Bayer to start Phase III study with finerenone in adults with chronic kidney disease and type 1 diabetes.

The primary objective of the study is to demonstrate superiority of finerenone over placebo in reducing urine albumin to creatinine ratio (UACR) over 6 months.

Finerenone is marketed as Kerendia or, in some countries, as Firialta, and approved for the treatment of chronic kidney disease associated with type 2 diabetes (T2D) in more than 70 countries worldwide. In contrast to T2D, which is primarily a chronic metabolic disease, in type 1 diabetes the insulin secreting cells of the pancreas are destroyed, which 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. CKD affects up to 40% of people with T1D. The prevalence of CKD due to T1D increased by 58.2% from 1990 to 2007 and by 21.7% from 2007 to 2017.

"Apart from diabetes and hypertension management, there are currently very 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 to reduce the risks of end-stage kidney disease and cardiovascular events. New strategies are needed to slow the 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 a first sign of kidney damage and may progress to macroalbuminuria and decrease in eGFR in later stages. Despite guideline-recommended therapies to control hyperglycemia, hypertension, and albuminuria in people with type 1 diabetes, residual risk remains high with up to a quarter progressing to end-stage-kidney-disease and CKD being a leading cause of mortality in T1D.

"Despite the toll that long-term kidney complications take on people with T1D, the research conducted to address the high residual risk of kidney disease progression in those living with T1D 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. "JDRF is thrilled that Bayer is pursuing a pivotal clinical trial evaluating finerenone’s ability to improve kidney outcomes in people with CKD associated with T1D with the goal of submission to regulatory agencies for consideration. JDRF is committed to collaborating with Bayer to help this critical trial succeed."

"For almost thirty years, there has been no innovative 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 these individuals," said Dr. Christian Rommel, member of the Executive Committee of Bayer AG’s Pharmaceutical Division and Global Head of Research and Development. "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 expect that finerenone will also reduce CKD progression in adults with T1D."

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 or placebo in addition to standard of care, consisting of a renin-angiotensin system (RAS)-blocking therapy such as an angiotensin-converting enzyme inhibitor (ACE) or an angiotensin II receptor blocker (ARB). The efficacy of finerenone in delaying kidney disease progression in the FINE-ONE study will be demonstrated based on a reduction of albuminuria, with the primary endpoint being a change in urine albumin-to-creatinine ratio (UACR) from baseline (ratio to baseline) over 6 months compared to placebo. UACR is planned to be used as a marker to demonstrate the delay of kidney disease progression. In the prespecified FIDELITY pooled analysis of the pivotal Phase III FIDELIO-DKD and FIGARO-DKD studies in people with chronic kidney disease associated with type 2 diabetes, finerenone reduced the risk of chronic kidney disease progression as well as fatal and nonfatal CV events, and also showed a consistent and sustained reduction in UACR by more than 30% versus placebo. Secondary endpoints 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).

Mineralocorticoid receptor (MR) overactivation contributes to CKD progression and CV damage which can be driven by metabolic, hemodynamic, or inflammatory and fibrotic factors. Finerenone offers protection as it selectively binds to the MR receptor, blocking harmful effects of MR overactivation.

The Phase III study program with finerenone , FINEOVATE, currently comprises six Phase III studies, FIDELIO-DKD, FIGARO-DKD, FINEARTS-HF, FIND-CKD, FIONA, and FINE-ONE, as well as the Phase II study CONFIDENCE.FIDELIO-DKD and FIGARO-DKD, the two completed and published Phase III studies with finerenone in CKD and T2D, randomized more than 13,000 people with CKD and T2D worldwide and evaluated the effect of finerenone versus placebo on top of standard of care on both renal and cardiovascular outcomes..