TEZSPIRE▼(TEZEPELUMAB) TO BE RECOMMENDED BY NICE AS AN ADD-ON TREATMENT FOR SEVERE UNCONTROLLED ASTHMA

• Tezspire (tezepelumab) is a first-in-class and will be the only biologic medicine to have no phenotype or biomarker limitation for people with severe uncontrolled asthma, aged 12 years and over in England and Wales.^[1],[2]  
• The final draft recommendation is based on results from the PATHFINDER programme, which included the pivotal NAVIGATOR Phase III trial, and showed that tezepelumab improved outcomes including significantly reducing the annualised rate of exacerbations compared with placebo.^[3]
• Severe uncontrolled asthma is the most serious and life-threatening type of asthma.^[4] It can be debilitating, with people experiencing frequent asthma attacks, significant limitations on lung function, and a poor quality of life.^[5],[6]^,[7]
• AstraZeneca estimates that approximately 98,000 patients in England and Wales who live with severe uncontrolled asthma may be potentially eligible for this new treatment.^[8]

London, UK, Tuesday 28 March 2023 – AstraZeneca today announced that the National Institute for Health and Care Excellence (NICE) has issued final draft guidance recommending Tezspire (tezepelumab) for use within NHS England and NHS Wales, as an add-on maintenance therapy in adult and adolescent patients, 12 years and older, with severe asthma who are inadequately controlled with high dose inhaled corticosteroids plus another medicinal product for maintenance treatment and had 3 or more exacerbations in the previous year, or are having maintenance oral corticosteroids.²  Final draft guidance is subject to appeal.

Owing to the complexity of severe asthma, many patients have unclear or multiple drivers of airway inflammation resulting in some patients not responding to the current standard of treatment, and being at increased risk of asthma attacks, hospitalisations, and a poor quality of life.^{6,[9],[10],[11]} An advancement in epithelial science has identified a pro-inflammatory cytokine or protein – thymic stromal lymphopoietin (TSLP) – implicated in multiple inflammatory pathways in asthma.^[12]

Professor David Jackson, Professor of Respiratory Medicine and Clinical Lead for Guy’s & St Thomas’ Asthma Service, said: “Today’s NICE recommendation is excellent news for our patients.  Many with severe uncontrolled asthma have multiple inflammatory drivers of disease and Tezepelumab's unique mechanism of action means it has the potential to treat a broad population of patients, irrespective of inflammatory phenotype.”

Tezepelumab is a first-in-class and the only biologic that targets TSLP, which is released by the epithelium – the inner lining of the airway in both asthma types – eosinophilic inflammation and allergic sensitisation.^[13],[14] TSLP plays a key role in the inflammatory pathway and is the first alarm that tells the body that the airway is being attacked.^[15] By blocking the action of TSLP, tezepelumab helps to suppress inflammation that contributes to asthma symptoms and exacerbations.^2,14,[16]

Today’s draft positive recommendation from NICE is based on data from the PATHFINDER clinical trial programme, including the NAVIGATOR Phase III clinical trial, published in The New England Journal of Medicine, which demonstrated a 56% reduction in the annualised asthma exacerbation rate (AAER) in severe, uncontrolled asthma patients compared to those receiving the placebo - 0.93 (95% CI, 0.80 to 1.07) with tezepelumab versus 2.10 (95% CI, 1.84 to 2.39) with placebo (rate ratio [RR], 0.44; 95% CI, 0.37 to 0.53; P<0.001).³ In patients with a blood eosinophil count of <300 cells per microlitre, the annualised rate was 1.02 (95% CI, 0.84 to 1.23) with tezepelumab and 1.73 (95% CI, 1.46 to 2.05) with placebo (RR, 0.59; 95% CI, 0.46 to 0.75; P<0.001). Importantly, Tezepelumab also demonstrated improvements in every key secondary endpoint compared to baseline, including lung function, asthma control, and health-related quality of life.³

Tezepelumab was well tolerated in patients with severe asthma and resulted in clinically meaningful reductions in asthma exacerbations in NAVIAGTOR & SOURCE clinical trials and no clinically meaningful differences in safety results between the tezepelumab and placebo groups.^[17]

An estimated 200,000 people are living with severe uncontrolled asthma in the UK.^[18] Evidence shows that patients with severe uncontrolled asthma are at greater risk of mortality than those with severe asthma.^[19] There is also a significant healthcare burden, with these patients accounting for approximately 50% of NHS asthma-related costs.^[20]

Tom Keith-Roach, President AstraZeneca UK, said: “This is an important step towards tezepelumab being considered for use in the treatment of eligible UK patients with severe uncontrolled asthma regardless of biomarker status or phenotype, opening up biologics as a treatment option for many patients across England and Wales who were historically ineligible.  We will work with NICE and the NHS in England and Wales to make tezepelumab an available and considered option in clinical practice for appropriate patients, expand system capacity, and continue to work constructively with the aim of improving outcomes for patients with severe uncontrolled asthma.”  

AstraZeneca is committed to improving asthma care for patients in the UK. We advocate the appropriate use of potentially effective therapies that address the underlying inflammation across all asthma severities. We are working towards a zero-tolerance approach to asthma attacks in the UK and are committed to reducing asthma-related exacerbations where possible in a sustainable way to benefit both patients and the environment.

[1] Electronic Medicines Compendium (EMC). Tezspire 210 mg solution for injection in pre-filled syringe – Summary of Product Characteristics (SmPC). Available at: https://www.medicines.org.uk/emc/product/14064 Last accessed March 2023.

[2] National Institute for Health and Care Excellence. Tezspire for severe uncontrolled asthma: Final appraisal document - Published 28 March 2023.

[3] Menzies-Gow A, et al. Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma. N Engl J Med. 2021;384:1800-1809.

[4] Asthma UK. What is severe asthma? Available at: https://www.asthma.org.uk/advice/severe-asthma/what-is-severe-asthma/#:~:text=Severe%20asthma%20is%20the%20most,with%20high%20doses%20of%20medicines  Last accessed March 2023.

[5] Chung KF, et al. International ERS/ATS guidelines on definition, evaluation, and treatment of severe asthma. Eur Respir J. 2014;43:343-373.

[6] Wenzel S, et al. Severe asthma in adults. Am J Respir Crit Care Med. 2005;172:149-160.

[7] Fernandes AG, et al. Risk factors for death in patients with severe asthma. J Bras Pneumol. 2014;40:364-372.

[8] AstraZeneca. Data on File. Veeva Approval ID REF- 181848. March 2023.

[9] 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.

[10]  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; r116:37–42.

[11] Godar M, et al. Personalized medicine with biologics for severe type 2 asthma: current status and future prospects. MAbs. 2018; 10 (1): 34‐45

[12] Duchesne M, et al. Epithelial cell alarmin cytokines: Frontline mediators of the asthma inflammatory response. Front Immunol. 2022 Oct 14;13:975914. doi: 10.3389/fimmu.2022.975914. PMID: 36311787; PMCID: PMC9616080.

[13] Varricchi G, et al. Thymic Stromal Lymphopoietin Isoforms, Inflammatory Disorders, and Cancer. Front Immunol. 2018; 9: 1595.

[14] Corren J, et al. Tezepelumab in Adults with Uncontrolled Asthma [published correction appears in N Engl J Med. 2019 May 23;380(21):2082]. N Engl J Med. 2017; 377 (10): 936-946.

[15] Gauvreau GM, et al. Sounding the alarmins-The role of alarmin cytokines in asthma. Allergy. 2023 Feb;78(2):402-417. doi: 10.1111/all.15609. Epub 2022 Dec 14. PMID: 36463491.

[16] 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. The Journal of Immunology. 2018; 200: 2253–2262.

[17] Menzies-Gow A, et al. S47 DESTINATION: tezepelumab long-term safety and efficacy versus placebo in patients with severe, uncontrolled asthma, BMJ Thorax 2022;77:A32.

[18] Oxford Academic Health Science Network. Consensus pathway for management of uncontrolled asthma in adults. Available at: https://www.oxfordahsn.org/our-work/respiratory/asthma-biologics-toolkit/aac-consensus-pathway-for-management-of-uncontrolled-asthma-in-adults/#:~:text=Up%20to%20200%2C000%20people%20in,high%20dose%20steroid%2Dbased%20medication Last accessed March 2023.

[19] Roche N, et al. Real-life impact of uncontrolled severe asthma on mortality and healthcare use in adolescents and adults: findings from the retrospective, observational RESONANCE study in France BMJ Open 2022;12:e060160. doi: 10.1136/bmjopen-2021-060160

[20] Nunes C, Pereira AM, Morais-Almeida M. Asthma costs and social impact. Asthma Res Pract. 2017 Jan 6;3:1. doi: 10.1186/s40733-016-0029-3. PMID: 28078100; PMCID: PMC5219738.