Finerenone

Finerenone
Names
Trade namesKerendia
Other namesBAY 94-8862
IUPAC name
  • (4S)-4-(4-Cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide
Clinical data
Drug classPotassium-sparing diuretic
Main usesChronic kidney disease in type 2 diabetes[1]
Side effectsHigh potassium, low blood pressure, low sodium[2]
InteractionsGrapefruit, CYP3A4 inhibitors[2]
Pregnancy
category
    Routes of
    use    		By mouth
    Typical dose10 to 20 mg OD[2]
    External links
    AHFS/Drugs.comMonograph
    Legal
    License data
    Legal status
    Chemical and physical data
    FormulaC21H22N4O3
    Molar mass378.432 g·mol−1
    3D model (JSmol)
    SMILES
    • NC(=O)C1=C(C)Nc2c(C)cnc(OCC)c2[C@@H]1c3ccc(C#N)cc3OC
    InChI
    • InChI=1S/C21H22N4O3/c1-5-28-21-18-17(14-7-6-13(9-22)8-15(14)27-4)16(20(23)26)12(3)25-19(18)11(2)10-24-21/h6-8,10,17,25H,5H2,1-4H3,(H2,23,26)/t17-/m1/s1
    • Key:BTBHLEZXCOBLCY-QGZVFWFLSA-N

    Finerenone, sold under the brand name Kerendia, is a medication used to treat chronic kidney disease in people with type 2 diabetes.[1] It is used in those with moderate to severe disease with protein in the urine.[1] It is taken by mouth.[1]

    Common side effects include high potassium, low blood pressure, and low sodium.[2] It should not be used in people with adrenal insufficiency.[2] It may interact with grapefruit.[2] There are concerns that use in pregnancy may harm the baby.[2] It is a non-steroidal mineralocorticoid receptor antagonist (MRA).[2]

    Finerenone was approved for medical use in the United States in 2021 and Europe in 2022.[2][1] In the United Kingdom 4 weeks of medication costs the NHS about £52 as of 2022.[7] This amount in the United States is about 560 USD.[8]

    Medical uses

    In the United States, it is indicated to reduce the risk of kidney function decline, kidney failure, cardiovascular death, non-fatal heart attacks, and hospitalization for heart failure in adults with chronic kidney disease associated with type 2 diabetes.[6]

    In the European Union, it is indicated for the treatment of chronic kidney disease (stage 3 and 4 with albuminuria) associated with type 2 diabetes in adults.[1]

    It reduces the risk of kidney function decline by about 3%.[1]

    Dosage

    It is generally started at a dose of 10 mg or 20 mg once per day and may be increased to 20 mg once per day.[2]


    Side effects

    Finerenone may cause electrolyte imbalances. In the case of potassium, people may experience a higher level in the blood. Symptoms that correlate to this clinical finding include nausea, weakness, chest pain and loss of movement.[9] Another common electrolyte imbalance which may occur for patients on Finerenone is that patients may have low sodium, which can manifest as headaches, confusion, weakness and feeling off balance for patients.[10]

    Pharmacology

    Finerenone has less relative affinity to other steroid hormone receptors than currently available aldosterone antagonists such as eplerenone and spironolactone, which should result in fewer adverse effects like gynaecomastia, impotence, and low libido.[11][12]

    Finerenone blocks mineralocorticoid receptors, which makes it a potassium-sparing diuretic.

    This table compares inhibitory (blocking) concentrations (IC50, unit: nM) of three antimineralocorticoids. Mineralocorticoid receptor inhibition is responsible for the desired action of the drugs, whereas inhibition of the other receptors potentially leads to side effects. Lower values mean stronger inhibition.[13]

    Spironolactone Eplerenone Finerenone
    Mineralocorticoid receptor 24 990 18
    Glucocorticoid receptor 2400 22,000 >10,000
    Androgen receptor 77 21,200 >10,000
    Progesterone receptor 740 31,200 >10,000

    The above-listed drugs have insignificant affinity for the estrogen receptor.

    Finerenone acts as an antagonist to mineralocorticoid receptors harboring the S810L mutation, unlike other traditional MR inhibitors such as spironolactone and eplerenone that incidentally act as agonists.[14]

    History

    The efficacy of finerenone to improve kidney and heart outcomes was evaluated in a randomized, multicenter, double-blind, placebo-controlled study in adults with chronic kidney disease associated with type 2 diabetes.[6] In this study, 5,674 participants were randomly assigned to receive either finerenone or a placebo.[6]

    The study compared the two groups for the number of participants whose disease progressed to a composite (or combined) endpoint that included at least a 40% reduction in kidney function, progression to kidney failure, or kidney death.[6] Results showed that 504 of the 2,833 participants who received finerenone had at least one of the events in the composite endpoint compared to 600 of the 2,841 participants who received a placebo.[6]

    The U.S. Food and Drug Administration (FDA) granted the application for finerenone priority review and fast track designations.[6] The FDA granted the approval of Kerendia to Bayer Healthcare.[6]

    Society and culture

    On 16 December 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Kerendia, intended for the treatment of chronic kidney disease associated with type 2 diabetes in adults.[15] The applicant for this medicinal product is Bayer AG.[15] Finerenone was approved for medical use in the European Union in February 2022.[1]

    Research

    In the Phase II ARTS-DN study, finerenone dose-dependently reduced urine albumin to creatinine ratio in patients with diabetic kidney disease.[16] Based on these findings, finerenone is being studied in the large Phase III FIDELIO and FIGARO outcome studies designed to assess whether finerenone reduces risk of CKD progression and adverse cardiovascular events in patients with Chronic Kidney Disease and Type 2 Diabetes. These trials have enrolled more than 13,000 patients with primary completion of FIDELIO anticipated in 2020 and FIGARO IN 2021.[17][18]

    References

    1. 1 2 3 4 5 6 7 8 9 "Kerendia EPAR". European Medicines Agency (EMA). 14 December 2021. Archived from the original on 16 March 2022. Retrieved 11 March 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
    2. 1 2 3 4 5 6 7 8 9 10 11 "Kerendia- finerenone tablet, film coated". DailyMed. Archived from the original on 21 August 2021. Retrieved 20 August 2021.
    3. ↑ "Updates to the Prescribing Medicines in Pregnancy database". Therapeutic Goods Administration (TGA). 12 May 2022. Archived from the original on 3 April 2022. Retrieved 13 May 2022.
    4. 1 2 "Kerendia APMDS". Therapeutic Goods Administration (TGA). 9 December 2021. Archived from the original on 13 June 2022. Retrieved 12 June 2022.
    5. ↑ "AusPAR: Finerenone". Therapeutic Goods Administration (TGA). 31 May 2022. Retrieved 12 June 2022.{{cite web}}: CS1 maint: url-status (link)
    6. 1 2 3 4 5 6 7 8 "FDA Approves Drug for Chronic Kidney Disease". U.S. Food and Drug Administration (FDA). 9 July 2021. Archived from the original on 9 July 2021. Retrieved 9 July 2021. Public Domain This article incorporates text from this source, which is in the public domain.
    7. ↑ "Finerenone". SPS - Specialist Pharmacy Service. 7 January 2016. Archived from the original on 3 March 2022. Retrieved 29 October 2022.
    8. ↑ "Kerendia". Archived from the original on 29 October 2022. Retrieved 29 October 2022.
    9. ↑ "Finerenone Uses, Side Effects & Warnings". Drugs.com. Archived from the original on 11 June 2022. Retrieved 11 June 2022.
    10. ↑ "Finerenone Uses, Side Effects & Warnings". Drugs.com. Archived from the original on 11 June 2022. Retrieved 11 June 2022.
    11. ↑ Ruilope LM, Tamargo J (April 2017). "Renin-angiotensin system blockade: Finerenone". Nephrologie & Therapeutique. 13 Suppl 1: S47–S53. doi:10.1016/j.nephro.2017.02.003. PMID 28577743.
    12. ↑ Pitt B, Anker SD, Böhm M, Gheorghiade M, Køber L, Krum H, et al. (February 2015). "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" (PDF). European Journal of Heart Failure. 17 (2): 224–32. doi:10.1002/ejhf.218. hdl:2027.42/110733. PMID 25678098. S2CID 205781715. Archived from the original on 28 October 2022. Retrieved 13 June 2022.
    13. ↑ Bärfacker, Lars; Kuhl, Alexander; Hillisch, Alexander; Grosser, Rolf; Figueroa-Pérez, Santiago; Heckroth, Heike; Nitsche, Adam; Ergüden, Jens-Kerim; Gielen-Haertwig, Heike; Schlemmer, Karl-Heinz; Mittendorf, Joachim (August 2012). "Discovery of BAY 94-8862: A Nonsteroidal Antagonist of the Mineralocorticoid Receptor for the Treatment of Cardiorenal Diseases". ChemMedChem. 7 (8): 1385–1403. doi:10.1002/cmdc.201200081. PMID 22791416. S2CID 36084480.
    14. ↑ Amazit L, Le Billan F, Kolkhof P, Lamribet K, Viengchareun S, Fay MR, et al. (September 2015). "Finerenone Impedes Aldosterone-dependent Nuclear Import of the Mineralocorticoid Receptor and Prevents Genomic Recruitment of Steroid Receptor Coactivator-1". The Journal of Biological Chemistry. 290 (36): 21876–89. doi:10.1074/jbc.M115.657957. PMC 4571943. PMID 26203193.
    15. 1 2 "Kerendia: Pending EC decision". European Medicines Agency (EMA). 16 December 2021. Archived from the original on 28 October 2022. Retrieved 18 December 2021. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
    16. ↑ Bakris GL, Agarwal R, Chan JC, Cooper ME, Gansevoort RT, Haller H, et al. (September 2015). "Effect of Finerenone on Albuminuria in Patients With Diabetic Nephropathy: A Randomized Clinical Trial". JAMA. 314 (9): 884–94. doi:10.1001/jama.2015.10081. PMID 26325557.
    17. ↑ Clinical trial number NCT02540993 for "Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease (FIDELIO-DKD)" at ClinicalTrials.gov
    18. ↑ Clinical trial number NCT02545049 for "Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Kidney Disease (FIGARO-DKD)" at ClinicalTrials.gov

    Further reading

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