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

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 nonsurgical bleeds, treatment during surgical events or who were receiving prophylaxis were included. Pharmacokineticswere 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 analyseswere 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.