von Willebrand factor/factor VIII concentrate (Wilate) prophylaxis in children and adults with von Willebrand disease

Abstract

Long-term prophylaxis with a von Willebrand factor (VWF) concentrate is recommended in von Willebrand disease (VWD) patients with a history of severe and frequent bleeds. However, data from prospective studies are scarce. WIL-31, a prospective, non-controlled, international phase 3 trial, investigated the efficacy and safety of wilate® prophylaxis in severe VWD patients. Male and female patients 6 years or older with VWD types 1, 2 (except 2N) or 3 who had completed a prospective, 6-month, on-demand, run-in study (WIL-29) were eligible to receive wilate® prophylaxis for 12 months. At baseline, patients (n = 33) had a median age of 18 years. Six (18%) patients had severe type 1, 5 (15%) had type 2, and 22 (67%) had type 3 VWD. The primary endpoint of a >50% reduction in mean total annualized bleeding rate (TABR) with wilate® prophylaxis versus prior on-demand treatment was met; mean TABR during prophylaxis was 5.2, representing an 84.4% reduction. The bleeding reduction was consistent across age, sex and VWD types. The mean spontaneous ABR was 3.2, representing an 86.9% reduction versus on-demand treatment. Ten (30.3%) and 15 (45.5%) patients had zero total or spontaneous bleeding events (BEs) during prophylaxis. Of 173 BEs, 84.4% were minor and 69.9% treated. No serious adverse events related to study treatment and no thrombotic events were recorded. Overall, WIL-31 showed that wilate® prophylaxis was efficacious and well-tolerated in pediatric and adult patients with VWD of all types. The WIL-29 and WIL-31 trials were registered at www.clinicaltrials.gov as #NCT04053699 and #NCT04052698, respectively.