Safety Pharmacology, Toxicokinetics and Pharmacodynamics of VMX-C001, an Intravenous Bypassing Agent for Factor Xa Inhibitors, in Animal Models.
5 affiliations
- 1VarmX, Emmy Noetherweg 2, Plus Ultra Building, 2333 BK Leiden, The Netherlands.
- 2Division of Thrombosis and Haemostasis, Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
- 3DGr Pharma, Hoge Mosten 2c1, 4822 NH Breda, The Netherlands.
- 4Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands.
- 5Thrombosis Expertise Center, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands.
Abstract
Background: Anticoagulation therapy confers increased risk of potentially life-threatening bleeding events. Limited options exist for anticoagulation reversal in patients treated with direct oral factor Xa (FXa) anticoagulants (aka FXa inhibitors). Clinical development of reltodecacog alfa (VMX-C001), a modified form of human zymogen FX, as an FXa inhibitor-bypassing agent is ongoing. We report non-clinical pharmacology, toxicokinetic and pharmacodynamic studies of VMX-C001. Methods: Dose-ranging and 2-week toxicity studies were conducted in which Sprague-Dawley rats and cynomolgus monkeys received VMX-C001 at various doses for ≤2 weeks. Safety, pharmacologic, toxicokinetic and pharmacodynamic parameters were assessed. The anticoagulation-bypassing ability of VMX-C001 against edoxaban (ex vivo spiking) and rivaroxaban (in vivo) in monkeys was also evaluated. Results: No safety concerns were noted in either species at VMX-C001 doses up to 10 mg/kg; no VMX-C001-related adverse clinical signs were observed. VMX-C001 exhibited approximately dose-proportional kinetics, with no accumulation after repeat dosing. Changes in thrombin-generation parameters in both species were mild and non-adverse. VMX-C001 restored rivaroxaban-induced decreases in thrombin generation toward pre-rivaroxaban levels. In blood samples spiked ex vivo with edoxaban, the ability of VMX-C001 to support thrombin generation was maintained, even after repeat dosing. Conclusions: Treatment with VMX-C001 for 2 weeks was well tolerated at all tested doses. VMX-C001 had an approximately dose-proportional toxicokinetic profile, and accumulation was not observed upon repeat dosing. VMX-C001 also displayed a favourable pharmacodynamic profile and supported thrombin generation in the presence of FXa inhibitors.
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BibTeX
@article{verhoef2026safety,
title = {{Safety Pharmacology, Toxicokinetics and Pharmacodynamics of VMX-C001, an Intravenous Bypassing Agent for Factor Xa Inhibitors, in Animal Models.}},
author = {Daniël Verhoef and Gerard Short and Tainá Gomes and Kees Groen and Henri Spronk and Jan Ohrstrom and Pieter H Reitsma},
journal = {Pharmaceutics},
year = {2026},
month = sep,
doi = {10.3390/pharmaceutics18101210},
url = {https://europepmc.org/article/MED/42942742},
note = {CC BY},
}
RIS
TY - JOUR
TI - Safety Pharmacology, Toxicokinetics and Pharmacodynamics of VMX-C001, an Intravenous Bypassing Agent for Factor Xa Inhibitors, in Animal Models.
AU - Daniël Verhoef
AU - Gerard Short
AU - Tainá Gomes
AU - Kees Groen
AU - Henri Spronk
AU - Jan Ohrstrom
AU - Pieter H Reitsma
PY - 2026
DA - 2026/09/23
JO - Pharmaceutics
DO - 10.3390/pharmaceutics18101210
UR - https://europepmc.org/article/MED/42942742
AB - Background: Anticoagulation therapy confers increased risk of potentially life-threatening bleeding events. Limited options exist for anticoagulation reversal in patients treated with direct oral factor Xa (FXa) anticoagulants (aka FXa inhibitors). Clinical development of reltodecacog alfa (VMX-C001), a modified form of human zymogen FX, as an FXa inhibitor-bypassing agent is ongoing. We report non-clinical pharmacology, toxicokinetic and pharmacodynamic studies of VMX-C001. Methods: Dose-ranging and 2-week toxicity studies were conducted in which Sprague-Dawley rats and cynomolgus monkeys received VMX-C001 at various doses for ≤2 weeks. Safety, pharmacologic, toxicokinetic and pharmacodynamic parameters were assessed. The anticoagulation-bypassing ability of VMX-C001 against edoxaban (ex vivo spiking) and rivaroxaban (in vivo) in monkeys was also evaluated. Results: No safety concerns were noted in either species at VMX-C001 doses up to 10 mg/kg; no VMX-C001-related adverse clinical signs were observed. VMX-C001 exhibited approximately dose-proportional kinetics, with no accumulation after repeat dosing. Changes in thrombin-generation parameters in both species were mild and non-adverse. VMX-C001 restored rivaroxaban-induced decreases in thrombin generation toward pre-rivaroxaban levels. In blood samples spiked ex vivo with edoxaban, the ability of VMX-C001 to support thrombin generation was maintained, even after repeat dosing. Conclusions: Treatment with VMX-C001 for 2 weeks was well tolerated at all tested doses. VMX-C001 had an approximately dose-proportional toxicokinetic profile, and accumulation was not observed upon repeat dosing. VMX-C001 also displayed a favourable pharmacodynamic profile and supported thrombin generation in the presence of FXa inhibitors.
SN - 1999-4923
ER -