·         Global clinical study conducted by AstraZeneca, including study population from India, shows positive results for its anti-diabetic drug dapagliflozin in reducing chronic kidney disease (CKD) progression in patients with or without type 2 diabetes

·         AstraZeneca’s dapagliflozin is the first medicine in SGLT-2i class to move into a new disease area by demonstrating efficacy and safety data for the treatment of patients with CKD.

AstraZeneca India (AstraZeneca Pharma India Limited), a leading science-led biopharmaceutical company, today announced the full results from the clinical trials of it’s  latest diabetes drug, dapagliflozin, showing significant benefits in reducing chronic kidney disease (CKD) progression in patients with and without type-2 diabetes. The DAPA-CKD study concluded globally on 30^th March 2020 based on its effectiveness and safety.

Chronic kidney disease (CKD) is an emerging public health problem. Global disease burden report of 2015 pointed that is CKD is the 12th most common cause of death with a 37.1% rise in mortality over 10 years. It is a serious, progressive condition defined by decreased kidney function and/or kidney damage, affecting nearly 70 Crore people worldwide, many of them still undiagnosed. The prevalence of CKD in India is estimated to be 17.2%, given its population >1 billion, the rising incidence of CKD is likely to pose major problems for both healthcare and the economy in future years. CKD is associated with significant patient death and an increased risk of cardiovascular (CV) events, such as heart failure and premature death. While there are medications that can address some of the risk factors for CKD or its associated problems, few work directly to slow renal disease progression.

Detailed results from the ground-breaking Phase III DAPA-CKD trial showed that AstraZeneca’s  Dapagliflozin on top of standard of care reduced the composite measure of worsening of renal function or risk of cardiovascular (CV) or renal death by 39% compared to placebo (p<0.0001) in patients with chronic kidney disease (CKD) Stages 2-4 and elevated urinary albumin excretion. The results were consistent in patients both with and without type-2 diabetes (T2D). CKD is a serious, progressive condition defined by decreased kidney function affecting nearly 700 million people worldwide, many of them still undiagnosed, and the most common causes are diabetes, hypertension and glomerulonephritis^.

The primary composite endpoint was ≥50% sustained decline in estimated glomerular filtration rate (eGFR), onset of end-stage kidney disease (ESKD) and CV or renal death. The absolute risk reduction (ARR) was 5.3% over the median time in study of 2.4 years. The trial also met all secondary endpoints, including significantly reducing death from any cause by 31% (ARR = 2.1%, p=0.0035) compared to placebo.

DAPA-CKD is the first trial to demonstrate efficacy, including improvement on survival, in CKD patients both with and without Type2 Diabetes.

Dr. Anil Kukreja, Vice President – Medical Affairs & Regulatory, AstraZeneca India said “AstraZeneca has always been on the forefront of innovative solution for non-communicable diseases. Despite currently available therapies, a significant unmet need for effective management of CKD continues to exist globally. The DAPA-CKD trial which included 4,304 patients with CKD into a global study, with 201 patients from India. Now Dapa -CKD results goes on show that Dapagliflozin,which is already effective in Type 2 Diabetes, select Heart Failure patients has demonstrated significant efficacy now even in Chronic Kidney Disease. Dapagliflozin is the first SGLT2 inhibitor to demonstrate such unprecedented efficacy in management of Chronic Kidney disease.”

Dr. Dinesh Khullar, national lead investigator of Dapa-CKD in India, said  “SGLT2 inhibitors of which dapagliflozin is a type have proved to be a very exciting and impressive class of drugs in the expanding armamentarium for our fight against diabetes. DAPA-CKD trial has shown an overwhelming advantage of the drug in slowing down the rate of progression of kidney disease in both diabetics as well as non-diabetic patients.”

In July 2020, Dapagliflozin was recently approved by USFDA as well as in India to reduce the risk of CV death and hospitalisation for heart failure (hHF) in adults with heart failure (NYHA class II-IV) with reduced ejection fraction (HFrEF) with and without T2D. Dapagliflozin is currently being assessed in patients with heart failure (HF) in the DELIVER (HF with preserved ejection fraction, HFpEF) and DETERMINE (HFrEF and HFpEF) trials, as well as in patients without T2D following an acute myocardial infarction (MI) or heart attack in the DAPA-MI trial – a first of its kind, indication-seeking registry-based randomised controlled trial.

Chronic Kidney Disease

CKD can be a serious, progressive condition defined by decreased kidney function (shown by reduced eGFR or markers of kidney damage, or both, for at least three months). The most common causes of CKD are diabetes, hypertension and glomerulonephritis. CKD is associated with significant patient morbidity and an increased risk of CV events, such as HF and premature death. In its most severe form, known as ESKD, kidney damage and deterioration of kidney function have progressed to the stage where dialysis or kidney transplantation are required. The majority of patients with CKD will die from CV causes before reaching ESKD.