Observational Study on Safety and Efficacy of Factor Replacement Therapy in the Management of Von Willebrand Disease Patients - Results from an Ongoing Study with a VWF/FVIII Concentrate
Authors: Yaish Hassan M. , Khair Kate , von Depka Mario , Cruz Maria Sol , Werner Sylvia , Knaub Sigurd , Rodgers George M. 
Published: October 2019

Abstract
Introduction and Objective
Prospective surveillance studies are a useful tool to monitor drug safety and efficacy in the post-approval period and provide treaters and caregivers with real-life information about von Willebrand disease (VWD) treatment. This ongoing study aims to demonstrate consistency of safety and efficacy data of a VWF/FVIII concentrate with a 1:1 ratio (wilate®) used in routine clinical practice with data obtained in previous clinical studies.
Methods
This non-interventional post-marketing surveillance study was designed to document the safety, tolerability, and efficacy of a 1:1 VWF/FVIII concentrate in the prophylaxis and treatment of bleeding, as well as in the perioperative bleeding management in VWD patients. Treatment regimens and dosages were at the discretion of the investigators. The primary endpoints were tolerability assessment on a 3-point verbal rating scale and the incidence of investigator reported adverse drug reactions (ADRs). Additionally, the efficacy was assessed using a pre-defined 4-point haemostatic scale for on-demand treatment and surgeries, and the frequency of breakthrough bleeding events (BEs) for prophylaxis.
Results
Eighty-nine patients qualified as safety population, having received at least one infusion of the VWF/FVIII concentrate. Tolerability was rated 'excellent' for 4261/4450 (96%) assessed infusions. No development of clinically relevant VWF inhibitors or thrombotic events occurred. ADRs were reported in 6 of 89 patients (6.7%). The efficacy population comprised 47 patients undergoing 74 surgeries, 22 patients treated on-demand for 93 BEs, 12 patients on continuous prophylactic treatment, and 4 patients treated for 20 menstrual BEs. Some patients were assessed in more than one treatment group.
100% of rated bleeds in patients on on-demand treatment were assessed as 'excellent/good', receiving a mean total dose per BE of 111.4 (+/-69.78) IU/kg. Of the 44 minor and 31 major surgeries, 73 (99%) were rated as 'excellent/good' efficacy and one (1%) as 'moderate'. Mean dose of VWF/FVIII concentrate used was 78.6 (+/-126.16) IU/kg and 132.4 (+/-102.71) IU/kg for minor and major surgeries, respectively. Patients on continuous prophylaxis received a mean of 111.4 (+/-69.78) IU/kg in a mean of 2.4 (+/-0.86) infusions per week and experienced a median annualized bleeding rate of 2.3 (mean 3.3±5.6; range 0-19.7) for spontaneous bleeds and 2.5 (mean 4.8±6.2; range 0-19.7) for all types of bleeds. Efficacy for menstrual bleeding was rated as excellent or good in 100% of rated episodes (16/20).
Conclusion
The data confirm the safety, tolerability and efficacy of the 1:1 VWF/FVIII concentrate in the treatment of VWD patients in routine clinical conditions.

Disclosures
Yaish: Octapharma: Other: Study investigator. Khair:Pfizer: Research Funding; NovoNordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Baxalta, now part of Shire: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Study Investigator, Research Funding; Octapharma: Consultancy, Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Study Investigator, Patents & Royalties, Research Funding, Speakers Bureau; Sobi/Biogen: Research Funding. von Depka:Octapharma: Other: Study Investigator, Speakers Bureau. Cruz:Octapharma: Other: Study Investigator. Werner:Octapharma: Employment. Knaub:Octapharma: Employment. Rodgers:Octapharma: Other: Study Investigator.