AstraZeneca presents new evidence on Symbicort (budesonide/formoterol) in COPD patients at risk of exacerbation

INCONTROL 1 demonstrates a protective benefit of budesonide/formoterol compared to formoterol against exacerbation in COPD patients with blood eosinophils 0.1 x10⁹ cells/L or more and particularly in patients who smoke

INCONTROL 1 findings help pave the way for personalised treatment approaches that minimise risk of exacerbation and maximise clinical benefit for COPD patients 

10 September 2017

AstraZeneca presented new evidence on budesonide/formoterol at the European Respiratory Society (ERS) International Congress 2017 from INCONTROL 1, a first of its kind post-hoc analysis of a large pooled data set of Phase III chronic obstructive pulmonary disease (COPD) studies (n=2,593).¹ INCONTROL 1 investigated patient characteristics that may interact with the treatment response to a combination of budesonide (inhaled corticosteroid or ICS) and formoterol (long-acting beta agonist or LABA), versus formoterol alone.¹ The majority of patients were treated with Symbicort 160/4.5 μg pMDI but some patients received a free combination of separate budesonide 160 μg pMDI and formoterol 4.5 μg DPI inhalers. Budesonide/formoterol has been approved in approximately 120 countries to treat asthma and/or COPD either as Symbicort Turbuhaler or Symbicort pMDI (pressurised metered-dose inhaler).

The novel analysis also examined the relationship between peripheral blood eosinophil (PBE) count and the treatment benefit of budesonide across the entire measured PBE range, rather than using arbitrary cut-off values explored in previous literature.¹ 

Mona Bafadhel, ‎Associate Professor and NIHR Postdoctoral Fellow Respiratory Medicine, University of Oxford said: "The INCONTROL 1 findings highlight that an increased blood eosinophil count may be predictive of a higher exacerbation risk in COPD patients with a history of exacerbations that do not receive inhaled corticosteroids as part of their daily treatment regimen. The combination of budesonide and formoterol may substantially reduce the risk of exacerbation in the order of 25 to ≥60% compared to formoterol alone over the measured peripheral blood eosinophil range. These data indicate that in the majority of patients with moderate to very severe COPD and a history of previous exacerbations, there is potential benefit from the combination of budesonide/formoterol which can be identified by measuring the peripheral blood eosinophil count."

In COPD patients who have experienced one or more exacerbations in the previous year², INCONTROL 1 showed that maintenance treatment with budesonide/formoterol 160/4.5 μg offered clinically relevant reductions in exacerbations compared with formoterol 4.5μg alone in patients with a PBE of 0.1 x10⁹ cells/L or greater.¹

The INCONTROL 1 findings demonstrated:

• The risk of exacerbation increased with rising PBE in patients treated with formoterol alone (non-budesonide containing therapy)
  • Risk of exacerbation increased >3 times, from 0.5 to 1.8 exacerbations per year, over the PBE continuum - 0 cells/L - ≥0.8 x10⁹ cells/L (1.05 mean exacerbations per year)¹
• In patients treated with budesonide/formoterol, the risk of exacerbation was consistent across the PBE continuum (0.74 mean exacerbations per year)¹
• The magnitude of protection against risk of exacerbation in patients treated with budesonide/formoterol compared with formoterol therapy alone increased with rising PBE:
  • 25% exacerbation rate reduction (relative) at PBE 0.10 - 0.19 x10⁹ cells/L¹
  • 26-50% exacerbation rate reduction at PBE 0.20 - 0.34 x10⁹ cells/L¹
  • 51-60% exacerbation rate reduction at PBE 0.35 - 0.63 x10⁹ cells/L¹
• This magnitude of effect was driven by the increased risk of exacerbation in patients with higher PBE counts treated with formoterol alone¹

INCONTROL 1 also evaluated the treatment interaction of budesonide/formoterol and formoterol alone with smoking status. In current smokers treated with formoterol alone, an increased PBE at baseline was associated with an increased risk of exacerbation. Budesonide/formoterol treatment significantly reduced the risk of exacerbation by 68% (in patients with PBE ≥0.6 x10⁹ cells/L), compared with formoterol treatment alone.¹ In contrast, in former smokers, budesonide/formoterol reduced the risk of exacerbation compared with formoterol alone by 34-39%; the treatment effect in former smokers was consistent across the PBE continuum.¹

These results indicate that in current smokers, PBE count may be a strong and independent predictor of future exacerbation in COPD.¹ These data suggest that COPD patients who have a history of exacerbations, have a normal-to-elevated blood eosinophil count and are current smokers have a higher risk of future exacerbation if treated with a LABA alone compared to treatment with ICS/LABA. In contrast, these same patients may be able to substantially reduce the risk of exacerbation with the addition of ICS to their maintenance bronchodilator therapy.

Alex de Giorgio Miller, Therapy Area Vice President - Respiratory, Global Medical Affairs at AstraZeneca said: “AstraZeneca is committed to advancing personalised medicine through exciting science programmes like INCONTROL 1. These data highlight that budesonide/formoterol could provide an important clinical benefit for those COPD patients at risk of debilitating exacerbations, based on a risk determined through a simple blood eosinophil count and their current smoking status. INCONTROL 1 adds to the wealth of data that already exists for Symbicort, which continues to be a key therapy in asthma and COPD.”

NOTES TO EDITORS

About Symbicort

Symbicort is a combination formulation containing budesonide, an inhaled corticosteroid (ICS), and formoterol, a long-acting beta2-agonist bronchodilator (LABA), in a single inhaler. Budesonide/formoterol was first launched in Sweden in 2000 and has been approved in approximately 120 countries to treat asthma and/or COPD either as Symbicort Turbuhaler or Symbicort pMDI (pressurised metered-dose inhaler).

About the INCONTROL 1 study

The INCONTROL 1 trial is a post-hoc, pooled analysis of three randomised, double-blind, double-dummy, parallel-group, multicentre trials of Symbicort pMDI in COPD.¹ Inclusion criteria were a clinical diagnosis of COPD, aged 40 or above, a pack-year history of ≥10 and one or more exacerbations experienced in the previous year.² The geometric mean (95%CI) of eosinophils was 0.17 (0.03 to 0.86) x10⁹ cells/L.¹

About INCONTROL

INCONTROL 1 is part of the large AstraZeneca science program INCONTROL (INflammation CONTROL of the Obstructive Lung) with the overarching objective to optimise treatment of COPD, by considering the patient heterogeneity in phenotypes and endotypes defined by biomarkers and predictors of treatment response and outcomes. Besides post hoc analyses of AstraZeneca’s large data sets to address questions within the scope of the objective, INCONTROL also consists of the NOVELTY (NOVEL observational longiTudinal study of patients with asthma and/or COPD) study, an innovative study that aims to enhance disease understanding and support future development of personalised treatment strategies by highlighting unmet clinical needs in particular groups of asthma and COPD patients, including those with overlapping disease. The study is a three-year real-world evidence of >14,000 patients.

About COPD

COPD (chronic obstructive pulmonary disease) is a progressive disease associated mainly with tobacco smoking, air pollution or occupational exposure, which can cause obstruction of airflow in the lungs resulting in debilitating bouts of breathlessness.³ It affects an estimated 329 million people worldwide⁴ and is predicted to be the third leading cause of death by 2020.³ Improving lung function, reducing exacerbations and managing daily symptoms such as breathlessness are important to the management of COPD.

About AstraZeneca in Respiratory Disease

Respiratory disease is one of AstraZeneca’s main therapy areas, and the Company has a growing portfolio of medicines that reached more than 18 million patients in 2016. AstraZeneca’s aim is to transform asthma and COPD treatment through inhaled combinations at the core of care, biologics for the unmet needs of specific patient populations, and scientific advancements in disease modification.

The Company is building on a 40-year heritage in respiratory disease and AstraZeneca’s capability in inhalation technology spans both pMDIs and dry powder inhalers, as well as the innovative Co-Suspension Delivery Technology. The company’s biologics include benralizumab (anti-eosinophil, anti-IL-5rɑ), which has been accepted for regulatory review in the US, EU and Japan, tralokinumab (anti-IL-13), which is currently in Phase III, and tezepelumab (anti-TSLP), which successfully achieved its Phase IIb primary endpoint. AstraZeneca’s research is focused on addressing underlying disease drivers focusing on the lung epithelium, lung immunity and lung regeneration.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three main therapy areas - Oncology, Cardiovascular & Metabolic Diseases and Respiratory. The Company also is selectively active in the areas of Autoimmunity, Neuroscience and Infection. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca.com and follow us on Twitter @AstraZeneca.

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References

1. Bafadhel M et al. Modelling peripheral blood eosinophils to identify response to budesonide in COPD: a post-hoc analysis. ERS poster. 2017.
2. Bafadhel M, Peterson S, De Blas Me, et al. Modelling peripheral blood eosinophils to identify response to budesonide in COPD: a post-hoc analysis. September 10, 2017; European Respiratory Society International Congress; Abstract 3748.
3. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017. Available from: http://goldcopd.org. Last accessed December 2016.
4. Bereza BG, Nielsen AT, Valgardsson S et al. Patient preferences in severe COPD and asthma: a comprehensive literature review. International Journal of COPD. 2015: 10: 739–744.