Abstract Number: PB1541
Meeting: ISTH 2020 Congress
Background: Recombinant von Willebrand factor (rVWF; vonicog alfa; Baxalta US Inc., Lexington, MA, USA) replacement therapy for von Willebrand disease (VWD) corrects VWF activity (measured by VWF:ristocetin cofactor [RCo]) and increases factor VIII (FVIII) activity to hemostatically effective levels. Increased understanding of the effects of rVWF dosing on VWF:RCo and FVIII activities could optimize outcomes for individual patient needs.
Aims: To develop population pharmacokinetic (PK)/pharmacodynamic (PD) models that describe VWF:RCo and endogenous FVIII activity-time profiles following administration of rVWF.
Methods: A population PK model for rVWF was developed from individual patient data (1664 samples; n=79) from 3 rVWF studies in patients with different VWD types (phase 1: NCT00816660; phase 3: NCT01410227, NCT02283268) and a phase 1 study in patients with severe hemophilia A. A population PK/PD model was subsequently developed using FVIII activity data from both phase 3 VWD studies (686 FVIII samples; n=41, different VWD types). The rVWF trials were approved by the institutional review boards or independent ethics committees of all participating sites, and all patients provided written informed consent.
Results: Standard methods including goodness-of-fit plots and visual predictive checks verified that the rVWF population PK/PD model captures the variability in VWF:RCo and FVIII activity after single and repeated rVWF doses. This model allows the prediction of the VWF:RCo-versus-time curves as well as the FVIII-activity-versus-time curves following single and multiple doses of rVWF. For example, simulation of repeated 50 IU/kg rVWF doses every 72 hours suggested that FVIII activity is maintained at highly hemostatically effective levels (trough level of ≥40 IU/dL) in a considerable proportion of patients with type 3 VWD.
Conclusions: This population PK/PD model describes VWF:RCo and FVIII activity in rVWF-treated patients with different VWD types, and could assist in the optimization of rVWF personalized dosing strategies.
To cite this abstract in AMA style:Bauer A, Ploder B, Li Z, Mellgård B, Friberg-Hietala S, Wolfsegger M. Population Pharmacokinetics and Pharmacodynamics of Recombinant von Willebrand Factor [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/population-pharmacokinetics-and-pharmacodynamics-of-recombinant-von-willebrand-factor/. Accessed November 30, 2020.
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