FIGARO-DKD finds finerenone offers CV benefits in mild to moderate kidney disease with T2DM; Reduces HF hospitalizations 29%

Finerenone, a nonsteroidal mineralocorticoid receptor antagonist (MRA) sold as Kerendia (Bayer), is designed to target overactivation of the mineralocorticoid receptor which results in kidney failure. It offers potent anti-inflammatory and antifibrotic effects and reduces urinary albumin to creatinine (UCR) ratio with fewer side effects than steroid MRAs.2

Last fall, during Kidney Week, the FIDELIO-DKD study reported positive results in patients with advanced renal failure (CKD stage 3 or 4 with severely elevated albuminuria) and T2D. categories: stage 2 to 4 CKD with moderately elevated albuminuria or stage 1 or 2 CKD with severely elevated albuminuria.

Among these patients with mild to moderate renal failure and T2DM, finerenone resulted in a 13% reduction in risk in the primary outcome, a composite of death from cardiovascular causes, non-fatal myocardial infarction, d non-fatal stroke or hospitalization for heart failure. Hospitalization was reduced by 29% for patients taking finerenone.

Understanding the renal end point

A secondary outcome was a composite endpoint of renal failure, sustained decrease from baseline of at least 40% in estimated glomerular filtration rate (eGFR), or renal death. Lead author of the study, Bertram Pitt, MD, of the University of Michigan, explained in an interview with The American Journal of Managed Care® how this end point was selected.

“We had a secondary outcome, which was kidney disease progression, and the primary outcome was a 40% reduction in eGFR that was sustained. This trend was positive, but it was not significant, ”Pitt said. “We chose this endpoint because the FDA and the [European Medicines Agency] at one point i thought it was a really good kidney endpoint. Subsequently, we learned that it is not very sensitive, and the most sensitive renal endpoint is a 57% reduction in eGFR, and it has been significantly reduced. “

“Most importantly, we have reduced the need for dialysis. We are reducing the progression to end-stage kidney disease, ”he said. “It’s really important.”

To be eligible, patients with stage 2 to 4 CRF had to have a urinary albumin / creatinine (UCR) ratio of 30-300 mg / g while those with stage 1 or 2 CRF had to have a UCR of 300-5000 mg / g.

All the patients in the study had to be treated with drugs to optimize the blockade of the renin-angiotensin system; 98% were on hypoglycaemic therapy, 70% were taking statins, 55% were taking insulin, 47% were taking a diuretic, and a smaller number were taking a sodium glucose 2 co-transporter inhibitor (SGLT2) (8.5%) or a glucagon-like peptide-1 (GLP-1) receptor agonist (8.4%).

Since finerenone increases serum potassium levels, patients’ serum potassium levels had to be 4.8 mmol / L or less at screening visits (but not at randomization) so that levels could be maintained. around 5.0 mmol / L or less.

The results showed the following:

  • 7437 patients were randomized; 7352 ended up in the analysis
  • Median follow-up of 3.4 years was affected by COVID-19, with the trial terminated prematurely for 27% in each arm due to the pandemic
  • A primary outcome event occurred in 458 of 3686 patients (12.4%) in the finerenone group and 519 of 3666 (14.2%) in the placebo group, for an RR of 0.87 (95% CI, 0.76-0.98; P = .03)
  • The lower incidence of hospitalization for heart failure was the main benefit factor for the primary outcome (RR: 0.71; 95% CI: 0.56-0.90)
  • Secondary composite results occurred in 350 patients (9.5%) in the finerenone group compared to 395 (10.8%) in the placebo group (RR: 0.87; 95% CI: 0.76-1 , 01)
  • The frequency of adverse events did not differ between the 2 groups overall; there were more discontinuations related to hyperkalaemia of the study drug in the finerenone group (1.2%) than in the placebo group (0.4%), but Pitt said it was necessary to ” expect more hyperkalaemia, and this rate is actually low

The results are important for other reasons, Pitt said. Not only does a nonsteroidal MRA give doctors and patients an option to avoid dialysis with treatment better tolerated than steroid therapy, but it gives cardiologists a reason to look for albuminuria, something that may not be on their screen. radar.

“Patients may have normal eGFR, but an increase in UCR. And most of us neglect these patients, ”Pitt said. “Now we know there is something we can do about it – the patient should start therapy. … I think this is a really important message.

Finerenone in the treatment regimen

With many new therapies for CRF, where will finerenone fit into the existing standard of care? Pitt said that for a start, too many patients don’t get good diabetes care – that their kidney function isn’t closely monitored to see if their albuminuria is above 30 mg / g.

“If they have an increased risk, then I would start finerenone,” he said.

The safety of the drug, as shown by the safety data of FIGARO, shows a clear advantage over steroidal MRAs. Patients taking finerenone should be on angiotensin converting enzyme inhibitor and possibly hypoglycaemic therapy.

“Now SGLT2 inhibitors and GLP-1 receptor agonists have shown benefits as well, and we had less than 10% each of those. [patients] in our trial. And all we can say is that in addition to these drugs, finerenone appears to be just as beneficial, but it was small numbers, and we need more.

Pitt said there is preclinical data in which finerenone has been combined with empagliflozin.

“It appears, at least in preclinical models, that there was an additive effect on fibrosis, inflammation and survival. So our expectation is that if we do the right tests we will show it, ”he said. “Patients would benefit from an SGLT2 inhibitor, MRA and possibly a GLP-1 receptor agonist,” with the latter treatment added to reduce the risk of stroke.

As for arguing for payers, Pitt said he doesn’t have a formal cost analysis, but “I think it will be cost-effective therapy – you save patients from heart failure and dialysis.” .

The references

1.Pitt B, Filippatos G, Agarwal R, et al, for FIGARO-DKD investigators. Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N English J Med. Published online August 28, 2021. doi: 10.1056 / NEJMoa2110956

2. Bakris GL, Agarwal R, Anker SD, et al, for FIDELIO-DKD investigators. Effect of finerenone on chronic kidney disease outcome on type 2 diabetes. N English J Med. 2020; 383 (23): 2219-2229. doi: 10.1056 / NEJMoa2025845

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