Dose–Exposure–Response Analysis of the Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone on UACR and eGFR: An Analysis from FIDELIO‑DKD
Clin Pharmacokinet 2022; Ahead of print doi: 10.1007/s40262-022-01124-3
The results of this model-based analysis quantified the dose–exposure–response relationship for urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). Overall, the relationship between finerenone exposure and UACR and eGFR effects was not modified by sodium-glucose co-transporter-2 inhibitor (SGLT2i) use and demonstrated independent and additive effects.
Blood pressure-lowering has been the mainstay of therapy for the treatment of chronic kidney disease (CKD), but the risk of kidney failure remains high despite current therapies. Finerenone is a novel, selective, nonsteroidal mineralocorticoid receptor antagonist that recently demonstrated efficacy in delaying CKD progression and reducing CV events in patients with CKD and type 2 diabetes (T2D) in the pivotal FIDELIO-DKD study. Finerenone also reduces the risk of kidney failure in patients with CKD and T2D.
Sine changes in UACR and eGFR are surrogates for kidney failure, this model performed dose–exposure–response analyses using individual patient data from FIDELIO-DKD. The aim was to determine the effects of finerenone on eGFR and UACR in the presence and absence of SGLT2i. Non-linear mixed-effects models were used to quantify disease progression during standard of care.
Findings showed that the early treatment effect of finerenone on UACR predicted its long-term effect on eGFR, supporting UACR as a surrogate. Furthermore, the relationship between finerenone exposure and UACR and eGFR effects was not modified by SGLT2i use and demonstrated independent and additive effects.