Dapagliflozin Meets All Targets in Patients With Chronic Kidney Disease, With and Without Diabetes

AstraZeneca’s dapagliflozin, the sodium-glucose cotransporter 2 (SGLT2) inhibitor sold as Farixga, met all its targets for slowing the decline of renal function, preventing kidney failure, and preventing cardiovascular or renal death in phase 3 trial that was halted earlier this year, according to topline results released today.

Data from DAPA-CKD show that the trial met all its primary and secondary end points for patients with chronic kidney disease (CKD), with and without type 2 diabetes (T2D). The announcement comes after a data monitoring committee halted the trial in March 2020 when it found the evidence of efficacy was overwhelming.

According to AstraZeneca’s statement, topline results show:

• Dapagliflozin “showed a statistically significant and clinically meaningful effect” on its primary end point, a composite of ≥50% sustained decline in estimated glomerular filtration rate (eGFR), onset of end-stage kidney disease, or cardiovascular or renal death in adult patients with CKD.
• The trial met all secondary end points in patients with and without T2D. Study authors previously outlined these as: (1) time to a composite renal end point of ≥50% eGFR decline from baseline (as confirmed by serum creatinine), ESRD defined as eGFR <15 mL/min/1.73m², the need for chronic dialysis or transplant, and renal death; (2) time to first occurrence of cardiovascular death or hospitalization for heart failure; and (3) time to death from any cause.

FDA previously granted dapagliflozin a Fast Track designation in August 2019 to delay renal progression and prevent cardiovascular and renal death in patients with CKD. The drug, which was first developed to treat T2D, has also received an indication for certain patients with heart failure, regardless of diabetes status.

According to the statement from AstraZeneca, the results show dapagliflozin is the first drug to reduce the risk from any cause among these patients. In a previous renal outcomes trial for the SGLT2 inhibitor canagliflozin (Invokana), investigators in the CREDENCE trial reported that “there was no significant between group difference in the risk of cardiovascular death,” and due to the study’s protocol, other outcomes, including death from any cause, were not tested.

There are limited treatment options for CKD, which can lead patients to cardiovascular events or eventually require dialysis or a kidney transplant. Kidney failure is one of the most expensive and debilitating conditions in Medicare—and so costly that once patients need dialysis, they quickly become eligible for Medicare regardless of age. According to the National Kidney Foundation, 37 million people in the United States have kidney disease, which can result from diabetes.

“DAPA-CKD is the first trial to demonstrate overwhelming efficacy, including improvement on survival, in chronic kidney disease patients both with and without type 2 diabetes,” Mene Pangalos, executive vice president, BioPharmaceuticals R&D for AstraZeneca, said in a statement. “We look forward to sharing these exciting Farxiga results with the scientific community and health authorities worldwide.”

Full results of DAPA-CKD will be presented during Kidney Week, the annual meeting of the American Society of Nephrology, set for October 20-25, 2020.