Dapagliflozin approved in Europe for CKD, regardless of diabetes status

Dapagliflozin (Forxiga) has been approved in the European Union for the treatment of chronic kidney disease (CKD) in adults with and without type-2 diabetes (T2D), according to AstraZeneca, the manufacturer of the sodium-glucose cotransporter 2 (SGLT2) inhibitor.¹

The approval is based on findings from the phase 3 DAPA-CKD trial, in which dapagliflozin reduced the relative risk of worsening of renal function, onset of end-stage kidney disease (ESKD), or cardiovascular or renal death by 39% (HR, 0.61; P <.0001) versus placebo in patients with stage 2 to 4 CKD and elevated urinary albumin excretion.²

Based on the same data from the DAPA-CKD trial, the FDA approved dapagliflozin in April 2021 for the treatment patients with CKD.³

“Today’s approval establishes dapagliflozin as the first SGLT2 inhibitor approved for the treatment of chronic kidney disease regardless of diabetes status in the European Union. Based on the unprecedented results from the DAPA-CKD phase 3 trial, dapagliflozin delays disease progression providing physicians a critical opportunity to improve the prognosis of patients with chronic kidney disease,” Hiddo L. Heerspink, PhD, co-chair of the DAPA-CKD trial and its executive committee, University Medical Center Groningen, the Netherlands, stated in a press release.

The phase 3 DAPA-CKD study evenly randomized 4304 patients with CKD to dapagliflozin or placebo. Patients had an estimated glomerular filtration rate (GFR) of 25 ml to 75 ml per minute per 1.73 m2 of body-surface area and a urinary albumin (mg)-to-creatinine (g) ratio of 200 to 5000. The primary end point of the study was a composite of a sustained decline of at least 50% in the estimated GFR, ESKD, or death from renal or cardiovascular causes.

At a median follow-up of 2.4 years, a primary outcome event had occurred in 9.2% of the dapagliflozin arm, compared with 14.5% of the placebo arm. The hazard ratio was 0.56 (44% risk reduction with dapagliflozin) for the composite of ESKD, ≥50 sustained decline in the estimated GFR, or death from renal causes. For the composite of death from cardiovascular causes or hospitalization for heart failure, the hazard ratio was 0.71 (29% risk reduction with dapagliflozin).

The investigators observed that the efficacy of dapagliflozin was similar in patients with and without T2D. Overall, there were 101 (4.7%) deaths in the dapagliflozin arm versus 146 (6.8%) deaths in the control arm. There were no new safety signals compared with dapagliflozin’s known safety profile.

According to the press release, approximately 840 million people across the globe are affected by CKD, included about 47 million in the European Union.

References

1. Forxiga approved in the EU for the treatment of chronic kidney disease in patients with and without type-2 diabetes. Published online August 9, 2021. Accessed August 12, 2021. https://bit.ly/3lXr8Bm.

2. Dapagliflozin in patients with chronic kidney disease. Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. N Engl J Med. 2020;383:1436-1446 doi: 10.1056/NEJMoa2024816

3. FDA Approves Treatment for Chronic Kidney Disease. Published online April 30, 2021. Accessed August 12, 2021. https://www.fda.gov/news-events/press-announcements/fda-approves-treatment-chronic-kidney-disease.