Bayer Submits Supplemental New Drug Application to U.S. FDA Seeking New Indication for KERENDIA® (finerenone) in Patients with Heart Failure with Left Ventricular Ejection[...]

January 10, 2025

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WHIPPANY, N.J.--(BUSINESS WIRE)-- Bayer today announced the submission of a supplemental new drug application (sNDA) to the U.S. Food and Drug Administration (FDA) for KERENDIA^® (finerenone) for the treatment of patients with heart failure (HF) with a left ventricular ejection fraction (LVEF) of ≥40%.

The submission is based on positive results from the Phase III FINEARTS-HF trial that showed finerenone achieved a statistically significant reduction of the composite of cardiovascular death and total (first and recurrent) HF events, defined as either an unplanned hospitalization for HF or an urgent HF visit, by 16% in patients with HF and a LVEF of ≥40% compared to placebo in addition to a patients' prescribed treatment regimen. Serious adverse events were comparable between treatment groups, occurring in 38.7% (1,157/2,993) of the finerenone group and 40.5% (1,213/2,993) of the placebo group.¹ The results were presented at the 2024 European Society of Cardiology (ESC) Congress and published in The New England Journal of Medicine .

KERENDIA is the first non-steroidal, selective mineralocorticoid receptor antagonist (nsMRA) to meet a primary cardiovascular endpoint in a Phase III study investigating patients with HF with mildly reduced or preserved ejection fraction (LVEF ≥40%).

KERENDIA already has established cardiovascular benefit (reduction in hospitalization for HF, CV death and non-fatal MI) in adults with chronic kidney disease (CKD) in type 2 diabetes (T2D); the data from the FINEARTS-HF trial provide positive results in a different patient population not limited to CKD in T2D- patients diagnosed with HF (LVEF ≥40%).¹

"More than half of the approximately 6.7 million adults in the U.S. diagnosed with heart failure have an LVEF ≥40%, but there are limited guideline-directed treatment options available for these patients," said Alanna Morris, M.D., MSc, Senior Medical Director of U.S. Medical Affairs, Bayer.^3,4 "If approved, Kerendia could serve as a new pillar of therapy in this disease and improve cardiovascular outcomes for patients with high unmet medical need."

HF is a complex clinical syndrome with symptoms and signs that result from any structural or functional impairment of ventricular filling or ejection of blood.⁵ Approximately 6.7 million adults in the U.S. live with HF, of which about 55% have a LVEF ≥40%.³ Despite the high prevalence, there are limited guideline-directed medical treatment options for patients with HF with LVEF ≥40%.⁴ This patient group is often balancing multiple comorbidities, such as obesity, diabetes, hypertension and CKD.⁵

About FINEARTS-HF⁶

The FINEARTS-HF trial, a randomized, double-blind, placebo-controlled, multicenter, event-driven Phase III trial investigated the efficacy and safety of finerenone for the reduction of risk of cardiovascular death and heart failure (HF) events in patients with a diagnosis of symptomatic heart failure (New York Heart Association class II-IV) with a left ventricular ejection fraction (LVEF) of ≥40%, measured by local imaging measurement within the last 12 months as well as receiving diuretic treatment for at least 30 days prior to randomization. The primary endpoint of FINEARTS-HF was the composite of cardiovascular death and total (first and recurrent) HF events, defined as hospitalizations for HF or urgent HF visits. Approximately 6,000 patients were randomized to receive finerenone or placebo once daily for up to 42 months.

Results from FINEARTS-HF, which were published in The New England Journal of Medicine and presented at the European Society of Cardiology (ESC) Congress earlier this year, showed the trial met its primary endpoint, achieving a 16% (rate ratio, 0.84; 95% confidence interval [CI], 0.74 to 0.95; P = 0.007) relative risk reduction of the composite primary endpoint of cardiovascular death and total (first and recurrent) heart failure (HF) events (defined as hospitalizations for HF or urgent HF visits) compared to placebo in addition to a patients' prescribed treatment regimen.¹

In the FINEARTS-HF trial, no new safety signals were identified compared with those seen in previous studies with the compound.¹ Serious adverse events were comparable between treatment groups, occurring in 38.7% (1,157/2,993) of the finerenone group and 40.5% (1,213/2,993) of the placebo group. Discontinuation of the trial drug for reasons other than death was similar between groups, with 20.4% (611/2,993) in the finerenone group and 20.6% (616/2,993) in the placebo group¹

Increases in creatinine and potassium levels were more frequent in patients receiving finerenone compared to placebo, with investigator-reported hyperkalemia in 9.7% (289/2,993) of finerenone-treated patients versus 4.2% (125/2,993) in the placebo group. Serum potassium levels >6 mmol/L were observed in 3% (n=86) of the finerenone group compared to 1.4% (41/2,993) in the placebo group. Hyperkalemia was more common with finerenone; it led to hospitalization in 0.5% [16/2,993] in the finerenone group versus 0.2% [6/2,993] in the placebo group, and no cases resulted in death.¹

With overall more than 15,000 patients, the MOONRAKER clinical trial program with finerenone, including FINEARTS-HF, is one of the largest HF trial programs to date, and aims to establish a comprehensive body of evidence for finerenone across a broad spectrum of patients and clinical settings.⁷

About KERENDIA^® (finerenone)²

KERENDIA is a non-steroidal mineralocorticoid receptor antagonist (nsMRA) and was approved by the U.S. Food and Drug Administration (FDA) in July 2021 to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, non-fatal myocardial infarction (MI), and hospitalization for HF in adult patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D).

In adults with CKD associated with T2D, KERENDIA has been recommended to improve cardiovascular outcomes and reduce the risk of CKD progression by the American Diabetes Association (ADA)⁸ and reduce CV and kidney failure risk on top of standard of care by the European Society of Cardiology (ESC).⁹

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 click here for full Prescribing Information for KERENDIA.

About Bayer's Commitment in Cardiovascular and Kidney Diseases

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 several 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.

Bayer is investigating potential treatment approaches for areas of high unmet medical need. Currently, Bayer is investigating nine CVR-related projects in different stages of development, including heart failure (HF) and non-diabetic chronic kidney disease (CKD).¹⁰

About Bayer

Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. In line with its mission, "Health for all, Hunger for none," the company's 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 2023, the Group employed approximately 100,000 people and had sales of 47.6 billion euros. R&D expenses before special items amounted to 5.8 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. Solomon S, et al. Finerenone in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. New England Journal of Medicine. https://www.nejm.org/doi/full/10.1056/NEJMoa2407107. Accessed November 20, 2024.
2. Bayer Pharmaceuticals. Kerendia (finerenone) [package insert]. U.S. Food and Drug Administration. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215341s000lbl.pdf. Accessed November 20, 2024.
3. Bozkurt A, et al. Heart Failure Epidemiology and Outcomes Statistics: A Report of the Heart Failure Society of America. J Card Fail. 2023; Oct;29(10):1412-1451. doi: 10.1016/j.cardfail.2023.07.006. Epub 2023 Sep 26. PMID: 37797885; PMCID: PMC10864030.
4. Desai N, et al. Heart failure with mildly reduced and preserved ejection fraction: A review of disease burden and remaining unmet medical needs within a new treatment landscape. Heart Fail Rev. 2024;29(3):631-662. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11035416/. Accessed November 20, 2024.
5. Heidenreich P, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2023. https://pubmed.ncbi.nlm.nih.gov/35379503. Accessed November 20, 2024
6. Trial to Evaluate the Efficacy (Effect on Disease) and Safety of Finerenone on Morbidity (Events Indicating Disease Worsening) & Mortality (Death Rate) in Participants With Heart Failure and Left Ventricular Ejection Fraction (Proportion of Blood Expelled Per Heart Stroke) Greater or Equal to 40% (FINEARTS-HF). Clinical trial registration No. NCT04435626. https://clinicaltrials.gov/study/NCT04435626. Accessed November 20, 2024.
7. Data on file.
8. American Diabetes Association (Section 10: Cardiovascular disease and risk management: standards of care in diabetes-2024.). Diabetes Care. 2024;47(Suppl. 1):S179-S218. doi:10.2337/dc24-S010.
9. Marx N, et al. ESC Guidelines for the management of cardiovascular disease in patients with diabetes. Eur Heart J . 2023;44(39):4043-4140. doi:10.1093/eurheartj/ehad192
10. Bayer Pharmaceuticals. Development Pipeline. U.S. https://www.bayer.com/en/pharma/development-pipeline. Accessed November 10, 2024.

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Source: Bayer