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Drug Profile

Finerenone: a mineralocorticoid receptor antagonist for the treatment of chronic kidney disease associated with type 2 diabetes

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Pages 501-513 | Received 25 Apr 2022, Accepted 23 Jun 2022, Published online: 03 Jul 2022

References

  • Wu B, Bell K, Stanford A, et al. Understanding CKD among patients with T2DM: prevalence, temporal trends, and treatment patterns-NHANES 2007–2012. BMJ Open Diabetes Res Care. 2016;4(1):e000154.
  • Koro CE, Lee BH, Bowlin SJ. Antidiabetic medication use and prevalence of chronic kidney disease among patients with type 2 diabetes mellitus in the United States. Clin Ther. 2009;31(11):2608–2617.
  • Centers for Disease Control and Prevention. Chronic kidney disease in the United States, 2021 [cited 2021 Sept 15]. Available from: https://www.cdc.gov/kidneydisease/pdf/Chronic-Kidney-Disease-in-the-US-2021-h.pdf
  • Alicic RZ, Rooney MT, Tuttle KR. Diabetic kidney disease: challenges, progress, and possibilities. Clin J Am Soc Nephrol. 2017;12(12):2032–2045.
  • Jankowski J, Floege J, Fliser D, et al. Cardiovascular disease in chronic kidney disease: pathophysiological insights and therapeutic options. Circulation. 2021;143(11):1157–1172.
  • United States Renal Data System (USRDS). 2018 USRDS annual data report. Volume 1: CKD in the United States. Chapter 1: CKD in the general population [cited 2022 Apr 20]. Available from: https://www.usrds.org/media/2282/2018_volume_1_ckd_in_the_us.pdf
  • Gonzalez-Perez A, Saez M, Vizcaya D, et al. Incidence and risk factors for mortality and end-stage renal disease in people with type 2 diabetes and diabetic kidney disease: a population-based cohort study in the UK. BMJ Open Diabetes Res Care. 2021;9(1):e002146.
  • Agarwal R, Anker SD, Bakris G, et al. Investigating new treatment opportunities for patients with chronic kidney disease in type 2 diabetes: the role of finerenone. Nephrol Dial Transplant. 2022;37(6):1014–1023.
  • Bauersachs J, Jaisser F, Toto R. Mineralocorticoid receptor activation and mineralocorticoid receptor antagonist treatment in cardiac and renal diseases. Hypertension. 2015;65(2):257–263.
  • Brown NJ. Contribution of aldosterone to cardiovascular and renal inflammation and fibrosis. Nat Rev Nephrol. 2013;9(8):459–469.
  • Buonafine M, Bonnard B, Jaisser F. Mineralocorticoid receptor and cardiovascular disease. Am J Hypertens. 2018;31(11):1165–1174.
  • Gomez-Sanchez E, Gomez-Sanchez CE. The multifaceted mineralocorticoid receptor. Compr Physiol. 2014;4(3):965–994.
  • Ong GS, Young MJ. Mineralocorticoid regulation of cell function: the role of rapid signalling and gene transcription pathways. J Mol Endocrinol. 2017;58(1):R33–R57.
  • Shibata S, Nagase M, Yoshida S, et al. Modification of mineralocorticoid receptor function by Rac1 GTPase: implication in proteinuric kidney disease. Nat Med. 2008;14(12):1370–1376.
  • Aldactone (spironolactone) [package insert]. New York, NY: Pfizer, Inc; 2021.
  • Inspra (eplerenone) [package insert]. New York, NY: Pfizer, Inc; 2020.
  • Agarwal R, Kolkhof P, Bakris G, et al. Steroidal and non-steroidal mineralocorticoid receptor antagonists in cardiorenal medicine. Eur Heart J. 2021;42(2):152–161.
  • Beldhuis IE, Myhre PL, Claggett B, et al. Efficacy and safety of spironolactone in patients with HFpEF and chronic kidney disease. JACC Heart Fail. 2019;7(1):25–32.
  • Food and Drug Administration. KERENDIA (finerenone) prescribing information. 2021 [cited 2022 Jun 9]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215341s000lbl.pdf
  • European Medicines Agency. KERENDIA (finerenone) summary of product characteristics. 2022 [cited 2022 Apr 20]. Available from: https://www.ema.europa.eu/en/documents/product-information/kerendia-epar-product-information_en.pdf
  • Duggan S. Esaxerenone: first global approval. Drugs. 2019;79(4):477–481.
  • Bakris GL, Agarwal R, Anker SD, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med. 2020;383(23):2219–2229.
  • Pitt B, Filippatos G, Agarwal R, et al. Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N Engl J Med. 2021;385(24):2252–2263.
  • Heinig R, Gerisch M, Engelen A, et al. Pharmacokinetics of the novel, selective, non-steroidal mineralocorticoid receptor antagonist finerenone in healthy volunteers: results from an Absolute Bioavailability Study and drug–drug interaction studies in vitro and in vivo. Eur J Drug Metab Pharmacokinet. 2018;43(6):715–727.
  • Heinig R, Gerisch M, Bairlein M, et al. Results from drug–drug interaction studies in vitro and in vivo investigating the effect of finerenone on the pharmacokinetics of comedications. Eur J Drug Metab Pharmacokinet. 2020;45(4):433–444.
  • Brem AS, Gong R. Therapeutic targeting of aldosterone: a novel approach to the treatment of glomerular disease. Clin Sci (Lond). 2015;128(9):527–535.
  • van der Heijden CDCC, Deinum J, Joosten LAB, et al. The mineralocorticoid receptor as a modulator of innate immunity and atherosclerosis. Cardiovasc Res. 2018;114(7):944–953.
  • Barrera-Chimal J, Lima-Posada I, Bakris GL, et al. Mineralocorticoid receptor antagonists in diabetic kidney disease — mechanistic and therapeutic effects. Nat Rev Nephrol. 2022;18(1):56–70.
  • Barrera-Chimal J, Girerd S, Jaisser F. Mineralocorticoid receptor antagonists and kidney diseases: pathophysiological basis. Kidney Int. 2019;96(2):302–319.
  • Bai M, Chen Y, Zhao M, et al. NLRP3 inflammasome activation contributes to aldosterone-induced podocyte injury. Am J Physiol Renal Physiol. 2017;312(4):F556–F564.
  • Shibata S, Nagase M, Yoshida S, et al. Podocyte as the target for aldosterone: roles of oxidative stress and Sgk1. Hypertension. 2007;49(2):355–364.
  • Diah S, Zhang G-X, Nagai Y, et al. Aldosterone induces myofibroblastic transdifferentiation and collagen gene expression through the Rho-kinase dependent signaling pathway in rat mesangial cells. Exp Cell Res. 2008;314(20):3654–3662.
  • Mathew JT, Patni H, Chaudhary AN, et al. Aldosterone induces mesangial cell apoptosis both in vivo and in vitro. Am J Physiol Renal Physiol. 2008;295(1):F73–F81.
  • Huang LL, Nikolic-Paterson DJ, Han Y, et al. Myeloid mineralocorticoid receptor activation contributes to progressive kidney disease. J Am Soc Nephrol. 2014;25(10):2231–2240.
  • Kolkhof P, Bärfacker L. 30 years of the mineralocorticoid receptor: mineralocorticoid receptor antagonists: 60 years of research and development. J Endocrinol. 2017;234(1):T125–T140.
  • Fagart J, Hillisch A, Huyet J, et al. A new mode of mineralocorticoid receptor antagonism by a potent and selective nonsteroidal molecule. J Biol Chem. 2010;285(39):29932–29940.
  • Amazit L, Le Billan F, Kolkhof P, et al. Finerenone impedes aldosterone-dependent nuclear import of the mineralocorticoid receptor and prevents genomic recruitment of steroid receptor coactivator-1. J Biol Chem. 2015;290(36):21876–21889.
  • Grune J, Benz V, Brix S, et al. Steroidal and nonsteroidal mineralocorticoid receptor antagonists cause differential cardiac gene expression in pressure overload-induced cardiac hypertrophy. J Cardiovasc Pharmacol. 2016;67(5):402–411.
  • Grune J, Beyhoff N, Smeir E, et al. Selective mineralocorticoid receptor cofactor modulation as molecular basis for finerenone’s antifibrotic activity. Hypertension. 2018;71(4):599–608.
  • Le Billan F, Perrot J, Carceller E, et al. Antagonistic effects of finerenone and spironolactone on the aldosterone-regulated transcriptome of human kidney cells. FASEB J. 2021;35(2):e21314.
  • Kolkhof P, Jaisser F, Kim SY, et al. Steroidal and novel non-steroidal mineralocorticoid receptor antagonists in heart failure and cardiorenal diseases: comparison at bench and bedside. Handb Exp Pharmacol. 2017;243:271–305.
  • Bärfacker L, Kuhl A, Hillisch A, et al. Discovery of BAY 94-8862: a nonsteroidal antagonist of the mineralocorticoid receptor for the treatment of cardiorenal diseases. ChemMedChem. 2012;7(8):1385–1403.
  • Pitt B, Kober L, Ponikowski P, et al. Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial. Eur Heart J. 2013;34(31):2453–2463.
  • Bakris GL, Agarwal R, Chan JC, et al. Effect of finerenone on albuminuria in patients with diabetic nephropathy: a randomized clinical trial. Jama. 2015;314(9):884–894.
  • Filippatos G, Anker SD, Böhm M, et al. A randomized controlled study of finerenone vs. eplerenone in patients with worsening chronic heart failure and diabetes mellitus and/or chronic kidney disease. Eur Heart J. 2016;37(27):2105–2114.
  • Ruilope LM, Agarwal R, Anker SD, et al. Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial. Am J Nephrol. 2019;50(5):345–356.
  • Filippatos G, Bakris GL, Pitt B, et al. Finerenone reduces new-onset atrial fibrillation in patients with chronic kidney disease and type 2 diabetes. J Am Coll Cardiol. 2021;78(2):142–152.
  • Agarwal R, Filippatos G, Pitt B, et al. Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis. Eur Heart J. 2022;43(6):474–484.
  • Kolkhof P, Hartmann E, Freyberger A, et al. Effects of finerenone combined with empagliflozin in a model of hypertension-induced end-organ damage. Am J Nephrol. 2021;52(8):642–652.
  • Rossing P, Filippatos G, Agarwal R, et al. Finerenone in predominantly advanced CKD and type 2 diabetes with or without sodium-glucose cotransporter-2 inhibitor therapy. Kidney Int Rep. 2022;7(1):36–45.
  • Rossing P, Agarwal R, Anker SD, et al. Efficacy and safety of finerenone in patients with chronic kidney disease and type 2 diabetes by GLP-1RA treatment: a subgroup analysis from the FIDELIO-DKD trial. Diabetes Obes Metab. 2022;24(1):125–134.
  • Goulooze SC, Snelder N, Seelmann A, et al. Finerenone dose-exposure-serum potassium response analysis of FIDELIO-DKD Phase III: the role of dosing, titration, and inclusion criteria. Clin Pharmacokinet. 2022;61(3):451–462.
  • Agarwal R, Joseph A, Anker SD, et al. Hyperkalemia risk with finerenone: results from the FIDELIO-DKD trial. J Am Soc Nephrol. 2022;33(1):225–237.
  • US FDA approves finerenone for the treatment of patients with chronic kidney disease associated with type 2 diabetes [press release]. Berlin Germany: Bayer; 2021 Jul 9. Available from: https://media.bayer.com/baynews/baynews.nsf/id/A1C007B1B40780CFC125870C0024B082?open&ref=irrefndcd
  • Oka T, Sakaguchi Y, Hattori K, et al. Mineralocorticoid receptor antagonist use and hard renal outcomes in real-world patients with chronic kidney disease. Hypertension. 2022;79(3):679–689.