Dr Rajiv Agarwal Discusses Finerenone, Results of FIDELIO-DKD

The investigational drug finerenone met its primary endpoint in FIDELIO-DKD of slowing progression of chronic kidney disease (CKD) in patients with type 2 diabetes and CKD, said Rajiv Agarwal, MD, MS, FASN, a professor of medicine at Indiana University School of Medicine and a staff physician at the Veterans Affairs Medical Center in Indianapolis, Indiana.

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What were the main findings of FIDELIO-DKD and why are they clinically relevant?

FIDELIO-DKD is a large trial looking at a non-steroidal mineralocorticoid receptor antagonist or MRA, that is called finerenone compared against placebo in 5734 patients with type 2 diabetes, and CKD with estimated glomerular filtration rate (EGFR) between 25 and 75. The primary endpoint of this trial was a kidney failure outcome. That was met, 18% relative risk reduction with a p value of .0014. The key secondary endpoint was a cardiovascular outcome. That key end point was also met with a p value of .038 and a relative risk reduction of 14%. In effect, it shows that on top of angiotensin-converting enzyme (ACE) and angiotensin II receptor blockers (ARB) therapy, which was optimized over a 4 to 16 week period, this drug can potentially reduce kidney failure outcome and cardiovascular outcome in people with both type 2 diabetes and chronic kidney disease.

Can you elaborate on the significance of this drug's mechanistic properties?

Finerenone is a non-steroidal MRA, which means that it doesn't have the steroidal structure that other existing molecules have, for example, spironolactone or eplerenone. This drug works differently at the genomic level, and transcribes a number of molecules that have anti-inflammatory and anti-fibrotic properties. It's believed, at least from animal models, that this is how this drug has salutary effects on both the heart and the kidney.

How do the findings compare with those observed in trials on the effects of sodium-glucose cotransporter-2 (SGLT 2) inhibitors on CKD?

The SGLT 2 inhibitors that have been tried so far, have been amazing discoveries. They have changed the way people with kidney disease and heart failure are treated. We have found these drugs after waiting for nearly 2 decades of using inhibitors of renin angiotensin system (RAS). But now we have a new therapy, which is finerenone. This is again an investigational drug so far it's not been approved yet. But it can potentially reduce kidney failure outcomes and heart disease outcomes in people with type 2 diabetes and chronic kidney disease. More importantly, FIDELIO-DKD is just the beginning. The EGFR range in this trial was between 25 and 75, the median EGFR was 44. More than half the patients in this trial had EGFR of less than 45. Nearly 90% of the people have macroalbuminuria. The sister trial called the FIGARO-DKD has mean EGFR of 68. That means more than half the people will have stage 2 kidney disease or better and nearly half the people have microalbuminuria. So next year, we hope to announce the results of the FIGARO-DKD trial, and that would broaden the implications of this investigational drug to a broader range of patients with kidney disease who might derive benefit from the use of this drug on top of RAS inhibition.