Bayer announces phase 3 plans for finerenone in diabetic nephropathy and publishes full phase 2b results in JAMA – September 13, 2015

Bayer announced plans recently to conduct two phase 3 studies of its oral mineralocorticoid receptor (MR) antagonist finerenone in diabetic nephropathy, as well as a phase 3 trial in chronic heart failure. The first diabetic nephropathy study – FIGARO-DKD – will enroll 6,400 patients with high albuminuria (defined as a urinary albumin/creatinine ratio [UACR] ≥30mg/g and <300mg/g.) FIGARO-DKD’s estimated primary completion date is January 2019, as we understand it from ClinicalTrials.gov. The second study – FIDELIO-DKD – will enroll 4,800 patients with very high albuminuria (UACR ≥300mg/g). FIDELIO-DKD’s estimated primary completion date as shown by ClinicalTrials.gov is April 2019. Both studies will compare finerenone to placebo on top of current standard of care and are expected to start enrolling patients by the end of the year. FIGARO-DKD is designed to study the cardioprotective potential of finerenone – hopes must be high to enroll such an expensive and long-range trial -  and has a composite primary endpoint of cardiovascular death and non-fatal cardiovascular events. FIDELIO-DKD will look at the nephroprotective effects, with a composite primary endpoint of onset of kidney failure, sustained decrease of estimated glomerular filtration rate (eGFR) ≥ 40% from baseline over at least four weeks, and renal death. As we understand it, the FDA is shifting toward greater acceptance of surrogate endpoints like change in eGFR in diabetic nephropathy trials rather than requiring hard outcomes. This should hopefully allow companies to conduct shorter, less expensive trials that enroll patients at earlier stages of the disease; the downside is that the data from such trials would not be quite as conclusive although presumably trials could be designed with passive outcomes. We see this sort of combined primary endpoint as a compromise approach that could possibly set a precedent for future trials.

It was an eventful week for Bayer, as full results for the phase 2b ARTS-DN study of finerenone were published in JAMA as well. As a reminder, the results were first presented at the World Congress of Nephrology this past March. The randomized, double-blind, placebo-controlled trial (n=821) examined the effect of various doses of finerenone on UACR after 90 days. At baseline, 37% of patients had very high albuminuria. The study found a dose-dependent relationship between finerenone and decrease in UCAR – the mean placebo-corrected UACR reductions after 90 days in the finerenone 7.5-, 10-, 15-, and 20-mg/day groups were 21% (p =0.004), 24% (p =0.001), 33% (p<0.001), and 38% (p<0.001), respectively – these strike us as very strong results in this area of such unmet need. There were no serious adverse events associated with finerenone, though 12 of the 821 (1.5%) patients receiving finerenone experienced increases in serum potassium of at least 5.6 mmol/l, leading to discontinuation of the treatment.

• Finerenone is the closest-to-market MR antagonist in the diabetic kidney disease competitive landscape. We’re certainly glad to see a novel therapeutic option for diabetic nephropathy (one of the greatest unmet needs in diabetes) advance to phase 3. Daiichi Sankyo has an oral MR antagonist (CS-3150) in phase 2 trials, with an estimated primary completion date of July 2016, and Mitsubishi Tanabe Pharma has an MR antagonist (MT-3995) in phase 1/2. See the table below for a full overview of the current competitive landscape for diabetic nephropathy.

Diabetic Nephropathy Competitive Landscape

-- by Helen Gao, Emily Regier, and Kelly Close