Abstract Number: OC 24.3
Meeting: ISTH 2022 Congress
Theme: Acquired Bleeding Disorders » Novel Therapies in the Management of Acquired Bleeding
Background: VMX-C001, a modified form of human zymogen factor X, is being developed to stop or prevent bleeding in patients taking factor Xa inhibitors and is currently in human phase I studies.
Aims: To examine the pharmacodynamics of VMX-C001 and factor Xa inhibitor reversal in rats and cynomolgus monkeys by means of thrombin generation (TG).
Methods: Subsequent to dose range finding studies, 2-week toxicity studies were performed at doses of 20, 50 and 100 IU/kg/day VMX-C001, followed by a two-week recovery period.
Results: In rats, regardless of sex, there were no VMX-C001 related changes compared to pre-dose and placebo in endogenous thrombin potential (ETP), thrombin peak height and time to initiation of thrombin generation (ie. lag time). Similarly, administration of VMX-C001 to monkeys was not associated with significant changes in TG parameters. There was no overshooting of TG parameters regardless of dose level, dose period, sex, or species. During dosing, reversal of anticoagulation was examined in two males and females receiving VMX-C001 (20 IU/kg/day) by ex-vivo spiking of plasma from the VMX-C001 dosed animals with edoxaban (250 ng/ml). Five minutes after intravenous administration, VMX-C001 corrected the effect of edoxaban on ETP and lag time and restored peak height to near normal levels (Figure 1). In another setup, five male monkeys received rivaroxaban by oral gavage (10 mg/kg) and VMX-C001 was administered once 3 hours after the factor Xa inhibitor. Rivaroxaban (plasma level 407 ng/ml) was associated with markedly suppressed TG parameters. These changes were fully reversed after administration of 50 IU/kg VMX-C001 (Figure 2).
Conclusion(s): VMX-C001 displays a favorable pharmacodynamic profile where repeated administration of VMX-C001, at levels of 20, 50 and 100 IU/kg in rats and monkeys is not associated with changes in TG parameters. In addition, VMX-C001, at a dose of 20 IU/kg, restores thrombin generation in the presence of factor Xa inhibitors.
To cite this abstract in AMA style:
Verhoef D, Gomes T, Spronk H, Short G, Reitsma P. VMX-C001 is an effective factor Xa inhibitor reversal agent and displays a favorable pharmacodynamic profile in animal models [abstract]. https://abstracts.isth.org/abstract/vmx-c001-is-an-effective-factor-xa-inhibitor-reversal-agent-and-displays-a-favorable-pharmacodynamic-profile-in-animal-models/. Accessed March 21, 2024.« Back to ISTH 2022 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/vmx-c001-is-an-effective-factor-xa-inhibitor-reversal-agent-and-displays-a-favorable-pharmacodynamic-profile-in-animal-models/