Analyses Examine Effects of Finerenone Dosing on Kidney Outcomes

Researchers, led by Thomas Eissing, PhD, conducted dose-exposure-response analyses of data from the FIGARO-DKD and FIDELIO-DKD trials to determine the effects of finerenone doses in patients with chronic kidney disease (CKD) and type 2 diabetes. Results were reported in Diabetes, Obesity and Metabolism.

FIGARO-DKD and FIDELIO-DKD were randomized, double-blind, placebo-controlled phase 3 trials that included 13,026 participants with type 2 diabetes at global sites. Eligible participants had estimated glomerular filtration rate (eGFR) of 25 to 90 mL/min/1.73 m², a urine albumin-creatinine ratio (UACR) of 30 top 5000 mg/g, and serum potassium ≤4.8 mmol/L. The trial interventions were titrated doses of finerenone of 10 or 20 mg or placebo in combination with standard care.

The outcomes of interest were trajectories of plasma finerenone and serum potassium concentrations, UACR, eGFR, and kidney composite outcomes. Outcomes were assessed using nonlinear mixed-effects population pharmacokinetic (PK)/pharmacodynamic (PD) and parametric time-to-event models.

Compared with a finerenone dose of 10 mg, a dose of 20 mg was associated with lower serum levels and lower rates of hyperkalemia (P<.001). The PK/PD model analysis linked this observed inverse association to potassium-guided dose titration. Simulations of a hypothetical trial with constant finerenone doses demonstrated a shallow but increasing exposure-potassium response relationship.

Likewise, increasing finerenone exposure led to less than dose-proportional increasing reduction in modeled UACR. Modelled UACR explained 95% of finerenone’s treatment effect in slowing chronic decline in eGFR. There were no UACR-independent finerenone effects identified.

There were no significant modifications to the effects of finerenone in reducing UACR or decline in eGFR with treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitor or glucagon-like peptide-1 receptor agonist (GLP-1RA). Modelled eGFR explained 87% of finerenone’s treatment effect on kidney outcomes. There were no eGFR-independent effects identified.

“The analyses provide strong evidence for the effectiveness of finerenone dose titration in controlling serum potassium elevations,” the researchers said. “UACR and eGFR are predictive of kidney outcomes during finerenone treatment. Finerenone’s kidney efficacy is independent of concomitant use of SGLT2 inhibitors and GLP-1RAs.”

Source: Diabetes, Obesity and Metabolism