Add-on treatment for severe uncontrolled asthma approved 

The National Institute for Health and Care Excellence (NICE) has issued final draft guidance recommending AstraZeneca’s Tezspire (tezepelumab). 

The drug is approved for use within NHS England and NHS Wales and as 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 have had three or more exacerbations in the previous year, or are having maintenance oral corticosteroids1,2. Final draft guidance is subject to appeal.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 life3,4,5,6. An advancement in epithelial science has identified a pro-inflammatory cytokine or protein – thymic stromal lymphopoietin (TSLP) – implicated in multiple inflammatory pathways in asthma.7

Background 

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.2,8,9

This 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.10

An estimated 200,000 people are living with severe uncontrolled asthma in the UK.11 Evidence shows that patients with severe uncontrolled asthma are at greater risk of mortality than those with severe asthma. There is also a significant healthcare burden, with these patients accounting for approximately 50% of NHS asthma-related costs.12

The trial

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.13

Official comment

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.”  

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.”    

References

  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. Wenzel S, et al. Severe asthma in adults. Am J Respir Crit Care Med. 2005;172:149-160. 
  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. Godar M, et al. Personalized medicine with biologics for severe type 2 asthma: current status and future prospects. MAbs. 2018; 10 (1): 34‐45 
  7. 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. 
  8. 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. 
  9. 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. 
  10. Menzies-Gow A, et al. Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma. N Engl J Med. 2021;384:1800-1809. 
  11. 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. 
  12. 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. 
  13. 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. 

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