Study Highlights Finerenone Benefits in CV Outcomes for Patients With CKD

Finerenone, an investigational, oral, first-in-class drug for individuals with chronic kidney disease (CKD) and type 2 diabetes (T2D), cut the risk of cardiovascular events in patients both with and without a history of cardiac issues.

The news follows study results released last month showing a benefit for patients both with and without kidney disease. The latest data, released Monday night at the American Heart Association (AHA) Scientific Sessions, comes after the full study results of the drug were released during Kidney Week. The trial, FIDELIO-DKD (FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease), showed that compared with placebo, finerenone slowed time to CKD progression by 18% and cut cardiovascular (CV) events by 14%.

In recent years, the intersection of T2D, CKD, and cardiovascular disease (CVD) has become an increased focus of pharmaceutical companies as these chronic diseases weigh on payers and insurers, and most especially, taxpayers.

Last year, HHS Secretary Alex Azar said CKD was costing Medicare $1 in every $5 Medicare spends and reached $113 billion in 2016.

Despite the advent of another class of drugs—sodium glucose cotransporter 2 inhibitors—there is still an unmet need in treating patients with both CKD and T2D, where there is a higher risk of CVD illness and death, the researchers said.

Finerenone may represent an important step forward in cutting cardiac illness and death in patients with CKD and T2D, wrote the authors, publishing in Circulation, a journal of the AHA.

In the current study, the researchers delved deeper into cardiovascular events, examining the effect of finerenone on individual CV outcomes and in patients with and without history of atherosclerotic CV disease.

The composite CV outcome included time to CV death, nonfatal heart attack, nonfatal stroke, or hospitalization for heart failure.

Finerenone targets overactivation of the mineralocorticoid receptor, which, when sent into overdrive, promotes further inflammation and fibrosis in individuals with CKD and T2D.

In a pre-specified exploratory subgroup analysis of FIDELIO-DKD, researchers evaluated the secondary composite CV outcomes by patient history of CVD (P for interaction, .85). The final analysis included 5674 patients, recruited from more than 1000 sites in 48 countries; nearly 46% had CVD at baseline, and they were followed for a median of 2.6 years.

Patient eligibility criteria included either:

• Urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of 30 to less than 300
• Estimated glomerular filtration rate (eGFR) of 25 to less than 60 mL per minute per 1.73 m² of body-surface area
• Serum potassium of serum potassium level of 4.8 mmol per liter or less
• Diabetic retinopathy

Or:

• Urinary albumin-to-creatinine ratio of 300 to 5000 and an eGFR of 25 to less than 75 ml per minute per 1.73 m².

These patients, with a mean age of 65, had moderate to advanced kidney disease, were already on a renin–angiotensin system inhibitor, and had well-controlled blood pressure and blood glucose levels.

Patients with a history of heart failure (HF) with reduced ejection fraction were excluded, as were those with nondiabetic kidney disease, uncontrolled hypertension, or a recent history of dialysis.

Of the 2605 patients with a history of CVD, 17.7% of patients taking finerenone suffered one of the CV outcomes, compared with 20.2% of patients in the placebo group (HR, 0.85; 95% CI, 0.71-1.01).

For 3069 patients without a history of CVD, 8.9% of patients taking finerenone had a CV event, compared with 10.2% of patients in the placebo group (HR, 0.86; 95 CI%, 0.68-1.08).

The incidence of treatment-emergent adverse events was similar between groups.

This is the first study of finerenone to show that it “can reduce risk of CV disease in a CKD population where patients with symptomatic heart failure with reduced ejection fraction were excluded, with only a minority of patients having a history of heart failure at baseline (7.7% of all patients)," the authors said.