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Kidney Week

Abstract: TH-OR53

FIGARO-BM, a Biomarker Study of FIGARO-DKD, Reveals New Insights into the Mode of Action of Finerenone

Session Information

Category: Diabetic Kidney Disease

  • 702 Diabetic Kidney Disease: Clinical

Authors

  • Berger, Mario, Bayer AG, Pharmaceuticals, R&D, Wuppertal/Berlin, Germany
  • Christopher, Lydia Jane, Bayer UK, Cardiology, Reading, United Kingdom
  • Goea, Laura, Bayer AG, Pharmaceuticals, R&D, Wuppertal/Berlin, Germany
  • Kolkhof, Peter, Bayer AG, Pharmaceuticals, R&D, Wuppertal/Berlin, Germany
  • Macnamara, Aidan, Bayer AG, Pharmaceuticals, R&D, Wuppertal/Berlin, Germany
  • Nkulikiyinka, Richard, Bayer AG, Pharmaceuticals, R&D, Wuppertal/Berlin, Germany
  • Scalise, Andrea, Bayer Hispania SL, Pharmaceutical Development, Barcelona, Spain
  • Skubala, Adam, Bayer AG, Pharmaceuticals, R&D, Wuppertal/Berlin, Germany
  • Voss, Sebastian, CHRESTOS Concept GmbH & Co. KG, Essen, Germany
  • Rohwedder, Katja, Bayer AG, Pharmaceuticals, Medical Affairs, Berlin, Germany
  • Ix, Joachim H., UCSD, Department of Medicine, San Diego, California, United States
  • Zannad, Faiez, Université de Lorraine, Nancy, France
  • Rossing, Peter, Steno Diabetes Center Copenhagen, Herlev, and University of Copenhagen, Copenhagen, Denmark
  • Heerspink, Hiddo Jan L., University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, Netherlands
Background

Mineralocorticoid receptor (MR) overactivation contributes to tissue fibrosis and organ damage found in cardiorenal disease. FIGARO-BM is an exploratory biomarker study aimed at advancing the understanding of the longitudinal pharmacodynamic response to finerenone, a non-steroidal, selective MR antagonist.

Methods

Samples were derived from the phase III parent trial FIGARO-DKD, which investigated finerenone’s efficacy on cardiorenal outcomes and safety in CKD patients with type 2 diabetes (T2D). This biomarker substudy included 945 subjects from 21 countries, overall comparable to the total population, and analyzed 2941 biomarkers in more than 4000 longitudinal post-randomization plasma samples using Olink EXPLORE proteomics. Subjects on treatment with either placebo or finerenone for at least 36 months, and alive to consent, were eligible to participate in FIGARO-BM. Biomarkers with a significant difference (p≤0.05) between treatment arms at more than one study visit (month 4, 12, 24, 36 and 48, based on a linear mixed model adjusted for gender) and with effect estimates above threshold were used for gene enrichment analysis using Metascape. Enriched terms were grouped into clusters based on membership similarities.

Results

373 plasma protein biomarkers were modulated by finerenone treatment. Gene enrichment of the biomarker profile identified two clusters of extracellular matrix (ECM)-related pathways, involving several well-established markers of inflammation and fibrosis such as fibronectin, osteopontin, and members of the interleukin-17 family, along with novel markers of ECM remodeling. Other clusters linked directly to mineralocorticoid/aldosterone biology and diuresis reflecting target modulation.

Conclusion

For the first time, FIGARO-BM provides human biomarker evidence that finerenone acts on inflammation and fibrosis pathways, one key driver of cardiorenal disease progression in T2D. The study supports preclinical findings from animal models and provides insights to mechanisms leading to clinical benefits in a broad cardiorenal patient population. Future studies are needed to validate these findings.

Funding

  • Commercial Support – The study and this analysis were funded by Bayer AG, Wuppertal, Germany.