The Food and Drug Administration (FDA) has approved Farxiga® (dapagliflozin) to reduce the risk of sustained estimated glomerular filtration rate (eGFR) decline, end stage kidney disease, cardiovascular (CV) death and hospitalization for heart failure in adults with chronic kidney disease (CKD) at risk of progression.
The approval was based on data from the phase 3 DAPA-CKD trial (ClinicalTrials.gov: NCT03036150), a double-blind, placebo-controlled study that compared the effect of dapagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, to placebo on renal outcomes and cardiovascular (CV) mortality in patients with CKD (N=4304). Patients were randomly assigned 1:1 to receive either dapagliflozin 10mg once daily or placebo, in addition to standard of care (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker).
The primary endpoint was a composite of worsening renal function or death, defined as a composite endpoint of 50% or greater sustained decline in estimated eGFR, onset of end stage kidney disease (sustained eGFR less than 15mL/min/1.73 m2, initiation of chronic dialysis treatment or renal transplant), CV or renal death in patients with CKD (Stages 2 to 4) irrespective of the presence of type 2 diabetes.
Study findings showed that dapagliflozin reduced the primary composite measure of worsening of renal function or risk of CV or renal death by 39% compared with placebo (hazard ratio [HR] 0.61 [95% CI, 0.51-0.72]; P <.0001); the absolute risk reduction was 5.3% over the median follow-up time of 28.5 months. Dapagliflozin also reduced the incidence of the composite endpoint of CV death or hospitalization for heart failure (hazard ratio [HR] 0.71 [95% CI, 0.55-0.92], P =.0089) and all-cause mortality (HR 0.69 [95% CI, 0.53-0.88], P =.0035).
Results of the primary composite endpoint were consistent across the subgroups examined, including CKD patients with and without type 2 diabetes, causes of CKD, age, sex, race, urine albumin creatinine ratio, and eGFR. Exploratory analyses of the DECLARE-TIMI 58 trial (ClinicalTrials.gov: NCT01730534), a randomized, double-blind, placebo-controlled study investigating the effect of dapagliflozin on CV outcomes, support the conclusion that the treatment is also likely to be effective in patients with less advanced CKD.
“Based on the unprecedented results of the DAPA-CKD trial, dapagliflozin is now the first SGLT2 inhibitor approved for the treatment of chronic kidney disease regardless of diabetes status,” said co-chair of the DAPA-CKD trial and its executive committee, Prof. Hiddo L. Heerspink, University Medical Center Groningen, the Netherlands. “This transformational milestone provides patients and physicians with a new and effective treatment option for this often debilitating and life-threatening disease.”
Prior to initiating treatment with Farxiga, renal function and volume status should be assessed and volume depletion should be corrected. Farxiga is not recommended for the treatment of CKD in patients with polycystic kidney disease or patients requiring or with a recent history of immunosuppressive therapy for kidney disease; it is not expected to be effective in these populations.
- Farxiga approved in the US for the treatment of chronic kidney disease in patients at risk of progression with and without type-2 diabetes. [press release]. AstraZeneca; April 30, 2021.
- Farxiga® prescribing information. Wilmington.DE: AstraZeneca. 2021.