Bayer's First-in-Class Drug Finerenone Succeeds in Phase III Cardiovascular Outcomes Study for Diabetic Kidney Disease and Submitted for Approval in China

May 12, 2021 /Bio ValleyBIOON/ --Bayer(Bayer) recently announced the results of the Phase III cardiovascular outcomes study FIGARO-DKD. The study was conducted in patients with both chronic kidney disease (CKD) and type 2Diabetes(T2D) patients, evaluating the efficacy and safety of finerenone (BAY 94-8862) versus placebo. Both groups received standard care, including glucose-lowering therapy and guideline-directed maximally tolerated doses of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs).

The results showed that the study met its primary endpoint: when combined with standard of care, compared with placebo,Finerenone significantly reduced the composite risk of first occurrence of cardiovascular (CV) death or nonfatal CV events (myocardial infarction, stroke, hospitalization for heart failure).. Detailed data from this study will be presented at the upcoming medicalConferencepublished above.

FIGARO-DKD is the second positive Phase 3 study in the Phase 3 clinical program of finerenone for the treatment of patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). Compared with FIDELIO-DKD, the first positive Phase 3 study in this program, FIGARO-DKD enrolled more patients with early-stage CKD and T2D. The previously published results from FIDELIO-DKD demonstrated that, when added to standard of care, finerenone, compared with placebo,Finerenone significantly reduced the risk of the composite primary endpoint of CKD progression, kidney failure, and renal death.

Professor Luis M. Ruilope from the Department of Public Health and Preventive Medicine at the Autonomous University of Madrid in Spain, co-principal investigator of the FIGARO-DKD study, stated: “Up to 40% of type 2DiabetesPatients may progress to chronic kidney disease, with a high likelihood of experiencing cardiovascular events and developing renal failure. The FIGARO-DKD study evaluated finerenone in patients with chronic kidney disease and type 2Diabetespotential impact on patients' cardiovascular outcomes.”

Dr. Christian Rommel, Member of the Executive Committee of Bayer’s Pharmaceuticals Division and Head of Research and Development, stated: “With the FIGARO-DKD study achieving positive results in its composite primary endpoint, by completing the largest Phase III trial to date covering a broad spectrum of disease severity in CKD and T2D”Clinical TrialsIn this project, we have achieved a significant milestone in the clinical development of finerenone. We are very pleased to see that the data from the FIGARO-DKD study further support the evidence generated by the FIDELIO-DKD study, reducing the composite risk of cardiovascular death and non-fatal cardiovascular events or outcomes in patients with CKD and T2D.”

Chemical structure of finerenone (Image source: newdrug)approvals.org）

Chronic Kidney Disease (CKD) isDiabetesOne of the most common complications and an independent risk factor for cardiovascular disease. Approximately 40% of patients with type 2 diabetes mellitus (T2DM) develop chronic kidney disease (CKD). CKD is a leading cause of end-stage renal disease (ESRD) and renal failure; in advanced stages, patients may require dialysis or kidney transplantation to survive. Over a 10-year period, patients with T2DM and CKD are three times more likely to die from cardiovascular-related causes than those with T2DM alone. It is well established that excessive activation of mineralocorticoid receptors in patients with CKD and T2DM triggers harmful processes, such as inflammation and fibrosis, in the kidneys and heart. Globally, CKD in patients with T2DM is the most common cause of renal failure.

Finerenone is a first-in-class, 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. Finerenone has been demonstrated to provide positive renal and cardiovascular benefits in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D).

Currently,Finerenone is under review by regulatory authorities in the United States, the European Union, and China.It is worth mentioning thatFinerenone is the first non-steroidal selective mineralocorticoid receptor antagonist (MRA) 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.

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

The Phase III clinical program for finerenone is the largest Phase III clinical program to date for chronic kidney disease (CKD) combined with type 2 diabetes (T2D). The program consists of two studies, enrolling 13,000 T2D patients with varying severities of CKD from around the world, including those with early renal impairment and more advanced renal disease. The program aims to evaluate the effects of finerenone versus placebo, both in combination with standard care, on renal and cardiovascular (CV) outcomes.

The Phase 3 FIDELIO-DKD study (Finerenone Reducing Renal Failure and Disease Progression in Diabetic Kidney Disease) enrolled approximately 5,700 patients, and the Phase 3 FIGARO-DKD study (Finerenone Reducing Cardiovascular Morbidity and Mortality in Diabetic Kidney Disease) enrolled approximately 7,400 patients.

The regulatory application for finerenone is based on the positive data from the FIDELIO-DKD study. The trial results were presented at the American Society of Nephrology (ASN) Kidney Week Reimagined 2020 and were 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.

FIDELIO-DKD Study Data (Click the image to view a larger version)

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. Both groups received standard 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: 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 demonstrated good tolerability, consistent with the safety profile 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 adverse events related to hyperkalemia 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 versus 0.9% in the placebo group. (Bioon.com)

Original Source: Bayer’s finerenone meets primary endpoint in Phase III FIGARO-DKD cardiovascular outcomes study in patients with chronic kidney disease and type 2 diabetes