HomeHealthMedicine“Rewriting the Textbook” for Precision Medicine

“Rewriting the Textbook” for Precision Medicine

Precision medicine puts the patient at the center of healthcare, using a variety of tools to develop tailored and targeted therapies and diagnostics.

Promised to “revolutionize” the landscape of modern medicine, precision medicine requires an in-depth understanding of the molecular underpinnings of healthy and diseased states. Advances in molecular biology techniques and bioinformatics platforms help to provide such knowledge, providing researchers and clinicians with the tools to implement precision medicine approaches in various disease areas.

So far, oncology – the field of cancer research and treatment – has arguably benefited most from precision medicine. However, pharmaceutical and biotech company AstraZeneca believes precision medicine will “rewrite the textbook” for the diagnosis and treatment of chronic diseases. Technology networks recently had the pleasure of working with Mark Fidockvice president of diagnostic development, precision medicine at AstraZeneca, to find out how the company “rises to the challenge” of delivering precision medicines for chronic diseases.

Molly Campbell (MC): Can you talk about the ways AstraZeneca is actively involved in precision medicine?

Mark Fidock (MF): I think an interesting statistic is that if we look at our portfolio, over 90% of it has a precision medicine strategy. Precision Medicine as a Strategy and as a discipline, it truly encompasses the full spectrum of drug research and development. That includes finding new goals – for which the use of advanced methods available – requires advancing and pioneering new technologies and, of course, striving for better patient outcomes and a more sustainable healthcare system.

One of the areas where we have made great strides is oncology. AstraZeneca has already achieved more than 50 regulatory-approved companion diagnostics for a variety of indications and for a variety of different sample types. This has enabled the development of innovative targeted therapies that benefit millions of cancer patients worldwide.

The work and success we have achieved in oncology has almost provided a “framework” for us to develop precision drug approaches for chronic disease. However, we must recognize that chronic diseases are biologically complex and highly heterogeneous in origin, so a key priority in this space is to explore the ways in which precision medicine can be deployed and used that enhance our understanding of disease and lead to better patient outcomes.

The opportunities in the field of precision medicine are enormous, especially for chronic diseases. We are now in an era where, through precision medicine, we are rewriting the handbook for many indications and changing the way we ultimately treat patients.

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MC: Let’s talk about the tools and technologies. What are the key technological advances that help us understand the biology behind disease and use that information to tailor treatments?

MV: One of the key technology areas (in which AstraZeneca is a leader) is genomics research. Our in-house Center for Genomics Research plans to sequence 2 million genomes by 2026—which, of course, isn’t that far now. Using highly innovative bioinformatics analysis methods, the groups behind this project will search for rare variants associated with diseases. In doing so, they discover new biological insights into disease, discover new therapeutic targets and describe the diseases in a much more detailed – almost molecular – or genetic way.

This creates opportunities for the development of targeted therapies for different segments of a particular disease.

Important examples are the discovery of new targets in respiratory and immunological diseases, cardiovascular research and renal and metabolic diseases. One of AstraZeneca’s areas of interest is pulmonary fibrosis, and the group previously published the discovery of a gene called SPDL1 identified in idiopathic pulmonary fibrosis.

The SPDL1 gene encodes a protein known as “Spindly” which is responsible for signaling during cell division. Previously, this gene had not been described in relation to idiopathic pulmonary fibrosis. The identification of a new mechanism underlying the disease opens the door for new therapeutic discoveries.

In cardiomyopathy, the group is also published a finding regarding the TTN gene. Both examples are important examples of how genomic techniques can be used to advance our understanding of a disease. These publications have been widely shared by the scientific community.

The TTN gene codes for a protein called “titin”. Truncated variants of the gene contribute to approximately 15-25% cases of non-ischemic dilated cardiomyopathy, a condition in which the left ventricle of the heart becomes enlarged.

MC: Can you say something about the importance of biomarkers in precision medicine? How are they used to identify patients and develop targeted therapies?

MV: I think the space for precision medicine for all the disease indications that AstraZeneca is investigating is huge. It will increase our ability to rewrite the medical textbooks that doctors use to understand, diagnose and treat diseases.

How do we do this? A core aspect of precision medicine is identifying predictive biomarkers, which is achieved through the insights gathered through genomic studies and other means. Predictive biomarkers provide the opportunity to include the right patients in our clinical trials and to develop targeted diagnostics and treatment approaches that are most appropriate.

In those disease areas where we already have multiple targeted treatment options available, we have also identified biomarkers for patient selection. An example is in non-alcoholic steatohepatitis (NASH) where: A second example is IL33 – a cytokine seen and elicited in many different indications, from asthma to diabetic kidney disease and even COVID-19.

These are areas where the biomarker – and the scientific research surrounding the biomarker – helps us identify the right patients, enabling us to determine where our targeted therapies will have the most beneficial clinical results.

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MC: Can you say something about the importance of collaboration in precision medicine? How does AstraZeneca pursue collaborative projects?

MV: AstraZeneca works in a very collaborative waywith many collaborations established in each of the different research spaces in which we choose to operate.

We need to develop companion diagnostics that are scalable and have global reach, so that they are not only aligned with our targeted treatments, but are also analytically and clinically validated and demonstrate patient benefit. We have built global partnerships to deliver these tests that can be commercialized, truly enabling maximum access to patients. It also ensures that these diagnostics are used consistently within legal requirements in whatever part of the world they will be used in.

Through one of our collaborations with Almac, we are developing and validating companion diagnostic tests for patient selection in a wide variety of clinical trials across a range of therapeutic areas, such as chronic kidney disease, NASH and respiratory disease. This is a robust framework that we can adapt for use with other ongoing collaborations, such as our work with Roche Diagnosticsamong others.

In terms of challenges, if you are innovative, lead a space and create information that “rewrites rulebooks” and “rewrites” the ways treatments are derived, there will of course be some challenges. I think we can all agree that health is a fundamental right that we should all have access to, and that it should be inclusive and tailored to the individual. We think precision medicine will be an essential part of this offering, it will improve health and improve health equity. We need to engage in discussions to ensure that all healthcare systems can fully adopt this approach in clinical practice, which is achieved through interactions, partnerships and participation in symposia and summits. Speaking recently at the World Health Summit, AstraZeneca is committed to discussing policies with panels of outside leaders from various diagnostic organizations and looking at ways we can help bring new approaches to the clinical community and healthcare structures.

MC: Looking to the future of precision medicine, what are the key priorities in precision medicine for AstraZeneca? What do you think this space will look like in, say, 10-15 years?

MV: The more we use precision medicine within chronic disease, and the more science really begins to discover how these complex chronic diseases are derived and their etiology, the more we can look at developing new therapeutic modalities.. We can identify the right patient populations for diagnostics to target treatments and ultimately this will yield much better outcomes for patients in the long run.

What will it look like in the future? I think an important point of attention is: how do we bring new diagnostics into clinical practice? How do we bring precision medicine to the patient? The future revolves around patient convenience. One day it would be fantastic to be able to introduce molecular diagnostic devices into the home so that patients can monitor their diseases as they occur. This means bringing digital advances – such as advances in artificial intelligence (AI) – into the various fields of precision medicine. How do we do this? How do we use digital media to derive useful diagnostic data, where patients can take a diagnostic test in their own environment, that data is then shared with their treating physician so that decisions and discussions can be made in favor of the patient? These will be important considerations.

Much of the future is focused on further developing the scientific understanding of chronic disease and bringing together all the lessons we have learned in precision medicine and maximizing patient outcomes. The future of precision medicine is about an in-depth understanding of chronic diseases at the molecular, genetic or metabolic level, in such a way that we can really ensure that the patient is at the center of everything, and that they have the benefit and the future in convenience of precision medicine.

Mark Fidock, VP for Diagnostic Development, Precision Medicine at AstraZeneca, spoke with Molly Campbell, senior science writer for technology networks.

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