By Ed Miseta, Chief Editor, Clinical Leader
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Many patients who suffer from cardiovascular, renal and metabolic (CVRM) diseases face not one, but several overlapping co-morbidities that can critically impact quality of life and overall health. For years, AstraZeneca has been at the forefront of advancements in cardiovascular disease (CVD) and diabetes. Now, the company is bringing renal into focus, by developing CVRM medicines that attempt to both answer important clinical questions and put patients’ needs first.
I spoke with Anna Sundgren, Renal Disease Strategy Leader, Global Medicines Development at AstraZeneca, to learn more about the company’s focus on CVRM diseases and what it means for patients.
Ed Miseta: Why is AstraZeneca placing this focus on the CVRM therapy area?
Anna Sundgren: Our aim was to follow the science to address the multiple risk factors associated with CVRM diseases. Research has shown that over the past 20 years, there has been a nearly 30 percent increase in renal impairment in people with Type 2 Diabetes. And more than 40 percent of people with heart failure also have chronic kidney disease (CKD).
CVD, CKD, and diabetes are among the most common causes of death in many countries, and research continues to uncover common underlying mechanisms and relationships among these diseases. Today, one in 10 people worldwide have CKD, and the number of deaths due to the disease has doubled since 1990. It is now the sixth-fastest growing cause of death. People with CKD are up to 20 times more likely to die from cardiac causes, and CVD is the leading cause of death in people with CKD. The unmet medical needs are significant.
AstraZeneca has a strong scientific heritage in developing treatments for cardiovascular, metabolic, as well as inflammatory disease. Since control of blood pressure, sugar levels, and inflammation are all important in renal disease, it is fitting that we have made renal disease a major focus of the research we are conducting. We’re hoping to address the unmet need for many patients with CKD who have often felt as if there was no help available to them. So, we decided to firmly put the “R” in CVRM and signal a clear strategic intent to develop novel innovative medicines for these patients.
Miseta: Why do we see so many people with CKD dying from cardiac causes?
Sundgren: This is a result of the close clinical interrelationship between the kidneys and heart. Cardiac damage increases a patient’s susceptibility to kidney damage primarily through high blood pressure, and heart disease can therefore accelerate the progression of CKD. In turn, declining kidney function can cause cardiac dysfunction. Patients with kidney disease are at risk of life-threatening complications, and even moderate renal dysfunction increases the risk of death and CVD-related complications.
Miseta: Can the company’s focus on CVRM help to create better clinical trials for these patients?
Sundgren: First of all, almost by default, patients with kidney disease were excluded in clinical trials. Compared to cardiovascular or metabolic disease, rather few trials were done. So absolutely, yes, it is one of our goals to do more trials with new medications, but also improve how trials are done in patients with CKD. Our pipeline includes around 25 therapies and therapy combinations across CVRM diseases. We are exploring therapies to manage life-threatening complications of CKD, such as hyperkalaemia and anemia, and therapies to modify the progressive decline of the disease itself. We are, for instance, interested in the role of lowering uric acid as a mechanism to slow CKD. With regard to how to improve trial designs, we firmly believe that biophysical or biochemical markers that can identify different CKD patients, which can lead to better targeting of the right medication for the right patients. All of this could not be possible without our scientific investments in metabolism, heart failure and cardiovascular disease, across very early science to late stage development.
Miseta: Can you give us an example of something innovative you are doing in a clinical setting?
Sundgren: Sure. Let me share some of our late-stage development work for life-threatening complications. We know that CKD patients with hyperkalaemia have a higher risk of mortality – nearly three times – than those without. There is also a well-established correlation between patients taking RAASi (Renin-Angiotensin-Aldosterone system inhibitors) therapies and hyperkalemic episodes. Now, RAASi therapies are good, commonly-prescribed life-saving medicines for heart failure and CKD patients, and these are often stopped when patients experience an increase in serum potassium. We have an expanding clinical development program for patients with hyperkalaemia, with nine Phase III clinical trials completed or in progress, that evaluate CVRM patients in a number of different specific clinical settings to understand optimal use and greatest patient benefit – patients with heart failure, patients on dialysis, and patients in specific geographic regions to name a few. We firmly believe that if we can treat hyperkalemia, we can help physicians to optimally treat their patient’s blood pressure with RAASi.
Miseta: How will AstraZeneca’s focus on CVRM help improve outcomes for CKD patients?
Sundgren: Well, if we look at diabetes with early kidney disease combined, life expectancy can be reduced by up to 15 years for men and 16 years for women. The number of therapies that can halt or modify CKD progression is currently limited and nephrology is a field that has seen little innovation in the last 30 years, as I touched on before. However, this doesn’t reflect the tremendous amount of research underway in this field, and I am very confident that the renal medical arena will see several new innovative therapies in the coming five years. These will, of course, have to prove effective on patient outcomes, but I am very positive about our ability to dramatically change the outlook for a newly diagnosed CKD patient going forward. We would like to see a world where people living with CKD are able to live longer, have greater vitality, and manage their complications and co-morbidities effectively. For me, a truly inspiring world would be if a diagnosis with CKD is no longer a death sentence, and that transplant rates would come down to more manageable numbers where demand and supply are more matched.
Miseta: Where do you go from here?
Sundgren: Renal is a relatively new disease area for AstraZeneca, and therefore there is plenty of room for us to advance our expertise and achieve scientific leadership. I am very committed to renal disease, and as we have a healthy portfolio of programs from preclinical through late-stage, our company is likely to keep me busy going forward. AstraZeneca has made a strong investment in this area and I believe that in the long-term we will make a real impact on people living with CKD and their nephrologists. I really want to be a big part of that and hope to be so for years.