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. 2024 Mar 26;8(6):1405-1414.
doi: 10.1182/bloodadvances.2023011742.

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

Robert F Sidonio Jr  1 , Ana Boban  2 , Leonid Dubey  3 , Adlette Inati  4   5 , Csongor Kiss  6 , Zoltan Boda  7 , Toshko Lissitchkov  8 , Laszlo Nemes  9 , Dzmitry Novik  10 , Elina Peteva  11 , Ali T Taher  12 , Margarita Arkadevna Timofeeva  13 , Kateryna V Vilchevska  14 , Vladimir Vdovin  15 , Sylvia Werner  16 , Sigurd Knaub  17 , Claudia Djambas Khayat  18
Affiliations

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

Robert F Sidonio Jr et al. Blood Adv. .

Abstract

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.

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Conflict of interest statement

Conflict-of-interest disclosure: R.F.S. Jr has received research funding from Octapharma and Takeda, honoraria for consulting and advisory boards from Octapharma, Takeda, Laboratoire français du Fractionnement et des Biotechnologies (LFB), Sanofi, SOBI, Novo Nordisk, Bayer, Pfizer, BioMarin, Vega, Guardian Therapeutics, payment for expert testimony from Sanofi; has participated on a data safety monitoring board or advisory board for Uniqure; and has had a role as American Thrombosis and Hemostasis Network board member, International Society on Thrombosis and Haemostasis (ISTH) Chair, Hemophilia Federation of America medical adviser, and with the Medical and Scientific Advisory Council of the National Hemophilia Foundation. A.B. has received research funding from Octapharma, honoraria from Amgen, AstraZeneca, Bayer, CSL Behring, Novo Nordisk, Octapharma, Pfizer, Roche, SOBI, Swixx, and Takeda and travel support from SOBI, Novo Nordisk, Takeda; has participated on a data safety monitoring board or advisory board for SOBI, Takeda, Bayer, Swixx, AstraZeneca, and has had a role in the European Association for Haemophilia and Allied Disorders and ISTH. L.D. has participated as a clinical trial investigator for Octapharma. A.I. has received consultancy and research funding from Novartis, Global Blood Therapeutics/Pfizer, Roche, Forma/Novo Nordisk, Vifor, and research funding from Agios and Octapharma. C.K. has received consulting fees from Novo Nordisk Hungaria, Takeda Pharma, and H-W-H; honoraria from Novo Nordisk Hungaria, Takeda Pharma, SOBI, Roche Hungary, and CSL Behring; and travel support from Novo Nordisk Hungaria, SOBI, and CSL Behring. Z.B. has received consulting fees, honoraria, and travel support from Novo Nordisk and Takeda. T.L. has received grant support and speakers fees from Octapharma. L.N. has received consulting fees from Octapharma, CSL Behring, Novo Nordisk, SOBI, and Takeda; honoraria from Octapharma, Takeda, Novo Nordisk, and SOBI; and received travel support from Octapharma, Novo Nordisk, and Takeda. A.T.T. has received grant support and consulting fees and consulting fees from Novartis, Bristol Myers Squibb, Vifor, Agios, and Pharmacosmos. S.W. is an employee of Octapharma USA. S.K is an employee of Octapharma AG. C.D.K. has received presentation and speaker fees from Octapharma, CSL Behring, and LFB and support for travel and attending meetings from Octapharma, CSL Behring, and LFB. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Patient disposition for WIL-31. AE, adverse event; ED, exposure day.
Figure 2.
Figure 2.
Individual TABR during 6-month on-demand treatment period and during 12-month prophylaxis by VWD type. ∗In 1 severe type 1 VWD patient with small bowel ulcers, the total ABR was higher in WIL-31 (35.81) than in WIL-29 (21.84) due in part to an increase in gastrointestinal BEs and a clip failure at an anastomosis site. Modified full analysis set, n = 33.
Figure 3.
Figure 3.
Occurrence of bleeds. Twenty-three of 33 patients in the modified full analysis set experienced 173 BEs (excluding menstrual bleeds) during Wilate prophylaxis in WIL-31. All 33 patients experienced a total of 593 BEs during on-demand treatment in WIL-29. (A) Number of BEs by site, type, and severity, (B) Percentage of BEs by site, type, and severity.
Figure 4.
Figure 4.
Patients with 0 bleeds during 12 months of prophylaxis. Modified full analysis set, n = 33.
Figure 5.
Figure 5.
Incremental IVR for VWF and FVIII over time. Modified full analysis set, n = 33. (A) VWF:RCo, (B) FVIIII:C (1-stage assay). BL, baseline; CI, confidence interval.
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