Management of von Willebrand disease with a factor VIII‐poor von Willebrand factor concentrate: Results from a prospective observational post‐marketing study

Abstract

Background A triple‐secured plasma‐derived von Willebrand factor (pdVWF) almost devoid of factor VIII (FVIII):WILFACTIN ® , was approved in France in 2003, and then in other countries for the treatment of patients with von Willebrand disease (VWD). Objective To investigate long‐term safety and efficacy of the product in real‐life over the first 5 post‐approval years. Patients/Methods This prospective, observational, national post‐marketing study (PMS) enrolled patients of all ages and VWD types. Patients were observed for up to 3 years and treated for one or more occasions. Efficacy was assessed for each major event. Breakthrough bleeding rate 3 days post‐infusion and annualized bleeding rate (ABR) were also evaluated for long‐term prophylaxis. Results Overall, 155 of 174 patients enrolled from 31 centers were eligible for efficacy assessment. Most patients (76.8%) were severely affected (VWF:RCo ≤ 15 IU/dL). They were treated for 743 bleeds and 140 surgeries including childbirth. Efficacy outcomes were excellent/good for 98.2% of 56 major surgeries and 94.0% of 67 major bleeds. Approximately 75% of 49 major mucosal bleeds were effectively managed without FVIII co‐administration. In 32 patients receiving prophylaxis, breakthrough bleeding occurred in 1.5% of infusions and median ABR was 1.0 for 20 patients treated ≥ 12 months. Excellent tolerability was confirmed with no safety concerns. No thrombotic events were observed. Conclusions Results from this PMS increase the clinical experience of a FVIII‐poor pdVWF in patients of all ages and VWD types including those with thrombotic risk factors and emphasize that giving FVIII is not always mandatory to effectively treat patients with severe VWD.

<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>

“…19 Similarly, a post-marketing study of WILFACTIN reported excellent or good efficacy for 94.0% of treated major bleeds and 98.2% of major surgical procedures. 20 The median number of NSB events per year in the prophylaxis arm (children: 22.2 events; adults: 0.6 events) was similar to the median reported in the prophylaxis arms…”

“…pdVWF/FVIII was well tolerated and the safety profile was consistent with observations in previous studies [27][28][29][30] and the safety profiles of other plasma-derived VWF/FVIII concentrates. 14,[17][18][19][20]31 Overall, the safety results observed in this study support a positive benefit-risk profile of pdVWF/FVIII.…”

“…In addition to pdVWF/FVIII (VONCENTO ® ), WILATE ® (Octapharma AG), WILFACTIN ® /WILLFACT ® (LFB Biopharmaceuticals), and HAEMATE ® P (CSL Behring) are plasma-derived VWF products approved in the EU for the treatment of VWD. These products have varying ratios of VWF:RCo to FVIII:C. [14][15][16][17][18][19][20] The VWF:RCo/FVIII:C ratio for pdVWF/FVIII is ~2.4:1. 21 A high ratio of VWF:FVIII may help to achieve therapeutic VWF plasma levels without causing long-term accumulation of FVIII levels, which have been associated with an increased risk of thromboembolic events.…”

Prophylactic management of patients with von Willebrand disease

“…Table 3 summarizes data on the efficacy of VWF/FVIII for short-term bleeding prophylaxis in patients undergoing surgery or invasive procedures according to our critical analysis and compilation of the main reports. [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] Haemate P The majority of data on the prophylactic use of VWF-/FVIII-containing products in surgical procedures, reported in Table 3, regard this product as the first to be largely employed in VWD. 18 A prospective multicenter trial reported in 2004 investigated its clinical use in surgery and documented both safety (no serious drug-related adverse events) and efficacy (100% of hemostatic efficacy).…”

“…36 This pioneering clinical study on the use of VWF-only replacement established the feasibility, efficacy, and safety of this novel therapeutic approach; these findings were recently confirmed by a large retrospective analysis of the data stemming from 5 years of use of Wilfactin in France. 37 Vonvendi A recombinant VWF concentrate (vonicog alfa) has been more recently produced and approved based on its efficacy and safety profile established in phase I and III trials, in which it was used at a fixed dosage ratio together with a recombinant FVIII product. 44,45 When infused alone, vonicog alfa rapidly produced (within 6 h post-infusion) and sustained (for 72 h) hemostatically effective plasma FVIII:C levels.…”