The effects and efficacy of fenelinone

Finerenone (Finerenone) is a nonsteroidal mineralocorticoid receptor antagonist (MR) indicated to reduce the risk of persistent decline in glomerular filtration rate, end-stage renal disease, cardiovascular death, heart attack, and hospitalization for heart failure in adults with chronic kidney disease associated with type 2 diabetes. Since fenelidone is administered once daily, its duration of action is moderate, and since patients in clinical trials were dosed from 1.25 mg to 80 mg, the therapeutic window is wide. Patients should be counseled regarding the risk of hyperkalemia.

Finelidone has no significant affinity or activity at androgen, progesterone, estrogen, and glucocorticoid receptors. Animal studies have shown that combining fenelidone with MR reduces inflammation and fibrosis, and a phase 2 clinical trial showed a reduction in proteinuria. Aldosterone is a mineralocorticoid that is involved in regulating blood pressure, sodium reabsorption, and potassium excretion. Aldosterone is an MR agonist, and binding to MR causes conformational changes that dissociate the receptor from the inactivated chaperone protein. Binding of fenelidone to MR prevents the binding of MR coactivators, thereby preventing the transcription of pro-inflammatory and pro-fibrotic genes.

Clinical trial data show that blockade of mineralocorticoid receptors reduces mortality and morbidity in patients with chronic severe congestive heart failure whose ejection fraction is ≤35%. Patients taking fenelidone had a hazard ratio of 0.71 for new-onset atrial fibrillation or atrial flutter (AFF). Fennelidone reduced the risk of first onset of renal failure, sustained eGFR decline of ≥40%, or death from renal causes to 0.82. Cardiovascular outcomes included cardiovascular death, nonfatal heart attack, nonfatal stroke, and hospitalization for heart failure. The hazard ratio was 0.86 for patients with a history of AFF and 0.85 for patients without a history of atrial fibrillation.