Efficacy, safety and pharmacokinetic profiles of a plasma-derived VWF/FVIII concentrate (VONCENTO®) in subjects with haemophilia A (SWIFT-HA study)

• Published in: Thrombosis research 2016-01, Vol.137, p.119-125
• Main Authors: Skotnicki, Aleksander, Lissitchkov, Toshko J, Mamonov, Vasily, Buevich, Evgeny, Kuliczkowski, Kazimierz, Goranov, Stefcho, Kłoczko, Janusz, Klukowska, Anna, Stankovic, Svetlana, Gercheva, Liana, Chernova, Tatiana, Hellmann, Andrzej, Dmoszyńska, Anna, Zawilska, Krystyna, Veldman, Alex, Joch, Christine, Seifert, Wilfried
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Annual bleeding rate; Double-Blind Method; Drug Combinations; Europe; Factor VIII - administration & dosage; Factor VIII - adverse effects; Factor VIII - pharmacokinetics; Female; Hematology, Oncology and Palliative Medicine; Hemophilia A - diagnosis; Hemophilia A - drug therapy; Hemophilia A - metabolism; Hemostatic efficacy; Hemostatic safety; Hemostatics - administration & dosage; Hemostatics - adverse effects; Hemostatics - pharmacokinetics; Humans; Male; Middle Aged; On-demand therapy; Plasma - chemistry; Prophylaxis; Surgery; Treatment Outcome; von Willebrand Factor - administration & dosage; von Willebrand Factor - adverse effects; von Willebrand Factor - pharmacokinetics; Young Adult
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2015.10.014

Abstract Introduction VONCENTO® (CSL Behring) is a plasma-derived, high-concentration, low-volume, high-purity concentrate, which contains a high level of von Willebrand factor (VWF) high-molecular-weight multimers and a VWF/factor VIII (FVIII) ratio of ~ 2.4:1, similar to Haemate® P (CSL Behring). Methods The pharmacokinetic, efficacy and safety profiles of VONCENTO® were investigated in this multicentre, double-blind, randomised study. Subjects aged ≥ 12 years with haemophilia A who required treatment of non-surgical bleeds, treatment during surgical events or who were receiving prophylaxis were included. Pharmacokinetics were investigated with a single dose of 50 IU FVIII/kg body weight of either VONCENTO® or BIOSTATE® reference product (Biostate-RP) (Day 1; Day 8 [n = 16], repeated on Day 180 [VONCENTO® only; n = 15]). Efficacy and safety analyses were performed either during on-demand treatment (n = 52) or prophylaxis (n = 29) for ≥ 6 months and ≥ 50 exposure days, respectively. Results Besides the confirmation of bioequivalence between VONCENTO® and Biostate-RP, which displayed comparable PK profiles, haemostatic efficacy was rated by the investigators as either ‘excellent’ or ‘good’ in 96.4% of all bleeding events (96.5% spontaneous, 96.6% traumatic, 96.9% joint bleeds) as well as in 80% of major and 100% of minor surgical procedures at discharge. The median number of annualised bleeding events per subject [range] was significantly lower in the prophylaxis group (2.0 [0.0–34.6]) than in the on-demand group (14.0 [0.0–87.8], p = 0.0013).VONCENTO® was well tolerated and no inhibitory antibodies were identified during the study period. Conclusions This study demonstrated the bioequivalence of VONCENTO® to Biostate-RP, and its excellent efficacy and safety profile in haemophilia A subjects.