FDA Approves KERENDIA (Finerenone) to Reduce the Risk of Sustained EGFR Decline, End Stage Kidney Disease, Cardiovascular Death, Non-Fatal Myocardial Infarction, and Hospitalization for Heart Failure in Adult Patients with CKD Associated with T2D

On July 9, 2021, the U.S. Food and Drug Administration (FDA) approved KERENDIA (finerenone) 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 adult patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D).

Dosing of KERENDIA is based on eGFR and serum potassium thresholds. The recommended initial dosage is 10 mg or 20 mg orally once daily, then, after 4 weeks, doses may be maintained, increased, or withheld depending on eGFR and serum potassium. The target daily dose of KERENDIA is 20 mg once daily. Tablets may be taken with or without food. For patients who are unable to swallow whole tablets, KERENDIA may be crushed and mixed with water or soft foods such as applesauce immediately prior to use.

Measure serum potassium levels and eGFR before initiation. Do not initiate treatment if serum potassium is > 5.0 mEq/L.

Additional information regarding dosage and administration as well as warnings and precautions about hyperkalemia can be found in the full prescribing information linked below.

Mechanism of Action (MOA), Pharmacokinetics (PK), and Pharmacodynamics (PD)

MOA: Finerenone is a non-steroidal mineralocorticoid receptor antagonist (MRA).

General PK: Finerenone exposure increased proportionally over a dose range of 1.25 to 80 mg (0.06 to 4 times the maximum approved recommended dosage). Steady state of finerenone is achieved after 2 days of dosing. The estimated steady-state geometric mean C_max,md is 160 μg/L and steady-state geometric mean AUC_τ,md is 686 μg.h/L following administration of finerenone 20 mg to patients.

Absorption: Finerenone is completely absorbed after oral administration but undergoes metabolism resulting in an absolute bioavailability of 44%. Finerenone C_max is achieved between 0.5 and 1.25 hours after dosing.

Distribution: The volume of distribution at steady-state (Vss) of finerenone is 52.6 L. Plasma protein binding of finerenone is 92%, primarily to serum albumin, in vitro.

Elimination: The terminal half-life of finerenone is about 2 to 3 hours, and the systemic blood clearance is about 25 L/h.

Metabolism: Finerenone is primarily metabolized by CYP3A4 (90%) and to a lesser extent by CYP2C8 (10%) to inactive metabolites.

Excretion: About 80% of the administered dose is excreted in urine (<1% as unchanged) and approximately 20% in feces (< 0.2% as unchanged).

PD: In FIDELIO-DKD, a randomized, double-blind, placebo-controlled, multicenter study in adult patients with chronic kidney disease associated with type 2 diabetes, the placebo-corrected relative reduction in urinary albumin-to-creatinine ratio (UACR) in patients randomized to finerenone was 31% at Month 4 (95% CI 29-34%) and remained stable for the duration of the trial. In patients treated with KERENDIA, the mean systolic blood pressure decreased by 3 mmHg and the mean diastolic blood pressure decreased by 1-2 mmHg at month 1, remaining stable thereafter.

Drug Interactions

Strong CYP3A4 Inhibitors: Co-administration of KERENDIA with strong CYP3A4 inhibitors is contraindicated. Avoid co-administration of KERENDIA with grapefruit or grapefruit juice. KERENDIA is a CYP3A4 substrate. Concomitant use with a strong CYP3A4 inhibitor increases finerenone exposure, which may increase the risk of KERENDIA adverse reactions.

Moderate and Weak CYP3A4 Inhibitors: Monitor serum potassium during drug initiation or dosage adjustment of either KERENDIA or the moderate or weak CYP3A4 inhibitor and adjust KERENDIA dosage as appropriate. KERENDIA is a CYP3A4 substrate; therefore, concomitant use with a moderate or weak CYP3A4 inhibitor increases finerenone exposure, which may increase the risk of KERENDIA adverse reactions.

Strong and Moderate CYP3A4 Inducers: Avoid concomitant use of KERENDIA with strong or moderate CYP3A4 inducers. KERENDIA is a CYP3A4 substrate. Concomitant use of KERENDIA with a strong or moderate CYP3A4 inducer decreases finerenone exposure, which may reduce the efficacy of KERENDIA.

Use in Specific Populations

There are no clinically significant effects of age (18 to 79 years), sex, race/ethnicity (White, Asian, Black, and Hispanic), weight (58 to 121 kg), patients with eGFR 15 to < 90, or mild to moderate hepatic impairment (Child Pugh A or B) on the PK of finerenone. The effect of severe hepatic impairment (Child Pugh C) on finerenone exposure was not studied.

Efficacy and Safety

Efficacy of KERENDIA was demonstrated in a randomized, double-blind, placebo-controlled, multicenter study in adult patients with CKD associated with T2D. The primary objective of the study was to determine whether KERENDIA reduced the incidence of a sustained decline in eGFR of ≥ 40%, kidney failure (defined as chronic dialysis, kidney transplantation, or a sustained decrease in eGFR to <15 mL/min/1.73m²), or renal death. Additional information regarding the efficacy trial(s) can be found in the full prescribing information linked below.

Adverse reactions occurring in ≥ 1% of patients on KERENDIA and more frequently than placebo are hyperkalemia, hypotension, and hyponatremia.

Full prescribing information is available at https://go.usa.gov/xFcKs.

Visit Drugs@FDA at http://go.usa.gov/cMsjT for prescribing and patient information, approval letters, reviews and other information for FDA-approved drug products, which are often available shortly following approval.

A non-comprehensive list of examples of clinical substrates, inhibitors and inducers for metabolic and transporter system related interactions may be found at https://go.usa.gov/xXY9C.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at https://www.fda.gov/safety/medwatch/default.htm, by faxing (1-800-FDA-0178), or by mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).

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This communication was prepared by Office of Clinical Pharmacology, Office of Translational Sciences, CDER, FDA.