Clinical efficacy, safety and pharmacokinetic properties of the factor VIII concentrate Haemoctin^® SDH in previously treated patients with severe haemophilia A

Abstract

Clinical efficacy, safety and pharmacokinetic properties of the high-purity double-virus inactivated plasma-derived factor VIII concentrate Haemoctin SDH (pdFVIII) were evaluated in three prospective open-label uncontrolled studies in previously treated patients (PTPs) with severe haemophilia A. The pharmacokinetic properties assessed at baseline and after 3 months of treatment are in accurate accordance with published data and remain unchanged over time (study A, n = 12). Mean terminal elimination half-life was 11.8 and 11.9 h, mean incremental recovery (IU dL(-1)/IU kg(-1)) was 2.3 and 2.0, respectively. Long-term efficacy and safety, in particular the potential immunogenicity, were investigated in a total of 53 PTPs (studies A and B) treated prophylactically and on-demand, as required. PdFVIII has shown to be effective in preventing and controlling bleeding episodes; 23.5% of patients were free of bleeding events. A total of 177 haemorrhages occurred with 74.0% resolving after a single infusion, 87.6% within two infusions. 98.3% of responses reported on haemorrhages were rated as 'excellent' or 'good'. Moreover, 'excellent' haemostatic efficacy has been demonstrated in 10 surgical procedures including general and severe orthopaedic interventions (study C). No complication occurred in any surgery. Few adverse events were reported, one patient developed a high-titre FVIII inhibitor without clinical relevance. In all three studies, over 6 million units were administered in nearly 4300 infusions, approximately 94% units or infusions were given for prophylaxis and only 6% for treatment on-demand. In conclusion, pdFVIII has shown to be effective, safe and well tolerated in long-term prophylaxis and treatment on-demand as well as after minor and major surgical procedures.

Pharmacokinetics, Efficacy and Safety of IMMUNATE® Solvent/Detergent (IMMUNATE® S/D) in Previously Treated Patients with Severe Hemophilia A: Results of a Prospective, Multicenter, Open-Label Phase III Study

“…The reevaluation of FVIII PK of IMMUNATE S/D in part 3 of the study showed that the PK parameters assessed for the IMMUNATE S/D infusion in part 1 and for the repeat infusion in part 3 of the study were consistent, suggesting that S/D treatment did not alter the FVIII PK parameters that were evaluated. Furthermore, half-life and IR of FVIII determined for IMMUNATE S/D in part 1 and in part 3 of the study were in accordance with published data with other FVIII product studies in PTPs with severe hemophilia A and in a long-term follow-up of prophylactic treatment in patients with severe and moderately severe hemophilia A [20, 21]. The data also demonstrate that IMMUNATE S/D increases VWF levels, which confirms efficacy in von Willebrand disease (VWD) that has been described by Auerswald et al[ 17] for IMMUNATE.…”

Proteomic characterization of plasma‐derived clotting factor VIII–von Willebrand factor concentrates

“…All values are given in corresponding units (international units – IU, or milligrams) per vial. According to the manufacturer’s declaration, each vial contains 1000 +/− 200 IU F VIII [11, 20, 21]. As shown in this Table, results of these analyses are very similar for Octanate and Haemoctin.…”

“…Most pd F VIII concentrates have been on the market for a long time [10], and intensive virological and clinical investigations have proved that these preparations are safe [11, 20]. However, for the next generation of pd F VIII, and also for other therapeutic proteins from human plasma, thorough proteomic investigations, in addition to routine biochemical and functional analyses, during product development [19, 36, 37] and for quality control and assurance of the final product have been highly recommended [38–40].…”

“…Biochemical analyses and determination of biological activity were performed as previously described [11, 20–24]. Each concentrate containing 1000 IU F VIII/vial was dissolved in 5 mL aqua bidest.…”

Allometry of Factor VIII and Informed Scaling of Next-Generation Therapeutic Proteins

“…The complete set of collected data is summarized in Table 1. A total of 60 publications were included representing mice, dogs, and humans with HA as well as normal mice, rats, rabbits, and monkeys 7–11,14–16,25–76. A summary of the NCA derived PK parameters CL, V ss , MRT, and half‐life ( t 1/2 ) are presented in Table 2.…”