By William Elliott, MD, FACP, and James Chan, PharmD, PhD

Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.

The FDA has approved the first nonsteroidal, third-generation, mineralocorticoid receptor antagonists to reduce risk of kidney and cardiovascular mortality and morbidity in patients with chronic kidney disease and type 2 diabetes. It received a priority review and fast-track designation.

INDICATIONS

Finerenone can be prescribed to lower the risk of sustained estimated glomerular filtration rate (eGFR) decline, cardiovascular death, non-fatal myocardial infarction, end-stage kidney disease, and hospitalization from heart failure in adults with chronic kidney disease associated with type 2 diabetes.1

DOSAGE

The recommended dose is 20 mg once daily if eGFR is > 60 mL/min/1.73m2 and 10 mg if eGFR is ≥ 25 mL/min/1.73m2 to < 60 mL/min/1.73m2.1 Withhold the dose if serum potassium is > 5.5 mEq/L. Serum potassium and eGFR should be measured before initiation of treatment and periodically during treatment.

POTENTIAL ADVANTAGES

Finerenone is a more selective antagonist vs. spironolactone and more potent than eplerenone.2 It is the only FDA-approved mineralocorticoid for chronic kidney disease. It produces no activity on androgen, estrogen, or glucocorticoid receptors while still lowering the risk of hyperkalemia.1-3

POTENTIAL DISADVANTAGES

The most common adverse reaction (vs. placebo) is hyperkalemia (18.3% vs. 8%).1 Finerenone is a substrate for CYP3A4; concomitant use with strong CYP3A4 inhibitors are contraindicated.1 Avoid concomitant use with grapefruit or grapefruit juice or strong or moderate CYP3A4 inducers.1

COMMENTS

The efficacy of finerenone was evaluated in a randomized, double-blind, placebo-controlled study in adults with chronic kidney disease associated with type 2 diabetes.1 The study population presented with a mean eGFR of 44 mL/min/1.73m2, median urine albumin-to-creatinine ratio of 852 mg/g, and 98.8% were treated with an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB). Approximately 46% presented with a history of atherosclerotic cardiovascular (CV) disease. Subjects were randomized to finerenone (n = 2,833) or placebo (n = 2,841) and were followed for a minimum of 2.6 years. Those designated as New York Heart Association class II to IV were excluded. The primary composite efficacy endpoint was sustained decline in eGFR of ≥ 40%, progression to kidney failure, or renal death. The secondary endpoint was a composite of CV death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure. Finerenone reduced the primary composite endpoint vs. placebo (17.8% vs. 21.1%; HR, 0.82; 95% CI, 0.73-0.93). This was driven by the decline in eGFR (HR, 0.81; 95% CI, 0.72-0.92). The secondary composite endpoint also was reduced (HR, 0.86; 95% CI, 0.75-0.99). None of the individual components reached statistical significance. The authors of a recently completed study assessed the efficacy and safety of finerenone vs. placebo for reducing clinically important CV and renal outcomes.4 The results are pending.

CLINICAL IMPLICATIONS

Type 2 diabetes is a primary cause of chronic kidney disease. Mineralocorticoid receptor overactivation in type 2 diabetes appears to be the main pathophysiology resulting in cardiorenal disease. Established first-line treatments to prevent chronic kidney disease are renin-angiotensin system inhibitors (ACEI and ARB). More recently, sodium-glucose cotransporter 2 inhibitors, particularly dapagliflozin, have provided robust clinical benefit in patients with or without diabetes or cardiovascular disease.5,6 Finerenone offers a potential alternative to spironolactone and eplerenone, with fewer side effects. Its ultimate role remains to be determined. The cost for a 30-day supply is $569.10.

REFERENCES

  1. Bayer. Kerendia prescribing information. July 2021.
  2. Agarwal R, Kolkhof P, Bakris G, et al. Steroidal and non-steroidal mineralocorticoid receptor antagonists in cardiorenal medicine. Eur Heart J 2021;42:152-161.
  3. Liu LC, Schutte E, Gansevoort RT, et al. Finerenone: Third-generation mineralocorticoid receptor antagonist for the treatment of heart failure and diabetic kidney disease. Expert Opin Investig Drugs 2015;24:1123-1135.
  4. ClinicalTrials.gov. Efficacy and safety of finerenone in subjects with type 2 diabetes mellitus and the clinical diagnosis of diabetic kidney disease (FIGARO-DKD).
  5. Wheeler DC, Stefánsson BV, Jongs N, et al. Effects of dapagliflozin on major adverse kidney and cardiovascular events in patients with diabetic and non-diabetic chronic kidney disease: A prespecified analysis from the DAPA-CKD trial. Lancet Diabetes Endocrinol 2021;9:22-31.
  6. McMurray JJV, Wheeler DC, Stefánsson BV, et al. Effect of dapagliflozin on clinical outcomes in patients with chronic kidney disease, with and without cardiovascular disease. Circulation 2021;143:438-448.