Thursday, 27 August 2015
It is increasingly well understood that medicine should be focused on the whole patient, and not just on individual diseases. To achieve this, it is essential to understand the associations between apparently independent conditions.
A good example is the link between cardiovascular disease, diabetes and chronic kidney disease (CKD). People with diabetes or CKD have an elevated likelihood of cardiovascular problems because these diseases predispose them to specific cardiovascular risks, such as dyslipidaemia, blood vessel damage, and overstimulation of inflammatory responses.1,2
The development of effective new treatments therefore requires an understanding of all of these diseases and how they interact in specific patient groups. It is this that drives AstraZeneca’s approach, which brings together its cardiovascular, metabolic and CKD activities into a single, integrated, therapeutic area: cardiovascular and metabolic disease (CVMD).
Our clinical development programmes are focused on some of the most difficult-to-treat patient groups, including those with more than one of these conditions – one patient, multiple diseases.
Inhibiting progression in one condition for potentially broader benefits
A key feature that binds cardiovascular disease, diabetes and CKD is that each is chronic and progressive. Halting or even reversing this progression is the ‘holy grail’ of treatment. Furthermore, the well-established links between these conditions raise the possibility that preventing progression in one disease could also have positive effects on the others.
Medicines and investigational therapies in AstraZeneca’s development pipeline are directed against a broad range of targets and employ a variety of approaches aimed at arresting or reversing disease progression in CVMD patients: from antisense oligonucleotides and modified ribonucleic acids (RNAs) that inactivate specific disease-associated genes or stimulate cellular repair, to peptides and antibodies that can inhibit disease pathways or promote an appropriate bodily response.
For example, we are working on a novel technique that uses synthetic modified RNA to produce transient, local expression of relevant proteins in the heart. It is focused on addressing one of the most fundamental unmet needs in cardiovascular medicine – the repair of dysfunctional cardiac tissue and the regeneration of lost function – through the stimulation of endogenous cardiac cells. This work is still in its early stages, but holds enormous promise for the future.
Innovation through collaboration
Developing novel therapies that address the multiple, interrelated diseases that characterise CVMD requires collaboration.
AstraZeneca works with many partner organisations with expertise that dovetails with our own – whether it is the complementary know-how of industry partners, the novel approaches of academic institutions, the clinical knowledge and leadership of scientific organisations, or the real-world experience of patient advocacy groups.
|Some of AstraZeneca’s key CVMD partners|
|American Association of Clinical Endocrinologists|
|American College of Cardiology|
|American Diabetes Association|
|American Heart Association|
|European Association for the Study of Diabetes|
|European Society of Cardiology|
|Federation of European Nurses in Diabetes|
|International Diabetes Federation|
|Juvenile Diabetes Research Foundation|
|Max Planck Institute of Molecular Physiology|
|Primary Care Diabetes Europe|
|Taking Control Of Your Diabetes|
|Harvard Stem Cell Institute|
Within these partnerships, AstraZeneca aims to address a range of scientific and clinical interests in CVMD:
1. Advancing understanding of disease mechanisms
Improved understanding of disease mechanisms is essential to developing the next generation of novel therapies. An excellent example is our collaboration with the Swedish medical university, Karolinska Institutet, to create an Integrated Translational Research Centre. This centre is conducting ground-breaking preclinical and clinical studies aimed at improving knowledge of the pathophysiology of CVMD, and assessing new drug targets.
Meanwhile, our partnership with the Max Planck Institute of Molecular Physiology in Germany has established a new satellite unit in CVMD. It is focused on the identification of new targets in key areas of CVMD research, such as cardiac regeneration, pancreatic islet health, and diabetic nephropathy.
2. Developing new medicines
In addition to this fundamental research, AstraZeneca is focused on bringing new therapies through to clinical practice.
For example, the acquisition of Omthera Pharmaceuticals in 2013 was targeted at the development of novel therapies for dyslipidaemia, a key risk factor that links diabetes, CKD and cardiovascular disease.1,2 Since acquiring Omthera, a new treatment has already been approved by the US Food and Drug Administration.
3. Improving disease management
Finally, ongoing patient support is essential to long-term care. With this in mind, AstraZeneca is contributing to the American College of Cardiology’s ‘Patient Navigator’ programme, which will have enrolled 35 hospitals across the USA by the end of 2015. Its aim is to establish ‘navigator’ teams to coordinate personalised support for patients following serious cardiovascular events like heart failure, during the difficult transition from hospital back to life at home.
AstraZeneca’s depth of expertise in CVMD therapy, disease understanding and long-term management is brought to bear in our work in non-industrialised nations. In 2014, AstraZeneca launched ‘Healthy Heart Africa’, a patient-focused programme supporting local health systems by increasing awareness of the symptoms and risks of hypertension, and offering education, screening, treatment and control. Cardiovascular disease is rapidly rising in Africa and hypertension is one of the main risk factors, making it vital that we address this growing problem.
A holistic approach to CVMD
Treating ‘the whole patient’ when that patient has multiple cardiovascular and metabolic conditions is not straightforward; it represents one of the great challenges in modern medicine. Through a focus on high-quality science, innovative partnerships and long-term patient support, AstraZeneca remains deeply committed to finding novel therapies for these patients.
- Dokken BB. The pathophysiology of cardiovascular disease and diabetes: beyond blood pressure and lipids. Diabetes Spectrum 2008;21:160-5.
- Yamamoto S, Kon V. Mechanisms for increased cardiovascular disease in chronic kidney dysfunction. Curr Opin Nephrol Hypertens 2009;18:181-8.