Long-term prophylaxis with a von Willebrand factor (VWF) concentrate is recommended in patients with von Willebrand disease (VWD) who have a history of severe and frequent bleeds. However, data from prospective studies are scarce. WIL-31, a prospective, noncontrolled, international phase 3 trial, investigated the efficacy and safety of Wilate prophylaxis in severe patients with VWD. 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 end point of a >50% reduction in mean total annualized bleeding rate (TABR) with Wilate prophylaxis vs 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 vs on-demand treatment. During prophylaxis, 10 (30.3%) patients had 0 bleeding events and 15 (45.5%) patients had 0 spontaneous bleeding events. 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,
respectivelyvon Willebrand disease (VWD) is the most common inherited bleeding disorder with a prevalence of 0.6% to 1.3%.1 In VWD, hemostasis is impaired due to deficiency or dysfunction of von Willebrand factor (VWF).2 The severity of the bleeding phenotypes differs widely between patients with VWD, ranging from mild to severe, with type 3 VWD characterized by a severe bleeding phenotype.3 Long-term prophylaxis is recommended and well established in hemophilia. The goal of prophylaxis is to reduce bleeding rates to a minimum, reduce the risk of joint damage, and improve quality of
life.4 The positive experience with prophylaxis in hemophilia provides a rationale for prophylaxis in VWD.5,6 Indeed, in a post-hoc analysis of 331 patients with VWD, patients on VWF prophylaxis had fewer bleeds, fewer hospitalizations due to bleeds, and a lower likelihood for joint damage and moderate chronic pain, compared with patients who were eligible for but not receiving prophylaxis.7 Current guidelines recommend that patients with VWD who have a history of severe and frequent bleeds should use long-term prophylaxis with a VWF product.8 However, long-term prophylaxis is not the current standard of care for patients with VWD. In a survey of 6208 patients with VWD, only 1.6% received prophylaxis, most of them type 3 patients who had experienced joint bleeding.9 Wilate is a plasma-derived factor concentrate containing VWF and factor VIII (FVIII) in a physiological 1:1 activity ratio, which is indicated in patients with VWD for treatment of bleeds and perioperative management of bleeding and for prophylaxis.10,11 Across 4 clinical trials of patients with VWD, 19 patients received Wilate for prophylaxis, and their bleeding rates were reduced during prophylaxis compared with previous treatment.12 Here, we present the efficacy and safety results of the phase 3 WIL-31 study, which collected data specifically in patients with VWD undergoing regular prophylaxis with Wilate after a prospective 6-month run-in phase of on-demand treatment (WIL-29).