Clinical Overview: Finerenone (Kerendia) Lowers Cardiovascular Events, Chronic Kidney Disease Progression

Background

Type 2 diabetes mellitus (T2DM) is a chronic disease that currently affects approximately 26 million people in the United States. Patients with T2DM are at an increased risk for both macrovascular and microvascular complications.

Long term complications of T2DM include cardiovascular disease, diabetic kidney disease, neuropathy, and retinopathy. Current treatments available for T2DM help prevent long term complications of the disease but do not reverse disease progression.

As medication experts, pharmacists should be informed about finerenone (Kerendia), the new medication to help reduce the risk of long-term complications of T2DM. Pharmacists can help recommend this medication, help with monitoring of safety parameters, and provide patient counseling.

Indication

In July of 2021, Bayer received FDA approval for finerenone, a first in its class nonsteroidal mineralocorticoid receptor antagonist (MRA) indicated in adults with chronic kidney disease (CKD) associated with T2DM. Finerenone was shown to reduce the risk of cardiovascular death, sustained estimated glomerular filtration rate (eGFR) decline, end-stage kidney disease, non-fatal myocardial infarction, and hospitalization for heart failure.

Mechanism of action

Finerenone inhibits mineralocorticoid receptor-mediated sodium reabsorption and overactivation in epithelial and nonepithelial tissues reducing fibrosis and inflammation.

Dosing:

Initial

• eGFR ≥ 60 mL/minute/1.73 m2: 20 mg once daily.
• eGFR ≥ 25 to < 60 mL/minute/1.73 m2: 10 mg once daily.
• eGFR < 25 mL/minute/1.73 m2: use not recommended.

Maintenance

Monitoring parameters

• Serum potassium: at baseline, 4 weeks after initiation or dose adjustments, and periodically in patients at risk for hyperkalemia.
• eGFR: at baseline and periodically.

Contraindications

• Adrenal insufficiency, concomitant treatment with strong CYP3A4 inducers, do not initiate if serum potassium > 5 mEq/L.

Most common adverse effects

• Hyperkalemia, hypotension, and hyponatremia.

Effectiveness

FIDELIO-DKD clinical trial (a prospective, double-blind, multicenter, randomized, placebo-controlled study).

• Primary Efficacy Outcome: Composite of kidney failure, sustained decrease in eGFR of at least 40% in eGFR from baseline, or death from renal causes at 2.6 years.
  • Results: Incidence of primary composite outcome was significantly lower in finerenone group compared to placebo (17.8% in finerenone group vs. 21.1% in placebo group, 95% CI 0.73 to 0.93 P = 0.001).
• Secondary Efficacy Outcome: Composite of death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure.
  • Results: Incidence of secondary composite outcome was significantly lower in Kerendia group compared to placebo (13% in Kerendia group vs. 14.8 % in placebo group, 95% CI 0.75 to 0.99 P = 0.03).

Conclusion

For patients with T2DM and CKD, finerenone was associated with a lower risk of cardiovascular events and CKD progression.

About the Author

Sara Varghese, PharmD, PGY1 Pharmacy Resident, Mayo Clinic Health System – Mankato.

Preceptor: Chelsea Morken, PharmD, PGY2 Pharmacy Resident, Mayo Clinic Health System – Mankato.

References

Bakris, G. L., Agarwal, R., Anker, S. D., Pitt, B., Ruilope, L. M., Rossing, P., Kolkhof, P., Nowack, C., Schloemer, P., Joseph, A., & Filippatos, G. (2020). Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. New England Journal of Medicine, 383(23), 2219–2229. https://doi.org/10.1056/nejmoa2025845

Type 2 Diabetes. National Institutes of Health (NIH). Published August 17, 2015. Accessed January 9,

2023. https://www.nih.gov/research-training/accelerating-medicines-partnership-amp/type-2 diabetes#:~:text=%EE%80%80Type%202%20diabetes%EE%80%81%20(T2D)%20currently%2 0affects%20about%2026

Kerendia (finerenone) [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc: July 2021.