Key result
VMX-C001 proves safe and supports thrombin generation despite FXa inhibitors in animal models.
Why the study?
Limited options exist for anticoagulation reversal in patients treated with direct oral factor Xa inhibitors, motivating evaluation of VMX-C001 as a bypassing agent.
Does VMX-C001 safely restore thrombin generation in the presence of Factor Xa inhibitors in animal models?
Does VMX-C001 safely restore thrombin generation in the presence of Factor Xa inhibitors in animal models?
In animal models, VMX-C001 was well tolerated and effectively supported thrombin generation in the presence of Factor Xa inhibitors, supporting its clinical development as a reversal agent.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“This publication underscores the robustness of VMX-C001's mechanism of action and our commitment to developing science-driven solutions for patients on FXa inhibitors. The ability to rapidly and reliably measure bypassing of the anticoagulant effect of FXa inhibitors by VMX-C001 will be critical as we advance into Phase 3 trials and ultimately into clinical practice.”
“We are happy and grateful that the ISTH Congress organizers have recognized the impact and importance of the new preclinical data package that details pharmacological and safety aspects of VMX-C001. This work has paved the way to initiation of our first-in-human study of VMX-C001, which is now ongoing, and the resulting transition of VarmX from a preclinical into a clinical company.”
Supports VMX-C001 advancement for FXa reversal; leaves open clinical safety and efficacy.
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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Verhoef et al. (2026) studied Anticoagulation reversal. VMX-C001 (reltodecacog alfa) was evaluated on Safety, pharmacologic, toxicokinetic and pharmacodynamic parameters. In animal models, VMX-C001 at doses up to 10 mg/kg for up to 2 weeks was well tolerated with no safety concerns and supported thrombin generation in the presence of FXa inhibitors.
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