Kidney Week

Abstract: PO0745

Finerenone Dose-Exposure-UACR Response Analyses of FIDELIO-DKD Phase 3 and the Effect of SGLT-2 Inhibitor Co-Medication

Session Information

• Diabetic Kidney Disease: Clinical
  November 04, 2021 | Location: On-Demand, Virtual Only
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 602 Diabetic Kidney Disease: Clinical

Authors

• L Heerspink, Hiddo Jan, Department Clinical Pharmacy and Pharmacology, University of Groningen & University Medical Center Groningen, Groningen, Groningen, Netherlands

Hiddo Jan L Heerspink, PhD

• Goulooze, Sebastiaan, Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics (LAP&P), Leiden, Netherlands

Sebastiaan Goulooze,

• van Noort, Martijn, Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics (LAP&P), Leiden, Netherlands

Martijn van Noort,

• Snelder, Nelleke, Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics (LAP&P), Leiden, Netherlands

Nelleke Snelder,

• Brinker, Meike Daniela, Bayer AG, Clinical Development, Wuppertal, Germany

Meike Daniela Brinker,

• Lippert, Jörg, Bayer AG, Pharmacometrics, Wuppertal, Germany

Jörg Lippert,

• Eissing, Thomas, Bayer AG, Pharmacometrics, Leverkusen, Germany

Thomas Eissing,

Group or Team Name

• TBC

Background

The mineralocorticoid receptor antagonist finerenone and sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to reduce albuminuria and the risk of kidney failure. The combination of these therapies holds promise to augment nephroprotection through activation of different pathways. Model-based approaches considering individual dosing and exposure and correcting for covariates can support stronger conclusions than stratification for baseline comedication. We developed a population pharmacokinetic/pharmacodynamics (popPKPD) model to assess the finerenone dose-exposure-response relationship for urine albumin-to-creatinine ratio (UACR) and the impact of combined SGLT2i-finerenone use on UACR.

Methods

We analysed 37296 UACR measurements in 5674 patients (549 patients with any recorded SGLT2i use) using nonlinear mixed-effects popPKPD modelling considering individual drug exposure. The model was used to characterize the trajectory of UACR progression over time, the exposure-response relationship of finerenone on UACR and the effect of SGLT2i.

Results

The popPKPD model described the observed UACR data well, with a proportional UACR progression over time, an indirect power model for the exposure-response relationship of finerenone and a constant effect of SGLT2i use. SGLT2i use did not modify finerenone efficacy (p=0.25) and indicated with 95% confidence that finerenone is at least 94.1% as efficacious in reducing UACR in patients using SGLT2i (Figure 1).

Conclusion

We successfully developed a popPKPD model that adequately described the dose-exposure-response of finerenone on UACR. The results demonstrate additive effects of SGLT2i on top of finerenone.

Funding

• Commercial Support –