Continuous Prophylaxis with Recombinant Von Willebrand Factor in People with Clinically Severe Congenital Types 1 and 2 Von Willebrand Disease in a Real-World Setting: Interim Analysis of Athn 9, a Natural History Study for People with Severe VWD

Background: Von Willebrand disease (VWD) presents with a spectrum of bleeding patterns and clinical symptoms, which can be independent of subtype (Rugeri. Haematologica. 2007; Kalot. Haemophilia. 2021). When there is recurrent and severe bleeding, prophylaxis may be appropriate (Connell, Blood Advances, 2021). Currently, real-world data on the use of prophylaxis with recombinant VWF (rVWF) in the United States are limited.

Objective: This study will characterize the safety and real-world effectiveness of routine prophylaxis with rVWF in people with clinically severe congenital Types 1 and 2 VWD.

Study Design and Methods: This is an interim analysis of a phase 4, longitudinal, prospective, observational cohort study (NCT03853486). Participants with severe VWD (Type 3 or VWF ≤30% of normal) or “clinically severe VWD” (VWF ≤40% of normal with severe bleeding and requiring prophylaxis with factor concentrates) were identified from the ATHNdataset. The American Thrombosis & Hemostasis Network (ATHN) is the steward of the ATHNdataset, a Health Insurance Portability and Accountability Act–compliant, limited dataset containing data from individuals with bleeding disorders receiving care through ATHN affiliates who opt in to contribute. Treatment regimens were at the discretion of each participant’s bleeding disorder provider. Participants are followed for 2 years from the time of enrollment. Bleeding events (BEs), safety, and satisfaction with rVWF prophylaxis were assessed. Descriptive statistics were used to analyze study outcomes.

Interim Results: As of May 31, 2024, 12 participants with Types 1 and 2 VWD received continuous prophylaxis with rVWF for at least 1 full year. Mean (SD) age was 43.1 (29.5) years; 75.0% (n=9) of participants were female. Most participants reported a family history of VWD (91.7%; n=11) and had no documented inhibitors (83.3%; n=10). VWF sequence defects and abnormal VWF multimers were identified in 91.7% (n=11) and 41.7% (n=5) of participants, respectively. The majority had Type 2 VWD (91.7%, n=11); 1 (8.3%) participant had Type 1 VWD. Prophylactic regimens ranged from 36.6 IU/kg once weekly to 99.01 IU/kg three times weekly. Five (41.6%) participants received 40–60 IU/kg at a frequency of 2–3 times/week as follows: 2 times/week (n=3), every 72 hours (n=1), 3 times/week (n=1).

A total of 34 BEs occurred in 3 (25.0%) participants while receiving rVWF prophylaxis; most spontaneous BEs (67.6%; 23/34) occurred in the gastrointestinal tract (n=22), and 1 bleed occurred in the ankle. The remaining BEs were associated with activity/exercise (n=5), unknown cause (n=4), or trauma (n=2). One participant reported 9 adverse events (AEs); all AEs were resolved and determined to be unrelated to rVWF treatment. When surveyed about their experience with rVWF, participants reported very or extremely satisfied as follows: 75% (n=9) with infusion time, 91.7% (n=11) with breakthrough bleed control time, 41.7% (n=5) with number of infusions required for breakthrough bleed control, and 58.3% (n=7) with frequency of achieving bleed control without concomitant hemostatic medication. The study is ongoing in 2 (16.7%) participants and 1 (8.3%) participant exited the study early.

Conclusions: In this real-world study assessing the use of rVWF prophylaxis in people with Types 1 and 2 clinically severe VWD, most participants were female with a family history of VWD and known VWF sequence defects. The majority of participants experienced no BEs or AEs and expressed overall satisfaction with their use of rVWF.