AstraZeneca’s Farxiga (dapagliflozin) dramatically prolonged survival in patients with chronic kidney disease in a Phase III clinical trial. Specifically, Farxiga with standard of care decreased the composite measure of worsening of renal function or risk of cardiovascular (CV) or renal death by 39% compared to placebo. This was in patients with chronic kidney disease (CKD) Stages 2-4 and elevated urinary albumin excretion. There were no differences observed in patients who had or did not have type 2 diabetes.
CKD is a serious, progressive disease marked by decreased kidney function. It affects about 700 million people around the world, many still undiagnosed. The most common causes are diabetes, hypertension and glomerulonephritis.
Farxiga is indicated in the U.S. as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes and to decrease the risk of hypertensive heart failure in adults with type 2 diabetes and established cardiovascular disease or multiple cardiovascular risk factors. It is not indicated to decrease the worsening of renal function or death in patients with CKD or to decrease cardiovascular risk in patients with heart failure with preserved ejection fraction (HFpEF) or after a myocardial infarction without type 2 diabetes. It was approved by the U.S. Food and Drug Administration (FDA) in May to reduce the risk of CV death and hospitalization for heart failure.
“The impressive DAPA-CKD trial results are a remarkable development for patients with chronic kidney disease,” said the co-chairs of the DAPA-CKD trial and its executive committee, David Wheeler, University of College London, UK and Hiddo L. Heerspink, University Medical Center Groningen, the Netherlands. “These data have the potential to transform the standard of care for this patient population, which has a significant unmet need for new and improved treatment options.”
The DAPA-CKD trial evaluated 4,304 patients with 10mg Farxiga compared to placebo. The patients had CKD Stages 2 through 4 and elevated urinary albumin excretion, with and without type 2 diabetes. The primary composite endpoint was worsening of renal function or risk of death, which was defined as a composite of an eGFR decline greater than or equal to 50%, onset of ESKD and death from CV or renal cause. Secondary endpoints included the time to first occurrence of the renal composite, the composite of CV death or hHF, and death from any cause. The trial was run in 21 countries.
In the trial, the absolute risk reduction (ARR) was 5.3% more than the median time in the study of 2.4 years. The trial also hit all secondary endpoints, including a 31% decrease in death from any cause compared to placebo.
“With today’s results, Farxiga becomes the first SGLT2 inhibitor proven to significantly prolong the survival of patients with chronic kidney disease with and without type 2 diabetes and we look forward to sharing these data with regulatory authorities around the world,” said Mene Pangalos, executive vice president, BioPharmaceuticals R&D for AstraZeneca. “Farxia is also the first medicine in its class to demonstrate benefit in treating both heart failure and chronic kidney disease in patients with and without type 2 diabetes, and reduce the risk of hospitalization for heart failure and nephropathy in type 2 diabetes.”