Bayer Submits New Drug Application in China for Finerenone, a First-in-Class Non-Steroidal MRA, Demonstrating Significant Reduction in Kidney and Cardiovascular Event Risks in Patients with Diabetic Kidney Disease

February 13, 2021 News /BioValleyBIOON/ --Bayer(Bayer) recently announced that it has submitted a regulatory application to the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA), seeking approval for finerenone (BAY 94-8862) for the treatment of chronic kidney disease (CKD) with type 2Diabetes(T2D) patients.Finerenone is a first-in-class, non-steroidal, selective mineralocorticoid receptor antagonist (MRA) that has been demonstrated to provide positive renal and cardiovascular benefits in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) in the Phase III FIDELIO-DKD study.

In mid-November 2020, Bayer simultaneously submitted regulatory applications for finerenone to the U.S. FDA and the European EMA. In January 2021, the United StatesFDAAccepted the new drug application for finerenone and granted priority review.

It is worth mentioning that,Finerenone is the first non-steroidal selective mineralocorticoid receptor antagonist proven to reduce the risk of renal and cardiovascular events in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD).Despite progress in recent years, many patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) continue to progress toward end-stage renal failure or premature death. Finerenone has a mechanism of action distinct from current therapies; if approved, it could slow disease progression by directly targeting inflammation and fibrosis, the key drivers of CKD progression.

Dr. Christian Rommel, Member of the Executive Committee of Bayer’s Pharmaceuticals Division and Head of Research and Development, stated: “Compared with the general population, chronic kidney disease (CKD) can make type 2Diabetes(T2D) patients have a shortened life expectancy by 16 years. This is a slowly progressing, often asymptomatic disease, with most symptoms not appearing until later stages. It is estimated that there are approximately 35 million people with type 2 diabetes in China.Diabetes“Patients are affected by chronic kidney disease. We are committed to helping these patients, as finerenone has the potential to offer a new strategy to slow the decline of renal function.”

Regulatory submission documents for finerenone, based on positive data from the Phase 3 FIDELIO-DKD study, which is the largest Phase 3 trial conducted to date in chronic kidney disease (CKD) and type 2 diabetes (T2D).Clinical TrialPart of the project. The trial results were presented at the American Society of Nephrology (ASN) Kidney Week Reimagined 2020 and simultaneously published in The New England Journal of Medicine (NEJM) in October 2020; see: Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes.

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

The results showed that the study met its primary endpoint: when added to 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, over a median follow-up of 2.6 years, finerenone significantly reduced the composite risk of first occurrence of kidney failure, a sustained decrease in estimated glomerular filtration rate (eGFR) of ≥40% from baseline for at least 4 weeks, or renal death by 18% compared with placebo (HR=0.82; 95% CI: 0.73–0.93; p=0.0014). At 36 months, the number needed to treat to prevent one primary composite endpoint event was 29 (95% CI: 16–166).

Furthermore, the study results showed that the effect of finerenone on the primary outcome was generally consistent across prespecified subgroups, and the treatment benefit was sustained throughout the study period. With 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 a 14% reduction in the composite risk of hospitalization for heart failure (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 incidence of treatment-emergent adverse events and serious adverse events was similar between the two groups. Most adverse events were mild or moderate in severity. Compared with the placebo group, the finerenone group had a lower frequency of serious adverse events (31.9% vs. 34.3%) but a higher incidence of hyperkalemia-related adverse events (18.3% vs. 9%). The incidence of serious hyperkalemia-related adverse events was 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 and 0.9% in the placebo group.

Chemical Structure of Finerenone (Image source: newdrug)approvals.org）

Finerenone (BAY 94-8862) is an investigational, nonsteroidal, selective mineralocorticoid receptor antagonist (MRA) that has been shown to reduce the harmful effects of excessive mineralocorticoid receptor (MR) activation. Excessive MR activation is a major driver of kidney and heart damage. In 2015, the United StatesFDAGranted Fast Track Designation (FTD) for finerenone.

Chronic kidney disease (CKD) is one of the most common complications of diabetes and an independent risk factor for cardiovascular disease. Approximately 40% of patients with type 2 diabetes 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 survive. Over a 10-year period, patients with both CKD and type 2 diabetes are three times more likely to die from cardiovascular-related causes than those with type 2 diabetes alone. It is well established that excessive activation of mineralocorticoid receptors in patients with CKD and type 2 diabetes triggers harmful processes, such as inflammation and fibrosis, in the kidneys and heart. Globally, CKD in patients with type 2 diabetes is the most common cause of renal failure.

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

The Phase III clinical program for finerenone is the largest Phase III clinical program in chronic kidney disease (CKD) to date. The program comprises two studies that enrolled 13,000 patients with type 2 diabetes (T2D) and CKD of varying severity from around the world, including those with early-stage kidney damage and those with more advanced kidney disease. The program aims to evaluate the effects of finerenone versus placebo, each added to standard care, on renal and cardiovascular (CV) outcomes.

FIDELIO-DKD (Finerenone to Reduce Renal Failure and Disease Progression in Diabetic Kidney Disease) was 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 more than 1,000 sites across 48 countries worldwide. In the study, these patients were randomly assigned to receive once-daily oral finerenone (10 mg or 20 mg) or placebo, in addition to standard of care, including glucose-lowering therapy and maximally tolerated doses of renin-angiotensin system (RAS) blockers, such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). The study has met its primary endpoint.

The FIGARO-DKD (Finerenone Reducing Cardiovascular Morbidity and Mortality in Diabetic Kidney Disease) study is ongoing. This study has enrolled approximately 7,400 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) across 48 countries, including Europe, Japan, China, and the United States, to investigate the efficacy and safety of finerenone versus placebo, each added to standard care, in reducing cardiovascular morbidity and mortality.

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

Original Source: Bayer Submits Finerenone for Marketing Authorization in China for the Treatment of Chronic Kidney Disease in Type 2 Diabetes