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Published in: Drugs 15/2021

01-10-2021 | Finerenone | AdisInsight Report

Finerenone: First Approval

Author: James E. Frampton

Published in: Drugs | Issue 15/2021

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Abstract

Finerenone (Kerendia®), a first-in-class, orally administered, selective, nonsteroidal mineralocorticoid receptor antagonist (MRA), is being developed by Bayer HealthCare Pharmaceuticals for the treatment of diabetic kidney disease (DKD) and heart failure (HF), including chronic HF (CHF). Finerenone has been approved in the USA to reduce the risk of sustained estimated glomerular filtration rate (eGFR) decline, end stage renal disease (ESRD), cardiovascular death, nonfatal myocardial infarction (MI), and hospitalization for HF in adults with chronic kidney disease (CKD) associated with type 2 diabetes (T2D). Finerenone is undergoing regulatory assessment in the EU and in China. A phase III trial is investigating finerenone in patients who have HF with preserved ejection fraction. This article summarizes the milestones in the development of finerenone leading to this first approval to reduce the risk of serious kidney and heart complications in adults with CKD and T2D.
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Literature
2.
go back to reference 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):2219–29.CrossRef 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):2219–29.CrossRef
3.
go back to reference Bramlage P, Swift SL, Thoenes M, et al. Non-steroidal mineralocorticoid receptor antagonism for the treatment of cardiovascular and renal disease. Eur J Heart Fail. 2016;18(1):28–37.CrossRef Bramlage P, Swift SL, Thoenes M, et al. Non-steroidal mineralocorticoid receptor antagonism for the treatment of cardiovascular and renal disease. Eur J Heart Fail. 2016;18(1):28–37.CrossRef
4.
go back to reference Capelli I, Gasperoni L, Ruggeri M, et al. New mineralocorticoid receptor antagonists: update on their use in chronic kidney disease and heart failure. J Nephrol. 2020;33(1):37–48.CrossRef Capelli I, Gasperoni L, Ruggeri M, et al. New mineralocorticoid receptor antagonists: update on their use in chronic kidney disease and heart failure. J Nephrol. 2020;33(1):37–48.CrossRef
5.
go back to reference US Food & Drug Administration. FDA approves drug to reduce risk of serious kidney and heart complications in adults with chronic kidney disease associated with type 2 diabetes [media release]. 9 Jul 2021. https://www.fda.gov/drugs. US Food & Drug Administration. FDA approves drug to reduce risk of serious kidney and heart complications in adults with chronic kidney disease associated with type 2 diabetes [media release]. 9 Jul 2021. https://​www.​fda.​gov/​drugs.
7.
go back to reference Bayer Healthcare Pharmaceuticals. Bayer submits regulatory applications for investigational drug finerenone in the U.S. and the EU for patients with chronic kidney disease and type 2 diabetes [media release]. 9 Nov 2020. http://www.bayer.us. Bayer Healthcare Pharmaceuticals. Bayer submits regulatory applications for investigational drug finerenone in the U.S. and the EU for patients with chronic kidney disease and type 2 diabetes [media release]. 9 Nov 2020. http://​www.​bayer.​us.
8.
go back to reference Bayer Healthcare Pharmaceuticals. Bayer submits finerenone for marketing authorization in China for the treatment of chronic kidney disease in type 2 diabetes [media release]. 9 Feb 2021. http://www.bayer.com. Bayer Healthcare Pharmaceuticals. Bayer submits finerenone for marketing authorization in China for the treatment of chronic kidney disease in type 2 diabetes [media release]. 9 Feb 2021. http://​www.​bayer.​com.
10.
go back to reference Barfacker 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):1385–403.CrossRef Barfacker 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):1385–403.CrossRef
11.
go back to reference 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;285:29932–40.CrossRef 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;285:29932–40.CrossRef
12.
go back to reference Pitt B, Filippatos G, Gheorghiade M, et al. Rationale and design of ARTS: a randomized, double-blind study of BAY 94–8862 in patients with chronic heart failure and mild or moderate chronic kidney disease. Eur J Heart Fail. 2012;14(6):668–75.CrossRef Pitt B, Filippatos G, Gheorghiade M, et al. Rationale and design of ARTS: a randomized, double-blind study of BAY 94–8862 in patients with chronic heart failure and mild or moderate chronic kidney disease. Eur J Heart Fail. 2012;14(6):668–75.CrossRef
13.
go back to reference Arhancet GB, Woodard SS, Dietz JD, et al. Stereochemical requirements for the mineralocorticoid receptor antagonist activity of dihydropyridines. J Med Chem. 2010;53:4300–4.CrossRef Arhancet GB, Woodard SS, Dietz JD, et al. Stereochemical requirements for the mineralocorticoid receptor antagonist activity of dihydropyridines. J Med Chem. 2010;53:4300–4.CrossRef
14.
go back to reference Dietz JD, Du S, Bolten CW, et al. A number of marketed dihydropyridine calcium channel blockers have mineralocorticoid receptor antagonist activity. Hypertension. 2008;51:742–8.CrossRef Dietz JD, Du S, Bolten CW, et al. A number of marketed dihydropyridine calcium channel blockers have mineralocorticoid receptor antagonist activity. Hypertension. 2008;51:742–8.CrossRef
15.
go back to reference Lavall D, Jacobs N, Mahfoud F, et al. The non-steroidal mineralocorticoid receptor antagonist finerenone prevents cardiac fibrotic remodeling. Biochem Pharmacol. 2019;168:173–83.CrossRef Lavall D, Jacobs N, Mahfoud F, et al. The non-steroidal mineralocorticoid receptor antagonist finerenone prevents cardiac fibrotic remodeling. Biochem Pharmacol. 2019;168:173–83.CrossRef
16.
go back to reference Gueret A, Harouki N, Favre J, et al. Vascular smooth muscle mineralocorticoid receptor contributes to coronary and left ventricular dysfunction after myocardial infarction. Hypertension. 2016;67(4):717–23.CrossRef Gueret A, Harouki N, Favre J, et al. Vascular smooth muscle mineralocorticoid receptor contributes to coronary and left ventricular dysfunction after myocardial infarction. Hypertension. 2016;67(4):717–23.CrossRef
17.
go back to reference Dutzmann J, Musmann RJ, Haertlé M, et al. The novel mineralocorticoid receptor antagonist finerenone attenuates neointima formation after vascular injury. PLoS ONE. 2017;12(9):e0184888. Dutzmann J, Musmann RJ, Haertlé M, et al. The novel mineralocorticoid receptor antagonist finerenone attenuates neointima formation after vascular injury. PLoS ONE. 2017;12(9):e0184888.
18.
go back to reference Barrera-Chimal J, André-Grégoire G, Nguyen Dinh Cat A, et al. Benefit of mineralocorticoid receptor antagonism in AKI: role of vascular smooth muscle Rac1. J Am Soc Nephrol. 2017;28(4):1216-26. Barrera-Chimal J, André-Grégoire G, Nguyen Dinh Cat A, et al. Benefit of mineralocorticoid receptor antagonism in AKI: role of vascular smooth muscle Rac1. J Am Soc Nephrol. 2017;28(4):1216-26.
19.
go back to reference Lattenist L, Lechner SM, Messaoudi S, et al. Nonsteroidal mineralocorticoid receptor antagonist finerenone protects against acute kidney injury-mediated chronic kidney disease: role of oxidative stress. Hypertension. 2017;69(5):870–8.CrossRef Lattenist L, Lechner SM, Messaoudi S, et al. Nonsteroidal mineralocorticoid receptor antagonist finerenone protects against acute kidney injury-mediated chronic kidney disease: role of oxidative stress. Hypertension. 2017;69(5):870–8.CrossRef
20.
go back to reference Barrera-Chimal J, Estrela GR, Lechner SM, et al. The myeloid mineralocorticoid receptor controls inflammatory and fibrotic responses after renal injury via macrophage interleukin-4 receptor signaling. Kidney Int. 2018;93(6):1344–55.CrossRef Barrera-Chimal J, Estrela GR, Lechner SM, et al. The myeloid mineralocorticoid receptor controls inflammatory and fibrotic responses after renal injury via macrophage interleukin-4 receptor signaling. Kidney Int. 2018;93(6):1344–55.CrossRef
21.
go back to reference Bonnard B, Pieronne-Deperrois M, Djerada Z, et al. Mineralocorticoid receptor antagonism improves diastolic dysfunction in chronic kidney disease in mice. J Mol Cell Cardiol. 2018;121:124–33.CrossRef Bonnard B, Pieronne-Deperrois M, Djerada Z, et al. Mineralocorticoid receptor antagonism improves diastolic dysfunction in chronic kidney disease in mice. J Mol Cell Cardiol. 2018;121:124–33.CrossRef
22.
go back to reference González-Blázquez R, Somoza B, Gil-Ortega M, et al. Finerenone attenuates endothelial dysfunction and albuminuria in a chronic kidney disease model by a reduction in oxidative stress. Front Pharmacol. 2018;9:1131.CrossRef González-Blázquez R, Somoza B, Gil-Ortega M, et al. Finerenone attenuates endothelial dysfunction and albuminuria in a chronic kidney disease model by a reduction in oxidative stress. Front Pharmacol. 2018;9:1131.CrossRef
23.
go back to reference Gil-Ortega M, Vega-Martín E, Martín-Ramos M, et al. Finerenone reduces intrinsic arterial stiffness in Munich Wistar Frömter rats, a genetic model of chronic kidney disease. Am J Nephrol. 2020;51(4):294–303.CrossRef Gil-Ortega M, Vega-Martín E, Martín-Ramos M, et al. Finerenone reduces intrinsic arterial stiffness in Munich Wistar Frömter rats, a genetic model of chronic kidney disease. Am J Nephrol. 2020;51(4):294–303.CrossRef
24.
go back to reference Hirohama D, Nishimoto M, Ayuzawa N, et al. The mineralocorticoid receptor antagonist finerenone limits podocyte injury in high-salt loaded db/db mice [abstract no. FR-PO207]. J Am Soc Nephrol. 2019;30:487. Hirohama D, Nishimoto M, Ayuzawa N, et al. The mineralocorticoid receptor antagonist finerenone limits podocyte injury in high-salt loaded db/db mice [abstract no. FR-PO207]. J Am Soc Nephrol. 2019;30:487.
25.
go back to reference Droebner K, Pavkovic M, Grundmann M, et al. The novel nonsteroidal and selective mineralocorticoid receptor antagonist finerenone differentiates from SGLT2 inhibitor empagliflozin by anti-fibrotic effects in a progressive mouse kidney fibrosis model [abstract no. PO0646]. J Am Soc Nephrol. 2020;31:244. Droebner K, Pavkovic M, Grundmann M, et al. The novel nonsteroidal and selective mineralocorticoid receptor antagonist finerenone differentiates from SGLT2 inhibitor empagliflozin by anti-fibrotic effects in a progressive mouse kidney fibrosis model [abstract no. PO0646]. J Am Soc Nephrol. 2020;31:244.
26.
go back to reference 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.CrossRef 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.CrossRef
27.
go back to reference Kolkhof P, Delbeck M, Kretschmer A, et al. Finerenone, a novel selective nonsteroidal mineralocorticoid receptor antagonist protects from rat cardiorenal injury. J Cardiovasc Pharmacol. 2014;64(1):69–78.CrossRef Kolkhof P, Delbeck M, Kretschmer A, et al. Finerenone, a novel selective nonsteroidal mineralocorticoid receptor antagonist protects from rat cardiorenal injury. J Cardiovasc Pharmacol. 2014;64(1):69–78.CrossRef
28.
go back to reference Pieronne-Deperrois M, Guéret A, Djerada Z, et al. Mineralocorticoid receptor blockade with finerenone improves heart function and exercise capacity in ovariectomized mice. ESC Heart Fail. 2021;8(3):1933–43.CrossRef Pieronne-Deperrois M, Guéret A, Djerada Z, et al. Mineralocorticoid receptor blockade with finerenone improves heart function and exercise capacity in ovariectomized mice. ESC Heart Fail. 2021;8(3):1933–43.CrossRef
29.
go back to reference Jaisser F, Pieronne-Deperrois M, Bonnard B, et al. Finerenone improves cardiovascular benefits after diet normalization in a mouse model of high-fat diet-induced obesity [abstract no. SA-PO322]. J Am Soc Nephrol. 2019;30:846–7. Jaisser F, Pieronne-Deperrois M, Bonnard B, et al. Finerenone improves cardiovascular benefits after diet normalization in a mouse model of high-fat diet-induced obesity [abstract no. SA-PO322]. J Am Soc Nephrol. 2019;30:846–7.
31.
go back to reference Lentini S, Heinig R, Kimmeskamp-Kirschbaum N, et al. Pharmacokinetics, safety and tolerability of the novel, selective mineralocorticoid receptor antagonist finerenone - results from first-in-man and relative bioavailability studies. Fundam Clin Pharmacol. 2016;30(2):172–84.CrossRef Lentini S, Heinig R, Kimmeskamp-Kirschbaum N, et al. Pharmacokinetics, safety and tolerability of the novel, selective mineralocorticoid receptor antagonist finerenone - results from first-in-man and relative bioavailability studies. Fundam Clin Pharmacol. 2016;30(2):172–84.CrossRef
32.
go back to reference 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):715–27.CrossRef 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):715–27.CrossRef
33.
go back to reference Snelder N, Heinig R, Drenth HJ, et al. Population pharmacokinetic and exposure-response analysis of finerenone: insights based on phase IIb data and simulations to support dose selection for pivotal trials in type 2 diabetes with chronic kidney disease. Clin Pharmacokinet. 2020;59(3):359–70.CrossRef Snelder N, Heinig R, Drenth HJ, et al. Population pharmacokinetic and exposure-response analysis of finerenone: insights based on phase IIb data and simulations to support dose selection for pivotal trials in type 2 diabetes with chronic kidney disease. Clin Pharmacokinet. 2020;59(3):359–70.CrossRef
34.
go back to reference Gerisch M, Heinig R, Engelen A, et al. Biotransformation of finerenone, a novel nonsteroidal mineralocorticoid receptor antagonist, in dogs, rats, and humans, in vivo and in vitro. Drug Metab Dispos. 2018;46(11):1546–55.CrossRef Gerisch M, Heinig R, Engelen A, et al. Biotransformation of finerenone, a novel nonsteroidal mineralocorticoid receptor antagonist, in dogs, rats, and humans, in vivo and in vitro. Drug Metab Dispos. 2018;46(11):1546–55.CrossRef
35.
go back to reference Heinig R, Kimmeskamp-Kirschbaum N, Halabi A, et al. Pharmacokinetics of the novel nonsteroidal mineralocorticoid receptor antagonist finerenone (BAY 94–8862) in individuals with renal impairment. Clin Pharmacol Drug Dev. 2016;5(6):488–501.CrossRef Heinig R, Kimmeskamp-Kirschbaum N, Halabi A, et al. Pharmacokinetics of the novel nonsteroidal mineralocorticoid receptor antagonist finerenone (BAY 94–8862) in individuals with renal impairment. Clin Pharmacol Drug Dev. 2016;5(6):488–501.CrossRef
36.
go back to reference Heinig R, Lambelet M, Nagelschmitz J, et al. Pharmacokinetics of the novel nonsteroidal mineralocorticoid receptor antagonist finerenone (BAY 94–8862) in individuals with mild or moderate hepatic impairment. Eur J Drug Metab Pharmacokinet. 2019;44(5):619–28.CrossRef Heinig R, Lambelet M, Nagelschmitz J, et al. Pharmacokinetics of the novel nonsteroidal mineralocorticoid receptor antagonist finerenone (BAY 94–8862) in individuals with mild or moderate hepatic impairment. Eur J Drug Metab Pharmacokinet. 2019;44(5):619–28.CrossRef
37.
go back to reference 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):433–44.CrossRef 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):433–44.CrossRef
38.
go back to reference Bakris GL, Agarwal R, Anker SD, et al. Design and baseline characteristics of the finerenone in reducing kidney failure and disease progression in diabetic kidney disease trial. Am J Nephrol. 2019;50(5):333–44.CrossRef Bakris GL, Agarwal R, Anker SD, et al. Design and baseline characteristics of the finerenone in reducing kidney failure and disease progression in diabetic kidney disease trial. Am J Nephrol. 2019;50(5):333–44.CrossRef
39.
go back to reference 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):345–56.CrossRef 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):345–56.CrossRef
40.
go back to reference Bayer HealthCare Pharmaceuticals. Bayers finerenone meets primary endpoint in phase III FIGARO-DKD cardiovascular outcomes study in patients with chronic kidney disease and type 2 diabetes [media release]. 10 May 2021. www.bayer.com. Bayer HealthCare Pharmaceuticals. Bayers finerenone meets primary endpoint in phase III FIGARO-DKD cardiovascular outcomes study in patients with chronic kidney disease and type 2 diabetes [media release]. 10 May 2021. www.​bayer.​com.
41.
go back to reference 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):2453–63.CrossRef 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):2453–63.CrossRef
42.
go back to reference Ruilope LM, Agarwal R, Chan JC, et al. Rationale, design, and baseline characteristics of ARTS-DN: a randomized study to assess the safety and efficacy of finerenone in patients with type 2 diabetes mellitus and a clinical diagnosis of diabetic nephropathy. Am J Nephrol. 2014;40(6):572–81.CrossRef Ruilope LM, Agarwal R, Chan JC, et al. Rationale, design, and baseline characteristics of ARTS-DN: a randomized study to assess the safety and efficacy of finerenone in patients with type 2 diabetes mellitus and a clinical diagnosis of diabetic nephropathy. Am J Nephrol. 2014;40(6):572–81.CrossRef
43.
go back to reference 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):884–94.CrossRef 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):884–94.CrossRef
44.
go back to reference Katayama S, Yamada D, Nakayama M, et al. A randomized controlled study of finerenone versus placebo in Japanese patients with type 2 diabetes mellitus and diabetic nephropathy. J Diabetes Complications. 2017;31(4):758–65.CrossRef Katayama S, Yamada D, Nakayama M, et al. A randomized controlled study of finerenone versus placebo in Japanese patients with type 2 diabetes mellitus and diabetic nephropathy. J Diabetes Complications. 2017;31(4):758–65.CrossRef
45.
go back to reference Pitt B, Anker SD, Böhm M, et al. Rationale and design of MinerAlocorticoid Receptor antagonist Tolerability Study-Heart Failure (ARTS-HF): a randomized study of finerenone vs. eplerenone in patients who have worsening chronic heart failure with diabetes and/or chronic kidney disease. Eur J Heart Fail. 2015;17(2):224-32. Pitt B, Anker SD, Böhm M, et al. Rationale and design of MinerAlocorticoid Receptor antagonist Tolerability Study-Heart Failure (ARTS-HF): a randomized study of finerenone vs. eplerenone in patients who have worsening chronic heart failure with diabetes and/or chronic kidney disease. Eur J Heart Fail. 2015;17(2):224-32.
46.
go back to reference 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):2105-14. 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):2105-14.
47.
go back to reference Sato N, Ajioka M, Yamada T, et al. A randomized controlled study of finerenone vs. eplerenone in Japanese patients with worsening chronic heart failure and diabetes and/or chronic kidney disease. Circ J. 2016;80(5):1113-22. Sato N, Ajioka M, Yamada T, et al. A randomized controlled study of finerenone vs. eplerenone in Japanese patients with worsening chronic heart failure and diabetes and/or chronic kidney disease. Circ J. 2016;80(5):1113-22.
48.
go back to reference Bayer Healthcare Pharmaceuticals. Bayer extends clinical development program for finerenone with phase III study in patients with heart failure and preserved ejection fraction [media release]. 15 Jun 2021. http://www.bayer.com. Bayer Healthcare Pharmaceuticals. Bayer extends clinical development program for finerenone with phase III study in patients with heart failure and preserved ejection fraction [media release]. 15 Jun 2021. http://​www.​bayer.​com.
Metadata
Title
Finerenone: First Approval
Author
James E. Frampton
Publication date
01-10-2021
Publisher
Springer International Publishing
Published in
Drugs / Issue 15/2021
Print ISSN: 0012-6667
Electronic ISSN: 1179-1950
DOI
https://doi.org/10.1007/s40265-021-01599-7

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