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

Le résumé fourni par la source

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. Conclusions: 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 reductionProteinuria (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.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.