Pioneers in Asthma: Where is the science leading us

Written by:

Maria Belvisi

SVP and Head of Research and Early Development Respiratory & Immunology


While recent treatment advances have helped millions of people worldwide better manage their asthma, we know many more remain underserved and continue to struggle – with uncontrolled symptoms leading to more than 176 million asthma attacks globally every year.1-3 Now more than ever, we must urgently prioritise continued innovation in asthma research.

At AstraZeneca, we are building on our 50-year heritage in respiratory care by pursuing scientific breakthroughs that will revolutionise our understanding of the pathophysiology of asthma and inform the development of much-needed new treatments that could improve patient care and outcomes.

Our bold research ambition is to eliminate preventable attacks among people with all severities of asthma and achieve on-treatment clinical remission.



New frontiers in research

In the past decade, scientific understanding of asthma has advanced considerably. Our knowledge of the complex biology behind asthma inflammation has led to an appreciation of the heterogeneous nature of the disease and the identification of a broad range of asthma phenotypes, marked by different drivers of airway inflammation.4-7

From this knowledge, the discovery of several biologic therapies has provided much-needed solutions for many severe asthma patients. However, there remains vast potential to improve treatment particularly for patients with unknown, unclear, or multiple drivers of inflammation.5-8 That’s why AstraZeneca is working to further expand scientific knowledge around the drivers and biological mechanisms of asthma to tackle the disease pathophysiology in new and powerful ways.

The importance of eosinophils' role in asthma is now well-established: as key effector cells, eosinophils are a common driver of the immune response that contributes to airway dysfunction and tissue remodelling found in asthma.9-13 We are improving knowledge of eosinophilic asthma and the link between the disease and other related inflammatory diseases that share common pathways and disease drivers.9,14 By improving awareness of these related pathologies, we believe our research will lead not only to innovative new medicines but also to earlier detection and intervention for those affected.

Advancing epithelial science

Epithelial science is a new frontier in asthma research, and we are working to better characterise the key role of the airway epithelium and epithelial cytokines – such as thymic stromal lymphopoietin (TSLP), interleukin (IL)-33 and IL-25 – in triggering inflammation in asthma.15-19

We are building on our understanding of epithelial biology by modelling the airway in vitro. This will allow us to better examine cell abnormalities, along with the effects of cytokines on cellular processes. We are also investigating non-invasive nasal sampling technology to assess detection of epithelial cytokines following exposure to an allergen. There are many benefits to non-invasive sampling, including that it is well tolerated by patients and thus suitable for frequent sampling.

Together, this research, and other research we have ongoing, will help us to better understand the role of the epithelium in asthma (and potentially other inflammatory diseases). This research is crucial in expanding our knowledge and providing new focus to help target the remaining unmet needs in asthma.

Next-generation therapeutics

Beyond understanding underlying biology, there are three key areas in which we are innovating to develop our next generation therapeutics to achieve our long-term goal of disease modification and clinical remission.

We are looking at new drug modalities such as bispecific fragment antibodies and Anticalin® proteins to complement the more established small molecules and monoclonal antibodies (mAbs) treatments. Our hope with this area of research is that we can open up new opportunities for targeting biological pathways that were previously seen as undruggable.

We're also leveraging multiple human genomic data sets, such as those from our real-world NOVELTY trial, and machine learning to advance the development of precision medicines for asthma.20 We will soon be able to move beyond identifying eligible patients by traditional biomarkers such as eosinophils, fractional exhaled nitric oxide (FeNO) and serum immunoglobulin E (IgE). Instead, matching patients to treatments via genetic signatures enabling physicians to deliver the right treatment to the right patient at the right time. 

And, because accelerating the speed at which these new therapy directions reach patients is vital, we're creating the next generation of clinical trials by leveraging digital health tools to enhance our capabilities around running virtual trials. This decentralized approach allows people to take part in a way that's more convenient for them whilst also using transformative endpoints to demonstrate disease modification.

The future of asthma

We know that many people with asthma are underserved today and that asthma remains a significant public, and personal, health challenge.1,2 As pioneers in asthma, AstraZeneca is committed to continuing to push the boundaries of science to transform the lives of people living with this condition and give them a better future with the care they deserve.

 

References

1. The Global Asthma Network. The Global Asthma Report 2018. [Online]. Available at: http://www.globalasthmanetwork.org/publications/Global_Asthma_Report_2018.pdf.[Last accessed: February 2021].

2. Chen S, et al. Systematic literature review of the clinical, humanistic, and economic burden associated with asthma uncontrolled by GINA Steps 4 or 5 treatment. Curr Med Res Opin. 2018;34:2075–2088

3. AstraZeneca Pharmaceuticals. Data on file. Annual Rate of Exacerbations Globally (ID:SD-3010-ALL-0017).

4. Wenzel S. Severe asthma in adults. Am J Respir Crit Care Med. 2005; 172: 149-160.

5. Hyland ME, Masoli M, Lanario JW, 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.

6. Tran TN, Zeiger RS, Peters SP, 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.

7. Godar M, Blanchetot C, de Haard H, et al. Personalized medicine with biologics for severe type 2 asthma: current status and future prospects. MAbs. 2018; 10 (1): 34‐45.

8. Amaral et al. Having concomitant asthma phenotypes is common and independently relates to poor lung function in NHANES 2007-2012. Clin Trans Allergy. 2018 May 4;8:13.

9. Ramirez GA, Yacoub MR, Ripa M, et al. Eosinophils from physiology to disease: a comprehensive review. Biomed Res Int. 2018; 9095275.

10. Rothenberg ME, Hogan SP. The eosinophil. Annu Rev Immunol. 2006; 24:147-174

11. Rosenberg HF, Dyer KD, Foster PS. Eosinophils: changing perspectives in health and disease. Nat Rev Immunol. 2013; 13 (1): 9-22.

12. Trivedi SG, Lloyd CM. Eosinophils in the pathogenesis of allergic airways disease. Cell Mol Life Sci. 2007; 64 (10):1269-1289.

13. Carr TF, Berdnikovs S, Simon HU, et al. Eosinophilic bioactivities in severe asthma. World Allergy Organ J. 2016; 9: 21.

14. Bachert C, Claeys SE, Tomassen P, et al. Rhinosinusitis and asthma: a link for asthma severity. Curr Allergy Asthma Rep. 2010; 10(3): 194-201.

15. Bartemes KR, Kita H. Dynamic role of epithelium-derived cytokines in asthma. Clinical Immunology 2012 Jun;143(3):222-235.

16. Al-Sajee D, Oliveria JP, Sehmi R, et al. Antialarmins for treatment of asthma: future perspectives. Curr Opin Pulm Med. 2018 Jan;24(1):32-41.

17. Lambrecht BN, Hammad H, Fahy JV. The Cytokines of Asthma. Immunity. 2019 Apr 16;50(4):975-991.

18. Wark PA, Gibson PG. Asthma exacerbations . 3: Pathogenesis. Thorax. 2006 Oct;61(10):909-15.

19. Wark PA, Simpson J, Hensley MJ, Gibson PG. Airway inflammation in thunderstorm asthma. Clin Exp Allergy. 2002 Dec;32(12):1750-6.

20. Clinicaltrials.gov. Observational Study of Obstructive Lung Disease (NOVELTY). Available at: https://clinicaltrials.gov/ct2/show/NCT02760329. [Last accessed: February 2021]. 


Veeva ID: Z4-31198
Date of Prep: February 2021


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