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Abstract: SA-PO247

Runcaciguat, a Novel Soluble Guanylate Cyclase (sGC) Activator, Shows Kidney Protection in Models of CKD

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Kraehling, Jan R., Bayer AG, Leverkusen, Nordrhein-Westfalen, Germany
  • Schomber, Tibor, Bayer AG, Leverkusen, Germany
  • Benardeau, Agnes M., Bayer AG, Leverkusen, Germany
  • Kahnert, Antje, Bayer AG, Leverkusen, Nordrhein-Westfalen, Germany
  • Popp, Laura, Bayer AG, Leverkusen, Nordrhein-Westfalen, Germany
  • Vienenkoetter, Julia, Bayer AG, Leverkusen, Nordrhein-Westfalen, Germany
  • Ellinger-Ziegelbauer, Heidrun Christine, Bayer AG, Leverkusen, Nordrhein-Westfalen, Germany
  • Pavkovic, Mira, Bayer AG, Leverkusen, Nordrhein-Westfalen, Germany
  • Kretschmer, Axel, Bayer AG, Leverkusen, Nordrhein-Westfalen, Germany
  • Lawrenz, Bettina, Bayer AG, Leverkusen, Nordrhein-Westfalen, Germany
  • Hartmann, Elke, Bayer AG, Leverkusen, Nordrhein-Westfalen, Germany
  • Siudak, Krystyna, Bayer AG, Leverkusen, Nordrhein-Westfalen, Germany
  • Freyberger, Alexius, Bayer AG, Leverkusen, Nordrhein-Westfalen, Germany
  • Hagelschuer, Ina, Bayer AG, Leverkusen, Nordrhein-Westfalen, Germany
  • Mathar, Ilka, Bayer AG, Leverkusen, Nordrhein-Westfalen, Germany
  • Hüser, Jörg, Bayer AG, Leverkusen, Nordrhein-Westfalen, Germany
  • Hahn, Michael G., Bayer AG, Leverkusen, Nordrhein-Westfalen, Germany
  • Stasch, Johannes-Peter, Bayer AG, Leverkusen, Nordrhein-Westfalen, Germany
  • Geiss, Volker, Bayer AG, Leverkusen, Nordrhein-Westfalen, Germany
  • Eitner, Frank, Bayer AG, Leverkusen, Nordrhein-Westfalen, Germany
  • Sandner, Peter, Bayer AG, Leverkusen, Nordrhein-Westfalen, Germany
Background

The novel sGC activator runcaciguat is currently being studied in a Phase II trial in proteinuric CKD patients (NCT04507061) and targets the oxidized and heme-free form of sGC, restoring cGMP production under oxidative stress.

Methods

Runcaciguat was tested in hypertensive rats, the renin transgenic (RenTG) rat, and angiotensin-supplemented (ANG-SD) rat as well as in rats with diabetic and metabolic CKD, Zucker diabetic fatty (ZDF), and ZSF-1 rats. The model specific treatment duration ranged up to 42 wks Runcaciguat was applied orally in doses of 1, 3, and 10 mg/kg/bid.

Results

In all four rat CKD models, runcaciguat significantly and dose-dependently reduced proteinuria by 40% to 55% (Table 1, Figure 1). Long-term, 42 wks treatment of ZDF rats demonstrated additional improvements in GFR decline as well as improvements in tubular degeneration, glomerulopathy, protein casts, and fibrosis.

Conclusion

Runcaciguat exhibits kidney protection in a broad range of CKD models with hypertensive as well as diabetic and metabolic etiologies that justifies its further exploration in proteinuric CKD patients.

uPCR reduction
 RenTGANG-SDZDFZSF-1
uPCR39.4%56.6%*49.8%*53.7%*

*, statistical significant difference at 3 mg/kg bid compared to placebo

Proteinuria (uPCR) in ZSF1 obese rats
black, placebo; red, 1 mg/kg/bid; blue, 3mg/kg/bid; green, 10 mg/kg/bid
At weeks 4 and at 12 of treatment, all three doses lower proteinuria significantly. At week 8, 3 mg/kg/bid and 10 mg/kg/bid lower proteinuria significantly.
Data are mean ± SEM. Statistics determined by one-way ANOVA followed by Tuckey’s multiple comparison test.