Dr Rajiv Agarwal on the Future of Finerenone

The FIDELIO-DKD program is perhaps just the beginning of seeing how finerenone can be used, 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.

Transcript

Can you elaborate on the hyperkalemia rates exhibited in the FIDELIO-DKD trial?

Hyperkalemia was the most important adverse effect noted in this trial. This adverse effect is expected because the drug is blocking the mineralocorticoid receptor that is important for the excretion of potassium in the urine. So, if we block this receptor hyperkalemia is going to be an expected side effect. This is what we saw, 2.3% of the patients who got finerenone permanently discontinued the drug because of hyperkalemia compared to 0.9% of people who were on placebo. What it means is the majority of the patients did not discontinue the study drug because of hyperkalemia. Nonetheless, as physicians, it tells us that you can't just prescribe the drug and forget about it. You need to be monitoring potassium in these patients, just like you would with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers, and be wary that these drugs can potentially cause hyperkalemia. But you would need to prescribe 71 patients with a prescription of finerenone and treat them for a median of 2.6 years before you will find one patient who permanently discontinues the drug. The important thing is to put the brakes on, don't use the drug if the potassium gets too high, and reintroduce the drug when the potassium is lowered just like we did in the trial.

Why were 70% of participants male?

Kidney disease appears to affect men more than women. We found that 70% of the patients in this worldwide trial were men. It's slightly more than some of the other trials. But it tells us about the demographics of this kidney disease. This trial was done in more than 1000 sites in 48 countries. We were including both men and women, but the patients who qualified for the study perhaps were a little bit more men than women.

What are the next steps for finerenone?

The finerenone FIDELIO-DKD program is perhaps just the beginning because the Efficacy and Safety of Finerenone in Subjects with Type 2 Diabetes Mellitus and the Clinical Diagnosis of Kidney Disease (FIGARO-DKD) program, together with the FIDELIO-DKD program, constitutes the largest program in patients with type 2 diabetes (T2D) and chronic kidney disease. Together, they have more than 13,000 patients randomized. We expect to announce the results of the FIGARO study next year. This is, as I said, being done in patients who have an earlier stage of chronic kidney disease and T2D. Therefore, we will find out whether an earlier use of this compound, finerenone, can protect from cardiovascular disease in patients with T2D. Now in early stage diabetes and chronic kidney disease, patients are much more likely to have a cardiovascular event or die from cardiovascular disease, than reach end stage kidney disease. Therefore that is a really important study for patients who have early stage kidney disease and T2D.

Besides this, there's the FINEARTS-HF study ongoing, which is looking at patients who have heart failure with preserved ejection fraction. There are no approved therapies in that area so far. The FINEARTS study would inform the use of finerenone compared to standard of care in patients who have heart failure with preserved ejection fraction. That would be really an important advance in patients with heart failure with preserved ejection fraction. I believe that there are a number of studies that will inform the use of finerenone in both patients with chronic kidney disease, T2D, and patients with heart failure with preserved ejection fraction. Other studies are also planned.

Do you have any final thoughts you'd like to share?

Patients who have T2D are not being screened for albuminuria, and if we don't screen for albuminuria we are unable to stage what kind of kidney disease we have. We have a grid system for staging patients with kidney disease. We want to know the estimated glomerular filtration rate (eGFR) and albuminuria. If we don't measure albuminuria, we can't tell whether these patients are going to be progressing or not. The most important predictor of progression in patients with T2D and kidney disease is albuminuria and if we have a lot of albuminuria, those are the patients at highest risk for progression to end stage kidney disease and cardiovascular disease. Those are the patients who need to be screened. In fact, the guidelines suggest that any patient who has 5 years of type 1 diabetes ought to have a screening for albuminuria, and anyone who has T2D needs to be screened for albuminuria, and annually thereafter. Very few patients are getting that test done. If you really want to make a difference, start looking at the urine for albumin.