Source – Bayer
On June 22, 2023, Bayer Initiates Phase III Trial of Finerenone, Bayer announced the initiation of a Phase III clinical trial called FINE-ONE. This global study aims to evaluate the effectiveness and safety of finerenone compared to a placebo in adults diagnosed with both chronic kidney disease (CKD) and type 1 diabetes (T1D). The primary objective of the trial is to demonstrate that finerenone is superior to the placebo in reducing the urine albumin to creatinine ratio (UACR) over a period of 6 months.
Finerenone, marketed as KerendiaTM or FirialtaTM in certain countries, is already approved for the treatment of CKD associated with type 2 diabetes (T2D) in over 70 countries worldwide. While T2D is primarily a chronic metabolic disease, type 1 diabetes is characterized by the destruction of insulin-secreting cells in the pancreas, often attributed to genetic and environmental factors. Although T1D typically develops during childhood or adolescence, it can also manifest in adults. CKD affects up to 40% of individuals with T1D. The prevalence of CKD resulting from T1D has increased by 58.2% from 1990 to 2007 and by 21.7% from 2007 to 2017.
In people with T1D, CKD typically involves an increased excretion rate of urinary albumin, which is an initial sign of kidney damage. This can progress to macroalbuminuria and a decline in estimated glomerular filtration rate (eGFR) in later stages. Despite recommended therapies to control hyperglycemia, hypertension, and albuminuria in individuals with type 1 diabetes, there remains a significant residual risk, with up to a quarter of patients progressing to end-stage kidney disease. CKD is 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. 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.”
– Sanjoy Dutta, PhD, Chief Scientific Officer of JDRF, the leading global type 1 diabetes research and advocacy organization
“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. 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.”
– Dr. Christian Rommel, member of the Executive Committee of Bayer AG’s Pharmaceutical Division and Global Head of Research and Development
As the Bayer Initiates Phase III Trial of Finerenone, The planned FINE-ONE study will investigate the efficacy of finerenone compared to a placebo in addition to standard of care in approximately 220 adults diagnosed with both CKD and T1D. Participants will be randomly assigned in a 1:1 ratio to receive either finerenone or the placebo alongside standard of care, which includes a renin-angiotensin system (RAS)-blocking therapy such as an angiotensin-converting enzyme inhibitor (ACE) or an angiotensin II receptor blocker (ARB).
The effectiveness of finerenone in delaying the progression of kidney disease will be evaluated based on a reduction in albuminuria, with the primary endpoint being the change in urine albumin-to-creatinine ratio (UACR) from baseline over a 6-month period compared to the placebo. UACR will serve as a marker to demonstrate the delay in kidney disease progression. In a pre-specified analysis of the pivotal Phase III FIDELIO-DKD and FIGARO-DKD studies, collectively known as FIDELITY, involving people with CKD associated with type 2 diabetes, finerenone demonstrated a consistent and sustained reduction in UACR of over 30% compared to the placebo. The analysis also revealed that finerenone reduced the risk of CKD progression as well as fatal and nonfatal cardiovascular events.
Secondary endpoints of the study will focus on assessing the safety of finerenone and will include monitoring treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), and hyperkalemia (an adverse event of special interest).
The overactivation of the mineralocorticoid receptor (MR) contributes to the progression of CKD and cardiovascular damage, which can be driven by metabolic, hemodynamic, inflammatory, and fibrotic factors. Finerenone selectively binds to the MR receptor, blocking its harmful effects caused by overactivation. This mechanism of action allows finerenone to provide protection against CKD and related complications.
