Finerenone slowed chronic kidney disease (CKD) progression by 18% and cut cardiovascular (CV) events by 14%, according to phase 3 trial results.
Even with the latest ground-breaking therapies for chronic kidney disease (CKD), there remains a high unmet need to combat this global problem, said an investigator Friday while presenting late-stage results of an investigational, oral, first-in-class drug at the American Society of Nephrology's Kidney Week.
The results of the drug, finerenone, were published simultaneously in the New England Journal of Medicine. Compared with placebo, it slowed time to CKD progression by 18% and cut cardiovascular (CV) events by 14%, said Rajiv Agarwal, MD, MS, FASN, a professor of medicine at Indiana University School of Medicine and a staff physician at the Veterans Affairs Medical Center in Indianapolis, Indiana.
Finerenone targets overactivation of the mineralocorticoid receptor, which, when sent into overdrive, promotes further inflammation and fibrosis in individuals with CKD and type 2 diabetes (T2D).
The trial, FIDELIO-DKD (FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease), was conducted in 48 countries and more than 1000 sites; the final analysis included 5674 patients. Patient eligibility criteria included either:
These patients, with a mean age of 65, had moderate to advanced kidney disease, Agarwal noted. Patient characteristics included a mean eGFR of 44, and more than half had a median urinary albumin-to-creatinine ratio of 850. Mean glycated hemoglobin (A1C) was 7.7 in both patient groups; of those using agents to lower glucose, the majority were on insulin and other analogues.
The primary composite outcome focused on time to kidney failure, a sustained decrease of at least 40% in the eGFR from baseline, or death from renal causes. Secondary composite outcomes were related to CV events: outcome was death from CV causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure.
There was a median follow-up time of 2.6 years.
During a run-in period, all patients were pretreated with an angiotensin-converting-enzyme inhibitor or angiotensin receptor blocker at the maximum tolerated dose for 4 or more weeks (up to 16 weeks).
After the run-in period, patients were randomly assigned in a 1:1 ratio to receive oral finerenone (n = 2833) or placebo (n = 2841); patients with an eGFR of 25 to less than 60 mL per minute per 1.73 m2 at the screening visit received a starting dose of 10 mg once daily.
Those with an eGFR of 60 mL per minute per 1.73 m2 or more at screening received an initial dose of 20 mg once daily. An increase in the dose from 10 to 20 mg once daily was encouraged after 1 month if serum potassium level was 4.8 mmol per liter or less and the eGFR was stable.
Looking at the changes in albuminuria, finerenone led to a 31% reduction at month 4 compared with placebo, he said. By 36 months, it narrowed just slightly, to a reduction of about 25%.
In the finerenone group, 504 patients progressed to kidney failure, compared with 600 patients on placebo, an 18% reduction (hazard ratio [HR], 0.82; 95% CI, 0.73-0.93; P = .001).
Looking at secondary outcomes the drug reduced the risk of a CV event: 13%, or 367 patients, on finerenone, compared with 14.8%, or 420 patients in the placebo group (HR, 0.86; 95% CI, 0.75-0.99; P = .03).
By numbers need to treat, Agarwal said 29 patients need to be treated to prevent 1 renal-related event, and 42 patients need to be treated to prevent 1 CV event.
Overall, the frequency of adverse events was similar between finerenone and placebo; the number of adverse events leading to discontinuation of the study drug were higher for finerenone, mainly hyperkalemia (51 compared with 19 for placebo) and increased serum potassium (13 compared with 6 for placebo). The mean increase of potassium was 0.2 mmol/L across subpopulations compared with placebo.
There were no deaths and a small amount of adverse events that led to permanent discontinuation, he said, adding that rates of discontinuation of study drugs in other classes that do not provide kidney or heart protection due to hyperkalemia were much higher.
The study was funded by Bayer, which said Friday it plans to submit a New Drug Application for finerenone to the FDA by the end of 2020.
Bakris GL, Agarwal R, Anker SD, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. Published online October 23, 2020. New Engl J Med. doi:10.1056/NEJMoa2025845