Bayer announced today late-breaking data from prespecified exploratory subgroup analyses of FIDELITY, a prespecified pooled analysis of the Phase III FIDELIO-DKD and FIGARO-DKD trials. These analyses investigated KERENDIA® (finerenone) versus placebo on composite cardiovascular (CV) and kidney outcomes in patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D), with and without a history of atherosclerotic cardiovascular disease (ASCVD).1 The subgroup analyses were presented today at the American College of Cardiology’s 71st Annual Scientific Session (ACC.22).
Out of the 13,026 patients included in the FIDELITY full analysis, 5935 (45.6%) had a history of ASCVD at baseline.1 Over a median follow-up of 3 years, patients with ASCVD versus those without had the following composite CV outcome of time to CV death, nonfatal myocardial infarction (MI), nonfatal stroke and hospitalization for heart failure (HHF; 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), composite outcome of time to CV death or HHF (IR/100 PY, 4.51 vs. 1.92; HR: 2.12; 95% CI 1.88–2.40) and composite kidney outcome (IR/100 PY 2.1 vs. 2.4; HR: 0.96; 95% CI 0.83–1.10).1
KERENDIA was approved in the United States on July 9, 2021, based on the results of FIDELIO-DKD, to reduce the risk of sustained estimated glomerular filtration rate (eGFR) decline, end-stage kidney disease, CV death, nonfatal MI and HHF in adult patients with CKD associated with T2D.3 The KERENDIA label contains a Warning and Precaution that KERENDIA can cause hyperkalemia.3 For more information, see “Important Safety Information” and the FIDELIO-DKD study results below.
The prespecified exploratory subgroup analyses of FIDELITY showed that the treatment effect of finerenone, when compared to placebo, was consistent in patients with or without history of ASCVD for the composite CV outcome of time to CV death, nonfatal MI, nonfatal stroke or HHF (HR: 0.83; 95% CI 0.74–0.94; HR: 0.91; 95% CI 0.78–1.06; P-value for interaction=0.38, respectively). The treatment effect, when compared to placebo, was also consistent in patients with or without history of ASCVD for the composite outcome of CV death or HHF (HR: 0.82; 95% CI 0.71–0.94; HR: 0.86; 95% CI 0.71–1.04; P-value for interaction: 0.68, respectively).1
Regarding the effects of finerenone on the composite kidney outcome of time to kidney failure, sustained ≥57% decrease in eGFR or kidney-related death, the treatment effect was consistent in patients with or without a history of ASCVD (HR: 0.71; 95% CI 0.57–0.88; HR: 0.81; 95% CI 0.68–0.97; P-value for interaction: 0.33, respectively).1
“In patients with chronic kidney disease associated with type 2 diabetes, cardiovascular complications are among the most frequent causes of death.4,5 However, there is limited data on how the risk of cardiovascular events could be reduced in these patients,” said Javed Butler, MD, MPH, MBA, president of the Baylor Scott & White Research Institute and senior vice president for Baylor Scott & White Health, and distinguished professor of medicine at the University of Mississippi. “These subgroup analyses investigate outcomes in patients suffering from chronic kidney disease associated with type 2 diabetes, with or without a history of atherosclerotic cardiovascular disease. The analyses show us that in both cases, there’s a need to treat patients irrespective of where they are on the atherosclerotic cardiovascular disease spectrum.”
“Patients with chronic kidney disease and type 2 diabetes are three times more likely to die from a cardiovascular event than those with type 2 diabetes alone.6 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.5 “The latest prespecified subgroup analyses of FIDELITY add to our growing body of data on the renal and CV outcomes of finerenone in adults with chronic kidney disease associated with type 2 diabetes.”
About KERENDIA (finerenone)
- 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)3
IMPORTANT SAFETY INFORMATION
- Concomitant use with strong CYP3A4 inhibitors3
- Patients with adrenal insufficiency3
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/L3 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 potassium3
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%)3
- Strong CYP3A4 Inhibitors: Concomitant use of KERENDIA with strong CYP3A4 inhibitors is contraindicated. Avoid concomitant intake of grapefruit or grapefruit juice3
- 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 appropriate3
- Strong and Moderate CYP3A4 Inducers: Avoid concomitant use of KERENDIA with strong or moderate CYP3A4 inducers3
USE IN SPECIFIC POPULATIONS:
- Lactation: Avoid breastfeeding during treatment with KERENDIA and for 1 day after treatment3
- 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)3
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 (SoC) on both renal and CV 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 m2.3,8 The trial excluded patients with known significant nondiabetic kidney disease and a clinical diagnosis of chronic heart failure with reduced ejection fraction and persistent symptoms (NYHA class II to IV).3 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).3 A total of 5,674 patients were randomized to receive finerenone (N=2,833) or placebo (N=2,841) and were followed for a median of 2.6 years.3 The mean age of the study population was 66 years, and 70% of patients were male.3 The trial population was 63% white, 25% Asian, and 5% Black.3
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]).3 The treatment effect reflected a reduction in a sustained decline in eGFR of ≥40% and progression to kidney failure.3 There were few renal deaths during the trial.3
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]).3 The treatment effect reflected a reduction in cardiovascular death, nonfatal myocardial infarction and hospitalization for heart failure.3
The most frequently reported adverse reaction was hyperkalemia (18.3% KERENDIA vs. 9% placebo).3 Hospitalization due to hyperkalemia for the KERENDIA group was 1.4% versus 0.3% in the placebo group.3 Hyperkalemia led to permanent discontinuation of treatment in 2.3% of patients receiving KERENDIA versus 0.9% of patients receiving placebo.3
FIGARO-DKD (FInerenone in reducinG cArdiovascular moRtality and mOrbidity in Diabetic Kidney Disease), a randomized, double-blind, placebo-controlled trial, randomly assigned 7,352 participants to finerenone (N=3686) or placebo (N=3666) on top of standard of care, including a maximum tolerated labeled dose of ACEis or ARBs.9 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/1.73m2.9 This data is under review with the FDA.
KERENDIA significantly reduced the risk of the composite primary endpoint of time to first occurrence of 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 ACEi or ARB in adults with CKD associated with T2D.9 The reduction in the CV composite outcome was primarily driven by hospitalization due to heart failure.9
The incidence of the 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.9 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.9
Overall, hyperkalemia-related adverse events occurred more often in patients receiving finerenone compared with placebo (10.8% and 5.3%, respectively).9 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. Treatment was discontinued due to hyperkalemia in 1.2% of patients treated with finerenone compared to 0.4% in the placebo group.9
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 (NYHA class II-IV) with a left ventricular ejection fraction of ≥40%.10 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 events (defined as hospitalizations for heart failure or urgent heart failure visits).10
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.6 CKD is a serious and progressive condition that is generally underrecognized.11 CKD is a frequent complication arising from T2D and is also an independent risk factor of CV disease.12-14 Approximately 40% of all patients with T2D develop CKD.14 Despite guideline-directed therapies, patients with CKD associated with T2D remain at high risk of CKD progression and CV events.12,13,15,16 T2D is the leading cause of end-stage kidney disease, which requires dialysis or a kidney transplant to stay alive.17-19
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.