New data for finerenone on the risk reduction of cardiovascular and renal outcomes in patients with a combination of atherosclerotic cardiovascular disease, chronic kidney disease and type 2 diabetes

Berlin, April 4, 2022 - Late-breaking data from prespecified subgroup analyses from FIDELITY, a prespecified pooled analysis of the Phase III FIDELIO-DKD and FIGARO-DKD trials, indicate that compared to placebo, finerenone consistently reduced the risk of the composite CV and kidney outcomes compared with placebo in addition to standard of care in patients across a broad spectrum of CKD associated with T2D, irrespective of a prior history of ASCVD. The subgroup analyses were presented today at the American College of Cardiology’s (ACC) 71st Annual Scientific Session (ACC.22). 

"In patients with chronic kidney disease and type 2 diabetes, cardiovascular complications are among the most frequent causes of death. However, there is currently limited data on how cardiovascular events could be effectively prevented or reduced in these patients," said Gerasimos Filippatos, M.D., Professor of Cardiology at the National and Kapodistrian University of Athens, Greece, and co-principal investigator of the FIDELIO-DKD and FIGARO-DKD Phase III clinical trials. "Building on the existing evidence on finerenone, these subgroup analyses indicate the potential of this novel treatment to improve outcomes in a particularly high-risk population of patients suffering from a combination of type 2 diabetes, chronic kidney disease and atherosclerotic cardiovascular disease, as well as to prevent the occurrence of these outcomes in patients without a history of atherosclerotic cardiovascular disease."

Out of the 13,026 patients included in the FIDELITY full analysis, 5935 (45.6%) had a history of ASCVD at baseline. Over a median follow-up of 3 years, patients with ASCVD versus those without had a higher incidence of the composite CV outcome (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), the outcome of CV death or HHF (IR/100 PY, 4.51 versus 1.92; HR: 2.12; 95% CI 1.88-2.40), and all-cause mortality (IR/100 PY 4.0 vs 2.1; HR: 1.72; 95% CI 1.52-1.94). There was no difference between the groups by history of ASCVD in the composite kidney outcome (IR/100 PY 2.1 vs 2.4; HR: 0.96; 95% CI 0.83-1.10). 

In the prespecified subgroup analyses of FIDELITY, it was observed that finerenone reduced the risk of the composite CV outcome of time to CV death, nonfatal MI, nonfatal stroke or HHF compared with placebo in patients with ASCVD (HR: 0.83; 95% CI 0.74-0.94) and in patients without ASCVD (HR: 0.91; 95% CI 0.78-1.06; P-value for interaction=0.38). Finerenone also reduced the risk of the composite outcome of CV death or HHF compared with placebo, irrespective of a history of ASCVD (with ASCVD, HR: 0.82; 95% CI 0.71-0.94; without ASCVD, HR: 0.86; 95% CI 0.71-1.04; P-value for interaction: 0.68). 

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

In addition, the effect of finerenone on all-cause mortality was not modified by history of ASCVD (with ASCVD, HR: 0.85; 95% CI 0.74-0.99; without ASCVD, HR: 0.95; 95% CI 0.79-1.14; P-value for interaction: 0.38). The safety profile of finerenone was comparable between the groups of patients with and without a history of ASCVD. 

"Patients with chronic kidney disease and type 2 diabetes are at a three times higher risk to die from a cardiovascular event than those with type 2 diabetes alone. 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. "We are delighted to see that finerenone shows cardiovascular and kidney benefits in a broad range of patients with chronic kidney disease and type 2 diabetes, particularly those with atherosclerotic cardiovascular disease, who are at the highest risk of death."

Based on the positive results of the FIDELIO-DKD Phase III study, finerenone was granted marketing authorization in the European Union in February 2022 under the brand name Kerendia to treat adult patients with chronic kidney disease (stage 3 and 4 with albuminuria) associated with type 2 diabetes. In July 2021, Kerendia was approved by the U.S. Food and Drug Administration (FDA) in July 2021. Based on the positive results of both pivotal Phase III studies, FIDELIO-DKD and FIGARO-DKD, Kerendia was approved in March 2022 by the Japanese Ministry of Health, Labour, and Welfare (MHLW). Finerenone has also been submitted for marketing authorization in multiple other countries worldwide and these applications are currently under review.

About Kerendia^™ (finerenone)
Kerendia is a non-steroidal, selective mineralocorticoid receptor (MR) antagonist that has been shown to block harmful effects of MR overactivation. In T2D, MR overactivation contributes to CKD progression and cardiovascular damage which can be driven by metabolic, hemodynamic or inflammatory and fibrotic factors. 

The Phase III study programme with finerenone, FINEOVATE, currently comprises five Phase III studies, FIDELIO-DKD, FIGARO-DKD, FINEARTS-HF, FIND-CKD, and FIONA, as well as the Phase II study CONFIDENCE.

Having randomized more than 13,000 patients with CKD and T2D around the world, the Phase III program with finerenone in CKD and T2D comprises two completed and published studies, evaluating the effect of finerenone versus placebo on top of standard of care on both renal and cardiovascular outcomes. FIDELIO-DKD (FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease) investigated the efficacy and safety of finerenone in comparison to placebo in addition to standard of care on the reduction of kidney failure and kidney disease progression in approximately 5,700 patients with CKD and T2D. 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 and T2D.

FIDELITY (FInerenone in chronic kiDney diseasE and type 2 diabetes: Combined FIDELIO-DKD and FIGARO-DKD Trial programme analYsis), including the FIDELIO-DKD and FIGARO-DKD studies, comprises the largest Phase III cardiorenal outcomes clinical trial program in >13,000 patients with CKD and T2D. The prespecified FIDELITY pooled analysis investigated the efficacy and safety of finerenone across the spectrum of patients with CKD in T2D in reducing the risk of chronic kidney disease progression as well as fatal and nonfatal CV events, and provided insights into the relationship between CKD stage (based on baseline Kidney Disease: Improving Global Outcomes risk categories) and the effects of finerenone on composite cardiovascular and kidney-specific endpoints.

In November 2021, Bayer announced the initiation of FIONA, a multicenter, randomized, double-blind, placebo-controlled Phase III study, to investigate the efficacy, safety and pharmacokinetics/pharmacodynamics (PK/PD) of finerenone, in addition to standard of care, in approximately 200 pediatric patients with chronic kidney disease (CKD) and severely increased proteinuria.

In September 2021, Bayer announced the initiation of the Phase III study FIND-CKD, a multicenter, randomized, double-blind, placebo-controlled Phase III study to investigate the efficacy and safety of finerenone in addition to guideline-directed therapy on the progression of chronic kidney disease (CKD) in more than 1,500 patients with non-diabetic chronic kidney disease etiologies, including hypertension and chronic glomerulonephritis (inflammation of the kidneys).

In June 2020, Bayer announced the initiation of the FINEARTS-HF study, a multicenter, randomized, double-blind, placebo-controlled Phase III study which will investigate finerenone compared to placebo in more than 5,500 patients with symptomatic heart failure (New York Heart Association class II-IV) with preserved ejection fraction, i.e., a left ventricular ejection fraction of ≥40%. 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).

In February 2022, Bayer announced the initiation of the CONFIDENCE study, a Phase II, three-arm study that will investigate simultaneous initial combination therapy with finerenone and the SGLT2 inhibitor empagliflozin, compared with finerenone alone and empagliflozin alone respectively in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). The primary objective of the study is to demonstrate that the simultaneous initiation and combined use of finerenone and empagliflozin is superior to either empagliflozin alone, or finerenone alone, in reducing urine albumin-to-creatinine ratio (UACR).

About Chronic Kidney Disease in Type 2 Diabetes
Chronic kidney disease (CKD) is a common and potentially deadly condition that is widely underrecognized. CKD progresses silently and unpredictably, with many symptoms not appearing until the disease is well-advanced. CKD is one of the most frequent complications arising from diabetes and is also an independent risk factor of cardiovascular disease. Up to 40% of all patients with type 2 diabetes develop chronic kidney disease. Despite guideline-directed therapies, patients with CKD and T2D remain at high risk of CKD progression and cardiovascular events. It is estimated that CKD affects more than 160 million people with T2D worldwide. Chronic kidney disease in type 2 diabetes is the main cause of end stage kidney disease, which requires dialysis or a kidney transplant to stay alive. Patients with chronic kidney disease and type 2 diabetes are three times more likely to die from a cardiovascular-related cause than those with type 2 diabetes alone.

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 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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