Abstract: TH-PO1206
Correlation of eGFR and pE-CCL2 in Older Adult Patients Treated with Varoglutamstat: Data from VIVIAD, a Phase 2B Randomized Clinical Trial
Session Information
- Late-Breaking Research Posters
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 702 Diabetic Kidney Disease: Clinical
Authors
- Schaeffer, Michael Karl, Vivoryon Therapeutics N.V., Halle (Saale), Germany
- Weber, Frank Thomas, Vivoryon Therapeutics N.V., Halle (Saale), Germany
- Hoffmann, Torsten, Vivoryon Therapeutics N.V., Halle (Saale), Germany
- Wenzkowski, Christine, Vivoryon Therapeutics N.V., Halle (Saale), Germany
- Schell-Mader, Sylvia, Vivoryon Therapeutics N.V., Halle (Saale), Germany
- Meyer, Antje, Vivoryon Therapeutics N.V., Halle (Saale), Germany
- Tasler, Stefan, Vivoryon Therapeutics N.V., Halle (Saale), Germany
- Fuchs, Katharina, Vivoryon Therapeutics N.V., Halle (Saale), Germany
- Carroll, Kevin, KJC Statistics Ltd, Dublin, Ireland
- Huber, Tobias B., Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
Background
Varoglutamstat is an oral, small molecule inhibitor of glutaminyl cyclases (QPCT/L), which are involved in the maturation of biologically active peptides/proteins by catalyzing the formation of an N-terminal pyroglutamyl (pE) residue required for full activity and/or stability of the respective peptides.
Methods
VIVIAD (NCT04498650) is a randomized clinical trial (Phase 2b) in 259 patients with early Alzheimer’s disease treated with 300 or 600 mg varoglutamstat, or placebo, BID for 48-96 weeks. Measurement of eGFR and biomarkers of inflammation were prospectively defined. pE-CCL2 serum levels were measured at baseline and at week 48 with an ELISA. Individual patient slopes of eGFR (MDRD formula) were calculated using random-coefficient analysis. Spearman correlations were calculated with R.
Results
Varoglutamstat improved kidney function as judged by a significant and clinically meaningful increase of the estimated glomerular filtration rate (eGFR). This effect was dose-dependent. Statistically significant improvement of eGFR above baseline was replicated in a second RCT (VIVA-MIND, data not shown). Furthermore, a treatment-related reduction of mature pE-CCL2, a chemokine involved in inflammation and fibrosis, was observed.
Dose dependent increase of eGFR and reduction of pE-CCL2 was observed under treatment with varoglutamstat. Further analysis on patient level confirmed a moderate (Spearman’s rho = -0.38, p = 1.1*10-8) inverse correlation between change in pE-CCL2 serum levels at week 48 and the slope in eGFR over time. Accordingly, a decrease in pE-CCL2 serum levels is associated with an increase of the eGFR slope over time.
Conclusion
Base-level pyroglutamylation of CCL2 occurs mainly intracellularly in the Golgi apparatus. This transformation increases its inflammatory potency and renders it more resistant against degradation. The results show that a beneficial effect on eGFR and a reduction of pE-CCL2 serum levels, both effector parameters of the inhibition of glutaminyl cyclases, are well correlated. Glutaminyl cyclase inhibition which can combine anti-inflammatory effects via reduction of chemokine activity with direct effects of on kidney function is a promising new approach to treat diabetic kidney disease.