Results of a phase 3 clinical trial suggested recombinant von Willebrand factor (VWF) was efficacious in reducing spontaneous bleeding for patients with severe von Willebrand disease (VWD) previously treated in an on-demand manner, and without new risks identified. Trial results were presented in a poster at the International Society on Thrombosis and Haemostasis (ISTH) 2021 Congress by Frank WG Leebeek, MD, PhD, of Erasmus University Medical Center in Rotterdam, The Netherlands, with Flora Peyvandi, MD, PhD, of University of Milan in Milan, Italy, and colleagues.

In this open-label, nonrandomized, prospective trial ( Identifier: NCT02973087), 23 patients with severe VWD, defined by VWF ristocetin cofactor activity (RCo) of <20 IU/dL, were placed into 1 of 2 treatment arms for receipt of recombinant VWF. The arms included a prior-on-demand arm (prior-OD arm) or a prior plasma-derived VWF prophylaxis arm (switch arm).

The prior-OD arm received 50 + 10 VWF:RCo IU/kg twice per week. The switch arm received a starting dose and frequency of administration based on the prior plasma-derived VWF weekly dose, split across 1 to 3 infusions. The primary study endpoint was the spontaneous annualized bleeding rate (ABR), which involved a comparison of the 12-month, on-study ABR versus historical ABR for treated, spontaneous bleeding events while receiving recombinant VWF prophylaxis.

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At screening, the prior-OD arm included 13 patients, and the switch arm contained 10 patients. From the overall population, type 3 VWD was present in 78.3% of patients. The treated, spontaneous ABR was 0 for 84.6% of the prior-OD patients and 70.0% of the switch group over the course of 12 months of study.

Historical spontaneous ABRs were 6.54 (95% CI, 2.52-17.00) for the prior-OD arm and 0.51 (95% CI, 0.04-6.31) for the switch arm. The on-study spontaneous ABRs while receiving prophylactic recombinant VWF were 0.56 (95% CI, 0.15-2.05) for the prior-OD arm and 0.28 (95% CI, 0.02-3.85) for the switch arm. In comparisons of on-study vs historical ABRs, reductions in spontaneous ABR were 91.5% for the prior-OD arm and 45.0% for the switch arm.

The researchers reported no new risks identified in this study. Adverse events (AEs) were reported in 76.9% of patients in the prior-OD arm and in 70.0% of patients of the switch arm. Serious AEs were reported in 7.7% of the prior-OD arm and in 20.0% of the switch arm, with none attributed to recombinant VWF.

There was 1 AE that was considered possibly related to recombinant VWF: a moderate headache in a patient in the prior-OD group that resulted in treatment discontinuation. No life-threatening or fatal serious AEs were reported, and development of VWF or factor VIII inhibitors was also reported to not have occurred.

The researchers concluded that for patients in the prior-OD group, recombinant VWF prophylaxis reduced the frequency of spontaneous bleeding events that required treatment. Those who experienced a switch from plasma-derived VWF to recombinant VWF for prophylaxis showed similar results for spontaneous bleeding events.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Leebeek FWG, Peyvandi F, Escobar M, et al. Phase 3 trial results: prophylaxis with recombinant von Willebrand factor in patients with severe von Willebrand disease. Paper presented at: International Society on Thrombosis and Haemostasis (ISTH) 2021 Congress; July 17-21, 2021; virtual. Abstract LPB0128.