Aiming for Disease Modification in Respiratory Disease

Written by:

Maria Belvisi

Senior Vice President and Head of Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D

At AstraZeneca our science is what defines us. It is at the core of everything we do and what drives our aspiration to transform treatment standards in areas of unmet medical need. In chronic respiratory disease, we focus our early research efforts on four diseases: asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and chronic cough.

We have a bold ambition for the future – to move beyond preventing and treating symptoms to treating the underlying cause of these four diseases. It means that we are aiming to find keys that could help us achieve early intervention, durable remission and disease modification. To do so, we need to improve our understanding of disease mechanisms and address the underlying biological drivers of disease. It is also crucial that we can target any novel biology we uncover with the right modalities, embracing new technologies making this possible. And maybe needless to say – we aim to ensure the right patients get the right treatment.

For clarity, let me explain this approach through four different chapters defining our early science efforts in Respiratory:

Focus on High Unmet Need

Respiratory diseases are leading causes of death and disability in the world.[1] Despite significant advances over the years, the unmet need remains substantial. The four diseases we focus our early research on are all characterised by significant remaining unmet medical need and in some cases increasing prevalence. Asthma and COPD are each affecting the health and day-to-day lives of over 300 million people worldwide, and COPD is ranked as the third most common cause of death in developed countries[2]. The average survival time for people with IPF ranges from two to five years from diagnosis, with very limited treatment options and people with chronic cough can cough hundreds or even thousands of times per day severely impacting their quality of life. We have been a leading force in the fight against respiratory disease for over forty years, and helping these patients remains a top priority for us at AstraZeneca.

Understand the Biology

Emerging science in respiratory has shed light on the enormous complexities behind what we today define as asthma and COPD. This is a challenge, but also a fantastic opportunity to offer better outcomes to specific patient populations based on the underlying drivers of their disease. At AstraZeneca, our ambition is to increase our understanding of these drivers to enable the development of disease modifying treatments. Our strategic research focus is divided into four mechanistic and complimentary biology approaches in chronic lung disease:

  • Lung epithelium - the lining of the lungs, has been proven to play an active role in triggering inflammation in the lungs. Our goal is to restore normal epithelial tissue architecture and function.
  • Lung immunity - Immunological imbalance in the lung is a driver of disease for many patients. We aim to reverse such imbalance by focusing on immunomodulation, lung microbiome and cell metabolism and plasticity.
  • Lung Regeneration – COPD and IPF can be classified as diseases of the ageing lung, as they are characterised by progressive lung damage and loss of lung function. Our aim is to develop approaches that enhance lung repair to prevent lung damage.
  • Neuronal Functions - Cough is a neuronal reflex which is normally protective, but in chronic cough this reflex is triggered inappropriately. Our research is focused on addressing these neurologic mechanisms by targeting specific neuronal receptors in the peripheral and central nervous system.

Leverage a Broad Modality Toolbox

New drug modalities are emerging as an attractive complement to more traditionally used small molecules and monoclonal antibodies (mAbs). This is especially true for targeting biological pathways that were previously seen as inaccessible or not appropriate to target.  As I said earlier, we want to be able to target any novel biology we may uncover.  AstraZeneca is exploring a range of emerging modalities for Respiratory, working in close collaboration with leading biotech companies around the world. Below are some modalities that play an increasing role in our early respiratory research pipeline.

Find the right patients

Last but not least, it’s about being able to identify the right patients for the right treatments. Each of us is unique in who we are, how we live and the types of disease that affects us. Today, this is well established knowledge in oncology where precision medicines effectively target a multitude of different tumour types. Respiratory diseases are also highly heterogenous, and as we expand our knowledge of disease drivers the future will likely offer more personalised treatment approaches.  That means improved diagnostics are needed to identify different patient phenotypes. We are therefore working to ensure that all our future respiratory medicines have a biomarker to identify the patients most likely to benefit.