Symbicort (budesonide/formoterol) Turbohaler 200/6 approved as first and only combination reliever for mild asthma in the UK

SYMBICORT (budesonide/formoterol) TURBOHALER 200/6 APPROVED AS FIRST AND ONLY COMBINATION RELIEVER FOR MILD ASTHMA IN THE UK

• Symbicort Turbohaler 200/6 is the first and only approved dual-combination, inhaled corticosteroid + long-acting beta2-agonist (ICS/LABA) reliever therapy (Symbicort Reliever Therapy) to be taken as needed, in response to symptoms in patients with mild asthma aged 12 years and older.^[1],[2],[3]
• The approval by the Medicines and Healthcare products Regulatory Agency (MHRA) was based on positive results from four clinical trials which evaluated the efficacy of Symbicort Reliever Therapy compared with standard of care (SoC) therapies in mild asthma.^1,2,[4],[5]
• All patients with asthma are at risk of asthma attacks, including patients with mild asthma.^[6] Asthma outcomes are suboptimal in the UK with death and hospitalisation rates among the worst in Europe.^[7]
• It is widely accepted that an over-reliance on short-acting beta2-agonist (SABA) reliever inhalers is associated with an increased risk of asthma attacks, and contributes to the observed poor health outcomes in the UK.^[8],[9]

 

London, UK, Thursday 23 March 2023 – AstraZeneca today announced that the Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing authorisation for Symbicort (budesonide/formoterol) Turbohaler 200/6 in the United Kingdom as reliever therapy for adults and adolescents (12 years and older) with mild asthma.³ It is already approved in the UK for patients with moderate to severe asthma as Maintenance and Reliever Therapy (MART), and as maintenance therapy only.³

 

Budesonide/formoterol 200/6 is the first and only dual-combination (ICS/LABA) treatment to be approved in the UK for mild asthma, where a high unmet clinical need exists.^1,2 Evidence shows that patients with mild asthma remain at risk of severe asthma attacks, often associated with frequent over-reliance on short-acting beta2-agonist (SABA) inhalers.⁸ SABAs do not address underlying airway inflammation and for safety reasons are no longer recommended for use as monotherapy.⁸

 

This approval is based on positive data from clinical trials in more than 9,500 patients published in The New England Journal of Medicine and The Lancet, and forms a robust body of evidence demonstrating the effectiveness of budesonide/formoterol 200/6 compared with standard of care (SoC) therapies in mild asthma.^1,2,4,5

 

Asthma is a chronic, variable, inflammatory disease characterised by asthma attacks and symptoms including breathlessness and wheezing.^[10] In the UK it affects an estimated 8 million people.^[11] Deaths from asthma have increased by more than 26% in the last ten years.^[12] AstraZeneca estimates that approximately 2.65 million adults in the UK who live with mild asthma could be eligible for this treatment.^[13]

 

Professor Ian Pavord, Professor of Respiratory Medicine at the University of Oxford said: “In the UK, asthma attacks remain a major burden in patients diagnosed with mild asthma and these are driven by airway inflammation. Budesonide/formoterol 200/6 reliever therapy helps target airway inflammation and also delivers rapid, long-acting relaxation of the airway. I’m excited by the MHRA’s approval based on data from four key clinical trials which could potentially help address the unmet need for patients living with mild asthma in the UK.”

 

Ed Piper, Medical & Scientific Affairs Director, AstraZeneca UK, said: “We are delighted that the MHRA is the first regulatory agency in Europe to approve budesonide/formoterol 200/6 for use as a reliever in patients with mild asthma. This approval recognises the clinical utility of budesonide/formoterol 200/6 as an important new treatment option for patients with mild asthma in the UK.”

 

The safety and tolerability data for budesonide/formoterol 200/6 as needed in mild asthma were consistent with the known profile of the medicine.^1,2,4,5

 

AstraZeneca is committed to improving asthma care for patients in the UK. We are working towards a zero-tolerance approach to asthma attacks in the UK and are committed to reducing asthma-related exacerbations in a sustainable way that benefits both the patient community and the environment alike.

 

– ENDS –

CONTACTS

 

UK Media Enquiries

UK Media Team, AstraZeneca: ukmediateam@astrazeneca.com

Jack Faulkner, Edelman: 07813 407324 / jack.faulkner@edelman.com

 

NOTES TO EDITORS

 

About Symbicort (budesonide/formoterol) 200/6 Turbohaler

Budesonide/formoterol 200/6 is a combination formulation containing budesonide, an inhaled corticosteroid (ICS) that treats underlying inflammation, and formoterol, a long-acting beta2-agonist bronchodilator (LABA) with a fast onset of action, in a single inhaler.³ Budesonide/formoterol 200/6 was launched in 2000 and is approved in approximately 120 countries to treat asthma and/or COPD either as Symbicort Turbohaler 200/6 or Symbicort pMDI (pressurised metered-dose inhaler).³ Budesonide/formoterol 200/6 is also licenced in the UK in adults and adolescents (12 years and older) for the regular treatment of asthma, where use of a combination (inhaled corticosteroid and long-acting beta2-agonist) is appropriate, including:³

 

• patients not adequately controlled with inhaled corticosteroids and as needed inhaled short-acting beta2-agonists.³
• patients already adequately controlled on both inhaled corticosteroids and long-acting beta2-agonists.³

 

For complete information on budesonide/formoterol, the summary of product characteristics, including a full list of adverse reactions is available here: https://www.medicines.org.uk/emc/product/1327/smpc#gref.

 

Novel START clinical trial

In the trial, budesonide/formoterol 200/6 as needed (200/6 µg; n=220) was compared to SABA treatment with albuterol (known as salbutamol in many countries, including the UK) taken as needed (100 μg; n=223), and maintenance ICS therapy with budesonide twice-daily plus albuterol as needed (200 µg and 100 μg, respectively; n=225).¹ The results of the primary outcome measurements are:

 

• Budesonide/formoterol 200/6 demonstrated a 51% reduction (absolute rate reduction (ARR), 0.205) in the rate of annual asthma exacerbations versus SABA treatment with albuterol as needed (absolute rate 0.195 vs 0.400 per patient per year, respectively; relative rate 0.49 (95% confidence interval (CI), 0.33 to 0.72), P<0.001).¹
• There was no difference in the exacerbation rate between budesonide/formoterol 200/6 as needed and maintenance budesonide plus as needed albuterol (absolute rate increase 0.020, absolute rate 0.195 and 0.175 per patient per year, respectively; relative rate 1.12 (95% CI 0.70 to 1.79), P=0.65).¹ The mean standard deviation (±SD) budesonide dose in the budesonide/formoterol 200/6 as needed group was 107±109µg/day and was 222±113µg/day in the budesonide maintenance group.¹

 

PRACTICAL clinical trial

The PRACTICAL trial (n=890) showed that budesonide/formoterol 200/6 taken as needed compared to budesonide maintenance plus terbutaline as needed in adults with mild to moderate asthma, was more effective at reducing the rate in severe exacerbations per patient per year (ARR, 0.053; absolute rate 0.119 versus 0.172 per patient per year; relative rate, 0.69; 95% CI 0.48-1.00; p=0.049).²

 

SYGMA clinical trials

The SYmbicort Given as needed in Mild Asthma (SYGMA) trial programme is composed of two, 52-week Phase III, randomised, double-blind, multicentre, parallel-group trials in more than 8,000 patients aged 12 years and older with a clinical diagnosis of asthma for at least six months, who would qualify for treatment with regular low-dose ICS maintenance.^4,5

 

SYGMA 1 randomised 3,849 patients to evaluate the efficacy and safety of budesonide/formoterol (200/6 µg*) as needed, compared with terbutaline (0.5 mg^†) as needed and budesonide (200 µg) twice-daily plus terbutaline (0.5 mg^†) as needed.⁴ The primary objective was to demonstrate that budesonide/formoterol 200/6 given as needed is superior to terbutaline as needed, as measured by electronically recorded well-controlled asthma weeks.⁴

 

SYGMA 2 randomised 4,215 patients to evaluate the efficacy and safety of budesonide/formoterol (200/6 µg*) as needed, compared with budesonide (200 µg) twice-daily maintenance plus terbutaline (0.5 mg^†) as needed.⁵ The primary objective was to demonstrate that budesonide/formoterol 200/6 given as needed is non-inferior to budesonide plus terbutaline as needed, as measured by the relative rate of annual severe asthma exacerbations^†.⁵ The results of the primary and key secondary efficacy outcome measurements are:

 

* Corresponds to a delivered dose of budesonide/formoterol of 160/4.5 µg 

^† Corresponds to a 0.4 mg delivered dose of terbutaline, delivered by a Turbohaler

 

SYGMA 1: versus SABA as needed

 

• Budesonide/formoterol 200/6 used as needed provided superior asthma-symptom control to SABA used as needed, assessed according to electronically recorded well-controlled asthma weeks (eWCAW) (ARI 3.3%; 34.4% versus 31.1%; odds ratio, 1.14; 95% CI, 1.00 to 1.30; p=0.046)), the primary efficacy outcome^.4
• Budesonide/formoterol 200/6 used as needed resulted in a 64% lower annual severe exacerbation rate than SABA used as needed (ARR, 0.13; annual rate of severe exacerbations, 0.07 versus 0.20; rate ratio, 0.36; 95% CI, 0.27 to 0.49).⁴

 

SYGMA 1: versus twice-daily budesonide plus SABA as needed

 

• Budesonide/formoterol 200/6 used as needed was inferior to twice-daily budesonide maintenance therapy plus SABA as needed, as measured by eWCAWs (mean % well controlled asthma weeks per patient, 34.4% versus 44.4% of weeks; ARR, 10.0% weeks per patient; odds ratio, 0.64; 95% CI, 0.57 to 0.73).⁴
• The rates of severe exacerbations in the budesonide/formoterol 200/6 as needed group and the budesonide maintenance group did not differ significantly (0.07 versus 0.09, ARR, 0.02; rate ratio, 0.83; 95% CI, 0.59 to 1.16); this was achieved at a lower steroid dose (17% of the budesonide maintenance dose).⁴

 

SYGMA 2: versus twice-daily budesonide plus SABA as needed

 

• Budesonide/formoterol 200/6 used as needed was non-inferior to twice-daily budesonide maintenance therapy plus SABA as needed in reducing the risk of severe asthma exacerbations (ARR, 0.01; 0.11 versus 0.12), the primary efficacy outcome.⁵ This was achieved at a lower steroid dose (25% of the budesonide maintenance dose).⁵
• Budesonide/formoterol 200/6 provided less symptom control than twice-daily budesonide maintenance therapy plus SABA as needed as measured by the Asthma Control Questionnaire-5 (mean difference of 0.11 units; 95% CI, 0.07 to 0.15).⁵

 

The safety and tolerability data from the Novel START, PRACTICAL, SYGMA 1, and SYGMA 2 trials in mild asthma patients for budesonide/formoterol 200/6 as needed, were consistent with the known profile of the medicine.^1,2,4,5 The most common drug related adverse reactions are pharmacologically predictable side effects of short-acting beta2-agonists, such as tremor and palpitations.^1,2,4,5

 

About Asthma

Asthma is a common chronic respiratory disease, and it affects the health and day-to-day lives of as many as 8 million adults, or over 12% of the UK population.¹¹ It is characterised by recurrent breathlessness and wheezing which varies over time, and which varies in severity and frequency from person to person.¹⁰

 

All asthma patients are at risk of severe attacks, regardless of their disease severity, adherence to treatment or level of control.^{[14],[15],[16]} Globally, it is estimated that 262 million people suffer from asthma,^[17] which could lead to approximately 136 million exacerbations per year;^[18] these exacerbations may be physically threatening and emotionally significant for many patients.^[19] However, despite the fact that asthma is a chronic, variable inflammatory disease, patients are either under-prescribed or under-use their anti-inflammatory ‘preventer’ therapy and over-rely on their SABA reliever, which can mask symptom worsening.^{[20],[21],[22],[23]}

 

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 different 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] Beasley R, Holliday M, Reddel HK, et al. Controlled Trial of Budesonide-Formoterol as Needed for Mild Asthma. N England Journal of Medicine. 2019;380(21):2020-2030.

[2] Hardy J, Baggott C, Fingleton J, et al. Budesonide-formoterol reliever therapy versus maintenance budesonide plus terbutaline reliever therapy in adults with mild to moderate asthma (PRACTICAL): a 52-week, open-label, multicentre, superiority, randomised controlled trial [published correction appears in Lancet. 2020 May 2;395(10234):1422]. Lancet. 2019;394(10202):919-928.

[3] Electronic Medicines Compendium (EMC). Symbicort 200mg/6mg Inhalation powder – Summary of Product Characteristics. Available at: https://www.medicines.org.uk/emc/product/1327/smpc#gref. Last accessed: March 2023.

[4] O’Byrne PM, FitzGerald JM, Bateman ED, et al. Inhaled combined budesonide-formoterol as needed in mild asthma. New England Journal of Medicine. 2018;378:1865-1876.

[5] Bateman ED, Reddel HK, O’Byrne PM, et al. As-needed budesonide-formoterol versus maintenance budesonide in mild asthma. New England Journal of Medicine. 2018;378:1877-1887.

[6] Asthma + Lung UK. What is Asthma. Available at: https://www.asthma.org.uk/conditions/asthma/what-asthma. Last accessed: March 2023

[7] Asthma + Lung UK. UK asthma death rates among worst in Europe. Available at: https://www.asthma.org.uk/about/media/news/press-release-uk-asthma-death-rates-among-worst-in-europe/. Last accessed: March 2023

[8] Kaplan A, Mitchell PD, Cave AJ, Gagnon R, Foran V, Ellis AK. Effective Asthma Management: Is It Time to Let the AIR out of SABA?. J Clin Med. 2020;9(4):921.

[9] Nwaru BI, Ekström M, Hasvold P, Wiklund F, Telg G, Janson C. Overuse of short-acting β₂-agonists in asthma is associated with increased risk of exacerbation and mortality: a nationwide cohort study of the global SABINA programme. Eur Respir J. 2020;55(4):1901872.

[10] World Health Organisation. Asthma. Available at: https://www.who.int/news-room/facts-in-pictures/detail/asthma#:~:text=disease%20among%20children.,Asthma%20is%20a%20chronic%20disease%20characterized%20by%20recurrent%20attacks%20of,with%20chest%20tightness%20and%20cough. Last accessed: March 2023

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

[12] Asthma + Lung UK. Transforming asthma care in the UK. Available at: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwiV-YTP0ur9AhUXhFwKHfedBzgQFnoECCsQAQ&url=https%3A%2F%2Fwww.asthmaandlung.org.uk%2Fsites%2Fdefault%2Ffiles%2FFighting%2520back_V3.pdf&usg=AOvVaw2nW5eXS5xsEjpnsM7MS45q. Last accessed: March 2023

[13] AstraZeneca. Data on file. REF-179537.

[14] Olaguibel JM, Quirce S, Julia B, et al. Measurement of asthma control according to Global Initiative for Asthma guidelines: a comparison with the Asthma Control Questionnaire. Respiratory Research. 2012;13:50.

[15] Bateman ED, Hurd SS, Barnes PJ, et al. Global strategy for asthma management and prevention: GINA executive summary. European Respiratory Journal. 2008;31:143–78

[16] Price D, Fletcher M, van der Molen T. Asthma control and management in 8,000 European patients: the REcognise Asthma and LInk to Symptoms and Experience (REALISE) survey. NPJ Primary Care Respiratory Medicine. 2014;24:14009.

[17] The Global Asthma Network. The Global Asthma Report 2022. [Online]. Available at: http://globalasthmareport.org/resources/Global_Asthma_Report_2022.pdf. Last accessed: March 2023

[18] AstraZeneca Pharmaceuticals. Data on file. Budesonide/formoterol: Annual Rate of Exacerbations Globally. REF-173201.

[19]Sastre J, Fabbri LM, Price D, et al. Insights, attitudes, and perceptions about asthma and its treatment: a multinational survey of patients from Europe and Canada. World Allergy Organization Journal. 2016;9:13.

[20] Humbert M, Andersson TL, Buhl R. Budesonide/formoterol for maintenance and reliever therapy in the management of moderate to severe asthma. Allergy. 2008;63:1567–80

[21] Rabe KF, Vermeire PA, Soriano JB, Maier WC. Clinical management of asthma in 1999: the asthma insights and reality in Europe (AIRE) study. European Respiratory Journal. 2000;16:802–7.

[22] Tattersfield AE, Postma DS, Barnes PJ, et al. on behalf of the FACET International Study Group. Exacerbations of asthma: a descriptive study of 425 severe exacerbations. American Journal of Respiratory and Critical Care Medicine. 1999;160:594–9.

[23] Adams RJ, Fuhlbrigge A, Guilbert T, et al. Inadequate use of asthma medication in the United States: results of the asthma in America national population survey. Journal of Allergy and Clinical Immunology. 2002;110:58–64.