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Recombinant von Willebrand Factor

Phase 3

Von Willebrand Disease | Monoclonal antibody | Hematology |Takeda Pharmaceutical Company Limited|Last Updated: May 19, 2021

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
CONTROLLEDDMCBiomarker
Total Trials2
Total Enrollment73
FDA Designations
No designations recorded
Clinical Trials (2)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT02283268Recombinant Von Willebrand Factor in Subjects With Severe Von Willebrand Disease Undergoing SurgeryPHASE3 COMPLETED 24Apr 1, 2015Jul 6, 2016May 19, 202134 United States, Australia +11
NCT01410227Pharmacokinetics, Safety and Efficacy of Recombinant Von Willebrand Factor (rVWF) in the Treatment of Bleeding Episodes in Von Willebrand Disease (VWD)PHASE3 COMPLETED 49Nov 1, 2011Feb 1, 2014May 19, 202152 United States, Australia +14
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Study Endpoints
Primary Endpoints
Overall Hemostatic Efficacy as Assessed by the Investigator (Hemophilia Physician)
24 hours after last peri-operative infusion or at completion of Day 14 (± 2 days) visit, whichever occurs earlier

Hemostatic efficacy will be rated on a scale of excellent - good - moderate - none. Excellent: Intra-, and postoperative hemostasis achieved with rVWF with our without ADVATE was as good or better than that expected for the type of surgical procedure performed in a hemostatically normal subject. Good: Intra-, and postoperative hemostasis achieved with rVWF with or without ADVATE was probably as good as that expected for the type of surgical procedure performed in a hemostatically normal subject. Moderate: Intra-, and postoperative hemostasis with rVWF with or without ADVATE was clearly less than optimal for the type of procedure performed but was maintained without the need to change the rVWF concentrate. None: Participant experienced uncontrolled bleeding that was the result of inadequate therapeutic response despite proper dosing, necessitating a change of rVWF concentrate.

Percentage of Participants With Treatment Success for Treated Bleeding Episodes
For 12 months after first infusion of rVWF:rFVIII or rVWF

Treatment success was defined as the extent of control of bleeding episodes (BEs) using a mean efficacy rating score of \<2.5 for a participant's BEs treated with study product (recombinant von Willebrand Factor \[rVWF\] with or without recombinant factor VIII \[rFVIII\]) during the study period. Scores used: Excellent = 1 - actual infusions ≤ estimated number of infusions required to treat BE; no additional VWF required (all BEs); Good = 2 - \>1-2 infusions (minor/moderate BEs) or \<1.5 infusions (major BEs) greater than estimated required to control BE; no additional VWF required (all BEs); Moderate = 3 ≥ 3 infusions (minor/moderate BEs) or ≥ 1.5 infusions (major BEs) greater than estimated required to control BE; no additional VWF required (all BEs); None = 4 - severe uncontrolled bleeding or intensity of bleeding not changed; additional VWF required. Included participants with available primary efficacy rating (prospective-excluding gastrointestinal bleeds) in the Full Analysis Set.

Secondary Endpoints
Intraoperative Actual Versus Predicted Blood Loss as Assessed by the Operating Surgeon
Day 0 (at completion of surgery)
Intraoperative Actual Blood Loss Relative to Predicted Blood Loss
Day 0 (at completion of surgery)
Intraoperative Actual Versus Predicted Blood Loss Score as Assessed by the Operating Surgeon
Day 0 (at completion of surgery)
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Study Design & Arms
AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
Recombinant von Willebrand Factor (rVWF)EXPERIMENTALSurgery participants treated with Recombinant von Willebrand Factor (rVWF)
PK 80 Arm (minimum of 22 subjects with severe VWD)EXPERIMENTALPK assessment (80 IU/kg rVWF) + 12-month treatment period
PK 50 Arm (14 subjects with type 3 VWD)EXPERIMENTALTwo single-blinded PK assessments (50 IU/kg rVWF + rFVIII/placebo) + 12-month treatment period
PK 50 Only Arm (minimum of 7 subjects with type 3 VWD)EXPERIMENTALPK assessment (50 IU/kg rVWF) only, no treatment of bleeding episodes
Treatment Only (up to 7 subjects independent of VWD subtype)EXPERIMENTALTreatment of bleeding episodes for a total of 12 months
Interventions
NameTypeDescription
Recombinant von Willebrand Factor (rVWF)BIOLOGICALrVWF will be administered by intravenous bolus infusion. Participants planned for major surgery will undergo a baseline pharmacokinetic assessment prior to surgery. The peri- and postoperative substitution regimen will be individualized according to the PK results, intensity and duration of the hemostatic challenge, and the institution´s standard of care.
PlaceboDRUGSyringe supplied with physiologic saline solution for infusion
Recombinant factor VIIII (rFVIII)BIOLOGICALIntravenous administration
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Eligibility Criteria
Age Range18 Years — N/A
SexALL
Healthy VolunteersNo
Study Sites34

Inclusion Criteria: * Diagnosis of severe von Willebrand disease (VWD) as listed below and elective surgical procedure planned 1. Type 1 (Von Willebrand factor : Ristocetin cofactor activity (VWF:RCo) \<20 IU/dL), or 2. Type 2A (as verified by multimer pattern), Type 2B (as diagnosed by genoty...

Countries:United StatesAustraliaAustriaCzechiaGermanyItalyNetherlandsRussiaSpainTaiwanTurkey (Türkiye)UkraineUnited KingdomBelgiumBulgariaCanadaIndiaJapanPolandSweden
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