Bayer Presents FIDELIO-DKD Phase III Study Cardiovascular Subgroup Analysis of Patients With Chronic Kidney Disease and Type 2 Diabetes
In this pre-specified exploratory subgroup analysis of FIDELIO-DKD study of finerenone, researchers evaluated the secondary composite CV outcomes by patient history of CVD (Interaction p-0.85).
Bayer announced today late-breaking data from a pre-specified exploratory subgroup analysis of the FIDELIO-DKD Phase III study, in which the investigational drug finerenone, compared to placebo, reduced the risk of cardiovascular (CV) outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D), with or without history of cardiovascular disease (CVD).1,2 The findings were presented in a Late-Breaking session today at the American Heart Association’s (AHA) Scientific Sessions 2020, and simultaneously published in Circulation.
“Patients with chronic kidney disease and type 2 diabetes are not only at high risk of progression to kidney failure, they are also exposed to a higher risk of cardiovascular events – and face increased cardiovascular morbidity and mortality,” said Gerasimos Filippatos, M.D., professor of cardiology at the National and Kapodistrian University of Athens, Greece, and co-principal investigator of FIDELIO-DKD. “These new findings for the investigational drug finerenone suggest the potential to reduce the risk of cardiovascular events in patients with chronic kidney disease and type 2 diabetes, with and without a history of cardiovascular disease.”1-5
Recently published FIDELIO-DKD data showed finerenone significantly reduced the risk of the key secondary endpoint, a composite of time to cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for heart failure compared to placebo by 14 percent (HR 0.86 [95 percent CI, 0.75-0.99; p=0.0339]) over a median duration of follow-up of 2.6 years.
In this pre-specified exploratory subgroup analysis of FIDELIO-DKD study of finerenone, researchers evaluated the secondary composite CV outcomes by patient history of CVD (Interaction p-0.85). Of the 2,605 patients with a history of CVD, the composite CV outcome occurred in 17.7 percent of patients in the finerenone group and 20.2 percent of patients in the placebo group (HR 0.85 [95% CI, 0.71–1.01]). For 3,069 patients without a history of CVD, the composite CV outcome occurred in 8.9 percent of patients in the finerenone group and in 10.2 percent of patients in the placebo group (HR 0.86; [95 percent CI, 0.68–1.08]).
“These findings underscore the life-threatening connection between chronic kidney disease and cardiovascular disease. Reducing cardiovascular risk is vitally important for people living with CKD and T2D is one of the many reasons we are pursuing FDA approval for finerenone,” said Joerg Moeller, M.D., Member of the Executive Committee of Bayer AG's Pharmaceutical Division and Head of Research and Development. “FIGARO-DKD, the cardiovascular outcomes study with finerenone, is due to complete in mid-2021, and we eagerly anticipate the new data from that study in the effort to bring a new therapeutic option to patients in need.“
Phase III data from the FIDELIO-DKD study were presented in October at the American Society of Nephrology’s (ASN) Kidney Week 2020, and simultaneously published in the New England Journal of Medicine. Based on these data, Bayer submitted applications for marketing authorization of finerenone in the U.S. and the EU.
About Finerenone
Finerenone (BAY 94-8862) is an investigational, non-steroidal, selective mineralocorticoid receptor antagonist (MRA) that has been shown to reduce many of the harmful effects of mineralocorticoid receptor (MR) overactivation.6 MR overactivation is a major driver of kidney and cardiovascular damage through inflammatory and fibrotic processes.7,8
The Phase III program with finerenone in CKD and T2D enrolled over 13,000 patients across a broad range of disease severity including those with early kidney damage and more advanced stages of kidney disease. It is the largest Phase III clinical trial program to date in CKD and T2D and comprises two studies, FIDELIO-DKD and FIGARO-DKD, which are evaluating the effect of finerenone versus placebo on top of standard of care on both renal and cardiovascular outcomes.1,2
FIDELIO-DKD (FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter, event-driven Phase III study that compared the efficacy and safety of finerenone to placebo in addition to standard of care in reducing the risk of kidney failure and kidney disease progression in approximately 5,700 patients with CKD and T2D enrolled at more than 1,000 sites across 48 countries worldwide. Patients with a history of heart failure with reduced ejection fraction (NYHA II-IV) were excluded. When added to standard of care, which included blood glucose-lowering therapies and a maximum tolerated dose of a renin-angiotensin system (RAS)-blocking therapy such as an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB), finerenone (10 mg or 20 mg orally once daily) significantly reduced the combined risk of time to kidney failure, a sustained decrease in estimated glomerular filtration rate (eGFR) ≥ 40 percent from baseline over a period of at least four weeks, or renal death by 18 percent (HR 0.82 [95 percent CI, 0.73-0.93; p=0.0014]) over a median duration of follow-up of 2.6 years. Finerenone also significantly reduced the risk of the key secondary endpoint, a composite of time to cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for heart failure by 14 percent, compared to placebo (, HR 0.86 [95 percent CI, 0.75-0.99; p=0.0339]) over a median duration of follow-up of 2.6 years.
Overall treatment-emergent adverse events and serious adverse events were similar between groups. The majority of adverse events were mild or moderate. The frequency of serious adverse events was lower in patients treated with finerenone (31.9 percent) compared to placebo (34.3 percent). Overall hyperkalemia-related adverse events occurred more often in patients receiving finerenone compared with placebo (18.3 percent and 9 percent, respectively). Hyperkalemia-related serious adverse events were 1.6 percent and 0.4 percent, respectively and there was no hyperkalemia-related death in either treatment group. Treatment was discontinued due to hyperkalemia in 2.3 percent of patients treated with finerenone compared to 0.9 percent in the placebo group.
FIGARO-DKD (FInerenone in reducinG cArdiovascular moRtality and mOrbidity in Diabetic Kidney Disease) is still ongoing and is investigating 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 across 47 countries including sites in Europe, Japan, China and the U.S.
Bayer also recently 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 symptomatic heart failure (HF) patients (New York Heart Association class II-IV) with a left ventricular ejection fraction of ≥40%. The primary objective of the study is to demonstrate the superiority of finerenone over placebo in reducing the rate of the composite endpoint of CV death and total (first and recurrent) HF events (defined as hospitalizations for HF or urgent HF visits).
About Chronic Kidney Disease in Type 2 Diabetes
Chronic kidney disease is a life-threatening condition that is under-recognized. CKD is one of the most frequent complications arising from diabetes and is also an independent risk factor of CVD.4 Approximately 40 percent of all patients with T2D develop CKD.3 Despite guideline-directed therapies, patients with CKD and T2D remain at high risk of CKD progression and CV events.3,10 In 2013, diabetes led to more than 51,000 new cases of kidney failure in the U.S.11 CKD in T2D is the main cause of end-stage kidney disease12 and kidney failure, and at advanced stages, patients may need dialysis or a kidney transplant to stay alive.13 Mineralocorticoid receptor overactivation is known to trigger detrimental processes (e.g., inflammation and fibrosis) in the kidneys and heart in patients with CKD and T2D.7
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 benefit people by supporting efforts to overcome the major challenges presented by a growing and aging global population. At the same time, the Group aims to increase its earning power and create value through innovation and growth. Bayer is committed to the principles of sustainable development, and the Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2019, the Group employed around 104,000 people and had sales of 43.5 billion euros. Capital expenditures amounted to 2.9 billion euros, R&D expenses to 5.3 billion euros. For more information, go to www.bayer.us.
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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.
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1 Data on file
2 Bakris, GL., et al. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. N Engl J Med. 2020 Oct 23. DOI: 10.1056/NEJMoa2025845.
3 Alicic RZ, et al. Diabetic kidney disease challenges, progress, and possibilities. Clin J Am Soc Nephrol. 2017;12:2032-2045.
4 Anders H J, et al; Nat Rev Nephro. 2018;361-377.
5 Afkarian M et al; J Am Soc Nephro. 2013;24:302-308.
6 Kolkhof et al. Steroidal and novel non-steroidal mineralocorticoid receptor antagonists in heart failure and cardiorenal diseases: comparison at bench and bedside. Handb Exp Pharmacol. 2017;243:271-305.
7 Bauersachs J, et al. Mineralocorticoid receptor activation and mineralocorticoid receptor antagonist treatment in cardiac and renal diseases. Hypertension. 2015 Feb;65(2):257-63.
8 Buonafine, M, et al. Mineralocorticoid Receptor and Cardiovascular Disease. Am J Hypertens. 2018;31(11):1165-1174.
9 International Diabetes Foundation. IDF diabetes atlas 8th edition 2017. Accessed October 5, 2020. https://www.diabetesatlas.org/en.
10 Pálsson, R, et al. Cardiovascular Complications of Diabetic Kidney Disease. Adv Chronic Kidney Dis. 2014;21(3): 273–280.
11 National Kidney Foundation. Diabetes and Chronic Kidney Disease. Accessed October 6, 2020. https://www.kidney.org/news/newsroom/factsheets/Diabetes-And-CKD.
12 Doshi SM et al. Diagnosis and management of type 2 diabetic kidney disease. Clin J Am Soc Nephrol. 2017 Aug 7;12(8):1366-1373.
13 KidneyFund.org. Kidney Failure. Accessed October 6, 2020. https://www.kidneyfund.org/kidney-disease/kidney-failure.
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