PB0841 Investigation of VWD in Women with Menorrhagia or Dysmenorrhea Associated with Bleeding

Background: Long-term prophylaxis is recommended for patients with von Willebrand disease (VWD) who have a history of severe, frequent bleeds.In previous clinical trials, prophylaxis with a human plasma-derived von Willebrand factor/factor VIII concentrate (wilate ® ; pdVWF/FVIII) reduced bleeding rates compared with previous on-demand treatment.Aims: To assess efficacy and safety of pdVWF/FVIII prophylaxis in patients with VWD.Methods: WIL-31, a prospective, non-controlled, international, phase 3 trial (NCT04052698), enrolled patients ≥6 years old of any gender with VWD type 1 (VWF:RCo < 30 IU/dL), type 2 (except 2N) or type 3.During a 6month run-in study (WIL-29), patients received on-demand treatment and those who experienced ≥6 non-menstrual bleeds, of which ≥2 were treated with a VWF-containing product, were eligible to enter WIL-31.During WIL-31, patients received pdVWF/FVIII prophylaxis (20-40 IU/kg 2-3 times per week) for 12 months.The primary endpoint was >50% reduction in mean total annualized bleeding rate (ABR) during prophylaxis compared with ondemand treatment.Results: 33 patients were included in the modified full analysis set; 9 were < 12 years, 22 had VWD type 3.The primary endpoint was met (mean total ABR decreased by 84%).The median treated total and spontaneous ABRs decreased from 22.4 and 16.4 during WIL-29 to 1.0 and 0.0 during WIL-31, respectively.18 (55%) patients had zero treated spontaneous bleeds during 12 months of prophylaxis.Median treated total ABRs decreased from 24.8 to 1.0 in type 3 patients and from 24.0 to 1.0 in patients < 12 years (Figure 1).The median weekly dose was 58 IU/kg, and at study end, 70% of patients were on twice-weekly dosing.No thrombotic events and no serious adverse events related to pdVWF/FVIII were reported. Conclusion(s):Prophylaxis with pdVWF/FVIII was effective and well tolerated in children and adults with VWD of all types.