The Food and Drug Administration (FDA) has granted Priority Review to dapagliflozin (Farxiga; AstraZeneca) for the treatment of new or worsening chronic kidney disease (CKD) in adults with and without type 2 diabetes (T2D).
The regulatory submission includes data from the phase 3 DAPA-CKD trial, which was stopped early in March 2020 due to “overwhelming efficacy”. The multicenter, event-driven, double-blind, placebo-controlled trial 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 randomized 1:1 to receive either dapagliflozin (5mg or 10mg) once daily or placebo in addition to standard of care.
The primary end point was a composite of worsening renal function or death (defined as a composite endpoint of ≥50% sustained decline in estimated glomerular filtration rate [eGFR], onset of end stage renal disease [ESRD] or CV or renal death) in patients with CKD irrespective of the presence of T2D. Secondary end points included time to first occurrence of the renal composite (sustained ≥50% eGFR decline, ESRD, and renal death), the composite of CV death or hospitalization for heart failure, and death from any cause.
Study findings showed that dapagliflozin reduced the composite measure of worsening of renal function or risk of CV or renal death by 39% compared with placebo (absolute risk reduction [ARR] 5.3%; P <.0001). Additionally, the trial met all secondary end points, including significantly reducing death from any cause by 31% compared with placebo (ARR 2.1%; P =.0035). As for safety, study findings showed that patients treated with dapagliflozin experienced fewer serious side effects than those in the placebo group (29.5% vs 33.9%, respectively).
In October 2020, the FDA granted Breakthrough Therapy designation to dapagliflozin for this indication. A Prescription Drug User Fee Act (PDUFA) date for the second quarter of 2021 has been set for this application.
Farxiga is currently approved as an adjunct to diet and exercise to improve glycemic control in adults with T2D. It is also indicated to reduce the risk of hospitalization for heart failure in patients with T2D and established CV disease or multiple CV risk factors; and to reduce the risk of CV death and hospitalization for heart failure in adults with heart failure (NYHA Class II-IV) with reduced ejection fraction.
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Farxiga granted Priority Review in the US for the treatment of patients with chronic kidney disease. [press release]. Wilmington, DE: AstraZeneca; January 6, 2021.