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

• Published in: Blood advances Vol. 8; no. 6; pp. 1405 - 1414
• Main Authors: Sidonio, Robert F., Boban, Ana, Dubey, Leonid, Inati, Adlette, Kiss, Csongor, Boda, Zoltan, Lissitchkov, Toshko, Nemes, Laszlo, Novik, Dzmitry, Peteva, Elina, Taher, Ali T., Timofeeva, Margarita Arkadevna, Vilchevska, Kateryna V., Vdovin, Vladimir, Werner, Sylvia, Knaub, Sigurd, Djambas Khayat, Claudia
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.03.2024; The American Society of Hematology
• Subjects: Adolescent; Adult; Child; Clinical Trials and Observations; Factor VIII - adverse effects; Female; Hemorrhage - chemically induced; Hemorrhage - prevention & control; Humans; Male; Prospective Studies; von Willebrand Diseases - drug therapy; von Willebrand Factor - adverse effects
• ISSN: 2473-9529; 2473-9537
• DOI: 10.1182/bloodadvances.2023011742

•Prophylaxis with a VWF/FVIII concentrate (Wilate) reduced bleeding in children/adults with all types of severe VWD vs on-demand treatment.•Prophylaxis with Wilate was well-tolerated with no thrombotic events. [Display omitted] 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, respectively.