Pharmaceutics
Safety Pharmacology, Toxicokinetics and Pharmacodynamics of VMX-C001, an Intravenous Bypassing Agent for Factor Xa Inhibitors, in Animal Models
By Daniël Verhoef, Gerard Short, Tainá Gomes and 4 others.
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.