Detailed findings from the Phase III DAPA-CKD trial show that adding AstraZeneca's Farxiga (dapagliflozin) to standard care reduced the composite measure of deteriorating renal function, or risk of death from cardiovascular (CV) or kidney disease, by 39% versus placebo in patients with chronic kidney disease (CKD), the company announced Sunday. AstraZeneca noted that the results, presented at the European Society of Cardiology (ESC) digital congress, were consistent in CKD patients both with and without type 2 diabetes.
In March, DAPA-CKD was stopped early as a result of "overwhelming efficacy," with AstraZeneca later releasing topline results showing that Farxiga had achieved all goals in the study. Mene Pangalos, head of BioPharmaceuticals R&D, said that "with today's results, Farxiga becomes the first SGLT2 inhibitor proven to significantly prolong the survival of patients with CKD with and without type 2 diabetes," adding that the company aims to request regulatory approval for expanded use of the drug in CKD over the next few months.
The trial randomised 4304 patients with CKD stages 2 to 4 and elevated urinary albumin excretion to receive once-daily Farxiga or placebo, both in combination with standard care. Patients with type 2 diabetes accounted for 67.5% of the total study population. The primary composite endpoint was at least a 50% sustained decline in estimated glomerular filtration rate, onset of end-stage kidney disease and CV or renal death.
AstraZeneca noted that the absolute risk reduction (ARR) on the primary composite endpoint was 5.3% over the median follow-up of 2.4 years. The trial also met all three secondary endpoints compared to placebo, including significantly reducing death from any cause by 31%, with the ARR being 2.1%. Farxiga was also associated with a 44% decrease in worsening renal function or death from kidney failure, and a 29% reduction in hospitalisation for heart failure or CV death.
Farxiga's safety and tolerability in DAPA-CKD were consistent with its known safety profile, according to the company. Patients treated with the drug experienced fewer serious adverse events compared to placebo, at rates of 29.5% versus 33.9%, respectively. In addition, there were no cases of diabetic ketoacidosis among Farxiga-treated patients, compared to two in the placebo group.
In May, Farxiga gained expanded FDA approval to reduce the risk of CV death and hospitalisation for heart failure (HF) in adults suffering from heart failure with reduced ejection fraction (HFrEF), regardless of whether they have type 2 diabetes. The drug, which generated sales of $1.5 billion in 2019, is also indicated to improve glycaemic control in adults with type 2 diabetes. For related analysis, read Physician Views snap poll results: Farxiga could fly.
Meanwhile, Farxiga is currently being assessed in the DELIVER trial, which involves HF patients with preserved ejection fraction (HFpEF), as well as in the DETERMINE study of both HFrEF and HFpEF patients. The drug is also being evaluated in the DAPA-MI trial of patients without type 2 diabetes following an acute myocardial infarction.
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