The US Food and Drug Administration (FDA) has approved dapagliflozin (Farxiga, AstraZeneca) to reduce the risk for kidney function decline, kidney failure, cardiovascular death, and hospitalization for heart failure in adult patients with chronic kidney disease (CKD) at risk for disease progression.
“Chronic kidney disease is an important public health issue, and there is a significant unmet need for therapies that slow disease progression and improve outcomes,” said Aliza Thompson, MD, deputy director of the Division of Cardiology and Nephrology at the FDA’s Center for Drug Evaluation and Research. “Today’s approval of Farxiga for the treatment of chronic kidney disease is an important step forward in helping people living with kidney disease.”
Dapagliflozin was approved in 2014 to improve glycemic control in patients with diabetes mellitus, and approval was expanded in 2020 to include treatment of patients with heart failure and reduced ejection fraction, based on results of the DAPA-HF trial.
This new approval in chronic kidney disease was based on results of the DAPA-CKD trial that was stopped early in March 2020 due to efficacy of the treatment.
DAPA-CKD randomly assigned 4304 patients with CKD but without diabetes to receive either dapagliflozin or placebo. The full study results, reported at the European Society of Cardiology Congress in 2020 and simultaneously published in the New England Journal of Medicine, showed that, during a median of 2.4 years, treatment with dapagliflozin led to a significant 31% relative reduction compared with placebo in the study’s primary outcome, a composite that included at least a 50% drop in estimated glomerular filtration rate compared with baseline, end-stage kidney disease, kidney transplant, renal death, or cardiovascular death.
Dapagliflozin treatment also cut all-cause mortality by a statistically significant relative reduction of 31%, and another secondary-endpoint analysis showed a statistically significant 29% relative reduction in the rate of cardiovascular death or heart failure hospitalization.
“Farxiga was not studied, nor is expected to be effective, in treating chronic kidney disease among patients with autosomal dominant or recessive polycystic (characterized by multiple cysts) kidney disease or among patients who require or have recently used immunosuppressive therapy to treat kidney disease,” the FDA statement notes.
Dapagliflozin should not be used by patients with a history of serious hypersensitivity reactions to this medication, or who are on dialysis, the agency adds. “Serious, life-threatening cases of Fournier’s Gangrene have occurred in patients with diabetes taking Farxiga,” it notes.
Patients should consider taking a lower dose of insulin or insulin secretagogue to reduce hypoglycemic risk if they are also taking dapagliflozin. Treatment can also cause dehydration, serious urinary tract infections, genital yeast infections, and metabolic acidosis, the announcement said. “Patients should be assessed for their volume status and kidney function before starting Farxiga,” the agency adds.
Dapagliflozin previously received Fast Track, Breakthrough Therapy, and Priority Review designations for this new indication.
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