Bayer HealthCare has announced the expansion of the clinical development programme for its oral non-steroidal mineralocorticoid receptor antagonist finerenone (BAY 94-8862) with three Phase III studies. The studies will investigate the efficacy and safety of finerenone in patients with diabetic kidney disease, and in patients with chronic heart failure, with the first patients expected to be enrolled by the year-end.
It is estimated that more than seven million people in the US suffer from diabetic kidney disease. Diabetic kidney disease is a common complication of diabetes and the most frequent cause of end-stage renal disease (ESRD) in Western countries. Diabetes causes more than 40% of new cases of ESRD. More than five million people in the US suffer from chronic heart failure, and about half of people who develop heart failure die within five years of diagnosis.
“The data we have seen for finerenone to date across the clinical development programme make us very confident to move finerenone forward into Phase III across two important indications of high unmet medical need,” said Dr Joerg Moeller, Member of the Bayer HealthCare Executive Committee and Head of Global Development.
The initiation of the Phase III studies FIGARO-DKD and FIDELIO-DKD in diabetic kidney disease is based on data from the Phase IIb ARTS-DN study (NCT01874431)(iv), which was presented at the World Congress of Nephrology (WCN) in March this year. ARTS-DN included 823 patients with type 2 diabetes and the clinical diagnosis of diabetic nephropathy from 23 countries, who were treated for 90 days.
The addition of once-daily oral finerenone to renin-angiotensin system (RAS)-blocking therapy resulted in a statistically significant reduction in change from baseline to day 90 in urine albumin-to-creatinine ratio (UACR) compared to placebo with the four highest doses of finerenone. The incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) were comparable between all finerenone treatment groups and standard therapy. The duration of the study did not allow assessment of the long-term effects of finerenone on renal function or cardiovascular outcomes.
The Phase III programme in Diabetic Kidney Disease (DKD) comprises two studies. FIGARO-DKD will investigate finerenone versus placebo in 6,400 patients with the clinical diagnosis of diabetic kidney disease mainly comprising patients with high albuminuria (previously known as ‘micro-albuminuria,’ defined as 300 mg/g > UACR >/= 30mg/g) while FIDELIO-DKD will investigate finerenone in comparison to placebo in 4800 patients with the clinical diagnosis of diabetic kidney disease mainly comprising of patients with very high albuminuria (previously known as ‘macro-albuminuria,’ defined as UACR >/= 300mg/g). Both studies will be conducted in about 40 countries including Europe, Japan, China and the US. Patients will receive finerenone or placebo on top of current standard of care, which includes RAS-blocking therapy such as angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs).
The initiation of the Phase III FINESSE-HF study in chronic heart failure is based on data from the exploratory Phase IIb ARTS-HF study (NCT01807221)(v), which was presented today in a Hot Line Session at ESC Congress Congress 2015 in London. ARTS-HF investigated the effects of different finerenone dosages compared to eplerenone in patients who presented in emergency departments with worsening chronic heart failure with reduced ejection fraction (HFrEF) and type 2 diabetes mellitus and/or chronic kidney disease.
Finerenone showed a reduction of surrogate marker N-terminal prohormone B-type natriuretic peptide (NT-proBNP) comparable to eplerenone when comparing Day 90 to baseline. Exploratory endpoints of all cause death, cardiovascular hospitalization or emergency presentation for worsening chronic heart failure were lower with the finerenone dose that will be used in the phase III program, compared with eplerenone. The incidence of treatment-emergent adverse events (TEAEs) was similar between eplerenone and all finerenone dose groups.
The planned Phase III study FINESSE-HF will investigate finerenone compared to eplerenone in chronic heart failure patients with reduced ejection fraction and type 2 diabetes mellitus and/or chronic kidney disease across more than 35 countries, including Europe, Japan, China and the US. Patients will receive finerenone or eplerenone on top of standard medical treatment currently represented by angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blocker (ARBs) and ß-blockers.