation more extensively, as other available biologics block only specific downstream components of the inflammatory cascade.

Keywords: airway hyperresponsiveness; allergic; eosinophilic; exacerbations; oral corticosteroid-dependent; type 2.

Plain language summary

Asthma is characterized by an immune response leading to airway inflammation. People with severe asthma may react to different triggers and develop different types of airway inflammation. In patients with asthma, a protein called thymic stromal lymphopoietin (TSLP) plays an important role in the immune response that leads to the signs and symptoms of asthma. TSLP is released by the airway lining in response to different asthma triggers, driving an immune chain reaction, leading to airway narrowing and tightening, increased airway inflammation, worsening asthma symptoms, and asthma attack. Tezepelumab is a monoclonal antibody (a type of protein) that prevents TSLP from attaching to its receptor, thereby blocking its activity, reducing airway inflammation and asthma symptoms. Tezepelumab is an add-on medicine for the treatment of people aged 12 years or older with severe asthma that is not controlled with their current medicines. In this article, we discuss how tezepelumab may work in different types of asthma, for example allergic asthma, eosinophilic asthma, and T2-low asthma. We also describe how effective tezepelumab is in these different asthma types, through the reduction of asthma attacks and improvement in lung function, symptom control, and quality of life, leading to fewer emergency department visits and hospitalizations for asthma.

PubMed Disclaimer

Conflict of interest statement

RP Jr received consulting/advisory board fees from AstraZeneca, Genentech, Praesidia Biotherapies Inc., RIFM, and TEVA; fees for speaking from AstraZeneca, Merck & Co, and Sanofi; and research grants from ACTIV-1, AgoMab, AstraZeneca, Janssen, Medimmune, RIFM, TEVA, and Vault Health. NL received consulting fees from Amgen, AstraZeneca, Avillion, Genentech, GSK, Novartis, Regeneron, Sanofi, and Teva; honoraria for non-speaker bureau presentations from GSK and Astra Zeneca; and travel support from Astra Zeneca, Sanofi and GSK; her institution received research support from Amgen, AstraZeneca, Avillion, Evidera, Gossamer Bio, Genentech, GSK, Janssen, Regeneron, Sanofi, Novartis and Teva. She is an honorary faculty member of Observational and Pragmatic Research Institute (OPRI) but does not receive compensation for this role. JC received grants and personal fees from AstraZeneca, Genentech and Vectura, and has received grants from Optinose, Regeneron, Novartis, Pulmatrix, Sanofi and Teva Pharmaceuticals. CA is an employee of AstraZeneca and holds stock and stock options. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Epithelial cytokines and other inflammatory mediators and cell types involved in asthma pathogenesis.,
Figure 2
Figure 2
Histopathological staining for TSLP (yellow) in asthmatic bronchiolar epithelial and stromal cells.
Figure 3
Figure 3
Summary of mechanisms and efficacy of tezepelumab in severe asthma, by asthma subtype.
Figure 4
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.
Figure 5
Figure 5
Micrograph images of airway eosinophils (brown staining) from CASCADE, before and after treatment with tezepelumab.
Figure 6
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.
Figure 7
Figure 7
Proportional representation of patients by baseline BEC and allergy to perennial aeroallergens in the pooled PATHWAY and NAVIGATOR populations.
See this image and copyright information in PMC

References

    1. Busse WW. Biological treatments for severe asthma: a major advance in asthma care. Allergol Int. 2019;68(2):158–166. doi: 10.1016/j.alit.2019.01.004 - DOI - PubMed
    1. Menzies-Gow A, Wechsler ME, Brightling CE. Unmet need in severe, uncontrolled asthma: can anti-TSLP therapy with tezepelumab provide a valuable new treatment option? Respir Res. 2020;21(1):268. doi: 10.1186/s12931-020-01505-x - DOI - PMC - PubMed
    1. The global asthma report 2022. Int J Tuberc Lung Dis. 2022;26(1):1–104. doi: 10.5588/ijtld.22.1010 - DOI - PubMed
    1. 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 - DOI - PubMed
    1. Backman H, Jansson SA, Stridsman C, et al. Severe asthma-A population study perspective. Clin Exp Allergy. 2019;49(6):819–828. doi: 10.1111/cea.13378 - DOI - PubMed