Bayer’s KERENDIA® (finerenone) Receives New Recommendations From American Diabetes Association for Improving Cardiovascular Outcomes and Managing Patients With Chronic Kidney Disease Associated With Type 2 Diabetes

• New grade A recommendation in updated ADA Standards of Medical Care in Diabetes—2022 for KERENDIA^® (finerenone) for improving cardiovascular (CV) outcomes and reducing risk of chronic kidney disease (CKD) progression in patients with CKD associated with type 2 diabetes (T2D)¹
• Update is based on evidence from more than 13,000 patients in largest cardiorenal outcomes Phase III program to investigate the occurrence of fatal and nonfatal CV events and progression of kidney disease in patients with CKD associated with T2D^1,2
• ADA and Kidney Disease: Improving Global Outcomes (KDIGO) orally presented a joint consensus statement that recommends use of finerenone for patients with T2D, an estimated glomerular filtration rate (eGFR) ≥25 mL/min/1.73m², normal serum potassium concentration and albuminuria (ACR≥30 mg/g) despite maximum tolerated dose of a renin-angiotensin-system (RAS) inhibitor.³ The consensus statement is to be officially published in the coming months

Bayer’s KERENDIA^® (finerenone) was recognized by the American Diabetes Association (ADA) Standards of Medical Care in Diabetes—2022 with a new grade A recommendation* for improving cardiovascular (CV) outcomes and reducing the risk of chronic kidney disease (CKD) progression in patients with CKD associated with type 2 diabetes (T2D).¹

KERENDIA was approved in the United States based on the results of FIDELIO-DKD, to reduce the risk of sustained eGFR decline, end-stage kidney disease, CV death, nonfatal myocardial infarction and hospitalization for heart failure in adult patients with CKD associated with T2D.⁴ The KERENDIA label contains a Warning and Precaution that KERENDIA can cause hyperkalemia.⁴ For more information, see Important Safety Information and the FIDELIO-DKD study results below.

The addendum, titled Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes—2022, was updated based on evidence from the FIDELIO-DKD and FIGARO-DKD Phase III studies as well as the FIDELITY prespecified pooled analysis,¹ which comprise the largest cardiorenal outcomes program to investigate the occurrence of fatal and nonfatal CV events and progression of kidney disease in patients with CKD associated with T2D in more than 13,000 patients. The program investigated the impact of finerenone in adults with CKD associated with T2D across a range of disease severity (CKD stages 1-4).²

The Standards of Medical Care in Diabetes—2022 were first released in December 2021 and included a grade A recommendation for KERENDIA in a new section emphasizing the importance of chronic kidney disease and risk management.

At the ADA’s 82nd Scientific Sessions on June 6, and aligned with the ADA interim update, the ADA and Kidney Disease: Improving Global Outcomes (KDIGO) orally presented a joint consensus statement on the management of CKD and diabetes, recommending the use of finerenone for patients with T2D, an estimated glomerular filtration rate (eGFR) of ≥25 mL/min/1.73 m², normal serum potassium concentration and albuminuria (albumin-to-creatinine ratio [ACR] ≥30 mg/g) despite maximum tolerated dose of renin-angiotensin-system (RAS) inhibitor.³ In the coming months, both the consensus statement and the final KDIGO update are expected to be published.

“Managing patients with chronic kidney disease and type 2 diabetes requires a multidisciplinary care team that works together to control the disease while working to reduce the risk of cardiovascular events and slow kidney disease progression,” said Professor George Bakris, M.D., University of Chicago Medicine and principal investigator of FIDELIO-DKD. “The ADA and KDIGO—two highly respected clinical bodies—aligned on an oral joint consensus statement at the ADA scientific sessions supporting KERENDIA as a pillar of established therapy to improve cardiovascular and renal outcomes for patients with chronic kidney disease associated with type 2 diabetes.”³

“The joint statement orally presented at the ADA scientific sessions from two prestigious professional organizations provide additional clinical information for health care providers to consider when looking for treatment options in the ongoing management of their patients with chronic kidney disease associated with type 2 diabetes,” said Sameer Bansilal, M.D., M.S., FACC, Vice President, Cardiovascular, U.S. Medical Affairs at Bayer. “At Bayer, we are committed to continuing our long history of researching and providing treatments to fight cardiovascular and kidney diseases.”

About the ADA Standards of Medical Care in Diabetes—2022 Update

The new grade A recommendation reads: “For patients with type 2 diabetes and chronic kidney disease treated with maximum tolerated doses of ACE inhibitors or angiotensin receptor blockers, addition of finerenone should be considered to improve cardiovascular outcomes and reduce the risk of chronic kidney disease progression. A”¹ Additionally, the “Lifestyle and Pharmacological Intervention” subsection now includes the following statement: “Patients with type 2 diabetes and chronic kidney disease should be considered for treatment with finerenone to reduce cardiovascular outcomes and the risk of chronic kidney disease progression.”¹

The December 2021 update included the following grade A recommendation for KERENDIA for CKD associated with T2D in section 11: “In patients with chronic kidney disease who are at increased risk for cardiovascular events or chronic kidney disease progression or are unable to use a sodium-glucose cotransporter 2 inhibitor, a nonsteroidal mineralocorticoid receptor antagonist (finerenone) is recommended to reduce chronic kidney disease progression and cardiovascular events (Table 9.2). A”⁵ The section was also updated to include evidence from the Phase III trial FIGARO-DKD and the prespecified pooled analysis FIDELITY, in addition to evidence from the Phase III trial FIDELIO-DKD.⁶

^*Recommendations with an A rating, the ADA's highest recommendation, are based on large, well-designed clinical trials or well-done meta-analyses that have the best chance of improving outcomes. Generally, these recommendations have the best chance of improving outcomes when applied to the population to which they are appropriate.⁷

About KERENDIA (finerenone)

INDICATION:

• KERENDIA is indicated to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, nonfatal myocardial infarction, and hospitalization for heart failure in adult patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D)⁴

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS:

• Concomitant use with strong CYP3A4 inhibitors⁴
• Patients with adrenal insufficiency⁴

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/L⁴
  
  
  
  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 potassium⁴

MOST COMMON ADVERSE REACTIONS:

• Adverse reactions reported in ≥1% of patients on KERENDIA and more frequently than placebo: hyperkalemia (18.3% vs. 9%), hypotension (4.8% vs. 3.4%), and hyponatremia (1.4% vs. 0.7%)⁴

DRUG INTERACTIONS:

• Strong CYP3A4 Inhibitors: Concomitant use of KERENDIA with strong CYP3A4 inhibitors is contraindicated. Avoid concomitant intake of grapefruit or grapefruit juice⁴
• 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 appropriate⁴
• Strong and Moderate CYP3A4 Inducers: Avoid concomitant use of KERENDIA with strong or moderate CYP3A4 inducers⁴

USE IN SPECIFIC POPULATIONS:

• Lactation: Avoid breastfeeding during treatment with KERENDIA and for 1 day after treatment⁴
• 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)⁴

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 (SoC) on both renal and CV outcomes.²

The FIDELIO-DKD (FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease) study was a randomized, double-blind, placebo-controlled, multicenter study in adult patients with CKD associated with T2D, defined as either having an uACR of 30 to 300 mg/g, eGFR 25 to 60 mL/min/1.73 m² and diabetic retinopathy, or as having an uACR of ≥300 mg/g and an eGFR of 25 to 75 mL/min/1.73 m².^4,8 The trial excluded patients with known significant nondiabetic kidney disease and a clinical diagnosis of chronic heart failure with reduced ejection fraction and persistent symptoms (NYHA class II to IV).⁴ 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).⁴ A total of 5,674 patients were randomized to receive finerenone (N=2,833) or placebo (N=2,841) and were followed for a median of 2.6 years.⁴ The mean age of the study population was 66 years, and 70% of patients were male.⁶ The trial population was 63% white, 25% Asian, and 5% Black.⁴

Finerenone 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]).⁴ The treatment effect reflected a reduction in a sustained decline in eGFR of ≥40% and progression to kidney failure.⁶ There were few renal deaths during the trial.⁴

Finerenone also reduced the incidence of the composite endpoint of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke or hospitalization for heart failure (HR 0.86 [95% CI, 0.75-0.99; P=0.034]).⁴ The treatment effect reflected a reduction in cardiovascular death, nonfatal myocardial infarction and hospitalization for heart failure.⁴

The most frequently reported adverse reaction was hyperkalemia (18.3% KERENDIA vs. 9% placebo).⁴ Hospitalization due to hyperkalemia for the KERENDIA group was 1.4% versus 0.3% in the placebo group.⁴ Hyperkalemia led to permanent discontinuation of treatment in 2.3% of patients receiving KERENDIA versus 0.9% of patients receiving placebo.⁴

FIGARO-DKD (FInerenone in reducinG cArdiovascular moRtality and mOrbidity in Diabetic Kidney Disease), a randomized, double-blind, placebo-controlled trial, randomly assigned 7,352 participants to finerenone (N=3686) or placebo (N=3666) on top of standard of care, including a maximum tolerated labeled dose of ACEis or ARBs.⁹ Patients had UACR ≥30–<300 mg/g and eGFR ≥25–≤90 mL/min/1.73m² or UACR ≥300–≤5000 mg/g and eGFR ≥60 mL/min/1.73m².⁹ This data is under review with the FDA.

KERENDIA significantly reduced the risk of the composite primary endpoint of time to first occurrence of CV death or nonfatal CV events (myocardial infarction, stroke or heart failure hospitalization) by 13% (relative risk reduction, HR 0.87 [95% CI, 0.76-0.98; P=0.0264]) over a median duration of follow-up of 3.4 years when added to maximum tolerated labeled dose of ACEi or ARB in adults with CKD associated with T2D.⁹ The reduction in the CV composite outcome was primarily driven by hospitalization due to heart failure.⁹

The incidence of the secondary endpoint, a composite of time to kidney failure, a sustained decrease of eGFR ≥40% from baseline over a period of at least four weeks, or renal death, was lower with finerenone than with placebo, affecting 350 (9.5%) and 395 (10.8%) patients, respectively.⁸ However, the difference was not statistically significant (HR 0.87 [95% CI, 0.76-1.01]) over a median duration of follow-up of 3.4 years.⁹

Overall, hyperkalemia-related adverse events occurred more often in patients receiving finerenone compared with placebo (10.8% and 5.3%, respectively).⁹ Hospitalization due to hyperkalemia for the finerenone group was 0.6% versus 0.1% in the placebo group, and there was no hyperkalemia-related death in either treatment group. Treatment was discontinued due to hyperkalemia in 1.2% of patients treated with finerenone compared to 0.4% in the placebo group.⁹

Bayer also initiated the FINEARTS-HF study, a multicenter, randomized, double-blind, placebo-controlled Phase III study that will investigate finerenone compared to placebo in more than 5,500 symptomatic heart failure patients (NYHA class II-IV) with a left ventricular ejection fraction of ≥40%.¹⁰ The primary objective of the study is to demonstrate superiority of finerenone over placebo in reducing the rate of the composite endpoint of cardiovascular death and total (first and recurrent) heart failure events (defined as hospitalizations for heart failure or urgent heart failure visits).¹⁰

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.¹¹ CKD is a serious and progressive condition that is generally underrecognized.¹² CKD is a frequent complication arising from T2D and is also an independent risk factor of CV disease.^13-15 Approximately 40% of all patients with T2D develop CKD.¹⁵ Despite guideline-directed therapies, patients with CKD associated with T2D remain at high risk of CKD progression and CV events.^13,14,16,17 T2D is the leading cause of end-stage kidney disease, which requires dialysis or a kidney transplant to stay alive.^18-20

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. ADA Professional Practice Committee. Addendum. 10. Cardiovascular disease and risk management: standards of medical care in diabetes—2022. Diabetes Care. 2022;45(suppl 1):S144-S174. doi:10.2337/dc22-ad08
2. Ruilope LM, et al. Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial. Am J Nephrol. 2019;50(5)345-356.
3. Rossing P. Consensus—new joint statement from the ADA and KDIGO on management of diabetes and CKD. Presented at: ADA 82nd Scientific Sessions; June 6, 2022.
4. KERENDIA (finerenone) [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; July 2021.
5. American Diabetes Association Professional Practice Committee. 11. Chronic kidney disease and risk management: standards of medical care in diabetes—2022. Diabetes Care. 2021;45(suppl 1). doi:10.2337/dc22-s011
6. American Diabetes Association Professional Practice Committee. Addendum. 11. Chronic kidney disease and risk management: Standards of medical care in diabetes—2022. Diabetes Care. 2022;45(suppl 1):S175-S184. doi:10.2337/dc22-ad08a
7. American Diabetes Association Professional Practice Committee. Chronic kidney disease and risk management: standards of medical care in diabetes—2017. Diabetes Care. 2017;40(Suppl 1):S1–S2. https://doi.org/10.2337/dc17-S001
8. Bakris G, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med. 2020;383:2219-2229.
9. Pitt B, et al. Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N Engl J Med. 2021;10.1056/NEJMoa2110956. doi:10.1056/NEJMoa2110956
10. ClinicalTrials.gov. Study to Evaluate the Efficacy (Effect on Disease) and Safety of Finerenone on Morbidity & Mortality in Participants with Heart Failure and Left Ventricular Ejection Fraction Greater or Equal to 40% (FINEARTS-HF). 2020. Accessed November 2021. https://clinicaltrials.gov/ct2/show/NCT04435626
11. Afkarian M, et al. Kidney disease and increased mortality risk in type 2 diabetes. J Am Soc Nephrol. 2013;24(2):302-308.
12. Breyer MD, et al. Developing treatments for chronic kidney disease in the 21st Century. Semin Nephrol. 2016;36(6):436-447.
13. Anders HJ, et al. CKD in diabetes: diabetic kidney disease versus nondiabetic kidney disease. Nat Rev Nephrol. 2018;14:361-377.
14. Thomas MC, et al. Diabetic kidney disease. Nat Rev Dis Primers. 2015;1:1-20.
15. 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.
16. 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/
17. American Diabetes Association. Standards of medical care in diabetes—2021. Diabetes Care. 2021;44(1):1-244.
18. 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
19. 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/
20. 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

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