FIGARO-DKD Finds Finerenone Offers CV Benefits in Mild to Moderate Kidney Disease With T2D; Cuts HF Hospitalization 29%

After an earlier study found finerenone slowed chronic kidney disease (CKD) progression and cut cardiovascular events in the highest-risk patients, a new study unveiled Saturday found the drug also offered benefits to patients with mild to moderate CKD and type 2 diabetes (T2D).

The phase 3 study, FIGARO-DKD, was presented during the European Society of Cardiology (ESC) Congress 2021, taking place in a virtual format for the second year due to COVID-19. Results were published simultaneously in the New England Journal of Medicine.¹

Finerenone, a nonsteroidal mineralocorticoid receptor antagonist (MRA) sold as Kerendia (Bayer), is designed to target overactivation of the mineralcorticoid receptor that leads to renal decline. It offers potent anti-inflammatory and antifibrotic effects and reduces the urinary albumin-to-creatinine (UCR) ratio with fewer adverse effects than steroidal MRAs.²

Last fall during Kidney Week, the FIDELIO-DKD study reported positive results in patients with advanced kidney disease (stage 3 or 4 CKD with severely elevated albuminuria) and T2D.2 Results reported Saturday for FIGARO-DKD involved patients who fell into 1 of 2 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 kidney disease and T2D, finerenone produced a 13% reduced risk in the primary outcome, a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Hospitalization was reduced 29% for patients taking finerenone.

Understanding the Renal End Point

A secondary outcome was a composite of kidney failure, a sustained decrease from the baseline of at least 40% estimated glomerular filtration rate (eGFR), or renal death. Lead study author 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 renal progression of disease, and the primary outcome was reduction of eGFR by 40% that was sustained. This trended positive, but it wasn't significant,” Pitt said. “We picked that end point because the FDA and the [European Medicines Agency] at one point thought that was a very good renal end point. Subsequently, we've learned it's not very sensitive, and the more sensitive renal end point is a 57% reduction eGFR, and that was significantly reduced.”

“But most importantly, we reduced the need for dialysis. We reduce the progression to end- stage renal disease,” he said. “That is really important.”

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

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

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

Results showed the following:

• 7437 patients were randomized; 7352 ended up in the analysis
• Follow-up over a median of 3.4 years was affected by COVID-19, with the trial being discontinued early for 27% in each arm due to the pandemic
• A primary outcome event occurred in 458 of 3686 patients (12.4%) of the finerenone group and 519 of 3666 (14.2%) of the placebo group, for an HR of 0.87 (95% CI, 0.76-0.98; P = .03)
• Lower incidence of heart failure hospitalization was the primary driver of the primary outcome benefit (HR, 0.71; 95% CI, 0.56-0.90)
• Secondary composite outcomes occurred in 350 patients (9.5%) in the finerenone group compared with 395 (10.8%) in the placebo group (HR, 0.87; 95% CI, 0.76-1.01)
• The frequency of adverse events did not differ between the 2 groups overall; here was more hyperkalemia-related discontinuation of the study drug in the finerenone group (1.2%) than the placebo group (0.4%), but Pitt said more hyperkalemia is to be expected, and this rate is actually low

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

“Patients might have a normal eGFR, but an increase in UCR. And most of us neglect these patients,” Pitt said. “Now, we know we can do something about that—the patient should be started on therapy. … I think that’s a really important message.”

Finerenone in the Treatment Regimen

With many new therapies for CKD, where will finerenone fit in to the existing standard of care? Pitt said that for starters, too many patients aren’t getting good diabetes care—that their renal function isn’t being closely monitored to see if their albuminuria is greater than 30 mg/g.

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

The drug’s tolerability, as seen in the safety data in FIGARO, shows a clear benefit over steroidal MRAs. Patients taking finerenone should be on an angiotensin-converting enzyme inhibitor and likely a glucose-lowering therapy.

“Now, the SGLT2 inhibitors and the GLP-1 receptor agonists have also shown benefits, and we had less than 10% each of these [patients] in our trial. And all we can say is that on top of those drugs, finerenone seems to be equally beneficial, but these were small numbers, and we need more.”

Pitt said there are preclinical data in which finerenone was combined with empagliflozin.

“It appears in the preclinical models at least, there was an additive effect on fibrosis, inflammation, and survival. So, our expectation is that if we do the right trials, we will show this,” he said. “The patients would benefit by being on an SGLT2 inhibitor, an MRA, and maybe a GLP-1 receptor agonist,” with the last therapy being added to reduce the risk of stroke.

As for making the case for payers, Pitt said he does not have a formal cost analysis, but “I think this is going to be a cost-effective therapy—you save patients from heart failure and dialysis.”

References

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

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