New Interim, Real-World Data Provides Additional Insights on Hyperkalemia and Safety of Kerendia® (finerenone) for Patients with Chronic Kidney Disease Associated with Type 2 Diabetes

• Interim results from FINE-REAL, a prospective, observational study evaluating clinical characteristics and treatment patterns in patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D) treated with finerenone in routine clinical practice, showed real-world study rates of hyperkalemia¹
• New data presented at the American Society of Nephrology’s (ASN) Kidney Week 2023

Bayer today announced new interim, real-world data on Kerendia^® (finerenone) that complement the hyperkalemia and safety data in its pivotal trials. The data was presented at the American Society of Nephrology’s (ASN) Kidney Week 2023.

Kerendia is the first non-steroidal, selective mineralocorticoid receptor (MR) antagonist to demonstrate dual cardiorenal risk reduction in adult patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). ² It 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 CKD associated with T2D.³

The interim results (median seven months follow-up) from FINE-REAL, a prospective, observational study, evaluated the clinical characteristics and treatment patterns of 504 patients with CKD and T2D treated with finerenone and identified several insights, including¹:

• The incidence rate of hyperkalemia in the real-world study setting was 5% (n=25/504). In the pivotal studies (pooled data from FIDELIO-DKD and FIGARO-DKD), 14% (n=912/6510) of patients treated with Kerendia reported hyperkalemia vs. 6.9% (n=447/6489) treated with placebo (See below for additional pivotal study information.)
• The proportion of participants on the low moderate, high, and very high KDIGO risk categories were 2, 22, 27.9, and 48.2%, respectively
• 88% of patients received finerenone at the 10mg and 12% the 20 mg dose
• After initiation of finerenone, treatment was continued in 92.3% of patients; it was interrupted or discontinued in 5.4% and 1% of patients, respectively

The patients included in the FINE-REAL study had a mean eGFR of 52.0 mL/min/1.73 m2, median UACR of 295.0 mg/g, and mean serum potassium of 4.4 mmol/L. Statins, angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs), insulin, sodium-glucose cotransporter 2 inhibitors, and glucagon-like peptide-1 receptor agonists were prescribed to 387 (76.8%), 362 (71.8%), 241 (47.8%), 235 (46.6%), and 168 (33.3%) participants, respectively.

“Kerendia provides healthcare providers with a treatment option to slow chronic kidney disease progression and reduce cardiovascular risk in patients with CKD associated with T2D,” said Robert Perkins, MD, Vice President, Cardiovascular & Renal, Bayer. “These interim results from the FINE-REAL study provide new insight to Kerendia's real-world clinical use and safety information on how patients and their healthcare teams are integrating Kerendia.”

In the analysis, nearly a quarter of patients treated with finerenone were at moderate risk,¹ indicating healthcare providers in a real-world setting are intervening sooner to deliver dual cardiorenal risk reduction rather than waiting until the patient has progressed into the more severe stages of the disease.

About Kerendia^® (finerenone)³

Kerendia is a non-steroidal mineralocorticoid receptor antagonist (MRA) approved by the FDA in July 2021 to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular (CV) death, non-fatal myocardial infarction, and hospitalization for heart failure (HF) in adult patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D).

Kerendia was studied in the largest CKD clinical trial program 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) across a broad range of CKD severity in adults with CKD associated with T2D. In the Kerendia Phase III program for CKD associated with T2D with over 13,000 people, FIDELIO-DKD and FIGARO-DKD showed Kerendia reduced the risk of CKD progression and CV events. Based on data from the clinical trial program, Kerendia has been recommended for adults with CKD associated with T2D in several major treatment guidelines, including the American Diabetes Association^® (ADA), the American Association of Clinical Endocrinology^®, and the Kidney Disease: Improving Global Outcomes^® (KDIGO) Foundation as well as the ADA/KDIGO Consensus Statement.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS:

• Concomitant use with strong CYP3A4 inhibitors
• Patients with adrenal insufficiency

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.
  
  
  
  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.
  
  

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% versus 6.9%), hypotension (4.6% versus 3.9%), and hyponatremia (1.3% versus 0.7%).

DRUG INTERACTIONS:

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

USE IN SPECIFIC POPULATIONS:

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

Please read the Prescribing Information for KERENDIA.

About Kerendia Phase III Clinical Trials Program³

Having randomized more than 13,000 patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D) around the world, the Phase III program with Kerendia in CKD associated with T2D comprises two studies, evaluating the effect of Kerendia versus placebo on top of standard of care (SoC) on both renal and cardiovascular (CV) outcomes.

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 CKD associated with T2D. 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. 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.

Both trials excluded patients with known significant non-diabetic kidney disease. All patients were to have a serum potassium ≤ 4.8 mEq/L at screening and be receiving SoC background therapy, including a maximum tolerated labeled dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB). Patients with a clinical diagnosis of chronic heart failure (HF) with reduced ejection fraction and persistent symptoms (New York Heart Association class II to IV) were excluded. 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). The dose of Kerendia could be titrated during the study, with a target dose of 20 mg daily.

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. The secondary outcome was a composite of time to first occurrence of CV death, non-fatal MI, non-fatal stroke or hospitalization for HF. 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 HF. 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.

In FIDELIO-DKD, a total of 5,674 patients were randomized to receive Kerendia (N=2,833) or placebo (N=2,841) and were followed for a median of 2.6 years. The mean age of the study population was 66 years, and 70% of patients were male. This global trial population was 63% White, 25% Asian, and 5% Black (24% Black in the US). 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. 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. Approximately 46% of patients had a history of atherosclerotic CV disease and 8% had a history of HF. At baseline, 99.8% of patients were treated with an ACEi or ARB. 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.

In FIGARO-DKD, a total of 7,352 patients were randomized to receive Kerendia (N=3,686) or placebo (N=3,666) and were followed for 3.4 years. 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). Otherwise, baseline patient characteristics and background therapies were similar in the two trials.

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

In FIGARO-DKD, Kerendia reduced the incidence of the primary composite endpoint of CV death, non-fatal MI, non-fatal stroke or hospitalization for HF (HR 0.87, 95% CI 0.76-0.98, P=0.026). The treatment effect was mainly driven by an effect on hospitalization for HF, though CV death also contributed to the treatment effect. The treatment effect on the primary composite endpoint was generally consistent across subgroups, including patients with and without pre-existing cardiovascular disease. 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 Kerendia group and in 395 (10.8%) in the placebo group (HR=0.87, 95% CI 0.76-1.01).

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 6,510 patients were treated with 10 or 20 mg once daily over a mean duration of 2.2 and 2.9 years, respectively. 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. 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). 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%). The most frequently reported (≥ 10%) adverse reaction in both studies was hyperkalemia. Hospitalization due to hyperkalemia for the Kerendia group was 0.9% vs 0.2% in the placebo group across both studies. Hyperkalemia led to permanent discontinuation of treatment in 1.7% receiving Kerendia versus 0.6% of patients receiving placebo across both studies.

About Chronic Kidney Disease Associated with Type 2 Diabetes

Patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D) are three times more likely to die from a CV-related cause than those with T2D alone.⁴ CKD is a serious and progressive condition that is generally underrecognized.⁵ CKD is a frequent complication arising from T2D and is also an independent risk factor of CV disease.^6,7,8 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.^9,10,11

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 research and treatment options.

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 CV and kidney diseases are treated.¹²

Bayer is investigating in potential treatment approaches for areas of high unmet medical need. At present, Bayer is investigating 12 CVR-related projects through different stages of development including heart failure (HF), non-diabetic chronic kidney disease (CKD) and Type 1 Diabetes associated with chronic kidney disease.¹²

Bayer is actively 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.¹²

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 driving sustainable development and generating 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 2022, the Group employed around 101,000 people and had sales of 50.7 billion euros. R&D expenses before special items amounted to 6.2 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.

¹ Data on file.

² Data on file.

³ KERENDIA (finerenone) [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; September 2022.

⁴ 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.

⁵ Breyer MD, Susztak K. Developing treatments for chronic kidney disease in the 21st century. Semin Nephrol. 2016;36(6):436-447.

⁶ 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.

⁷ Thomas MC, Brownlee M, Susztak K, et al. Diabetic kidney disease. Nat Rev Dis Primers. 2015;1:1-20.

⁸ 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.

⁹ 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.

¹⁰ 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.

¹¹ 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.

¹² Data on file.

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