Results from FIDELIO-DKD suggest finerenone was associated with reductions in progression of chronic kidney disease and potential improvements in cardiovascular health.
Data from a phase 3 clinical trial indicate finerenone, a non-steroidal, selective mineralocorticoid receptor agonist made by Bayer, was effective at slowing the progression of chronic kidney disease (CKD) in patients with type 2 diabetes.
Presented at the American Society of Nephrology's Kidney Week 2020, results of the FIDELIO-DKD study suggest finerenone lowered risk CKD progression by 18% while also providing a 16% reduction in the study's cardiovascular outcome in a population of more than 5500 patients.
"We now have evidence that doctors can safely slow diabetic kidney disease progression and reduce cardiovascular event rates using finerenone, a novel nonsteroidal mineralocorticoid receptor blocker, not yet approved by the FDA. This is very important for a group of patients who've historically had very few options," said George Bakris, MD, Professor of Medicine at the University of Chicago, in a statement. "This promising target for a new therapy means patients are able to delay dialysis and, in turn, further delay the possible need for kidney transplants. The reduction in cardiovascular events is an added bonus to slowing kidney disease progression."
With previous studies reporting reductions in albuminuria during short-term trials involving patients with CKD and type 2 diabetes, FIDELIO-DKD was designed to provide a comprehensive understanding of the investigational therapy’s long-term effects on kidney and cardiovascular outcomes. Event-driven by design, the trial randomized a population of patients in a 1:1 ratio to treatment with finerenone or placebo.
For inclusion in the study, patients needed to be at least 18 years of age with type 2 diabetes and CKD while also being treated with an ACE inhibitor or ARB at maximum dose that did not cause unacceptable side effects. Investigators defined CKD as having a urinary albumin-to-creatinine ratio of 30 to less than 300, an eGFR of 25-60 ml/min/1.73 m2 of body surface area, and diabetic retinopathy, or as having urinary albumin-to-creatinine ratio of 300 to 5000 and an eGFR of 25-75 ml/min/1.73 m2.
Of note, patients randomized to finerenone with an eGFR of 25-60 ml/min/1.73 m2 at the screening visit received an initial dose of 10 mg once daily and those with an eGFR of 60 ml/min/1.73 m2 or more at the screening visit received an initial dose of 20 mg once daily.
For the primary outcome of the study, investigators assessed a composite of kidney failure, a sustained decrease of at least 40% in the eGFR from baseline over a period of at least 4 weeks, or death from renal causes in a time-to-event analysis. The key secondary outcome of the study, which was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure, was also assessed in a time-to-event analysis.
In total, 13,911 patients from 48 countries underwent screening and 5734 were included in randomization in the study. From this population, 5674 patients—2833 to finerenone and 2841 to placebo—were included in the final analysis.
Over a median follow-up of 2.6 years, investigators observed a primary outcome event among 17.8% (n=504) of patients randomized to finerenone and 21.1% (n=600) of patients randomized to the placebo group (HR, 0.82; 95% CI, 0.73-0.93; P=.001). The key secondary outcome of the study occurred in 13% (n=367) of patients randomized to finerenone and 14.8% of those in the placebo group (HR, 0.86; 95% CI, 0.75-0.99; P=.03).
In regard to safety, results indicate frequency of adverse events was similar in both arms of the study. However, investigators pointed out the incidence of hyperkalemia-related discontinuation of the trial regimen was greater among those randomized to finerenone (2.3%) than those randomized to placebo (0.9%).
This study, “Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes,” was presented at Kidney Week 2020 and simultaneously published in the New England Journal of Medicine.