WHIPPANY, N.J.--(BUSINESS WIRE)--Bayer announced today that it received approval from the United States (U.S.) Food and Drug Administration (FDA) for an update to the label for KERENDIA^® (finerenone), a first-in-class nonsteroidal mineralocorticoid receptor antagonist (MRA), to include findings from the FIGARO-DKD cardiovascular (CV) outcomes study in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D).¹ FIGARO-DKD is the first contemporary Phase III CV outcomes trial with the majority of patients with earlier stage (1-2) CKD (defined as estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m²) with albuminuria to show CV benefit in patients with CKD associated with T2D.¹

KERENDIA provides dual cardiorenal risk reduction in adults with CKD associated with T2D.¹ KERENDIA was approved in the U.S. by the FDA in July 2021 to reduce the risk of sustained eGFR decline, end-stage kidney disease, CV death, non-fatal myocardial infarction (MI) and hospitalization for heart failure in adult patients with CKD associated with T2D, based on the results of the FIDELIO-DKD pivotal trial.¹ The KERENDIA label contains a Warning and Precaution that KERENDIA can cause hyperkalemia.¹ For more information, see “Important Safety Information” below.

FIGARO-DKD showed that KERENDIA significantly reduced the risk of the primary composite endpoint of time to first occurrence of CV death, non-fatal MI, non-fatal stroke or hospitalization for heart failure (HF) by 13% (relative risk reduction, HR 0.87 [95% CI, 0.76-0.98; P=0.026]) over a median duration of follow-up of 3.4 years when added to maximum tolerated dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) in adults with CKD associated with T2D.¹ In FIGARO-DKD, the treatment effect was primarily driven by a 29% risk reduction in hospitalization for HF (HR 0.71 [95% CI, 0.56-0.90]).¹ A 10% risk reduction in CV death (HR 0.90 [95% CI, 0.74-1.09]) also contributed to the treatment effect.¹

With the addition of these study findings, the U.S. label now includes data from KERENDIA’s comprehensive Phase III clinical trial program investigating kidney and CV outcomes in more than 13,000 patients with CKD associated with T2D.¹

“The FIDELIO-DKD and FIGARO-DKD studies demonstrated KERENDIA’s dual cardiorenal risk reduction in patients with chronic kidney disease associated with type 2 diabetes,” said Professor George Bakris, M.D., University of Chicago Medicine and principal investigator of FIDELIO-DKD.¹ “This label update reaffirms KERENDIA as a fundamental pillar in the treatment algorithm to improve cardiovascular and renal outcomes in patients with chronic kidney disease associated with type 2 diabetes.”¹

KERENDIA works by blocking overactivation of the mineralocorticoid receptor (MR) in the kidney, heart and blood vessels, which is thought to lead to inflammation and fibrosis.¹ Mineralocorticoid receptor overactivation is an important factor to consider when evaluating the risk of CV events and CKD progression in patients with CKD associated with T2D.¹

“Our large body of clinical data demonstrates that KERENDIA preserves kidney function and provides dual cardiorenal risk reduction in type 2 diabetes patients with a broad range of chronic kidney disease severity,” said Sameer Bansilal, M.D., M.S., FACC, Vice President, Cardiovascular, U.S. Medical Affairs at Bayer.¹ “We are committed to equipping clinicians with treatment options, such as KERENDIA, that offer benefits to patients with chronic kidney disease associated with type 2 diabetes as patients work with their treatment teams to manage their disease and slow their chronic kidney disease progression.”¹

The patient population in the FIDELIO-DKD and FIGARO-DKD trials was at risk of CKD progression despite receiving the maximum tolerated dose of an ACEi or ARB and standard of care medications to control blood pressure and blood glucose levels.¹

About KERENDIA (finerenone)

INDICATION:

• KERENDIA is indicated to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, non-fatal myocardial infarction, and hospitalization for heart failure in adult patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D).¹

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS:

• Concomitant use with strong CYP3A4 inhibitors¹
• Patients with adrenal insufficiency¹

WARNINGS AND PRECAUTIONS:

• Hyperkalemia: KERENDIA can cause hyperkalemia. The risk for developing hyperkalemia increases with decreasing kidney function and is greater in patients with higher baseline potassium levels or other risk factors for hyperkalemia. Measure serum potassium and eGFR in all patients before initiation of treatment with KERENDIA and dose accordingly. Do not initiate KERENDIA if serum potassium is >5.0 mEq/L.¹

Measure serum potassium periodically during treatment with KERENDIA and adjust dose accordingly. More frequent monitoring may be necessary for patients at risk for hyperkalemia, including those on concomitant medications that impair potassium excretion or increase serum potassium.¹

MOST COMMON ADVERSE REACTIONS:

• From the pooled data of 2 placebo-controlled studies, the adverse reactions reported in ≥1% of patients on KERENDIA and more frequently than placebo were hyperkalemia (14% vs 6.9%), hypotension (4.6% vs 3.9%), and hyponatremia (1.3% vs 0.7%).¹

DRUG INTERACTIONS:

• Strong CYP3A4 Inhibitors: Concomitant use of KERENDIA with strong CYP3A4 inhibitors is contraindicated. Avoid concomitant intake of grapefruit or grapefruit juice.¹
• Moderate and Weak CYP3A4 Inhibitors: Monitor serum potassium during drug initiation or dosage adjustment of either KERENDIA or the moderate or weak CYP3A4 inhibitor and adjust KERENDIA dosage as appropriate.¹
• Strong and Moderate CYP3A4 Inducers: Avoid concomitant use of KERENDIA with strong or moderate CYP3A4 inducers.¹

USE IN SPECIFIC POPULATIONS:

• Lactation: Avoid breastfeeding during treatment with KERENDIA and for 1 day after treatment.¹
• Hepatic Impairment: Avoid use of KERENDIA in patients with severe hepatic impairment (Child Pugh C) and consider additional serum potassium monitoring with moderate hepatic impairment (Child Pugh B).¹

Please read the Prescribing Information for KERENDIA.

About Finerenone Phase III Clinical Trials Program

Having randomized more than 13,000 patients with CKD associated with T2D around the world, the Phase III program with finerenone in CKD associated with T2D comprises two studies, evaluating the effect of finerenone versus placebo on top of standard of care on both renal and CV outcomes.¹

FIDELIO-DKD (FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease) and FIGARO-DKD (FInerenone in reducinG cArdiovascular moRtality and mOrbidity in Diabetic Kidney Disease) studies were randomized, double-blind, placebo-controlled, multicenter studies in adult patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D).¹ In FIDELIO-DKD, patients needed to either have an UACR of 30 to < 300 mg/g, eGFR 25 to < 60 mL/min/1.73 m² and diabetic retinopathy, or an UACR of ≥ 300 mg/g and an eGFR of 25 to < 75 mL/min/1.73 m² to qualify for enrollment.¹ In FIGARO-DKD, patients needed to have an UACR of 30 mg/g to < 300 mg/g and an eGFR of 25 to 90 mL/min/1.73 m², or an UACR ≥ 300 mg/g and an eGFR ≥ 60 mL/min/1.73 m².¹

Both trials excluded patients with known significant non-diabetic kidney disease.¹ All patients were to have a serum potassium ≤ 4.8 mEq/L at screening and be receiving standard of care background therapy, including a maximum tolerated labeled dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB).¹ Patients with a clinical diagnosis of chronic heart failure with reduced ejection fraction and persistent symptoms (New York Heart Association class II to IV) were excluded.¹ The starting dose of KERENDIA was based on screening eGFR (10 mg once daily in patients with an eGFR of 25 to < 60 mL/min/1.73 m² and 20 mg once daily in patients with an eGFR ≥ 60 mL/min/1.73 m²).¹ The dose of KERENDIA could be titrated during the study, with a target dose of 20 mg daily.¹

The primary objective of the FIDELIO-DKD study was to determine whether KERENDIA reduced the incidence of a sustained decline in eGFR of ≥ 40%, kidney failure (defined as chronic dialysis, kidney transplantation, or a sustained decrease in eGFR to < 15 mL/min/1.73 m²), or renal death.¹ The secondary outcome was a composite of time to first occurrence of CV death, non-fatal MI, non-fatal stroke or hospitalization for heart failure.¹ The primary objective of the FIGARO-DKD study was to determine whether KERENDIA reduced the time to first occurrence of CV death, non-fatal MI, non-fatal stroke or hospitalization for heart failure.¹ The secondary outcome was a composite of time to kidney failure, a sustained decline in eGFR of 40% or more compared to baseline over at least 4 weeks, or renal death.¹

In FIDELIO-DKD, a total of 5674 patients were randomized to receive KERENDIA (N=2833) or placebo (N=2841) and were followed for a median of 2.6 years.¹ The mean age of the study population was 66 years, and 70% of patients were male.¹ This global trial population was 63% White, 25% Asian, and 5% Black (24% Black in the US).¹ At baseline, the mean eGFR was 44 mL/min/1.73 m², with 55% of patients having an eGFR < 45 mL/min/1.73 m².¹ Median urine albumin-to-creatinine ratio (UACR) was 852 mg/g, mean glycated hemoglobin A1c (HbA1c) was 7.7%, and the mean blood pressure was 138/76 mmHg.¹ Approximately 46% of patients had a history of atherosclerotic cardiovascular disease and 8% had a history of heart failure.¹ At baseline, 99.8% of patients were treated with an ACEi or ARB.¹ Approximately 97% were on an antidiabetic agent (insulin [64.1%], biguanides [44%], glucagon-like peptide-1 [GLP-1] receptor agonists [7%], sodium-glucose cotransporter 2 [SGLT2] inhibitors [5%]), 74% were on a statin, and 57% were on an antiplatelet agent.¹

In FIGARO-DKD, a total of 7352 patients were randomized to receive KERENDIA (N=3683) or placebo (N=3666) and were followed for 3.4 years.¹ As compared to FIDELIO-DKD, baseline eGFR was higher in FIGARO-DKD (mean eGFR 68, with 62% of patients having an eGFR ≥ 60 mL/min/1.73 m²) and median UACR was lower (308 mg/g).¹ Otherwise, baseline patient characteristics and background therapies were similar in the two trials.¹

In FIDELIO-DKD, KERENDIA reduced the incidence of the primary composite endpoint of a sustained decline in eGFR of ≥ 40%, kidney failure, or renal death (HR 0.82, 95% CI 0.73-0.93, P=0.001).¹ The treatment effect reflected a reduction in a sustained decline in eGFR of ≥ 40% and progression to kidney failure.¹ There were few renal deaths during the trial.¹ KERENDIA also reduced the incidence of the secondary composite endpoint of cardiovascular (CV) death, non-fatal myocardial infarction (MI), non-fatal stroke or hospitalization for heart failure (HR 0.86, 95% CI 0.75-0.99, P=0.034).¹ The treatment effect reflected a reduction in CV death, non-fatal MI, and hospitalization for heart failure.¹ The treatment effect on the primary and secondary composite endpoints was generally consistent across subgroups.¹

In FIGARO-DKD, KERENDIA reduced the incidence of the primary composite endpoint of CV death, non-fatal MI, non-fatal stroke or hospitalization for heart failure (HR 0.87, 95% CI 0.76-0.98, P=0.026).¹ The treatment effect was mainly driven by an effect on hospitalization for heart failure, though CV death also contributed to the treatment effect.¹ The treatment effect on the primary composite endpoint was generally consistent across subgroups, including patients with and without pre-existing cardiovascular disease.¹

The secondary composite outcome of kidney failure, sustained eGFR decline of 40% or more or renal death occurred in 350 patients (9.5%) in the finerenone group and in 395 (10.8%) in the placebo group (hazard ratio, 0.87; 95% CI, 0.76 to 1.01).^1,3

The safety of KERENDIA was evaluated in 2 randomized, double-blind, placebo-controlled, multicenter pivotal phase 3 studies, FIDELIO-DKD and FIGARO-DKD, in which a total of 6510 patients were treated with 10 or 20 mg once daily over a mean duration of 2.2 and 2.9 years, respectively.¹ Overall, serious adverse events occurred in 32% of patients receiving KERENDIA and in 34% of patients receiving placebo in the FIDELIO-DKD study; the findings were similar in the FIGARO-DKD study.¹ Permanent discontinuations due to adverse events also occurred in a similar proportion of patients in the two studies (6-7% of patients receiving KERENDIA and in 5-6% of patients receiving placebo).¹ From the pooled data of 2 placebo-controlled studies, the adverse reactions reported in ≥1% of patients on KERENDIA and more frequently than placebo were hyperkalemia (14% vs 6.9%), hypotension (4.6% vs 3.9%), and hyponatremia (1.3% vs 0.7%).¹ The most frequently reported (≥ 10%) adverse reaction in both studies was hyperkalemia.¹ Hospitalization due to hyperkalemia for the KERENDIA group was 0.9% vs 0.2% in the placebo group across both studies.¹ Hyperkalemia led to permanent discontinuation of treatment in 1.7% receiving KERENDIA versus 0.6% of patients receiving placebo across both studies.¹

About Chronic Kidney Disease Associated With Type 2 Diabetes

Patients with CKD associated with T2D are three times more likely to die from a CV-related cause than those with T2D alone.² CKD is a serious and progressive condition that is generally underrecognized.⁴ CKD is a frequent complication arising from T2D and is also an independent risk factor of CV disease.^5-7 Approximately 40% of all patients with T2D develop CKD.⁷ Despite guideline-directed therapies, patients with CKD associated with T2D remain at high risk of CKD progression and CV events.^5,6,8,9 T2D is the leading cause of end-stage kidney disease, which requires dialysis or a kidney transplant to stay alive.^10-12

About Bayer’s Commitment in Cardiovascular and Kidney Diseases

Bayer is an innovation leader in the area of cardiovascular diseases, with a long-standing commitment to delivering science for a better life by advancing a portfolio of innovative treatments. The heart and the kidneys are closely linked in health and disease, and Bayer is working in a wide range of therapeutic areas on new treatment approaches for cardiovascular and kidney diseases with high unmet medical needs. The cardiology franchise at Bayer already includes a number of products and several other compounds in various stages of preclinical and clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cardiovascular diseases are treated.

About Bayer

Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to drive sustainable development and generate a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2021, the Group employed around 100,000 people and had sales of 44.1 billion euros. R&D expenses before special items amounted to 5.3 billion euros. For more information, go to www.bayer.com.

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Forward-Looking Statements

This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

References

1. KERENDIA (finerenone) [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; September 2022.
2. Afkarian M, et al. Kidney disease and increased mortality risk in type 2 diabetes. J Am Soc Nephrol. 2013;24(2):302-308.
3. Pitt B, et al. Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N Engl J Med. 2021;385(24):2252-2263. doi: 10.1056/NEJMoa2110956.
4. Breyer MD, et al. Developing treatments for chronic kidney disease in the 21st Century. Semin Nephrol. 2016;36(6):436-447.
5. Anders HJ, et al. CKD in diabetes: diabetic kidney disease versus nondiabetic kidney disease. Nat Rev Nephrol. 2018;14:361-377.
6. Thomas MC, et al. Diabetic kidney disease. Nat Rev Dis Primers. 2015;1:1-20.
7. Bailey R, et al. Chronic kidney disease in US adults with type 2 diabetes: an updated national estimate of prevalence based on Kidney Disease: Improving Global Outcomes (KDIGO) staging. BMC Res Notes. 2014;7(1):415. doi:10.1186/1756-0500-7-415.
8. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 2013;3:1-150. https://kdigo.org/guidelines/ckd-evaluation-and-management/
9. American Diabetes Association. Standards of medical care in diabetes—2021. Diabetes Care. 2021;44(1):1-244.
10. National Diabetes Statistics Report 2020: Estimates of Diabetes and Its Burden in the United States. Centers for Disease Control and Prevention. Accessed July 9, 2021. https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf
11. Stages of CKD. American Kidney Fund. Accessed May 11, 2021. https://www.kidneyfund.org/kidney-disease/chronic-kidney-disease-ckd/stages-of-chronic-kidney-disease/
12. United States Renal Data System. USRDS Annual Data Report. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2020. Accessed November 2021. https://adr.usrds.org/2020/chronic-kidney-disease/6-healthcare-expenditures-for-persons-with-ckd