Takeda's Recombinant von Willebrand Factor Meets Primary Endpoint in Phase 3 Prophylaxis Trial for von Willebrand Disease

Compiled & Translated | newborn

On July 21, Takeda Pharmaceutical Company Limited announced the results of a Phase 3 clinical trial at the 2021 Congress of the International Society on Thrombosis and Haemostasis (ISTH). The trial, conducted in adult patients with von Willebrand disease (VWD), aimed to evaluate the efficacy and safety of recombinant von Willebrand factor (rVWF; brand name: Veyvondi/Vonvendi) for prophylactic treatment. The results showed that the trial met its primary endpoint of reducing the annualized bleeding rate (ABR) for spontaneous and treated bleeding events.

VWD is the most common inherited bleeding disorder, caused by a deficiency or dysfunction of von Willebrand factor (VWF), which is one of several proteins in the blood required for normal coagulation. Due to VWF deficiency or insufficiency, the blood of patients with VWD cannot clot effectively, leading to prolonged bleeding time. The severity of the disease varies widely, but any patient with VWD may experience severe bleeding.

This prospective, open-label, international, multicenter phase 3 study enrolled a total of 23 patients with severe VWD over a 12-month period and comprised two groups: (1) the prior on-demand (OD) group, which included patients who had previously received on-demand VWF therapy and initiated prophylactic rVWF treatment in the study, administered twice weekly at a dose of 50±10 IU/kg per infusion; and (2) the switch group, which included patients who had previously received prophylactic plasma-derived von Willebrand factor (pdVWF) therapy and initiated prophylactic rVWF treatment in the study, with the dose matched (±10%) to the weekly dose of their prior pdVWF prophylactic regimen. In this study, a total of 23 patients received prophylactic rVWF treatment (prior OD group: n=13; switch group: n=10), and 18/23 (78.3%) of the patients had type 3 VWD.

The results showed that during the 12-month study period: prophylactic treatment with rVWF effectively reduced the annualized bleeding rate for spontaneous and treated bleeding events (sABR) in the prior on-demand treatment group, while patients in the switch group (transitioning from pdVWF prophylaxis to rVWF prophylaxis) maintained the same level of hemostatic control. During the study (while receiving rVWF prophylaxis), in the prior on-demand treatment group, rVWF prophylaxis reduced sABR by 91.5% compared with patients' historical sABR data (sABR study-to-historical ratio = 0.09 [95% CI: 0.02, 0.35]). In the switch group, rVWF prophylaxis maintained sABR compared with patients' historical sABR data (sABR study-to-historical ratio = 0.55 [95% CI: 0.09, 3.52]).

During the 12-month study period, 84.6% (11/13) of patients in the prior on-demand treatment group and 70.0% (7/10) of patients in the switch group had a post-treatment sABR of 0. In contrast, prior to study entry, 100% (13/13) of patients in the prior on-demand treatment group and 10% (1/10) of patients in the switch group had an sABR > 2.

In this study, rVWF maintained a favorable benefit-risk profile. No new risks were identified, and no serious adverse events related to rVWF were reported. One adverse event that occurred during the study—moderate headache—was considered by the investigator to be possibly related to rVWF, resulting in the discontinuation of rVWF treatment and withdrawal from the study.

On-demand therapy can effectively control bleeding in patients with von Willebrand disease (VWD), but it cannot prevent subsequent bleeding episodes. For many patients receiving on-demand therapy, the complications and unpredictability of these bleeding events impact their daily lives. The aforementioned Phase 3 trial results are crucial for enhancing awareness of the potential benefits of prophylactic treatment with recombinant von Willebrand factor (rVWF) and for helping VWD patients reduce future spontaneous bleeding episodes.

Source: Takeda Data at ISTH 2021 Highlight the Benefits of Prophylaxis for Patients with Rare Bleeding Disorders