Kerendia (finerenone) is the first oral, non-steroidal selective mineralocorticoid receptor antagonist indicated for the treatment of CKD (stage 3 and 4 with albuminuria) in adults with type II diabetes.
In CKD, overactivation of the mineralocorticoid receptor is thought to be the driver of inflammation and fibrosis.
Lower risk of CKD progression
The MHRA authorised the use of Kerendia based on results from the phase III FIDELIO-DKD study investigating the efficacy and safety of finerenone in 5734 adults with CKD and type II diabetes.
Patients were randomised in a 1:1 ratio to receive finerenone (n=2866) or placebo (n=2868). Eligible patients were treated with a maximum dose of an ACE inhibitor or angiotensin II antagonist, and had a urinary albumin-to-creatinine ratio of 30–300, an eGFR of 25–59ml/min/1.73m2 and diabetic retinopathy; or an albumin-to-creatinine ratio of 300–5000 and an eGFR of 25–75ml/min/1.73m2. The primary composite outcome was kidney failure, a sustained reduction in eGFR of ≥40% from baseline over at least 4 weeks, or death from renal causes.
Over a median follow-up period of 2.6 years, the incidence of the primary composite outcome was significantly lower in the finerenone group than in the placebo group, occurring in 504 patients (17.8%) and 600 patients (21.1%), respectively (hazard ratio 0.82 [95% CI 0.73–0.93], p=0.01).
Patients in the finerenone group also had a significantly lower risk of a key secondary outcome (death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke, or hospitalisation for heart failure), which occurred in 367 patients (13.0%) in the finerenone group and 420 patients (14.8%) in the placebo group (hazard ratio 0.86 [95% CI 0.75–0.99], p=0.03).
The most common adverse reactions reported in patients treated with finerenone were hyperkalaemia, hyponatraemia, hypotension, pruritus and reduced eGFR. Serum potassium and eGFR must be monitored 4 weeks after initiation of treatment, restarting treatment or increasing the dose.
Other studies have shown that finerenone is associated with smaller increases in serum potassium and lower incidences of hyperkalaemia than spironolactone.
David Wheeler, professor of kidney medicine at University College London and honorary consultant nephrologist at the Royal Free London NHS Foundation Trust said: 'Chronic kidney disease associated with type 2 diabetes is the most common cause of kidney failure and often leads to patients requiring dialysis or a kidney transplant to stay alive. There remains a critical medical need to protect these patients by delaying kidney disease progression and reducing their risk of cardiovascular events, which is why this is welcoming news for patients living with the condition. Physicians in the UK now have another new treatment option to help improve kidney outcomes in this patient population.'