Comparative analysis of prophylaxis with 1:1 ratio pdVWF/FVIII concentrate vs. recombinant VWF in type 3 von willebrand disease adults in the United States: Clinical and economic perspective

Abstract

Abstract Background Prophylactic treatment with von Willebrand factor (VWF) concentrates is recommended for patients with type 3 von Willebrand disease (VWD). In the United States (U.S.), plasma-derived VWF/FVIII (pdVWF/FVIII; wilate®) and recombinant VWF (rVWF; Vonvendi®) are the only two VWF concentrates approved for routine prophylaxis in VWD. pdVWF/FVIII contains VWF and FVIII in a 1:1 activity ratio and is indicated for patients aged 6 years and older across all VWD types, whereas rVWF is currently approved solely for prophylaxis in adults with type 3 VWD. While both therapies have demonstrated clinical efficacy, comparative cost data remain limited. This analysis evaluates the annual prophylaxis costs of pdVWF/FVIII versus rVWF in adult patients with type 3 VWD, using clinical trial data and current U.S. average sales prices (ASPs) adjusted to 2025 dollars. Methods A cost model was developed from a U.S. payer perspective for an adult patient. Prophylactic dosing regimens, breakthrough bleeding rates, and were obtained from pivotal clinical trials: WIL-31 (NCT04052698) for pdVWF/FVIII and NCT02973087 for rVWF. Annual drug costs were calculated using average weekly dosing and July 2025 ASPs from Medi-Span: $1.271/IU for pdVWF/FVIII and $1.846/IU for rVWF. Healthcare resource utilization costs for minor and major bleeds were derived from published literature. Results The mean weekly pdVWF/FVIII dose was 61.8 ± 19.5 IU/kg, corresponding to approximately 4,326 IU/week for a 70-kg adult. The estimated annual prophylaxis cost was approximately $285,960 ± $90,216. The mean weekly rVWF dose was 92.6 ± 33.9 IU/kg (approximately 6,482 IU/week), yielding an estimated annual cost of $622,000 ± $227,789. Prophylaxis with pdVWF/FVIII resulted in a 54.0% ± 30.2% lower annual drug cost compared to rVWF. Even assuming an equal weekly dose for both products, the annual prophylaxis product costs with pdVWF/FVIII ($357,184.30 ± $71,224.04) remained substantially lower compared to rVWF ($518,774.37 ± $103,445.78) by 31.2% or $161,590 annually. Among patients switching from on-demand to prophylaxis with pdVWF/FVIII, the median total annualized bleeding rate (ABR) decreased by 93.6%, from 29.7 (range: 17.9-114.5) to 1.9 (range: 0.0-21.1). In patients switching to prophylaxis with rVWF, the median total ABR decreased by 52%, from 5.0 (range: 3.0-159.0) to 2.4 (range: 0.0-157.9). Median ABRs were comparable for both products. These low rates translated into modest annual costs to treat breakthrough bleeds: $7,880 for pdVWF/FVIII vs $13,970 for rVWF. The greater relative reduction observed with pdVWF/FVIII is largely attributable to higher baseline ABRs observed in the on-demand cohort, as well as differences in study design, specifically, the prospective nature of the on-demand phase in the WIL-31 study versus the retrospective design used in the rVWF study. Conclusions While the analysis is limited by its reliance on data from clinical trials with different designs and inclusion criteria, the results suggest that pdVWF/FVIII provides a substantial cost advantage over rVWF for adult patients with severe type 3 VWD. Based on current prophylaxis regimens and U.S. pricing, pdVWF/FVIII demonstrates favorable economic value. These findings support its consideration as a cost-saving, first-line prophylactic option in this population.