WHIPPANY, N.J.--(BUSINESS WIRE)-- Bayer announced today the initiation of FINE-ONE, a global, multicenter, randomized, placebo-controlled, double-blind, parallel-group Phase III study to evaluate the efficacy and safety of a new investigational use of finerenone versus placebo in adults with chronic kidney disease (CKD) and type 1 diabetes (T1D). The primary objective of the study is to demonstrate efficacy of finerenone over placebo in reducing urine albumin to creatinine ratio (UACR) over 6 months.

Finerenone is marketed as Kerendia^® and approved for the treatment of adults with CKD associated with type 2 diabetes (T2D) in more than 70 countries worldwide, including the United States. CKD affects up to 40% of people with T1D. ² The prevalence of CKD due to T1D increased by 58.2% from 1990 to 2007 and by 21.7% from 2007 to 2017.⁴

“Apart from diabetes and hypertension management, there are currently limited treatment options to slow kidney disease progression in people with chronic kidney disease and type 1 diabetes,” said Janet McGill, Professor of Medicine in the Division of Endocrinology, Metabolism and Lipid Research at Washington University, and Co-chair of the study’s Executive Committee. “Despite progress in risk reduction in type 2 diabetes, chronic kidney disease in type 1 diabetes remains understudied, leaving a huge unmet need for this population. New strategies are needed to slow their rate of decline in kidney function, which is why this important study comes as welcome news for people with chronic kidney disease and type 1 diabetes and the clinical community alike.”

The clinical course of CKD in people with T1D is characterized by an increased urinary albumin excretion rate, which is the first sign of kidney damage and may progress to macroalbuminuria and decrease in estimated glomerular filtration rate (eGFR) in later stages.⁵ Despite guideline-recommended therapies to control hyperglycemia, hypertension, and albuminuria in patients with T1D, residual risk remains high with up to a quarter progressing to end-stage kidney disease. ^3,6

“Despite the toll that long-term kidney complications take on people with type 1 diabetes, the research conducted to address the high residual risk of kidney disease progression in those living with type 1 diabetes and chronic kidney disease is extremely scarce,” said Sanjoy Dutta, PhD, Chief Scientific Officer of JDRF, the leading global type 1 diabetes research and advocacy organization.⁷ “JDRF is thrilled that Bayer is pursuing a pivotal clinical trial investigating finerenone in adults with CKD associated with type 1 diabetes with the goal of submission to regulatory agencies for consideration. JDRF is committed to collaborating to help this critical trial succeed.”

“For almost 30 years, there has been no new treatment approved to address the high risk of kidney disease progression in adults with chronic kidney disease and type 1 diabetes. We are excited about the prospect to be able to help adults with chronic kidney disease and type 1 diabetes,” said Robert Perkins, MD, MPH, FACP, Vice President, US Medical Affairs/Renal. “Given the shared underlying cause of chronic kidney disease in both types of diabetes, the strong association of albuminuria with kidney disease progression and the robust body of evidence of efficacy of finerenone in individuals with CKD and type 2 diabetes, we are hopeful about the potential of finerenone in adults with CKD and type 1 diabetes.”

The planned study will investigate finerenone compared to placebo in addition to standard of care in approximately 220 adults with CKD and T1D. Individuals will be randomized in a 1:1 ratio to receive either finerenone (10 mg or 20 mg once daily depending on their eGFR level) or placebo in addition to standard of care, consisting of a renin-angiotensin system (RAS)-blocking therapy such as an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin II receptor blocker (ARB). The efficacy of finerenone in delaying kidney disease progression in the FINE-ONE study will be evaluated based on a reduction of albuminuria, with the primary endpoint being a change in UACR from baseline (ratio to baseline) over 6 months compared to placebo. UACR is planned to be used as a marker for the delay of kidney disease progression. Secondary endpoints will assess the safety of finerenone and include the number of individuals with treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs) and hyperkalemia (adverse event of special interest).

About Kerendia^® (finerenone)
Kerendia is a non-steroidal mineralocorticoid receptor antagonist (MRA) and was approved by the FDA in July 2021 to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, non-fatal myocardial infarction, and hospitalization for heart failure in adult patients with CKD associated with T2D.

Kerendia was studied in the largest CKD clinical trial program FIDELIO-DKD (Finerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease) and FIGARO-DKD (Finerenone in reducinG cArdiovascular moRtality and mOrbidity in Diabetic Kidney Disease) across a broad range of CKD severity in adults with CKD associated with T2D. In the finerenone Phase III program for CKD associated with T2D with over 13,000 people, FIDELIO-DKD and FIGARO-DKD showed finerenone reduced the risk of chronic kidney disease progression. Based on data from the clinical trial program, Kerendia has been recommended for adults with CKD associated with T2D in several major treatment guidelines, including the American Diabetes Association^® (ADA), the American Association of Clinical Endocrinology^®, and the Kidney Disease: Improving Global Outcomes^® (KDIGO) Foundation as well as the ADA/KDIGO Consensus Statement.

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% vs 6.9%), hypotension (4.6% vs 3.9%), and hyponatremia (1.3% vs 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 read the Prescribing Information for KERENDIA.

About Chronic Kidney Disease in Type 1 Diabetes
T1D is a chronic autoimmune disorder characterized by destruction of pancreatic beta cells leading to insulin deficiency and requiring lifelong insulin treatment.⁸ Among the U.S. population overall, crude estimates for 2018 indicated that 1.4 million adults aged 20 years or older (or 5.2% of all US adults with diagnosed diabetes), reported both having T1D and using insulin.⁹

In contrast to T2D, which is primarily a chronic metabolic disease, T1D is deemed to be attributable to factors such as genetics and environmental triggers. While T1D usually appears during childhood or adolescence, it can also develop in adults.¹⁰

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.¹¹

CKD affects up to 40% of people with T1D and 25% of those progress to end-stage renal disease (ESRD).^2,3 In a systematic analysis for the Global Burden of Disease study, it was reported that the prevalence of CKD due to T1D had increased by 58.2% from 1990 to 2007 and by 21.7% from 2007 to 2017. The 2017 global prevalence of CKD due to T1D was an estimated 32.5 per 100,000 individuals.⁴

The clinical course of CKD in patients with T1D is characterized by an increased urinary albumin excretion rate, which is the first sign of kidney damage and may progress to macroalbuminuria and decrease in eGFR in later stages.⁷ The treatment of T1D consists of insulin treatment to control hyperglycemia. In patients with T1D, blood glucose intervention targeting HbA1c levels ≤7% can slow onset and progression of kidney disease.³ Despite guideline-recommended treatment with ACEis and ARBs, residual risk remains high in patients with CKD and T1D, with up to a quarter progressing to end-stage kidney disease and CKD being a leading cause of mortality in T1D.³

About Bayer’s Commitment in Cardiovascular and Kidney Diseases
A leader in the cardiovascular (CV) space, 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 a number of 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 focused on advancing new treatment approaches for areas of high unmet medical need in CV and kidney diseases by identifying resources and programs aimed at better understanding the real-world management of CKD, expanding screening and early care management for CKD, aligning with and supporting groups and institutions that share the common goals of improving health outcomes, promoting health literacy and education and promoting research and initiatives that represent the diversity required to address the needs of all patients.

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 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 2022, the Group employed around 101,000 people and had sales of 50.7 billion euros. R&D expenses before special items amounted to 6.2 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 Fleming TR, et al. Innovations in Pediatric Therapeutics Development: Principles for the Use of Bridging Biomarkers in Pediatric Extrapolation. Ther Innov Regul Sci. 2023 Jan;57(1):109-120. https://pubmed.ncbi.nlm.nih.gov/36057747/.
² Costacou T. and Orchard T. Cumulative Kidney Complication Risk by 50 Years of Type 1 Diabetes: The Effects of Sex, Age, and Calendar Year at Onset. Diabetes Care. 2018;41:426–433. https://doi.org/10.2337/dc17-1118.
³ Barkis G. and Molitch M. Are All Patients With Type 1 Diabetes Destined for Dialysis if They Live Long Enough? Probably Not. Diabetes Care. 2018;41:389-390. https://doi.org/10.2337/dci17-0047.
⁴ GBD Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018 Nov 10;392(10159):1789-858.
⁵ Groop PH, et al. The presence and severity of chronic kidney disease predicts all-cause mortality in type 1 diabetes. Diabetes. 2009 Jul;58(7):1651-8. doi: 10.2337/db08-1543.
⁶ Bjornstad P, Cherney D, Maahs DM. Early diabetic nephropathy in type 1 diabetes: new insights. Curr Opin Endocrinol Diabetes Obes. 2014 Aug;21(4):279-86.
⁷ Alicic R Z, et al; Clin J Am Soc Nephrol 2017;12:2032–2045.
⁸ Thomas NJ, Jones SE, Weedon MN, Shields BM, Oram RA, Hattersley AT. Frequency and phenotype of type 1 diabetes in the first six decades of life: a cross-sectional, genetically stratified survival analysis from UK Biobank. Lancet Diabetes Endocrinol. 2018 Feb;6(2):122-9.
⁹ National Diabetes Statistics Report 2020. Centers for Disease Control and Prevention. 2020. Available at: https://www.cdc.gov/diabetes/data/statistics-report/index.html [Last accessed: June 2023].
¹⁰ What is Type 1 Diabetes? Centers for Disease Control and Prevention. March 2022.
¹¹ Zhong J, et al. A perspective on chronic kidney disease progression. American Journal of Physiology-Renal Physiology. 2017. 312(3), F375-F384.

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