First and only biologic recommended for EU approval in patients with severe asthma with no phenotype or biomarker limitations.
Tezspire is the first and only biologic for severe asthma that acts at the top of the inflammatory cascade by blocking thymic stromal lymphopoietin (TSLP), an epithelial cytokine.1-4 Tezspire consistently and significantly reduced asthma exacerbations across Phase II and III clinical trials, which included a broad population of severe asthma patients irrespective of key biomarkers, including blood eosinophil counts, allergic status and fractional exhaled nitric oxide (FeNO).1,2
Dr.
Results from the NAVIGATOR Phase III trial were published in
In clinical trials, the most common adverse events in patients who received Tezspire were pharyngitis, rash, arthralgia and injection site reactions.5
Tezspire was approved as an add-on maintenance treatment of adult and paediatric patients aged 12 years and older with severe asthma in the US in
Notes
Severe asthma
Asthma is a heterogeneous disease affecting approximately 14 million people living with the disease in the
Severe, uncontrolled asthma is debilitating with patients experiencing frequent exacerbations, significant limitations on lung function and a reduced quality of life.9,10,14 Patients with severe asthma are at an increased risk of mortality and compared to patients with persistent asthma have twice the risk of asthma-related hospitalisations.15-17 There is also a significant socio-economic burden, with these patients accounting for approximately 50% of asthma-related costs.18
Clinical trials
In addition to the Phase IIb PATHWAY trial, the PATHFINDER programme included two Phase III trials, NAVIGATOR1,19 and SOURCE.20,21 The programme also includes additional mechanistic and long-term safety trials.22,23
NAVIGATOR is a Phase III, randomised, double-blinded, placebo-controlled trial in adults (18-80 years old) and adolescents (12-17 years old) with severe, uncontrolled asthma, who were receiving standard of care (SoC). SoC was treatment with medium- or high-dose inhaled corticosteroids plus at least one additional controller medication with or without daily OCS treatment. The trial population included approximately equal proportions of patients with high (≥300 cells per microlitre) and low (<300 cells per microlitre) blood eosinophil counts. The trial comprised a five-to-six-week screening period, a 52-week treatment period and a 12-week post-treatment follow-up period. All patients received their prescribed controller medications without change throughout the trial.1
The primary efficacy endpoint was the annualised asthma exacerbation rate (AAER) during the 52-week treatment period. Key secondary endpoints included the effect of Tezspire on lung function, asthma control and health-related quality of life.1
As part of prespecified analyses, the AAER over 52 weeks was also assessed in patients grouped by baseline blood eosinophil count, FeNO level and serum specific immunoglobin E (IgE) status (perennial aeroallergen sensitivity positive or negative).1 These are inflammatory biomarkers used by clinicians to inform treatment options and involve tests analysing a patient's blood (eosinophils/IgE) and exhaled air (FeNO).
There were no clinically meaningful differences in safety results between the Tezspire and placebo groups in the NAVIGATOR trial.1 The most frequently reported adverse events for Tezspire were nasopharyngitis, upper respiratory tract infection and headache.1
NAVIGATOR is the first Phase III trial to show benefit in severe asthma irrespective of eosinophils by targeting TSLP.1 These results support the FDA Breakthrough Therapy Designation granted to Tezspire in
Patients who participated in our Phase III trials were eligible to continue in DESTINATION, a Phase III extension trial assessing long-term safety and efficacy.22
Tezspire
Tezspire (tezepelumab) is being developed by
Tezspire is approved in the US for the add-on maintenance treatment of adult and paediatric patients aged 12 years and older with severe asthma.6 Tezspire is also in development for other potential indications including chronic obstructive pulmonary disease (COPD), chronic rhinosinusitis with nasal polyps, chronic spontaneous urticaria and eosinophilic esophagitis (EoE). In
In 2020,
Respiratory & Immunology, part of BioPharmaceuticals, is one of
With common pathways and underlying disease drivers across respiratory and immunology,
Contacts
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References
- Menzies-Gow A, et al. Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma. N Engl J Med. 2021;384:1800-1809. DOI: 10.1056/NEJMoa2034975.
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Corren J, et al. Tezepelumab in adults with uncontrolled asthma [supplementary appendix; updated
April 18, 2019 ]. N Engl J Med. 2017;377:936-946. - Varricchi G, et al. Thymic Stromal Lymphopoietin Isoforms, Inflammatory Disorders, and Cancer. Front Immunol. 2018;9:1595.
- Li Y, et al. Elevated Expression of IL-33 and TSLP in the Airways of Human Asthmatics In Vivo: A Potential Biomarker of Severe Refractory Disease. J Immunol. 2018;200:2253-2262.
European Medicines Agency . Tezspire Summary of Committee for Medicinal Products for Human Use Opinion Available at: https://www.ema.europa.eu/en/medicines/human/summaries-opinion/tezspire [Last accessed: July 2022].- Tezspire (tezepelumab) US prescribing information; 2021.
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Demoly P, et al. Prevalence of asthma control among adults in
France ,Germany ,Italy ,Spain and theUK . Eur Respir Rev. 2009;18:105-112. - The Global Asthma Network. The Global Asthma Report 2018. [Online]. Available at: http://globalasthmareport.org/resources/Global_Asthma_Report_2018.pdf. [Last accessed: July 2022].
- Chung KF, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014;43:343-373.
Wenzel S. Severe asthma in adults. Am J Respir Crit Care Med. 2005;172:149-160.- Peters SP, et al. Uncontrolled asthma: a review of the prevalence, disease burden and options for treatment. Respir Med 2006:100:1139-1151.
- Hyland ME, et al. A Possible Explanation for Non-responders, Responders and Super-responders to Biologics in Severe Asthma. Explor Res Hypothesis Med. 2019;4:35-38.
- Tran TN, et al. Overlap of atopic, eosinophilic, and TH2-high asthma phenotypes in a general population with current asthma. Ann Allergy Asthma Immunol. 2016;116:37-42.
Fernandes AG , et al. Risk factors for death in patients with severe asthma. J Bras Pneumol. 2014;40:364-372.- Chastek B, et al. Economic Burden of Illness Among Patients with Severe Asthma in a Managed Care Setting. J Manag Care Spec Pharm. 2016;22:848-861.
- Hartert TV, et al. Risk factors for recurrent asthma hospital visits and death among a population of indigent older adults with asthma. Ann Allergy Asthma Immunol. 2002;89:467-473.
- Price D, et al. Asthma control and management in 8,000 European patients: the REcognise Asthma and LInk to Symptoms and Experience (REALISE) survey. NPJ Prim Care Respir Med. 2014;24:14009.
World Allergy Organization (WAO). The management of severe asthma: economic analysis of the cost of treatments for severe asthma. Available at: https://www.worldallergy.org/educational_programs/world_allergy_forum/anaheim2005/blaiss.php. [Last accessed: July 2022].- Menzies-Gow A, et al. NAVIGATOR: a phase 3 multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy and safety of tezepelumab in adults and adolescents with severe, uncontrolled asthma. Respir Res. 2020;21:266.
- Wechsler ME, et al. Evaluation of the oral corticosteroid-sparing effect of tezepelumab in adults with oral corticosteroid-dependent asthma (SOURCE): a randomised, placebo-controlled, phase 3 study. Lancet Respir Med. 2022;S2213-S2600(21):00537-3.
- Wechlser ME, et al. SOURCE: A Phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel group trial to evaluate the efficacy and safety of Tezepelumab in reducing oral corticosteroid use in adults with oral corticosteroid dependent asthma. Respir Res. 2020;21:264.
- Clinicaltrials.gov. Extension Study to Evaluate the Safety and Tolerability of Tezepelumab in Adults and Adolescents With Severe, Uncontrolled Asthma (DESTINATION) [Online]. Available at: https://clinicaltrials.gov/ct2/show/NCT03706079. [Last accessed: July 2022].
- Diver S et al. Effect of tezepelumab on airway inflammatory cells, remodelling, and hyperresponsiveness in patients with moderate-to-severe uncontrolled asthma (CASCADE): a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet Respir Med. 2021;9:1299-1312.
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