TWO KEY MEDICINES FOR SEVERE ASTHMA AND CHRONIC HEART FAILURE ACCEPTED FOR USE IN SCOTLAND BY THE SCOTTISH MEDICINES CONSORTIUM

• Tezspire▼(tezepelumab) is a first-in-class biologic medicine and now has the widest patient access for any severe asthma biologic in Scotland.[1]^,[2]^,[3]^,[4]^,[5]^,[6]
• Forxiga (dapagliflozin) has been accepted for symptomatic chronic heart failure (HF) with left ventricular ejection fraction (LVEF) >40%.[7] Having already been accepted for use in Scotland as a treatment option for HF patients with reduced ejection fraction (LVEF ≤40%)[8] healthcare professionals can now prescribe the same medicine for patients with chronic heart failure, no matter what their ejection fraction.7
• Based on our estimations, approximately 4,000 people in Scotland may be eligible for tezepelumab to treat their severe asthma,2 while more than 23,000 people in Scotland could be eligible for dapagliflozin to treat their symptomatic chronic heart failure (HF) with left ventricular ejection fraction (LVEF) >40%. [9]
• The SMC's decisions will ensure that people with severe asthma and chronic heart failure in Scotland have access to these treatments on the NHS, in line with people in the rest of the United Kingdom, where the medicines are already approved by the National Institute for Health and Care Excellence (NICE).^2,7,[10]^,[11]

 

London, UK, Monday 7 August 2023 – AstraZeneca is pleased that the SMC has today published advice recommending the use of Tezspire (tezepelumab) in severe asthma and Forxiga (dapagliflozin) in chronic heart failure within NHS Scotland by the Scottish Medicines Consortium (SMC).^2,7

 

Tezepelumab has been accepted for restricted use by the SMC as an add-on maintenance treatment for adult and adolescent patients, 12 years and older, with severe asthma who are inadequately controlled despite high dose inhaled corticosteroids plus another medicinal product for maintenance treatment.² Patients must have either had three or more exacerbations (asthma attacks) in the previous year and not be receiving maintenance treatment with oral corticosteroids; or patients must have blood eosinophils (white blood cells released in response to allergic reactions) ≥150 cells per microlitre and be receiving maintenance treatment with oral corticosteroids.²

 

Dapagliflozin has also been accepted for use by the SMC in adults for the treatment of symptomatic chronic heart failure (HF) with left ventricular ejection fraction (LVEF) >40%,7 meaning that it is now available in Scotland for people with HF across the full spectrum of ejection fraction.7

 

AstraZeneca estimates that over 27,000 people (more than 4,000 people with severe uncontrolled asthma and more than 23,000 people with symptomatic chronic heart failure with LVEF >40%) may potentially be eligible for treatment in Scotland.^2,9 These decisions will now enable people across the entire United Kingdom to be treated with these medicines.^2,7,10^,11

 

Tezepelumab in severe uncontrolled asthma

 

Due to the complexity of severe asthma, many patients have multiple drivers of airway inflammation or overlapping phenotypes,[12] resulting in some patients not responding well to the current standard of care treatment and therefore being at increased risk of an asthma attack, hospitalisation, and a poor quality of life.[13]^{,[14],[15],[16]}   Tezepelumab has demonstrated efficacy across multiple phenotypes, and today's acceptance by the SMC provides a valuable and efficacious biologic option for people with uncontrolled severe asthma.[17]

 

Professor Tom Fardon, Honorary Professor at the University of Dundee and Consultant Physician in Respiratory Medicine at NHS Tayside said: “Tezepelumab has the potential to treat a broad population of patients as a first-in-class biologic treatment for severe asthma, affecting multiple steps in the inflammatory cascade, demonstrating efficacy across multiple phenotypes. Today’s acceptance by the SMC for restricted use importantly widens access for biologic treatment to more patients in Scotland.”

 

Today’s decision from the SMC 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.[18] Results demonstrated a 56% reduction in the annualised asthma exacerbation rate (AAER) for the tezepelumab arm in a broad population of severe, uncontrolled asthma patients irrespective of eosinophil level compared with those receiving the placebo: 0.93 (95% CI, 0.80 to 1.07) versus 2.10 (95% CI, 1.84 to 2.39) respectively, (rate ratio [RR], 0.44; 95% CI, 0.37 to 0.53; p<0.001). 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).18 Importantly, tezepelumab also demonstrated improvements in every key secondary endpoint compared to baseline, including lung function, asthma control, and health-related quality of life.18

 

Tezepelumab is a first-in-class licensed biologic which significantly reduced asthma exacerbations versus placebo across the PATHWAY and NAVIGATOR clinical trials, which included a broad population of severe uncontrolled asthma patients irrespective of key biomarkers.^1,11,18,[19]  Tezepelumab was well tolerated in patients with severe asthma and resulted in clinically meaningful reductions in asthma exacerbations in NAVIGATOR & SOURCE clinical trials and no clinically meaningful differences in safety results were identified between the tezepelumab and placebo groups.[20]

 

Dapagliflozin in chronic heart failure

 

Around 48,000 people in Scotland have been diagnosed with HF, of which approximately 50% of these patients have HF with LVEF >40%.^9,[21] HF accounts for more than 100,000 hospitalisations each year in the UK and admissions have risen by nearly a third in the past five years.[22] HF significantly impacts patients’ physical, mental and social wellbeing and around half of all patients with HF die within five years of diagnosis.[23]^,[24],[25]

 

This decision by the SMC is based on results from the DELIVER Phase III trial, which showed that dapagliflozin was more effective than placebo in patients with heart failure with a left ventricular ejection fraction of more than 40%, in reducing the risk of a primary composite outcome of: worsening heart failure, defined as either an unplanned hospitalisation for heart failure or an urgent visit for heart failure, or cardiovascular death (16.4% vs 19.5% patients with event respectively) [hazard ratio {HR} =0.82 {95% CI 0.73-0.92}; p<0.001 median follow up of 2.3 years].[26]  

 

Professor John McMurray, Professor of Medical Cardiology at the University of Glasgow, and honorary Consultant Cardiologist at the Queen Elizabeth University Hospital, Glasgow, UK, said: “Dapagliflozin has the potential to reduce cardiovascular deaths, heart failure hospitalisations and ease growing pressures on cardiac services within Scotland, as demonstrated in the DELIVER trial. The decision by the SMC, which comes on the heels of the recent NICE announcement, importantly ensures equitable access for patients living with heart failure in Scotland, in line with patients in England and Wales.”

 

Tom Keith-Roach, President AstraZeneca UK, said: “We are pleased that the SMC has now accepted dapagliflozin for use in patients with chronic heart failure with preserved or mildly reduced ejection fraction and tezepelumab has been accepted for restricted use in severe asthma within NHS Scotland. We’re now committed to working with NHS Scotland at all levels to ensure that appropriate patients have access to these medicines in day-to-day medical practice as soon as possible.”

 

– ENDS –

 

NOTES TO EDITORS

 

About tezepelumab

Tezepelumab has been developed by AstraZeneca in collaboration with Amgen as a human monoclonal antibody that inhibits the action of thymic stromal lymphopoietin (TSLP), an epithelial-cell-derived cytokine implicated in multiple downstream processes involved in asthma pathophysiology.18 TSLP is released in response to multiple triggers associated with asthma exacerbations, including allergens, viruses, and other airborne particles.19^,[27] Expression of TSLP is increased in the airways of patients with asthma and has been correlated with disease severity.19^,[28] Blocking TSLP may prevent the release of pro-inflammatory cytokines by immune cells, which may result in the prevention of asthma exacerbations.19^,28

 

Common (frequency ≥1/100 to <1/10) adverse events (AEs) associated with tezepelumab include pharyngitis, arthralgia, rash and injection site reactions.¹

 

For complete information on tezepelumab, the summary of product characteristics, including a full list of adverse reactions is available here: https://www.medicines.org.uk/emc/product/14064.

 

NAVIGATOR and the PATHFINDER clinical trial programme

Building on the Phase IIb PATHWAY trial, the Phase III PATHFINDER programme included the NAVIGATOR phase III clinical trial.[29]^,[30]

 

NAVIGATOR is a Phase III, randomised, double-blinded, placebo-controlled trial in 1,589 adults and adolescents aged 12–80 years old with severe, uncontrolled asthma, who were receiving standard of care (SoC).30 SoC was treatment with medium or high dose inhaled corticosteroids plus at least one additional controller medication with or without oral corticosteroids.18 The trial population included patients with blood eosinophils at both ≥300 cells per microlitre and <300 cells per microlitre.18 The trial comprised a five-to-six-week screening period, a 52-week treatment period and a 12-week post-treatment follow-up period.18 All patients received their prescribed corticosteroid and controller medications without change throughout the trial.18

 

The NAVIGATOR Phase III trial met its primary endpoint in demonstrating that patients with severe uncontrolled asthma who were treated with tezepelumab (n=528) demonstrated a significantly reduced annualised rate of asthma exacerbations (reduction, 56%; rate ratio [RR], 0.44; 95% CI, 0.37 to 0.53; p<0.001), when compared to those treated with placebo (n=531).18 In patients with a blood eosinophil count of <300 cells per microliter, 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).18

 

The NAVIGATOR Phase III trial also met a key secondary endpoint, with patients treated with tezepelumab demonstrating improved lung function (difference in prebronchodilator FEV₁ at 52 weeks, 0.13 litres; 95% CI, 0.08 to 0.18; p<0.001) compared to patients treated with placebo.18 In an additional secondary endpoint, a reduction of asthma exacerbations associated with hospitalisation was observed in patients treated with tezepelumab (reduction, 79%; RR, 0.21; 95% CI, 0.12 to 0.37), when compared to placebo.18

 

About asthma and severe uncontrolled asthma

Around 8 million people, or over 12% of the population, are living with asthma in the UK.[31] Every 10 seconds someone in the UK has a potentially life-threatening asthma attack, and on average, three people die from asthma every day.[32]

 

An estimated 200,000 people are living with severe asthma in the UK.[33] There is also a significant healthcare burden, with these patients accounting for approximately 50% of NHS asthma-related costs.[34] Due to the complexity of severe uncontrolled asthma, approximately 60% of patients have multiple drivers of inflammation and may not qualify for or respond well to a current biologic medicine.14^,[35]  

 

Amgen collaboration

In 2020, Amgen and AstraZeneca updated a 2012 collaboration agreement for tezepelumab. AstraZeneca continues to lead development, and Amgen continues to lead manufacturing. All aspects of the collaboration are under the oversight of joint governing bodies.

 

About Heart Failure

Heart Failure (HF) is a life-threatening chronic disease in which the heart is unable to pump blood around the body properly.[36]^,[37] An estimated 920,000 people live with HF in the UK.[38] Around half of all patients will die within five years of diagnosis.23 The mortality risk from HF at five years, is worse than some of the most common cancers including, prostate, breast, and bladder cancer in men.[39]

 

About HF and Ejection Fraction

There are three main types of HF according to left ventricular ejection fraction (LVEF),[40] a measurement of the percentage of blood leaving the heart each time it contracts,[41] including: 

• HF with reduced ejection fraction (HFrEF) classified as LVEF ≤40%.10
• HF with mildly reduced ejection fraction (HFmrEF) classified as LVEF 41-49%.10
• HF with preserved ejection fraction (HFpEF) classified as LVEF ≥50%.¹⁰

 

Heart failure with LVEF >40% affects approximately 50% of patients with HF.⁹ HFpEF, also commonly known as diastolic HF occurs when the left ventricle is unable to fill efficiently with blood.41  The risk of HFpEF is increased by the presence of diabetes, hypertension, or obesity.10^,36 Until recently, the only therapies recommended for HFpEF have been diuretics, used to manage symptoms by removing fluid, alongside management of comorbidities.[42]^,[43]

 

About dapagliflozin

Dapagliflozin is an oral, once-daily selective and reversible inhibitor of human sodium-glucose co-transporter 2 (SGLT2). Dapagliflozin is indicated in adults for the treatment of symptomatic chronic HF.[44]

 

Common (frequency ≥1/100 to <1/10) adverse events (AEs) associated with dapagliflozin in placebo-controlled clinical studies and post-marketing experience include genital infections; urinary tract infection; dizziness; rash; back pain; dysuria; polyuria; haematocrit increased, creatinine renal clearance decreased during initial treatment and dyslipidaemia.44

 

For complete information on dapagliflozin the summary of product characteristics, including a full list of side effects and adverse reactions is available here:

https://www.medicines.org.uk/emc/product/7607/smpc#gref

 

About DELIVER

DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure) was an international, randomised, double-blind, parallel-group, placebo-controlled, event-driven Phase III trial designed to evaluate the efficacy of dapagliflozin, compared with placebo, in the treatment of HF patients with LVEF >40%, with or without type 2 diabetes (T2D).24 DELIVER is the largest clinical trial to date in HF patients with LVEF above 40%, with 6,263 randomised patients.26  

 

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. AstraZeneca operates in over 100 countries and its medicines are used by millions of patients worldwide.

 

With a proud 100-year heritage in advancing UK science, today AstraZeneca is the UK’s leading biopharmaceutical company. AstraZeneca is based in six separate locations across the UK, with its global headquarters in Cambridge. In the UK, around 8,600 employees work in research and development, manufacturing, supply, sales, and marketing. We supply around 35 different medicines to the NHS.

 

For more information, please visit www.astrazeneca.co.uk and follow us on Twitter @AstraZenecaUK.

 

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: August 2023.

[2] Scottish Medicine Consortium. Tezepelumab solution for injection in pre-filled syringe (Tezspire^®): Detailed advice document SMC2541 – published 07 August 2023.

[3] Scottish Medicines Consortium. Omalizumab 150mg solution for injection (Xolair^®). SMC 708/11. Published May 2011.

[4] Scottish Medicines Consortium. Mepolizumab 100mg powder for solution for injection (Nucala^®). SMC1149/16. Published May 2016.

[5] Scottish Medicines Consortium. Benralizumab 30mg solution for injection in pre-filled syringe (Fasenra^®). SMC2155. Published May 2019.

[6] Scottish Medicines Consortium. Dupilumab 200mg and 300mg solution for injection in pre-filled syringe and pen (Dupixent^®). SMC2317. Published March 2021.

[7] Scottish Medicine Consortium. Dapagliflozin film-coated tablets (Forxiga®): Detailed advice document SMC2577– published 07 August 2023.

[8] Scottish Medicines Consortium. Dapagliflozin film-coated tablets (Forxiga®): Detailed Advice Document SMC 2322 – Published March 2021.

[9] AstraZeneca UK Ltd. Data on File. ID: REF-199029. Number of HF patients with LVEF>40% in Scotland - data for SMC press release. 2023.

[10] National Institute of Health and Care Excellence. Forxiga Health Technology Evaluation. TA902. Available at: https://www.nice.org.uk/guidance/ta902/resources/dapagliflozin-for-treating-chronic-heart-failure-with-preserved-or-mildly-reduced-ejection-fraction-pdf-82615423312069. Last accessed: August 2023.

[11] National Institute of Health and Care Excellence. Tezspire Health Technology Evaluation. TA880. Available at: https://www.nice.org.uk/guidance/ta880/resources/tezepelumab-for-treating-severe-asthma-pdf-82613726899909. Last accessed: August 2023.

[12] Kuruvilla ME, Lee FE, Lee GB. Understanding Asthma Phenotypes, Endotypes, and Mechanisms of Disease. Clin Rev Allergy Immunol. 2019 Apr;56(2):219-233

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

[14] 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.

[15] 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.

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

[17] Corren J et al. Efficacy of tezepelumab in patients with severe, uncontrolled asthma: a pooled analysis of the phase 2b PATHWAY and phase 3 NAVIGATOR studies. Poster presented at: AAAAI 2022 (Poster 044).

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

[19] 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.

[20] 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.

[21] British Heart Foundation. Scotland Factsheet. Available at: https://www.bhf.org.uk/-/media/files/for-professionals/research/heart-statistics/bhf-cvd-statistics-scotland-factsheet.pdf?rev=fb6f0291616249529cf89e612f2b7bd7&hash=1DBC3E7DB796ED76405E18B20A4BD1CD. Last accessed: August 2023.

[22] British Heart Foundation. Heart Failure: A blueprint for change. Available at: https://www.bhf.org.uk/-/media/files/health-intelligence/heart-failure-a-blueprint-for-change.pdf?rev=f89dedb7c933452e8086cc063ff98c26&hash=CF140A8A7C54679044042151B809E97C. Last accessed: August 2023

[23] Taylor CJ, Ordóñez-Mena JM, Roalfe AK, et al. Trends in survival after a diagnosis of heart failure in the United Kingdom 2000-2017: population-based cohort study. BMJ. 2019;364:l223.

[24] NHS Inform. Adjusting to life with a heart condition. Available at: https://www.nhsinform.scot/illnesses-and-conditions/heart-and-blood-vessels/living-with-a-heart-condition/adjusting-to-life-with-a-heart-condition. Last accessed: August 2023.

[25] Freedland KE, et al. Improving quality of life in heart failure. Curr Cardiol Rep. 2021;23(11):159.

[26] Solomon SD, McMurray JJV, Claggett B, et al. Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. N Engl J Med. 2022;387:1089-1098.

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

[28] 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.

[29] Clinicaltrials.gov. Study to Evaluate Tezepelumab in Adults & Adolescents With Severe Uncontrolled Asthma (NAVIGATOR). Available at: https://clinicaltrials.gov/ct2/show/NCT03347279. Last accessed: August 2023.

[30] 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.

[31] British Lung Foundation. Asthma statistics. Available at: https://statistics.blf.org.uk/asthma. Last accessed: August 2023.

[32] Asthma UK. Slipping through the net: The reality facing patients with difficult and severe asthma. Available at: auk-severe-asthma-gh-final.pdf. Last accessed: August 2023.

[33] 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: August 2023.

[34] Nunes C, Pereira AM, Morais-Almeida M. Asthma costs and social impact. Asthma Res Pract. 2017;(6)3:1. doi: 10.1186/s40733-016-0029-3.

[35] Denton E, et al. Cluster analysis of inflammatory biomarker expression in the International Severe Asthma Registry. J Allergy Clin Immunol Pract. 2021;9:2680-2688e7.

[36] Dunlay SM, et al. Epidemiology of heart failure with preserved ejection fraction. Nat Rev Cardiol. 2017;14:591–602.

[37] British Heart Foundation. UK Factsheet. Available at: https://d1qotm6w854ck0.cloudfront.net/Uploads/a/f/a/bhfcvdstatisticsukfactsheet1_343908.pdf. Last accessed: August 2023.

[38] Conrad N, Judge A, Tran J, et al. Temporal trends and patterns in heart failure incidence: a population-based study of 4 million individuals. The Lancet. 2018;391:10120:572–580.

[39] Mamas MA, Sperrin M, Watson MC, et al. Do patients have worse outcomes in heart failure than in cancer? A primary care-based cohort study with 10-year follow-up in Scotland. Eur J Heart Fail. 2017;19:1095-1104.

[40] Hajouli S and Ludhwani. Heart failure and ejection fraction. 2022 Dec 23. StatPearls Publishing.

[41] Heart.org. Types of heart failure. Online. Available at: https://www.heart.org/en/health-topics/heart-failure/what-is-heart-failure/types-of-heart-failure. Last accessed: August 2023.

[42] Jasinska-Piadlo A, & Campbell P. Management of patients with heart failure and preserved ejection fraction. Heart. 2023;109:11:874–883.

[43] Taylor CJ, Moore J, & O’Flynn N. Diagnosis and management of chronic heart failure: NICE guideline update 2018. British Journal of General Practice. 2019;69:682:265–266.

[44] Electronic Medicines Compendium (EMC). Forxiga 10 mg film-coated tablets. Summary of Product Characteristics (SmPC). Available at: https://www.medicines.org.uk/emc/product/7607/smpc#gref. Last accessed: August 2023.