Bayer to Highlight Additional Analyses From Comprehensive KERENDIA® (finerenone) Clinical Trial Program at the American Society of Nephrology’s 2022 Kidney Week

• Further post-hoc analysis from FIDELITY, a prespecified, exploratory pooled analysis of FIDELIO-DKD and FIGARO-DKD Phase III studies, investigates the efficacy and safety of KERENDIA in patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D) who have sustained an acute change in estimated glomerular filtration rate (eGFR) upon drug initiation¹
• The FINE-REAL study, the first prospective observational study with KERENDIA in patients with CKD associated with T2D, is expected to provide insights into the use of KERENDIA in routine clinical practice and inform decision-making on initiating KERENDIA in patients with CKD associated with T2D²

Bayer will present data from the comprehensive KERENDIA^® (finerenone) clinical trial program, conducted in patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D), at the American Society of Nephrology’s (ASN) Kidney Week 2022, scientific sessions and exchange, from November 3-6. Additional sets of data will be presented including a late-breaking pooled, post-hoc analysis of FIDELITY, further analyses of FIDELIO-DKD and the design of the first prospective observational study, FINE-REAL.^1-4 Bayer will also present findings on social determinants’ effects on CKD screening during the meeting.⁵

KERENDIA was approved on July 9, 2021, based on the results of the FIDELIO-DKD trial to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular (CV) death, non-fatal myocardial infarction and hospitalization for heart failure in adult patients with CKD associated with T2D.⁶ In September 2022, the FDA approved an updated label for KERENDIA to include findings from the Phase III FIGARO-DKD CV outcomes study. The KERENDIA label contains a Warning and Precaution that KERENDIA can cause hyperkalemia.⁶ For more information, see Important Safety Information below.

Post-hoc Analysis of FIDELITY

The prespecified, exploratory pooled analysis FIDELITY, including the FIDELIO-DKD and FIGARO-DKD Phase III studies, comprises data from over 13,000 patients with CKD associated with T2D across a broad range of CKD severity.⁷

Late-breaking data from a pooled, post-hoc analysis of FIDELITY will investigate the efficacy and safety of KERENDIA in patients with CKD associated with T2D who have sustained an acute change in eGFR upon drug initiation.¹

• Efficacy and safety of finerenone in patients with an acute change in estimated glomerular filtration rate: FIDELITY analysis
  • November 3, 10:00 am – 12:00 pm ET

Post-hoc Analyses of FIDELIO-DKD

FIDELIO-DKD investigated the efficacy and safety of KERENDIA in comparison to placebo on the reduction of CKD progression, in addition to standard of care, in approximately 5,700 patients with CKD associated with T2D.⁶

A post-hoc, subgroup analysis of the study will explore the cardiorenal effects of KERENDIA in patients with CKD associated with T2D from Asia.³ Asian patients were also randomized inside the U.S.

• Cardiorenal Outcomes with Finerenone in Asian Patients with CKD and Type 2 Diabetes: Post hoc Analysis from FIDELIO-DKD
  • SA-PO274: Diabetic Kidney Disease: Clinical – II
  • November 5, 10:00 am – 12:00 pm ET

An additional subgroup analysis will evaluate the efficacy and safety of KERENDIA in patients with CKD associated with T2D from China.⁴

• Effect of Finerenone on CKD Outcomes in Type 2 Diabetes: A Chinese Subgroup Analysis of the FIDELIO-DKD Study
  • SA-PO273: Diabetic Kidney Disease: Clinical – II
  • November 5, 10:00 am – 12:00 pm ET

FINE-REAL Study Design

FINE-REAL is the first prospective observational study with KERENDIA in patients with CKD associated with T2D. The study will investigate the use of KERENDIA in routine clinical practice and inform decision-making on initiating KERENDIA in patients with CKD associated with T2D.²

• Design and rationale of FINE-REAL: A Prospective Study Providing Insights Into the Use of Finerenone in Routine Clinical Settings
  • INFO10: Informational Poster
  • November 3-5, 10:00 am – 12:00 pm ET

Social Determinants of Health in CKD in T2D Screening and Disease Development Exploratory Analysis

Social determinants of health (SDOH) can impact access to routine care, including CKD screening. This presentation studies how SDOH factors from electronic health records (EHR) predict CKD screening and disease progression among newly diagnosed hypertension and T2D patients.⁵

• Social Determinants of Health Predict Annual CKD Screening and Disease Development Among Newly Diagnosed Hypertensive and Type 2 Diabetic Patients in a Large Midwestern Health System
  • TH-PO718: Diversity and Equity in Kidney Health – I
  • November 3, 10:00 am – 12:00 pm ET

Estimating CKD Underdetection Exploratory Analysis

Albuminuria testing is widely underused among patients at risk for CKD despite being crucial to guide implementation of evidence-based treatments to prevent disease progression and reduce CV morbidity. This presentation estimates the extent of albuminuria underdetection due to lack of testing in a large real-world U.S. cohort of patients with hypertension or diabetes.⁸

• Estimating Underdetection of CKD in Real-World Health Systems
  • FR-PO924 CKD: Epidemiology, Risk Factors, Prevention – II
  • November 4, 10:00 am – 12:00 pm ET

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).⁶

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS:

• Concomitant use with strong CYP3A4 inhibitors⁶
• Patients with adrenal insufficiency⁶

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.⁶

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.⁶

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%).⁶

DRUG INTERACTIONS:

• Strong CYP3A4 Inhibitors: Concomitant use of KERENDIA with strong CYP3A4 inhibitors is contraindicated. Avoid concomitant intake of grapefruit or grapefruit juice.⁶
• 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.⁶
• Strong and Moderate CYP3A4 Inducers: Avoid concomitant use of KERENDIA with strong or moderate CYP3A4 inducers.⁶

USE IN SPECIFIC POPULATIONS:

• Lactation: Avoid breastfeeding during treatment with KERENDIA and for 1 day after treatment.⁶
• 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).⁶

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.⁶

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).⁶ 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.⁶ 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 m².⁶

Both trials excluded patients with known significant non-diabetic kidney disease.⁶ 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).⁶ 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.⁶ 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).⁶ The dose of KERENDIA could be titrated during the study, with a target dose of 20 mg daily.⁶

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.⁶ 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.⁶ 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.⁶ 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.⁶

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.⁶ The mean age of the study population was 66 years, and 70% of patients were male.⁶ This global trial population was 63% White, 25% Asian, and 5% Black (24% Black in the US).⁶ At baseline, the mean eGFR was 44 mL/min/1.73 m², with 55% of patients having an eGFR < 45 mL/min/1.73 m².⁶ 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.⁶ Approximately 46% of patients had a history of atherosclerotic cardiovascular disease and 8% had a history of heart failure.⁶ At baseline, 99.8% of patients were treated with an ACEi or ARB.⁶ 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.⁶

In FIGARO-DKD, a total of 7352 patients were randomized to receive KERENDIA (N=3686) or placebo (N=3666) and were followed for 3.4 years.⁶ 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).⁶ Otherwise, baseline patient characteristics and background therapies were similar in the two trials.⁶

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).⁶ 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.⁶ 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).⁶ The treatment effect reflected a reduction in CV death, non-fatal MI, and hospitalization for heart failure.⁶ The treatment effect on the primary and secondary composite endpoints was generally consistent across subgroups.⁶

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).⁶ The treatment effect was mainly driven by an effect on hospitalization for heart failure, though CV death also contributed to the treatment effect.⁶ The treatment effect on the primary composite endpoint was generally consistent across subgroups, including patients with and without pre-existing cardiovascular disease.⁶ 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 (HR=0.87, 95% CI 0.76-1.01).⁶

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.⁶ 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.⁶ 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).⁶ 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%).⁶ The most frequently reported (≥ 10%) adverse reaction in both studies was hyperkalemia.⁶ Hospitalization due to hyperkalemia for the KERENDIA group was 0.9% vs 0.2% in the placebo group across both studies.⁶ Hyperkalemia led to permanent discontinuation of treatment in 1.7% receiving KERENDIA versus 0.6% of patients receiving placebo across both studies.⁶

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.⁹ CKD is a serious and progressive condition that is generally underrecognized.¹⁰ CKD is a frequent complication arising from T2D and is also an independent risk factor of CV disease.^11-13 Approximately 40% of all patients with T2D develop CKD.¹³ Despite guideline-directed therapies, patients with CKD associated with T2D remain at high risk of CKD progression and CV events.^11,12,14,15 T2D is the leading cause of end-stage kidney disease, which requires dialysis or a kidney transplant to stay alive.^16-18

About Bayer’s Commitment in Cardiovascular and Kidney Diseases

A leader in the cardiovascular (CV) space, Bayer upholds a long-standing commitment to delivering science for a better life by advancing innovative treatments.

Bayer’s cardiorenal franchise, which began with the discovery and development of a number of vital therapies, now includes a number of products and compounds in various stages of preclinical and clinical development with the potential to impact the way that cardiovascular and kidney diseases are treated.

Bayer is focused on advancing new treatment approaches for areas of high unmet medical need in CV and kidney diseases by identifying resources and programs aimed at better understanding the real-world management of CKD, expanding screening and early care management for CKD, aligning with and supporting groups and institutions that share the common goals of improving health outcomes, promoting health literacy and education and promoting research and initiatives that represent the diversity required to address the needs of all patients.

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 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. Navaneethan, S. Efficacy and safety of finerenone in patients with an acute change in estimated glomerular filtration rate: FIDELITY analysis. American Society of Nephrology Kidney Week 2022. November 3, 2022.
2. Nicholas, S. Design and rationale of FINE-REAL: A prospective study providing insights into the use of finerenone in routine clinical settings. American Society of Nephrology Kidney Week 2022. November 3-5, 2022. https://www.asn-online.org/education/kidneyweek/2022/program-abstract.aspx?controlId=3789452
3. Koya, D. Cardiorenal outcomes with finerenone in Asian patients with chronic kidney disease and type 2 dabetes: Post hoc Analysis from FIDELIO-DKD. American Society of Nephrology Kidney Week 2022. November 5, 2022. https://www.asn-online.org/education/kidneyweek/2022/program-abstract.aspx?controlId=3765674
4. Zhang, H. Effect of finerenone on CKD outcomes in type 2 diabetes: A Chinese subgroup analysis of the FIDELIO-DKD study. American Society of Nephrology Kidney Week 2022. November 5, 2022. https://www.asn-online.org/education/kidneyweek/2022/program-abstract.aspx?controlId=3763174
5. Ingle, M. Social Determinants of health predict annual CKD screening and disease development among newly diagnosed hypertensive and type 2 diabetic patients in a large midwestern health system. American Society of Nephrology Kidney Week 2022. November 3, 2022. https://www.asn-online.org/education/kidneyweek/2022/program-abstract.aspx?controlId=3767921
6. KERENDIA (finerenone) [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; September 2022.
7. 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.
8. Chu, C. Estimating underdetection of CKD in real-world health systems. American Society of Nephrology Kidney Week 2022. November 4, 2022. https://www.asn-online.org/education/kidneyweek/2022/program-abstract.aspx?controlId=3767606
9. 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.
10. Breyer MD, Susztak K. Developing treatments for chronic kidney disease in the 21st century. Semin Nephrol. 2016;36(6):436-447.
11. Anders HJ, Huber TB, Isermann B, et al. CKD in diabetes: diabetic kidney disease versus nondiabetic kidney disease. Nat Rev Nephrol. 2018;14:361-377.
12. Thomas MC, Brownlee M, Susztak K, et al. Diabetic kidney disease. Nat Rev Dis Primers. 2015;1:1-20.
13. Bailey RA, Wang Y, Zhu V, 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
14. 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/
15. American Diabetes Association. Standards of medical care in diabetes—2021. Diabetes Care. 2021;44(1):1-244.
16. 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
17. 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/
18. 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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