Abstract
Tezepelumab, a biologic therapy for severe asthma, blocks TSLP activity, subsequently downregulating multiple type 2 inflammatory pathways and reducing airway hyperresponsiveness via eosinophil-independent effects https://bit.ly/3XGpaV3
Extract
Tezepelumab is a human monoclonal antibody (IgG2λ) approved in several countries and regions, including the USA and the EU, for the treatment of severe asthma. Approval was based on evidence from the phase 2b PATHWAY study (NCT02054130) and the phase 3 NAVIGATOR study (NCT03347279) [1, 2]. Tezepelumab blocks the activity of thymic stromal lymphopoietin (TSLP), an epithelial cytokine. Questions have been raised about the mechanisms of action of tezepelumab in patients with asthma, particularly regarding the effects beyond reductions in eosinophil counts in the blood and airways [3]. Here, we outline clinical evidence and mechanistic insights from randomised clinical trials supporting the multiple mechanisms of tezepelumab, including those relevant to type 2 (T2)-high and T2-low asthma.
Acknowledgements
Medical writing support was provided by Priyanka Narang of PharmaGenesis London, London, UK, with funding from AstraZeneca and Amgen Inc. Andrew Menzies-Gow has a new and additional affiliation of Respiratory and Immunology, BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK.
Footnotes
Conflict of interest: J. Corren has received grants from AstraZeneca, Genentech, Optinose, Sanofi, Teva Pharmaceuticals and Vectura, and has received personal fees from AstraZeneca, Genentech and Vectura. C.E. Brightling has received grants and consultancy fees from 4D Pharma, AstraZeneca, Chiesi, Genentech, GlaxoSmithKline, Mologic, Novartis, Regeneron Pharmaceuticals, Roche and Sanofi. L-P. Boulet has received grants and consultancy fees from Amgen, AstraZeneca, Biohaven, Cipla, Covis Pharma, GlaxoSmithKline, Merck, Novartis, Sanofi-Regeneron and Teva Pharmaceuticals. C. Porsbjerg has received grants and consultancy fees from ALK, AstraZeneca, Chiesi, GlaxoSmithKline, Teva Pharmaceuticals, Novartis and Sanofi. M.E. Wechsler is an employee of National Jewish Health and has received consultancy, advisory or speaking fees from Amgen, AstraZeneca, Ayala Therapeutics, Boehringer Ingelheim, Cerecor, Cohero Health, Cytoreason, Eli Lilly, Equillium, GlaxoSmithKline, Incyte, Kinaset Therapeutics, Novartis, Pylaxis, Pulmatrix, Rapt Therapeutics, Regeneron Pharmaceuticals, resTORbio, Roche/Genentech, Sanofi/Genzyme, Sentien, Sound Biologics, Teva Pharmaceuticals and Upstream Bio. A. Menzies-Gow is an employee of AstraZeneca and may own stock or stock options in AstraZeneca, has attended advisory boards for AstraZeneca, GlaxoSmithKline, Novartis, Regeneron Pharmaceuticals, Sanofi and Teva Pharmaceuticals, has received speaker fees from AstraZeneca, Novartis, Roche 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. C.S. Ambrose, B. Cook, N. Martin and J. Spahn are employees of AstraZeneca and may own stock or stock options in AstraZeneca. J-P. Llanos is an employee of Amgen and owns stock in Amgen.
Support statement: Supported by Amgen and AstraZeneca. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received November 16, 2022.
- Accepted February 10, 2023.
- Copyright ©The authors 2023. For reproduction rights and permissions contact permissions{at}ersnet.org