Precision medicine
What is precision medicine?
Precision medicine is an innovative approach for tailoring disease treatment and prevention. It makes it possible for doctors and researchers to more accurately predict which treatments are more likely to work for a patient, taking into account individual genetic and molecular make-up, environment, and lifestyle.
By unravelling the complex underlying biology of many diseases, and pioneering and applying advanced technologies, we are leading the way in the application of precision medicine. Our work, and our collaborations with partners across industry, biotech and academia, are driving for better treatments for patients as well as a more sustainable future for healthcare systems.
Shaping the future of medicine across our portfolio
We are applying precision medicine approaches across our R&D portfolio deepening our understanding of disease biology, developing novel therapies and supporting the development of innovative diagnostic tests to improve clinical trial success and help target the right medicines to the right people across oncology, chronic and rare diseases.
Precision medicine in oncology
We’re pushing the boundaries of science in oncology, aiming to provide precision medicines matched to the patients who can benefit most from them. We are committed to our visionary pipeline, focused on the development of precision medicine advances across multiple hard to treat tumour types that can help shape the cancer environment by changing both clinical and medical practice.
Our advances across our six scientific platforms have helped to improve the patient experience while developments in epigenetics and across cell, gene and combination therapy hold the promise of new possibilities.
Precision medicine in chronic diseases
Chronic diseases – such as asthma, chronic obstructive pulmonary disease (COPD), heart failure, and chronic kidney disease (CKD) – affect billions of people worldwide.
They are complex and heterogeneous, meaning that they can manifest in many ways, which can make accurate diagnosis challenging. This complexity reflects a wide range of underlying biological causes that can each require different treatments. It is for these reasons that COPD and CKD have seen little innovation in decades and metabolic dysfunction-associated steatohepatitis (MASH) still has no approved treatment.
Using a precision medicine approach could help to detect disease earlier and identify the causes of disease, which has the potential to inform and improve treatment decisions.
Precision medicine in rare diseases
While a single rare disease may affect a small number of people, collectively the more than 7,000 known rare diseases affect an estimated 400 million people globally.
Studying rare diseases poses unique challenges as patient populations are often small and dispersed. The underlying biology of many of these conditions is not well understood and few diagnostic tools exist, leading to a lack of awareness among scientific and medical communities. As a result, the majority of rare conditions still do not have an approved treatment.
Precision medicine is creating opportunities to understand the fundamental biology of rare diseases, identify new molecular targets and enable new research pathways with the potential to accelerate the pace of discovery for new treatment options.
Our scientists are working hard to deliver the benefits of precision medicine. Using multi-omics, novel technologies, imaging, artificial intelligence, and machine learning they are digging deep into the biological processes that cause and drive disease. Our ambition is to develop and validate new treatments that make it possible to diagnose and intervene earlier, halt disease progression, achieve remission, and enable patients to have better outcomes and healthier futures across the world.
Our approach to precision medicine
Our pioneering research into precision medicine harnesses huge networks of scientific and patient data to uncover new knowledge and important disease insights that will enable us to:
- Identify novel drug targets that are expected to have a higher probability of success.
- Identify biomarkers that can help characterise patients into subgroups most likely to benefit from treatment.
- Support the design of better clinical trials, where the right patients are recruited to participate.
- Develop diagnostic tests that can help guide treatment in the real world.
We’re applying a precision medicine approach across 90% of our R&D portfolio. We put patients at the heart of our medical research, confident that by matching the right treatment to the right patient at the right time, and intervening earlier before progression, we can change the course of disease and allow patients to live better, healthier lives.
Asthma
Asthma
In respiratory diseases, like asthma, there is intense interest in precisely targeting molecules that stimulate key inflammatory pathways that could lead to the development of novel precision medicines in the future.
Asthma can be a devastating disease with 176 million attacks each year and debilitating symptoms, particularly for those living with more severe forms.1
By targeting the inflammatory drivers that play an important pathological role in asthma we can break whole patient populations into subgroups depending on their individual disease biomarkers.
One example is our work to identify specific leukotrienes that drive inflammation, bronchoconstriction and mucus production in disease. Our precision medicine research is exploring these molecules as urinary biomarkers to help classify patients’ disease and match them with targeted treatments they are more likely to respond to.
Chronic kidney disease
Chronic kidney disease (CKD)
Chronic Kidney Disease (CKD) encompasses various primary disorders and stages of progression, and the patient population is highly heterogeneous. The current symptom-based approach ignores the different underlying mechanisms. Our aim is to close this gap, by uncovering the underlying genetic and molecular drivers of disease to identify the right treatment for the right patient.
Using unique datasets, the team has applied machine learning and artificial intelligence algorithms to classify patients into subclasses. For the first time, our research has shown that these disease categories based on molecular data are different from previous clinical classifications for CKD. We are now looking to identify urinary biomarkers which could be used to identify patients’ molecular disease classes non-invasively, allowing us greater precision when aligning the right patients to the right trials. In the future, our ambition is to provide tailored treatments based on individual disease, or patient, categories determined by molecular disease drivers.
Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease (COPD)
In chronic obstructive pulmonary disease (COPD) we have seen little innovation in decades despite it being the third leading cause of death world-wide.2 To address this, we are dissecting the 500+ abnormally expressed genes and defining their role in disease. This precision medicine approach will help us identify potential novel targets for life-changing medicines.
By targeting disease drivers of COPD, such as oxidative stress, cell senescence, chronic inflammation and fibrosis, we aim to develop precision medicines focused on disease modification so as to slow and stop disease progression. To find the right patients for these novel treatments, we need to understand more about COPD in different people and find new ways to assess the effects the disease. Access to data from cohorts of people with COPD is providing new insights into the molecular mechanisms of COPD and has helped us to develop non-invasive imaging methods that could be used in future to help stratify patients or monitor treatment response. Incorporation of precision medicine approaches like this early in the clinical development pipeline will support the identification of the right patients for subsequent clinical trials.
Heart failure
Heart failure
In heart failure (HF), patients are likely to have multiple co-morbidities, any of which may affect their outcome and response to heart failure therapies. To deliver our precision medicine approach we need to understand the molecular and genetic landscape, including the impact of comorbidities such as chronic kidney disease or obesity.
Targeting key mechanisms of HF including widespread inflammation, fibrosis, hypertrophy and microvascular dysfunction is a major priority.
Many HF cases have a hereditary component and by identifying variants in the genome we can gain new genetic insights. Among the genetic drivers in dilated cardiomyopathy is a mutation in the gene for phospholamban, which is linked to impaired heart muscle contraction and relaxation. This understanding enables the exploration of this genetic variant for the development of potential new therapeutic targets.
Metabolic-disorder associated steatohepatitis
Metabolic-dysfunction associated steatohepatitis
Our precision medicine approach in metabolic-disorder associated steatohepatitis (MASH) is two-fold; firstly, we aim to identify the right patients with the presence of disease-causing gene variants, then we selectively disrupt this protein expression with novel antisense oligonucleotide (ASO) therapy.
MASH is a multi-component disease with high unmet needs and severe patient outcomes. At the forefront of precision medicine research, we are targeting genetic mutations associated with MASH, which are responsible for an approximately four-fold increase in risk of the disease.
For example, a single nucleotide substitution in the PNPLA3 gene severely impairs normal fat breakdown in liver cells. We are investigating ways to downregulate PNPLA3 and so potentially restore lipid metabolism.
Systemic lupus erythematosus
Systemic lupus erythematosus (SLE)
Our research is unlocking the science of the immune system to address significant unmet needs in Systemic Lupus Erythematosus (SLE). This complex disease is driven by multiple cell types and mediators, and we are exploring these with our precision medicine approach.
SLE is a chronic immune-driven disease in which the body’s immune system attacks healthy tissue in any part of the body.
At the forefront of our precision medicine approach is the Interferon (IFN) pathway which plays a central inflammatory role in SLE. Approximately three quarters of patients with SLE have an elevated IFN gene signature and clinical trials have shown that over expression correlates with a positive treatment response.
Harnessing this precision guided research could hold great potential to expand this approach into other conditions where, even though symptoms may differ, the underlying type 1 IFN gene signature is conserved.
Applying state-of-the-art technologies
Our technology-driven approach is accelerating the way we design and develop new precision medicines and diagnostics tests, powering a new era of scientific discovery.
Understanding the genome: Patient data banks are advancing our knowledge by helping to match genetic profiles and gene mutations to specific health outcomes. Ongoing advances in genome technology allow us to characterise patients into subgroups based upon their underlying disease mechanisms and identify the most appropriate genetic targets. We have also made major investments in multi-omic technologies (genomics, transcriptomics, proteomics, metabolomics, lipidomics) that are key to building a more complete picture of the complexities of disease, which can inform new tests and therapies.
Finding novel targets: We are combining our rich datasets with external sources of patient data and applying AI and machine learning to discover associations between data and disease, achieving healthcare breakthroughs more rapidly than ever before. For example, we are partnering with Benevolent AI to create knowledge graphs which allow us to analyse vast amounts of scientific data to see potential interactions between gene targets, expression and disease.
Revolutionising imaging: Using advanced imaging technologies we can now capture at a molecular level the cellular interactions that can both define a disease, as well as monitor the efficacy of treatments based on the modulation of tissue biomarkers in response to a drug.
We are taking these advances in imaging technology into our clinical trials, redefining endpoints to demonstrate disease modification with targeted treatment.
Accelerating design of new diagnostic tests: Finding the right patients depends on reliable diagnostic tests. Ideally these should be capable of detecting early-stage disease and minimally invasive so they can be used to screen patients before symptoms develop.
We are collaborating with external partners to identify biomarkers and develop them into non-invasive tests, which could be validated for use in helping to diagnose patients.
Striving for better, healthier futures for patients
Across the globe, healthcare systems are seeking new strategies manage the effects of a growing population living with complex disease comorbidities. Precision medicine provides clear advantages for patients, healthcare systems and those involved in the provision of care – through earlier diagnosis, avoidance of unnecessary treatments, improvements in the course of disease and better outcomes.
The potential of a precision medicine
Patients
Reduced trial and error
Physicians
Patient benefit with improved outcomes
Payer
Pay for only the correct treatment
Regulators
Efficacy and safety
Science
Disease understanding, tailored therapy
By enabling treatments to be targeted to the right patients, precision medicine represents a new model of care, evolving from the current untargeted approaches that often rely on ‘trial and error’ to find the best available treatment. As therapies that are unlikely to be effective are avoided, there is less drug wastage, fewer side effects and total healthcare utilisation including length of hospital stays is reduced, providing savings to already stretched healthcare systems and building more sustainable care for everyone.
Precision Medicine FAQs
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References
1. AstraZeneca Pharmaceuticals. Data on file. Budesonide/formoterol: Annual Rate of Exacerbations Globally (ID:SD-3010-ALL-0017).
2. World Health Organisation. Chronic obstructive pulmonary disease (COPD). Available at: http://www.who.int/news-room/fact-sheets/detail/chronic-obstructive-pulmonary-disease-(copd)
3. Rinella ME, Lazarus JV, Ratziu V et al. NAFLD Nomenclature consensus group. A multi-society Delphi consensus statement on new fatty liver disease nomenclature. Hepatology. 2023 Jun 24. doi: 10.1097/HEP.0000000000000520.
Veeva ID: Z4-59521
Date of preparation: November 2023