Bayer’s First-in-Class Drug Kerendia (finerenone) Approved by U.S. FDA for Diabetic Kidney Disease, Under Regulatory Review in China

Kidney (Image source: diabetes.co.uk)

July 12, 2021 /BioonBIOON/ --Bayer(Bayer) recently announced that the U.S. Food and Drug Administration (FDA) ApprovedKerendia (finerenone), indicated for the treatment of chronic kidney disease (CKD) associated with type 2 diabetesDiabetes mellitusadult patients with (T2D), to reduce the risk of sustained decline in estimated glomerular filtration rate (eGFR), end-stage kidney disease (ESKD), cardiovascular death, non-fatal myocardial infarction, and hospitalization for heart failure.Kerendia was approved through the Priority Review pathway. Currently, the drug is also under review in the European Union,Chinaand regulatory review in some other countries.

Kerendia is a first-in-class, nonsteroidal, selective mineralocorticoid receptor antagonist (MRA) that reduces the harmful effects of mineralocorticoid receptor (MR) overactivation. MR overactivation can lead to inflammation and fibrosis, which are key drivers of CKD progression and cardiac damage.

It is worth noting that,Kerendia is the first nonsteroidal selective mineralocorticoid receptor antagonist (MRA) to demonstrate positive renal and cardiovascular outcomes in patients with CKD and T2D.Despite guideline-directed therapies, many patients with CKD and T2D still progress to loss of kidney function and remain at high risk for cardiovascular events. With a mechanism of action distinct from existing therapies, Kerendia directly targets inflammation and fibrosis by blocking excessive mineralocorticoid receptor (MR) activation to slow disease progression.

FDAThe approval of Kerendia is based on the positive results from the pivotal Phase 3 FIDELIO-DKD study. The relevant data were presented at ASN Kidney Week 2020 and published in *The New England Journal of Medicine* (NEJM) in October 2020. For details, see:Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes。

Professor George L. Bakris, Principal Investigator of the FIDELIO-DKD study at the University of Chicago Pritzker School of Medicine, stated: “Worldwide, there are over 160 million patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). Even when blood glucose and blood pressure are well controlled, patients remain at risk of CKD progression. This underscores a high unmet medical need for early intervention to prevent further end-organ damage and premature death by slowing the decline of kidney function and reducing cardiovascular risk. The approval of finerenone provides a new pathway to protect patients from further renal damage by addressing mineralocorticoid receptor (MR) overactivation—a key driver of CKD progression—which is not addressed by currently available therapies.”

Chemical structure of finerenone (Image source: newdrugapprovals.org）

The FIDELIO-DKD study was conducted in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) to evaluate the efficacy and safety of finerenone versus placebo. Patients in both groups received standard of care, including glucose-lowering therapy and renin-angiotensin system (RAS) blockade at the maximum tolerated dose, such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs).

The results showed that the study met its primary endpoint: in combination with standard of care, finerenone significantly reduced the risk of the composite primary endpoint of CKD progression, kidney failure, and renal death compared with placebo. Specifically, with a median follow-up of 2.6 years,Compared with placebo, finerenone significantly reduced the composite risk of first occurrence of kidney failure, a sustained decline of ≥40% in estimated glomerular filtration rate (eGFR) from baseline for at least 4 weeks, and death from renal causes by 18%.(HR=0.82; 95% CI: 0.73-0.93; p=0.0014). In prespecified subgroups, the effect of finerenone on the primary outcome was generally consistent, and the treatment effect was sustained throughout the study period.

Additionally, at a median follow-up of 2.6 years, finerenone also significantly reduced the risk of key secondary endpoints compared with placebo:cardiovascular death, nonfatal myocardial infarction, nonfatalStrokeor the composite risk of heart failure hospitalization was reduced by 14%(relative risk reduction, HR = 0.86 [95% CI: 0.75-0.99; p = 0.0339]).

In this study, finerenone was well tolerated, with a safety profile consistent with that observed in previous studies. The overall incidences of treatment-emergent adverse events and serious adverse events were similar between the two groups. Most adverse events were mild or moderate in severity. The incidence of serious adverse events was lower in the finerenone group than in the placebo group (31.9% vs. 34.3%), while the incidence of hyperkalemia-related adverse events was higher (18.3% vs. 9.0%). The rates of hyperkalemia-related serious adverse events were low in both groups (1.6% vs. 0.4%), and there were no hyperkalemia-related deaths in either group. The proportion of patients who discontinued treatment due to hyperkalemia was 2.0% in the finerenone group versus 0.9% in the placebo group.

FIDELIO-DKD Clinical Data (Click image to enlarge)

Chemical structure of finerenone (Image source: newdrugapprovals.org）

Chronic kidney disease (CKD) isDiabetesOne of the most common complications, and an independent risk factor for cardiovascular disease. Among all type 2DiabetesAmong patients, approximately 40% will develop CKD. CKD is a leading cause of end-stage renal disease and renal failure. In advanced stages, patients may require dialysis or kidney transplantation to sustain life. Over a 10-year period, type 2 diabetes patients with CKDDiabetesPatients are three times more likely to die from cardiovascular-related diseases than those with type 2 diabetes alone.It is well known that in patients with type 2 diabetes and CKD, overactivation of mineralocorticoid receptors triggers deleterious processes in the kidneys and heart (e.g., inflammation and fibrosis). Globally, CKD in patients with type 2 diabetes is the most common cause of kidney failure.

The finerenone Phase III clinical program is the largest Phase III clinical program for chronic kidney disease (CKD) to date. Comprising two studies, it enrolled 13,000 patients with type 2 diabetes (T2D) and CKD across a wide spectrum of severity from around the world, including those with early kidney impairment and those with more advanced kidney disease. The program aims to evaluate the effects of finerenone plus standard of care versus placebo plus standard of care on renal and cardiovascular (CV) outcomes.

Mechanism of Action of Finerenone (Image source: researchgate.net)

FIDELIO-DKD (Finerenone to Reduce Renal Failure and Disease Progression in Diabetic Kidney Disease) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter, event-driven Phase III study that enrolled approximately 5,700 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) from over 1,000 sites across 48 countries worldwide. In the study, these patients were randomized to receive once-daily oral finerenone at 10 mg or 20 mg, or placebo, alongside standard of care, including glucose-lowering therapy and renin-angiotensin system (RAS) blockers at the maximum tolerated dose, such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). The study has met its primary endpoint.

The FIGARO-DKD (finerenone for reducing cardiovascular morbidity and mortality in diabetic kidney disease) study is still ongoing. It has enrolled approximately 7,400 patients with T2D and CKD across 48 countries, including Europe, Japan, China, and the United States, and is investigating the efficacy and safety of finerenone versus placebo, each in combination with standard of care, in reducing cardiovascular morbidity and mortality.

Additionally, Bayer has initiated the FINEARTS-HF study, a multicenter, randomized, double-blind, placebo-controlled Phase III trial investigating finerenone versus placebo in more than 5,500 patients with symptomatic heart failure (HF) (New York Heart Association [NYHA] class II-IV) and a left ventricular ejection fraction (LVEF) ≥40%. The primary objective of the study is to demonstrate the superiority of finerenone over placebo in reducing the incidence of a composite endpoint of cardiovascular (CV) death and total (first and recurrent) HF events (defined as HF hospitalization or urgent HF visit). (Bioon.com)

Original Source:Bayer’s KERENDIA® (finerenone) Receives U.S. FDA Approval for Treatment of Patients with Chronic Kidney Disease Associated with Type 2 Diabetes