• Late-breaking data from prespecified subgroup analyses of FIDELITY evaluate KERENDIA^® (finerenone) on cardiovascular (CV) and kidney outcomes, including patients with stages 1-4 chronic kidney disease (CKD) associated with type 2 diabetes (T2D), with or without a history of atherosclerotic cardiovascular disease¹
• FIDELITY, a prespecified exploratory pooled analysis of the FIDELIO-DKD and FIGARO-DKD studies, comprises the largest Phase III cardiorenal outcomes clinical trial program to evaluate the risk of progression of kidney disease as well as fatal and nonfatal CV events in >13,000 patients with CKD associated with T2D^1,2

Bayer announced today late-breaking data from prespecified exploratory subgroup analyses of FIDELITY, a prespecified pooled analysis of the Phase III FIDELIO-DKD and FIGARO-DKD trials. These analyses investigated KERENDIA^® (finerenone) versus placebo on composite cardiovascular (CV) and kidney outcomes in patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D), with and without a history of atherosclerotic cardiovascular disease (ASCVD).¹ The subgroup analyses were presented today at the American College of Cardiology’s 71st Annual Scientific Session (ACC.22).

Out of the 13,026 patients included in the FIDELITY full analysis, 5935 (45.6%) had a history of ASCVD at baseline.¹ Over a median follow-up of 3 years, patients with ASCVD versus those without had the following composite CV outcome of time to CV death, nonfatal myocardial infarction (MI), nonfatal stroke and hospitalization for heart failure (HHF; incident rate [IR]/100 patient-years [PY] 6.9 vs. 3.0; hazard ratio [HR] 2.09; 95% confidence interval [CI] 1.89–2.30), composite outcome of time to CV death or HHF (IR/100 PY, 4.51 vs. 1.92; HR: 2.12; 95% CI 1.88–2.40) and composite kidney outcome (IR/100 PY 2.1 vs. 2.4; HR: 0.96; 95% CI 0.83–1.10).¹

KERENDIA was approved in the United States on July 9, 2021, based on the results of FIDELIO-DKD, to reduce the risk of sustained estimated glomerular filtration rate (eGFR) decline, end-stage kidney disease, CV death, nonfatal MI and HHF in adult patients with CKD associated with T2D.³ The KERENDIA label contains a Warning and Precaution that KERENDIA can cause hyperkalemia.³ For more information, see “Important Safety Information” and the FIDELIO-DKD study results below.

The prespecified exploratory subgroup analyses of FIDELITY showed that the treatment effect of finerenone, when compared to placebo, was consistent in patients with or without history of ASCVD for the composite CV outcome of time to CV death, nonfatal MI, nonfatal stroke or HHF (HR: 0.83; 95% CI 0.74–0.94; HR: 0.91; 95% CI 0.78–1.06; P-value for interaction=0.38, respectively). The treatment effect, when compared to placebo, was also consistent in patients with or without history of ASCVD for the composite outcome of CV death or HHF (HR: 0.82; 95% CI 0.71–0.94; HR: 0.86; 95% CI 0.71–1.04; P-value for interaction: 0.68, respectively).¹

Regarding the effects of finerenone on the composite kidney outcome of time to kidney failure, sustained ≥57% decrease in eGFR or kidney-related death, the treatment effect was consistent in patients with or without a history of ASCVD (HR: 0.71; 95% CI 0.57–0.88; HR: 0.81; 95% CI 0.68–0.97; P-value for interaction: 0.33, respectively).¹

“In patients with chronic kidney disease associated with type 2 diabetes, cardiovascular complications are among the most frequent causes of death.^4,5 However, there is limited data on how the risk of cardiovascular events could be reduced in these patients,” said Javed Butler, MD, MPH, MBA, president of the Baylor Scott & White Research Institute and senior vice president for Baylor Scott & White Health, and distinguished professor of medicine at the University of Mississippi. “These subgroup analyses investigate outcomes in patients suffering from chronic kidney disease associated with type 2 diabetes, with or without a history of atherosclerotic cardiovascular disease. The analyses show us that in both cases, there’s a need to treat patients irrespective of where they are on the atherosclerotic cardiovascular disease spectrum.”

“Patients with chronic kidney disease and type 2 diabetes are three times more likely to die from a cardiovascular event than those with type 2 diabetes alone.⁶ That said, the severity of kidney impairment correlates with a higher incidence of cardiovascular events,” said Dr. Christian Rommel, member of the executive committee of Bayer AG's pharmaceutical division and head of research and development.⁵ “The latest prespecified subgroup analyses of FIDELITY add to our growing body of data on the renal and CV outcomes of finerenone in adults with chronic kidney disease associated with type 2 diabetes.”

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)³

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS:

• Concomitant use with strong CYP3A4 inhibitors³
• Patients with adrenal insufficiency³

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/L³
  
  
  
  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 potassium³

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%)³

DRUG INTERACTIONS:

• Strong CYP3A4 Inhibitors: Concomitant use of KERENDIA with strong CYP3A4 inhibitors is contraindicated. Avoid concomitant intake of grapefruit or grapefruit juice³
• 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 appropriate³
• Strong and Moderate CYP3A4 Inducers: Avoid concomitant use of KERENDIA with strong or moderate CYP3A4 inducers³

USE IN SPECIFIC POPULATIONS:

• Lactation: Avoid breastfeeding during treatment with KERENDIA and for 1 day after treatment³
• 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)³

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.⁷

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.^3,8 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).³ 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).³ 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.³ The mean age of the study population was 66 years, and 70% of patients were male.³ The trial population was 63% white, 25% Asian, and 5% Black.³

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]).³ The treatment effect reflected a reduction in a sustained decline in eGFR of ≥40% and progression to kidney failure.³ There were few renal deaths during the trial.³

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]).³ The treatment effect reflected a reduction in cardiovascular death, nonfatal myocardial infarction and hospitalization for heart failure.³

The most frequently reported adverse reaction was hyperkalemia (18.3% KERENDIA vs. 9% placebo).³ Hospitalization due to hyperkalemia for the KERENDIA group was 1.4% versus 0.3% in the placebo group.³ Hyperkalemia led to permanent discontinuation of treatment in 2.3% of patients receiving KERENDIA versus 0.9% of patients receiving placebo.³

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.⁹ However, the difference was not statistically significant (HR 0.87 [95% CI, 0.76-1.01; P=0.0689]) 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 recently announced the initiation of 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.⁶ CKD is a serious and progressive condition that is generally underrecognized.¹¹ CKD is a frequent complication arising from T2D and is also an independent risk factor of CV disease.^12-14 Approximately 40% of all patients with T2D develop CKD.¹⁴ Despite guideline-directed therapies, patients with CKD associated with T2D remain at high risk of CKD progression and CV events.^12,13,15,16 T2D is the leading cause of end-stage kidney disease, which requires dialysis or a kidney transplant to stay alive.^17-19

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. Filippatos G, et al. Finerenone and cardiorenal outcomes by history of cardiovascular disease in patients with type 2 diabetes and chronic kidney disease: FIDELITY analyses. Oral presentation at: ACC.22. April 4, 2022. Washington, D.C. https://www.abstractsonline.com/pp8/#!/10461/presentation/22134
2. Agarwal R, Filippatos G, Pitt B, et al. Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis. Eur Heart J. 2022;43(6):474-484.
3. KERENDIA (finerenone) [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; July 2021.
4. Einarson TR, Acs A, Ludwig C, Panton UH. Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007-2017. Cardiovasc Diabetol. 2018;17:83.
5. Fox CS, Matsushita K, Woodward M, et al. Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis [published correction appears in Lancet. 2013 Feb 2;381(9864):374]. Lancet. 2012;380(9854):1662-1673.
6. Afkarian M, Sachs MC, Kestenbaum B, et al. Kidney disease and increased mortality risk in type 2 diabetes. J Am Soc Nephrol. 2013;24(2):302-308..
7. 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.
8. Bakris G, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med. 2020. 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. Breyer MD, et al. Developing treatments for chronic kidney disease in the 21st Century. Semin Nephrol. 2016. 2016;36(6):436-447.
12. Anders HJ, et al. CKD in diabetes: diabetic kidney disease versus nondiabetic kidney disease. Nat Rev Nephrol. 2018;14:361-377.
13. Thomas MC, et al. Diabetic kidney disease. Nat Rev Dis Primers. 2015;1:1-20.
14. 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.
15. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2013;3:1-150.
16. American Diabetes Association standards of medical care in diabetes – 2021. Diabetes Care. 2021;44(1):1-244.
17. 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
18. 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/
19. United States Renal Data System. USRDS Annual data report. Volume 1: Chronic kidney disease. Chapter 6: Healthcare expenditures for persons with CKD. Bethesda, MD: 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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