Evaluation of pharmacokinetics, efficacy and safety of Immunate^® solvent detergent in previously treated patients with severe haemophilia A

Abstract

Immunate Solvent Detergent (S/D) is a plasma derived, purified, human factor VIII (FVIII) - von Willebrand factor (VWF) complex subjected to two virus inactivation/removal processes: S/D and vapor heat treatment. This prospective, multicentre, three-part clinical study evaluated the pharmacokinetics (in comparison to the predecessor product Immunate), efficacy and safety of Immunate S/D in 56 previously treated patients with severe haemophilia A. Subjects received Immunate S/D on-demand, as a prophylactic regimen or both. The results of the pharmacokinetic population demonstrate that Immunate and Immunate S/D were equivalent with respect to the FVIII - and to the retrospectively VWF - parameters assessed. A total of 623 bleeding episodes were reported in 47/56 subjects. The duration of prophylaxis ranged from 0.1-5.2 months with a total of 175.6 months. The median number of bleeds per month in subjects on prophylaxis was 0 (range 0-10). Ninety-six percent of bleeding episodes were rated as having an excellent or good response. For most bleeding episodes (89%), subjects required only one infusion with a mean dose of 29.6 IU kg(-1). No FVIII inhibitory antibodies were observed in any subject. No related serious adverse events were reported. Thus, the introduction of S/D treatment did not alter the PK characteristics and function of VWF and FVIII molecules of Immunate S/D which is effective and safe for treatment of bleeding episodes, management of surgical procedures, and prophylaxis.

Thrombotic adverse events to coagulation factor concentrates for treatment of patients with haemophilia and von Willebrand disease: a systematic review of prospective studies

“…Types and brands of factor concentrates administered in the selected studies are shown in Table 1. Forty‐five studies [20–64] reported patients with HA receiving FVIII concentrates (Table 2), 15 studies [65–79] patients with HB treated with FIX concentrates (Table 3) and 11 studies [80–90] VWD patients treated with VWF containing products (Table 4). Owing to the peculiar pathophysiologic situation, six studies [91–96] reporting haemophilia patients who had central venous access devices (CVAD) in order to facilitate long‐term regular concentrate administration (prophylaxis, immune tolerance induction) were analyzed separately (Table 5).…”

Inhibitor development in previously treated hemophilia A patients: a systematic review, meta‐analysis, and meta‐regression

“…We decided that case series with fewer than 25 patients or not clearly reporting follow‐up over time of a cohort of patients were not providing sufficient information to be included. We retrieved 33 articles (see S2–S8 and S11–S31, Supporting Information) in addition to the three articles (see S1, S9, and S10, Supporting Information) that met our inclusion criteria within the studies included in Wight and Paisley , and we included 28 of them (see S2–S8 and S11–S31, Supporting Information) in the analysis (Fig. ).…”

Treatment of haemophilia A and B and von Willebrand’s disease: summary and conclusions of a systematic review as part of a Swedish health‐technology assessment

“…In most instances, the studies are non‐randomized and do not include control groups. For example the search for haemophilia A, 27 studies and 7 reviews fulfilled the criteria [2–35]. Given the fact that haemophilia is a rare disease, it is likely that there will never be sufficient evidence from a large number of RCT to meet the standard of sufficient scientific evidence.…”