Finerenone


Finerenone is a nonsteroidal antimineralocorticoid that is in phase III clinical trials for the treatment of chronic kidney disease in people with type II diabetes. It has less relative affinity to other steroid hormone receptors than currently available antimineralocorticoids such as eplerenone and spironolactone, which should result in fewer adverse effects like gynaecomastia, impotence, and low libido.

Pharmacology

Finerenone blocks mineralocorticoid receptors, which makes it a potassium-sparing diuretic.
This table compares inhibitory concentrations 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.
SpironolactoneEplerenoneFinerenone
Mineralocorticoid receptor2499018
Glucocorticoid receptor240022,000>10,000
Androgen receptor7721,200>10,000
Progesterone receptor74031,200>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.

Chemistry

Unlike currently marketed antimineralocorticoids, finerenone is not a steroid but a dihydropyridine derivative.

Research

In the Phase II ARTS-DN study, finerenone dose-dependently reduced urine albumin to creatinine ratio in patients with diabetic kidney disease. 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.