Farxiga Demonstrates Significant Reduction in Risk of Kidney Function Deterioration and Death in CKD Patients Regardless of Underlying Cause: New Subgroup Analysis from Phase III DAPA-CKD Trial

Compiled by Keke

On October 23, AstraZeneca announced new subgroup analysis results from the groundbreaking Phase 3 DAPA-CKD clinical study. The data demonstrated that Farxiga (dapagliflozin), when added to standard of care, reduced the risk of worsening kidney function or cardiovascular (CV) and renal death in patients with chronic kidney disease (CKD), regardless of the underlying cause.

In this subgroup analysis, treatment with Farxiga, compared with placebo, resulted in a relative risk reduction (RRR) of 37% (absolute risk reduction [ARR] = 5.8%) in patients with chronic kidney disease (CKD) primarily caused by diabetic nephropathy; an RRR of 25% (ARR = 2.2%) for hypertension; an RRR of 57% (ARR = 7.5%) for glomerulonephritis; and an RRR of 42% (ARR = 5.0%) for CKD due to other or unknown causes (p-value for interaction = 0.53). Furthermore, regardless of the underlying cause of CKD, Farxiga treatment demonstrated a reduction in all-cause mortality compared with placebo (p-value for interaction = 0.55) (secondary endpoint). In addition, the safety and tolerability profile of Farxiga was consistent with the safety previously observed with this medication.

DAPA-CKD was an international, multicenter, randomized, double-blind Phase 3 trial that enrolled 4,304 patients with chronic kidney disease (CKD). The study aimed to evaluate the efficacy of 10 mg Farxiga versus placebo in patients with Stage 2–4 CKD and elevated urinary albumin excretion, with or without type 2 diabetes (T2D). In the study, patients received once-daily Farxiga in addition to standard care. Detailed results published by AstraZeneca in The New England Journal of Medicine in August 2020 showed that, compared with placebo, Farxiga reduced the risk of worsening kidney function (defined as a sustained ≥50% decline in eGFR, onset of end-stage kidney disease [ESKD], and death from cardiovascular [CV] or renal causes) or renal/CV mortality (the primary composite endpoint) by 39% (p<0.0001).

This positive result was consistent in patients with and without T2D. Farxiga also met all secondary endpoints, reducing by 31% the proportion of composite outcomes including first occurrence of kidney disease (sustained ≥50% decline in eGFR, ESKD, and renal death), CV death or hospitalization for heart failure (hHF), and all-cause mortality (ARR=2.1%, p=0.0035).

Professor Hiddo L. Heerspink, Co-Chair of the Executive Committee of the DAPA-CKD trial at the University Medical Center Groningen in the Netherlands, stated: “The results released today demonstrate the potential of Farxiga to transform the standard of care for a broad population of patients with chronic kidney disease, regardless of the underlying etiology. This offers significant promise for millions of patients with chronic kidney disease worldwide.”

Mene Pangalos, Executive Vice President of BioPharmaceuticals R&D at AstraZeneca, stated: “In trials assessing renal outcomes in patients with chronic kidney disease, with or without type 2 diabetes, DAPA-CKD demonstrated that Farxiga is the first SGLT2 inhibitor with the potential to significantly prolong patient survival.”

Chronic kidney disease (CKD) is a serious, progressive condition defined by a decline in kidney function (a reduced glomerular filtration rate [eGFR] or markers of kidney damage, or both, persisting for at least three months). It is estimated that approximately 700 million people worldwide are affected, many of whom remain undiagnosed. In the United States, one-third of adults (approximately 80 million people) are at risk of developing CKD. The primary causes of CKD are diabetes (38%), hypertension (26%), and glomerulonephritis (kidney inflammation, 16%). Its most severe form, end-stage kidney disease (ESKD), occurs when kidney damage and functional deterioration have progressed to the point where dialysis or kidney transplantation is required. Most patients with CKD die from cardiovascular disease before progressing to ESKD.

In early October, Farxiga received Breakthrough Therapy designation in the United States for the treatment of patients with chronic kidney disease (CKD), with or without type 2 diabetes (T2D), and was recommended by the European Committee for Medicinal Products for Human Use for the treatment of heart failure (HF). Furthermore, in May 2020, Farxiga was approved in the United States to reduce the risk of cardiovascular death and hospitalization for heart failure (hHF) in adult patients with heart failure with reduced ejection fraction (HFrEF) (NYHA class II–IV), with or without T2D.

Farxiga (dapagliflozin) is a first-in-class, once-daily oral sodium-glucose cotransporter-2 (SGLT2) inhibitor. It is used as monotherapy and as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes (T2D) who have inadequate glycemic control, with additional benefits of weight loss and blood pressure reduction. In the cardiovascular outcomes trial DECLARE-TIMI 58 involving adult patients with T2D, Farxiga demonstrated a reduced risk of the composite endpoint of hospitalization for heart failure (hHF) or cardiovascular (CV) death compared with placebo.

Currently, the drug is being studied in patients with heart failure (HF) in the DELIVER trial (for HF with preserved ejection fraction [HFpEF]) and the DETERMINE trial (for HFrEF and HFpEF); it is also being evaluated in the DAPA-MI trial in patients without type 2 diabetes (T2D) following acute myocardial infarction (MI) or heart attack.

Reference source: Farxiga DAPA-CKD Phase III trial reduced worsening of kidney function, risk of cardiovascular or renal death in patients with chronic kidney disease, irrespective of underlying cause