Bayer Healthcare Pharmaceuticals
Nonsteroidal mineralocorticoid receptor antagonist (MRA)
Chronic kidney disease (CKD) associated with type 2 diabetes
Approved in the US
KERENDIA® (finerenone) is a first-in-class, nonsteroidal mineralocorticoid receptor antagonist (MRA) indicated to reduce the progression of chronic kidney disease, risk of kidney failure and risk of cardiovascular disease in adult patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D).
The drug reduces several cardiovascular risks, including non-fatal myocardial infarction (MI), hospitalisation for heart failure and cardiovascular death in adult patients with CKD associated with T2D.
Developed by German multinational pharmaceutical company Bayer, KERENDIA is available as film-coated, oblong tablets in two strengths, including pink-coloured 10mg tablets and yellow-coloured 20mg tablets.
Approvals for KERENDIA
In November 2020, Bayer submitted a new drug application (NDA) to the US Food and Drug Administration (FDA) for KERENDIA (finerenone). The NDA was accepted and granted priority review for patients with CKD and T2D in January 2021. The drug also holds fast track designation for the condition.
The FDA approved KERENDIA in July 2021. The drug currently awaits marketing authorisation in the European Union (EU).
Chronic kidney disease (CKD) causes and symptoms
CKD is a gradual loss of kidney function leading to renal failure. The disease is often associated with T2D and around 40% of the T2D patients develop CKD.
The condition develops when the kidneys are damaged and become unable to filter blood normally. Patients may experience problems associated with fluid, electrolytes and waste build-up due to improper filtration, and the disease can increase the risk of developing heart disease. Diabetes is currently the primary cause of CKD and kidney failure in the US.
Symptoms associated with CKD are fatigue, loss of appetite, weight loss, swollen ankles, feet or hands, tiredness, itchy skin, muscle cramps, headache, insomnia, and blood in the urine.
Finerenone mechanism of action
Finerenone is a selective antagonist of the mineralocorticoid receptor (MR). Activated by aldosterone and cortisol, the nonsteroidal MRA regulates gene transcription. The overexpression of the MR is believed to contribute to fibrosis and inflammation.
The drug inhibits MR-mediated sodium reabsorption as well as MR overexpression in both epithelial (kidney) and nonepithelial (heart and blood vessel) tissues.
Finerenone has a high potency and selectivity for the MR but no significant affinity for androgen, progesterone, oestrogen or glucocorticoid receptors.
Clinical trials on KERENDIA
KERENDIA’s approval was supported by the positive outcomes of a double-blind, multi-centre, randomised, placebo-controlled, pivotal Phase III trial, FIDELIO-DKD, in patients with CKD associated with T2D.
The study was part of a comprehensive finerenone clinical trial programme that enrolled 13,000 patients with a wide spectrum of disease severity, including those with early kidney impairment and those in more advanced stages of kidney disease.
In the FIDELIO-DKD trial, 5,674 patients were randomly assigned to receive either KERENDIA (N=2,833) or placebo (N=2,841). The starting dose was determined by screening the estimated glomerular filtration rate (eGFR), which could be titrated, with a target dose of 20mg daily.
The study’s primary goal was to determine KERENDIA’s efficacy in reducing the incidence of a sustained decline in kidney function, progression to kidney failure or renal death compared to a placebo.
Results showed that 17.8% of the KERENDIA-treated patients demonstrated the incidence of a sustained decline in kidney function, progression to kidney failure or renal death compared to 21.1% of patients in the placebo group.
KERENDIA also lowered the incidence of cardiovascular death, non-fatal MI, non-fatal stroke or hospitalisation for heart failure.
The adverse reactions reported in KERENDIA-treated patients during the trial include hyperkalaemia, hypotension and hyponatraemia.
Another randomised, double-blind, placebo-controlled, parallel-group, event-driven Phase III clinical trial, FIGARO-DKD, was conducted under the finerenone study programme to determine the cardiovascular outcomes in patients with CKD and T2D.
Around 7,400 patients from more than 1,000 locations across 47 countries, including Canada, were enrolled in the study.
The study showed that finerenone significantly reduced the risk of cardiovascular death and non-fatal cardiovascular events in patients compared to placebo together with the standard of care.
Bayer subsequently initiated a multicentre, randomised, double-blind, placebo-controlled Phase III study, FINE ARTS-HF, to determine finerenone’s superiority over placebo in more than 5,500 patients with symptomatic heart failure and a left ventricular ejection fraction of ≥40%.
The trial’s primary endpoint is to demonstrate finerenone’s superiority over placebo in reducing the rate of cardiovascular death and total heart failure events.