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The FDA approved the anti-mineralocorticoid agent in type 2 diabetes patients, the agency announced on Friday.

The first non-steroidal, selective mineralocorticoid receptor antagonist was approved to reduce the risk of sustained estimated glomerular filtration rate (eGFR) decline, end-stage kidney disease, cardiovascular death, non-fatal myocardial infarction, and hospitalization for heart failure in adults with chronic kidney disease associated with type 2 diabetes.

After being granted priority review designation in January, the once-daily oral tablet is now approved at two doses -- 10 mg and 20 mg -- for this indication.

Finerenone is contraindicated for patients with adrenal insufficiency and for patients receiving simultaneous treatment with strong CYP3A4 inhibitors.

Working differently from other approved agents with the same indication currently on the market, such as canagliflozin (Invokana), finerenone acts by blocking mineralocorticoid receptor overactivation, which is linked to fibrosis and inflammation contributing to kidney damage.

Approval was based on results of FIDELIO-DKD, a phase III trial of over 5,600 participants with type 2 diabetes. Only 17.8% of patients on finerenone experienced a primary outcome event -- kidney failure, a sustained decrease of at least 40% in eGFR from baseline, or death from renal causes -- versus 21.1% of those assigned to placebo (HR 0.82, 95% CI 0.73-0.93, P=0.001), the researchers reported.

Regarding cardiovascular outcomes, those on finerenone saw a 14% reduced risk for death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure (HR 0.86, 95% CI 0.75-0.99, P=0.03).

"This is an exciting discovery because we have had many other failed discoveries in this high-risk population of diabetes and chronic kidney disease," explained study investigator Rajiv Agarwal, MD, of Indiana University in Indianapolis, when the findings were first presented last year at the American Society of Nephrology's virtual Kidney Week.

The most common adverse events in the trial were hyperkalemia (18% vs 9% for those on placebo), hypotension, and hyponatremia. Finerenone should therefore not be used if serum potassium is above 5.0 mEq/L. Serum potassium and eGFR should also be measured in all patients prior to and during treatment and should be dosed according to these measures.

Likewise, patients at risk for hyperkalemia -- and those on concomitant medications that impair potassium excretion or increase serum potassium -- should be monitored more frequently.

"An ideal drug would cause no hyperkalemia," Agarwal noted. "But if you look at the absolute risk, it's a fraction of what we saw when we used spironolactone [in the AMBER trial] in this vulnerable population."

Finerenone is expected to be available in the U.S. by the end of July 2021. Drugmaker Bayer is currently seeking approval of finerenone in other countries as well, including the European Union and China.

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