Finerenone delays diabetic kidney disease progression: FIDELIO-DKD
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Topline findings from the FIDELIO-DKD study show the investigational drug finerenone delayed the progression of chronic kidney disease and reduced risk for cardiovascular events among adults with type 2 diabetes compared with placebo.
Results from the phase 3 study, a randomized controlled trial enrolling 5,700 international participants with type 2 diabetes and CKD, demonstrated that finerenone delayed the progression of CKD by reducing the combined risk for time to first occurrence of renal failure, defined as a sustained decrease of estimated glomerular filtration rate of at least 40% from baseline for at least 4 weeks, or renal death. Finerenone also reduced the risk for the key secondary endpoint, a composite of time to first occurrence of CV death, non-fatal myocardial infarction, non-fatal stroke, or heart failure hospitalization, Bayer stated in a press release.
“The rate of decline in kidney function among patients with chronic kidney disease and type 2 diabetes under ideal clinical trial circumstances is approximately twofold normal, age-related decline,” George L. Bakris, MD, professor of medicine and director of the American Heart Association Comprehensive Hypertension Center at the University of Chicago Medicine, told Healio. “Therefore, we clearly need additional medications to slow loss of kidney function. Currently available mineralocorticoid receptor antagonists have a clear reno-protective role; however, they have as a limiting factor hyperkalemia in clinical practice. Finerenone is an investigational non-steroidal mineralocorticoid receptor antagonist that has been shown in phase 2 clinical trials to have an acceptable safety profile in patients with CKD and type 2 diabetes. The phase 3 FIDELIO study results with finerenone are highly relevant, as they show improvement in both renal and CV outcomes for patients with advanced CKD with type 2 diabetes who currently have limited options.”
Finerenone is the first investigational non-steroidal, selective mineralocorticoid receptor antagonist to demonstrate renal and CV benefits in patients with CKD and type 2 diabetes, Bakris said.
“Unlike other agents that have slowed progression of CKD in patients, finerenone has shown a limited effect on blood pressure in phase 2 studies,” Bakris said. “Thus, finerenone is not believed to work via hemodynamic effects, but rather by targeting inflammation and fibrosis caused by mineralocorticoid overactivation, a currently unaddressed driver of CKD progression in type 2 diabetes.”
The FIDELIO-DKD study is part of the largest phase 3 clinical trial program to date in CKD, enrolling 13,000 participants across a broad range of disease severity, according to Bayer. For FIDELIO-DKD, 5,700 participants from more than 1,000 sites across 48 countries were randomly assigned to 10 mg or 20 mg daily oral finerenone or placebo added to standard care, which included glucose-lowering therapies and maximally tolerated renin–angiotensin system-blocking therapy, such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs).
“Despite optimal care to manage risk factors like elevated blood glucose or blood pressure, patients with CKD and type 2 diabetes remain at increased risk for CV events,” Bakris said. “Unfortunately, there are few approved therapies that have demonstrated the ability to reduce risk of CV events in this patient population. Data on the CV benefit of finerenone are currently being analyzed and will be presented at a scientific conference by the end 2020.”
Bayer said data from FIDELIO-DKD will be presented at an upcoming scientific meeting.
Perspective
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Robert C. Stanton, MD
The number of people with diabetic kidney disease (DKD) continues to rise worldwide and is a major health care problem, as DKD is strongly associated with increased risks for heart disease, hypertension, kidney failure and death. It is critical to find new treatments that slow development and progression of DKD. The renin-angiotensin-aldosterone system has been shown to play a significant pathogenic role and ACE inhibitors and angiotensin II receptor blockers are mainstays of treatment for DKD. In addition, many studies have shown that increased aldosterone plays a major pathogenic role in DKD. Inhibition of aldosterone with spironolactone appears to be beneficial in slowing progression of DKD. But spironolactone and eplerenone are steroids that may have undesirable side effects for people with DKD. Thus, the development of non-steroidal inhibitors of aldosterone is a welcome development.
Of the non-steroidal aldosterone inhibitors, finerenone is the closest to being FDA approved and available for people with DKD. The current press release about the phase 3 FIDELIO-DKD trial in which finerenone was added to the maximum tolerated dose of an ACE inhibitor or angiotensin II receptor blocker is very promising. It will be very interesting to review the results in detail when this important trial is published.
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