<p>An Open-Label Extension Study to Assess the Long-Term Efficacy and Safety of a Plasma-Derived von Willebrand Factor (VWF)/Factor VIII (FVIII) Concentrate in Patients with von Willebrand Disease (SWIFT-VWDext Study)</p>

Abstract

Objective: Plasma-derived von Willebrand factor/factor VIII (pdVWF/FVIII; VONCENTO ® , CSL Behring) is a high-concentration, low-volume, high-purity concentrate, which contains a high level of high-molecular-weight multimers and a VWF/FVIII ratio of ~2.4:1. The SWIFT ("Studies with von Willebrand factor/Factor VIII") program is evaluating pdVWF/FVIII in patients with von Willebrand disease (VWD). The long-term efficacy and safety profile of pdVWF/FVIII was investigated in this multicenter, open-label, extension study. Methods: Pediatric, adolescent, and adult patients with VWD who required treatment of nonsurgical bleeds (NSBs), treatment during surgical events or who were receiving prophylaxis and who had completed one of two previous clinical trials of pdVWF/FVIII were included. Efficacy and safety analyses were performed for on-demand (n=10), prophylaxis (n=8), or on-demand and prophylaxis (n=2) treatment in patients pre-treated with pdVWF/FVIII for ≥12 months. Results: Seven patients experienced a total of 402 NSBs in the on-demand arm, of which 77 required treatment and nine NSB events in three patients were considered major. Nine patients reported 118 NSBs in the prophylaxis arm, with 96 events requiring treatment and seven patients experiencing 12 major NSB events. Excellent or good hemostatic efficacy was reported by the investigator for 98.7% (on-demand) and 97.9% (prophylaxis) of NSB events treated with pdVWF/FVIII, without relevant differences between subgroups by age. pdVWF/ FVIII was well tolerated, and the adverse events seen were mild-moderate and consistent with the safety profile for this product seen in other studies. There were no cases of anaphylactic reactions and angioedema, development of VWF/FVIII inhibitors, thromboembolic events, or viral infections. Conclusion: This contemporary comprehensive development program evaluating pdVWF/ FVIII across all ages demonstrates long-term safety and efficacy for treatment and prevention of bleeds in patients with severe VWD, supporting the benefit-risk profile of pdVWF/FVIII.

Effectiveness of long‐term prophylaxis using pdFVIII/VWF concentrate in patients with inherited von Willebrand disease

“…Despite the use of a pdVWF/FVIII, no thrombotic event was reported, supporting the observations previously made on the safety of this type of concentrates, which are similar to those reported in series using FVIII‐poor VWF concentrates 12,14,17 …”

“…Despite the use of a pdVWF/FVIII, no thrombotic event was reported, supporting the observations previously made on the safety of this type of concentrates, which are similar to those reported in series using FVIII-poor VWF concentrates. 12,14,17 Some limits in our study warrant discussion. Some types of bleeding episodes such as GI bleeding were not reported because of the T A B L E 5 (Continued)…”

“…A search in the medical literature has revealed that among the 13 studies showing a benefit of the prophylaxis regimen, only 7 are prospectively designed, and they all suffer from a large heterogeneity in study design, study population, VWD subtypes, and use of type of concentrate (Table 5). 5,12,14–24 …”

“…A search in the medical literature has revealed that among the 13 studies showing a benefit of the prophylaxis regimen, only 7 are prospectively designed, and they all suffer from a large heterogeneity in study design, study population, VWD subtypes, and use of type of concentrate (Table 5). 5,12,[14][15][16][17][18][19][20][21][22][23][24] Most patients included in the study were type 3 patients, reflecting the severity of the clinical forms leading the clinicians to broadly initiate a prophylaxis regimen. The number of type 2B patients requiring prophylaxis was also high, due to their low baseline platelet count.…”

“…10 Some authors have recently showed the effectiveness and safety of Voncento ® for the perioperative management of VWD patients (all types), as well as the long-term safety and effectiveness for the treatment and prevention of bleeding events in patients with severe VWD. 11,12 In addition, a reduced incidence of major bleedings, including joint bleedings, has been reported among children with VWD treated prophylactically with Voncento ® compared to patients treated OD. 13 Because the experts agree on the lack of large prospective studies that could inform and provide recommendations on the dose and frequency of treatments to be administered depending on the subtype of VWD or on the clinical symptoms, the objective of this study was to provide data about the effectiveness and safety of a pdFVIII/VWF (Voncento ® ) administrated in LTP in patients with symptomatic VWD.…”