General Information

Wilate is a human plasma-derived, sterile, purified, double virus inactivated von Willebrand Factor (VWF)/coagulation factor VIII complex (human), both of which are normal constituents of human plasma. Patients suffering from VWD have a deficiency or abnormality of VWF. This reduction in VWF concentration in the bloodstream results in a correspondingly low FVIII activity and an abnormal platelet function, thereby resulting in excessive bleeding. The administration of VWF allows for the following: 1) The VWF re-establishes platelet adhesion, providing primary hemostasis, as shown by the shortening of the bleeding time, and 2) The VWF induces correction of the associated FVIII deficiency in VWD.

Wilate is specifically indicated for the treatment of spontaneous and trauma-induced bleeding episodes in patients with severe von Willebrand disease (VWD) as well as patients with mild or moderate VWD in whom the use of desmopressin is known or suspected to be ineffective or contraindicated. Wilate was approved for an expanded indication in October 2019 to include the treatment of adults and adolescents with hemophilia A for routine prophylaxis to reduce the frequency of bleeding episodes and on-demand treatment and control of bleeding episodes.

Mechanism of Action

Wilate is a human plasma-derived, sterile, purified, double virus inactivated von Willebrand factor (VWF)/coagulation factor VIII complex (human). VWF and FVIII are normal constituents of human plasma. VWF is a multimeric protein with two key functions. It is an adhesive molecule, which mediates the binding between platelets and damaged sub-endothelial tissues. It is also a carrier protein, involved in the transport and stabilization of FVIII. Patients suffering from VWD have a deficiency or abnormality of VWF. This reduction in VWF concentration in the bloodstream results in a correspondingly low FVIII activity and an abnormal platelet function, thereby resulting in excessive bleeding. The VWF in Wilate is derived from normal human plasma and is expected to behave in the same way as endogenous VWF. Thus, administration of VWF allows correction of the hemostatic abnormalities in VWD patients at two levels: 1) The VWF re-establishes platelet adhesion to the vascular sub-endothelium at the site of vascular damage, providing primary hemostasis, as shown by the shortening of the bleeding time; and 2) The VWF induces correction of the associated FVIII deficiency in VWD.

Side Effects

Adverse events associated with the use of Wilate may include, but are not limited to, the following:

• Urticaria
• Dizziness

Dosing/Administration

Wilate is supplied as a powder for reconstitution designed for intravenous administration. The dosage should be adjusted according to the extent and location of the bleeding. In VWD type 3 patients, especially in those with gastrointestinal bleeding, higher doses may be required. The recommended initial dosages are as follows:

Minor Hemorrhages Loading dosage: 20 to 40 IU/kg; maintenance dosage: 20 to 30 IU/kg every 12 to 24 hours, which may need to be continued for up to three days; therapeutic goal: VWF:RCo and FVIII activity trough levels of >30 percent.
Major Hemorrhages loading dosage: 40 to 60 IU/kg Maintenance dosage: 20 to 40 IU/kg every 12 to 24 hours, which may need to be continued for up to seven days; therapeutic goal: VWF:RCo and FVIII activity trough levels of >50 percent.

Clinical Trial Results

FDA Approval
The FDA approval of Wilate was based on four clinical studies in 70 subjects and 1,068 bleeding episodes (BEs). The treated BEs were analyzed for efficacy using a set of objective criteria in addition to a subjective four-point hemostatic efficacy scale (excellent, good, moderate and none). Among the 70 VWD patients administered Wilate in clinical studies, 45 received on-demand treatment for BEs. Using the objective criteria, corresponding efficacy for each bleeding event was rated as being successful in 84 percent of the episodes. In these 45 patients with BEs, 93 percent of the successfully treated BEs occurred in VWD type 3 patients (n=25).