Finerenone, an investigational mineralocorticoid receptor antagonist (MRA), slows progression of chronic kidney disease (CKD) in patients with diabetic kidney disease compared with placebo, according to phase 3 trial results presented October 23 at the American Society of Nephrology’s Kidney Week 2020 Reimagined virtual conference and published simultaneously in the New England Journal of Medicine.
“This is great news for people with type 2 diabetes and CKD,” said study investigator Rajiv Agarwal, MD, MS, professor of medicine at Indiana University in Indianapolis, Indiana, who presented study findings at the conference. “They now have another option to protect their heart and their kidneys through finerenone.”
Finerenone is a selective nonsteroidal MRA. In the FIDELIO-DKD (Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease) trial, the drug, when added to the maximum tolerated dose of guideline-directed therapy, was associated with an 18% decreased risk of a composite endpoint of time to kidney failure, a sustained decrease in estimated glomerular filtration rate (eGFR) of 40% or more from baseline over a period of at least 4 weeks, or renal death compared with placebo over a median follow-up duration of 2.6 years. According to investigators, 29 patients would need to be treated to prevent a primary composite endpoint event at 36 weeks, which Dr Agarwal said “would be considered pretty good.”
In addition, finerenone treatment was significantly associated with a 14% decreased risk of a key secondary endpoint — a composite of time to cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure — compared with placebo over a median follow-up of 2.6 years.
The FIDELIO-DKD trial is the first large contemporary positive outcomes study in patients with both CKD and type 2 diabetes mellitus with a primary composite endpoint exclusively consisting of kidney-specific outcomes, according to a press release from Bayer, the pharmaceutical company developing the drug. Investigators randomly assigned 5734 patients to receive finerenone or placebo. Enrollment criteria include an eGFR (in mL/min/1.73 m2) of 25 or higher but less than 75 and a urinary albumin-to-creatinine ratio of 30 to 5000 mg/g.
Patients in both study arms received standard of care, including glucose-lowering medications and maximum tolerated doses of drugs that block the renin-angiotensin system such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs).
Dr Agarwal noted that nearly 90% of the patients in FIDELIO-DKD had macroalbuminuria and more than half had an eGFR less than 45. If results of the sister study FIGARO-DKD (Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease) — in which approximately half of the patients have microalbuminuria and a mean eGFR of 68 — are also positive “the impact of finerenone will be even more broadly felt. It may then be used by most patients with type 2 diabetes and CKD.” Results of FIGARO-DKD are expected in 2021, he said.
He cautioned that finerenone use requires close monitoring of serum potassium levels, “much like we do currently with ACE inhibitors and ARBs.”
Disclosure: The study was sponsored by Bayer, which is developing finerenone.
Bakris GL, Agarwal R, Anker SD, et al. Effect of finerenone on CKD outcomes in type 2 diabetes. Presented at: Kidney Week 2020 Reimagined, October 19-25. Oral presentation FR-OR51.