Bayer Announces KERENDIA® (finerenone) Reduces the Risk of Cardiovascular Outcomes in New Phase III FIGARO-DKD Study in Adults With Chronic Kidney Disease (Stages 1-4) Associated With Type 2 Diabetes

WHIPPANY, N.J.–(BUSINESS WIRE)–Bayer announced today that detailed results from the Phase III FIGARO-DKD study demonstrated that compared with placebo, KERENDIA^® (finerenone) – a first-in-class nonsteroidal mineralocorticoid receptor antagonist (MRA)^3,4 – significantly reduced the risk of the composite primary endpoint of time to first occurrence of cardiovascular (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 angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) in adults with chronic kidney disease (CKD) associated with type 2 diabetes (T2D).¹ The reduction in the CV composite outcome was primarily driven by hospitalization due to heart failure. These data were presented today during a Hot Line session at the ESC Congress 2021 and simultaneously published in the New England Journal of Medicine.

FIGARO-DKD is the first contemporary Phase III cardiorenal trial with the majority of patients with stages 1-2 CKD (estimated glomerular filtration rate [eGFR] ≥60 ml/min/1.73m²) to show CV benefit in CKD associated with T2D.¹ Patients were included in this study if they had urine albumin-to-creatinine ratio (UACR) levels 30–5000 mg/g.¹ KERENDIA^® was approved in the United States on July 9, 2021 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” below.

“The unfortunate reality is that patients living with chronic kidney disease associated with type 2 diabetes are three times more likely to die from a cardiovascular event than those with type 2 diabetes alone.⁵ As chronic kidney disease progresses, the risk for cardiovascular events and heart failure hospitalization increases, so early diagnosis and treatment is critical,”⁶ said Bertram Pitt, professor of medicine emeritus at the University of Michigan School of Medicine in Ann Arbor and co-principal investigator of the FIGARO-DKD clinical trial. “The FIGARO-DKD study adds to the body of evidence that supports the benefits of finerenone for patients with chronic kidney disease associated with type 2 diabetes.”^1,3,7

FIGARO-DKD: Second Phase III Study for Finerenone to Meet Primary Endpoint

FIGARO-DKD (FInerenone in reducinG cArdiovascular moRtality and mOrbidity in Diabetic Kidney Disease), a randomized, double-blind, placebo-controlled trial, randomly assigned 7,437 participants from 48 countries to finerenone 10 mg or 20 mg orally once daily or placebo when added to standard of care, including blood glucose-lowering therapies and a maximum tolerated labeled dose of ACEis or ARBs.¹ 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/1.73m².¹

In this study, the incidence of the key 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.¹ 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.¹ In the FIDELIO-DKD study, 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. There were few renal deaths during the trial.⁴

In FIGARO-DKD, safety and tolerability profile were generally consistent with that of previously reported FIDELIO-DKD results. Overall, hyperkalemia-related adverse events occurred more often in patients receiving finerenone compared with placebo (10.8% and 5.3%, respectively).¹ 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.¹ Treatment was discontinued due to hyperkalemia in 1.2% of patients treated with finerenone compared to 0.4% in the placebo group.¹

FIDELITY: Prespecified Meta-analysis

Also presented within the ESC Hot Line session were select data from FIDELITY (FInerenone in chronic kiDney diseasE and type 2 diabetes: combined FIDELIO-DKD and FIGARO-DKD Trial program analYsis), which is a prespecified meta-analysis of the FIDELIO-DKD and FIGARO-DKD studies. FIDELITY is a meta-analysis of the largest Phase III program to evaluate the occurrence of progression of kidney disease as well as fatal and nonfatal CV events in >13,000 adult patients with CKD associated with T2D.^2,7

In this prespecified exploratory meta-analysis, finerenone reduced the risk of the composite CV outcome of time to CV death, nonfatal myocardial infarction, nonfatal stroke or hospitalization for heart failure by 14% compared with placebo.² The composite CV outcome occurred in 825 (12.7%) patients receiving finerenone and 939 (14.4%) patients receiving placebo (HR 0.86 [95% CI, 0.78–0.95]), with a number needed to treat of 46 at 36 months.² The reduction in the CV composite outcome was primarily driven by hospitalization for heart failure. Cardiovascular death and nonfatal myocardial infarction were directionally consistent with the CV composite outcome.² The composite kidney outcome of time to first onset of kidney failure, sustained ≥57% decrease in eGFR from baseline over ≥4 weeks, or renal death occurred in 360 (5.5%) patients receiving finerenone and 465 (7.1%) receiving placebo (HR 0.77 [95% CI, 0.67–0.88]).²

In FIDELIO-DKD, this exploratory composite kidney outcome of kidney failure, sustained decrease in eGFR by 57% or more from baseline, or renal death occurred in 252 (8.9%) patients and 326 (11.5%) patients in the finerenone and placebo groups, respectively (HR 0.76 [95% CI, 0.65–0.90]).³ In FIGARO-DKD, this exploratory composite kidney outcome of kidney failure, sustained decrease in eGFR by 57% or more from baseline, or renal death occurred in 108 (2.9%) patients and 139 (3.8%) patients in the finerenone and placebo groups, respectively (HR 0.77 [95% CI, 0.60–0.99]).¹ KERENDIA^® is not indicated to reduce the risk of renal death.⁴

“With the results of the FIGARO-DKD study and FIDELITY analysis, we are very pleased to build on our growing body of evidence for finerenone in patients with chronic kidney disease associated with type 2 diabetes,” said Amit Sharma, M.D., Vice President of Cardiovascular and Renal, Bayer U.S. Medical Affairs. “Together, these findings reinforce our commitment to improving the lives of these patients.”

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 cardiovascular 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 m.^3,4 The trial excluded patients with known significant non-diabetic 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 ACEi or ARB.⁴ A total of 5,674 patients were randomized to receive finerenone (N=2833) or placebo (N=2841) 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.⁴ 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.⁴ 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 Adverse reactions that occurred more commonly on finerenone than on placebo, and in at least 1% of patients treated with finerenone, were hyperkalemia (18.3% vs. 9%), hypotension (4.8% vs. 3.4%) and hyponatremia (1.4% vs. 0.7%).⁴

FIGARO-DKD (FInerenone in reducinG cArdiovascular moRtality and mOrbidity in Diabetic Kidney Disease) investigated the efficacy and safety of finerenone versus placebo in addition to standard of care on the reduction of cardiovascular morbidity and mortality in approximately 7,400 patients with CKD associated with T2D across 48 countries including sites in Europe, Japan, China and the U.S.^7,8 Finerenone 10 mg or 20 mg, orally once daily, was added to standard of care, including blood glucose-lowering therapies and a maximum tolerated labeled dose of an ACEi or an ARB.^7,8

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 (New York Heart Association class II-IV) with a left ventricular ejection fraction of ≥40%.⁹ 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 (HF) events (defined as hospitalizations for HF or urgent HF visits).⁹

About KERENDIA

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 Chronic Kidney Disease Associated with Type 2 Diabetes

Patients with CKD associated with T2D are three times more likely to die from a cardiovascular-related cause than those with T2D alone.⁵ 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 cardiovascular disease.^11,12,13 Approximately 40% of all patients with T2D develop CKD.¹¹ Despite guideline-directed therapies, patients with CKD associated with T2D remain at high risk of CKD progression and cardiovascular events.^12,13,14,15 T2D is the leading cause of end-stage kidney disease, which requires dialysis or a kidney transplant to stay alive.^16,17,18

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 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 2020, the Group employed around 100,000 people and had sales of 41.4 billion euros. R&D expenses before special items amounted to 4.9 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. Pitt B. FIGARO-DKD: finerenone in patients with chronic kidney disease and type 2 diabetes. Oral presentation at: ESC Congress 2021: The Digital Experience. August 28, 2021. Sophia Antipolis, France. https://digital-congress.escardio.org/ESC-Congress/sessions/2831-hot-line-figaro-dkd-fidelity-analysis
2. Filippatos G. FIDELITY Analysis: finerenone in mild-to-severe chronic kidney disease and type 2 diabetes. Oral presentation at: ESC Congress 2021: The Digital Experience. August 28, 2021. Sophia Antipolis, France. https://digital-congress.escardio.org/ESC-Congress/sessions/2831-hot-line-figaro-dkd-fidelity-analysis
3. Bakris GL, Agarwal R, Anker SD, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med. 2020;383:2219-2229. doi:10.1056/NEJMoa2025845
4. KERENDIA (finerenone) [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; July 2021.
5. 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. doi:10.1681/ASN.2012070718
6. Bansal N, Zelnick L, Bhat Z, et al. Burden and outcomes of heart failure hospitalizations in adults with chronic kidney disease. J Am Coll Cardiol. 2019;73(21):2691-2700. doi:10.1016/j.jacc.2019.02.071
7. Ruilope LM, Agarwal R, Anker SD, 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. doi:10.1159/000503712
8. Efficacy and safety of finerenone in subjects with type 2 diabetes mellitus and the clinical diagnosis of diabetic kidney disease (FIGARO-DKD). ClinicalTrials.gov. Accessed August 12, 2021. https://clinicaltrials.gov/ct2/show/NCT02545049
9. 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). ClinicalTrials.gov. Accessed August 12, 2021. https://clinicaltrials.gov/ct2/show/NCT04435626
10. Breyer MD, Susztak K. Developing treatments for chronic kidney disease in the 21st century. Semin Nephrol. 2016;36(6):436-447. doi:10.1016/j.semnephrol.2016.08.001
11. Bailey R, Wang Y, Zhu V, Rupnow MFT. 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
12. Anders HJ, Huber TB, Isermann B, Schiffer M. CKD in diabetes: diabetic kidney disease versus nondiabetic kidney disease. Nat Rev Nephrol. 2018;14(6):361-377. doi:10.1038/s41581-018-0001-y
13. Thomas MC, Brownlee M, Susztak K, et al. Diabetic kidney disease. Nat Rev Dis Primers. 2015;1:15018. doi:10.1038/nrdp.2015.18
14. American Diabetes Association standards of medical care in diabetes – 2021. Diabetes Care. 2021;44(1):1-244. https://care.diabetesjournals.org/content/diacare/suppl/2020/12/09/44.Supplement_1.DC1/DC_44_S1_final_copyright_stamped.pdf
15. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3:5-14. https://kdigo.org/wp-content/uploads/2017/02/KDIGO_2012_CKD_GL.pdf
16. National diabetes statistics report 2020: estimates of diabetes and its burden in the United States. Center 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. Incidence, prevalence, patient characteristics, and treatment modalities. United States Renal Data System. Accessed July 9, 2021. https://adr.usrds.org/2020/end-stage-renal-disease/1-incidence-prevalence-patient-characteristics-and-treatment-modalities