Skip to main content

Advertisement

Springer Nature Link
Log in

Finerenone: First Approval

  • AdisInsight Report
  • Published:
Drugs Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Explore related subjects

Discover the latest articles and news from researchers in related subjects, suggested using machine learning.

References

  1. 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. 2020. https://doi.org/10.1093/ndt/gfaa294.

    Article  PubMed  PubMed Central  Google Scholar 

  2. 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.

    Article  CAS  Google Scholar 

  3. 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.

    Article  CAS  Google Scholar 

  4. 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.

    Article  Google Scholar 

  5. 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.

  6. Bayer HealthCare Pharmaceuticals Inc. KERENDIA (finerenone) tablets, for oral use: US prescribing information. 2021. https://labeling.bayerhealthcare.com. Accessed 13 Jul 2021.

  7. 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. 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.

  9. Synthesis of 4-amino-5-methyl-1h-pyridin-2(1h)-on (intermediate compound for the synthesis of the mr antagonist finerenone) from 2-chloro-5-methyl-4-nitro-pyridine-1-oxide using the intermediate compound 2-chloro-5-methyl-4-pyridinamine. 2021. https://patents.google.com/patent/WO2020178175A1/en. Accessed 12 Jul 2021.

  10. 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.

    Article  Google Scholar 

  11. 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.

    Article  Google Scholar 

  12. 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.

    Article  CAS  Google Scholar 

  13. 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.

    Article  CAS  Google Scholar 

  14. 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.

    Article  CAS  Google Scholar 

  15. 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.

    Article  CAS  Google Scholar 

  16. 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.

    Article  CAS  Google Scholar 

  17. 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. 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. 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.

    Article  CAS  Google Scholar 

  20. 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.

    Article  CAS  Google Scholar 

  21. 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.

    Article  CAS  Google Scholar 

  22. 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.

    Article  Google Scholar 

  23. 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.

    Article  CAS  Google Scholar 

  24. 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. 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. 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.

    Article  CAS  Google Scholar 

  27. 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.

    Article  CAS  Google Scholar 

  28. 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.

    Article  Google Scholar 

  29. 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.

    Google Scholar 

  30. 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. https://doi.org/10.1159/000516213.

    Article  PubMed  Google Scholar 

  31. 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.

    Article  CAS  Google Scholar 

  32. 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.

    Article  CAS  Google Scholar 

  33. 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.

    Article  CAS  Google Scholar 

  34. 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.

    Article  CAS  Google Scholar 

  35. 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.

    Article  CAS  Google Scholar 

  36. 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.

    Article  CAS  Google Scholar 

  37. 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.

    Article  CAS  Google Scholar 

  38. 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.

    Article  CAS  Google Scholar 

  39. 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.

    Article  CAS  Google Scholar 

  40. 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. 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.

    Article  CAS  Google Scholar 

  42. 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.

    Article  CAS  Google Scholar 

  43. 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.

    Article  CAS  Google Scholar 

  44. 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.

    Article  Google Scholar 

  45. 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. 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. 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. 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.

Download references

Author information

Authors and Affiliations

  1. Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand

    James E. Frampton

Authors
  1. James E. Frampton
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to James E. Frampton.

Ethics declarations

Funding

The preparation of this review was not supported by any external funding.

Authorship and Conflict of interest

During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the authors on the basis of scientific completeness and accuracy. James E. Frampton is a salaried employee of Adis International Ltd/Springer Nature, and declares no relevant conflicts of interest. All authors contributed to the review and are responsible for the article content.

Ethics approval, Consent to participate, Consent to publish, Availability of data and material, Code availability

Not applicable.

Additional information

This profile has been extracted and modified from the AdisInsight database. AdisInsight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch and beyond.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PPTX 503 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Frampton, J.E. Finerenone: First Approval. Drugs 81, 1787–1794 (2021). https://doi.org/10.1007/s40265-021-01599-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-021-01599-7