An open clinical study assessing the efficacy and safety of Factor IX Grifols^®, a high‐purity Factor IX concentrate, in patients with severe haemophilia B

Abstract

Factor IX Grifols is a new high-purity plasma-derived FIX concentrate with two specific pathogen elimination steps. Until this study was performed, there were no detailed reports with an adequate number of patients on the clinical evaluation of this product. To determine the efficacy and safety of Factor IX Grifols for replacement therapy in previously treated patients with severe haemophilia B, this open, multicentre and non-randomized study included 25 male subjects over the age of 12 with severe haemophilia B. Patients underwent prophylaxis and treatment of bleeding episodes with Factor IX Grifols for 1 year. The clinical efficacy and safety of this product were assessed. Forty percent of the patients were children and adolescents (12-17 years old). During the 12 months follow-up, 1 446 000 IU of Factor IX Grifols were administered in 961 infusions (range 12-83 infusions per patient): 31% for prophylaxis and 69% for bleeding episodes. Only five major bleeding events were reported in two patients. These haemorrhages were successfully treated with a mean of 2900 IU per bleed (range 1500-4000 IU), and 1-3 infusions per bleed. The average time elapsed from the first infusion to resolution of bleeding was 43 h (median). Overall, haemostasis was rated as excellent or good by the investigator in 96% of the infusions. No product-related adverse events were reported. Factor IX Grifols is an effective and safe Factor IX concentrate and can be considered as a first line option for replacement therapy in haemophilia B patients.

Long-term efficacy and safety of a pasteurized, plasma-derived factor VIII concentrate (Beriate® P) in patients with haemophilia A

“…Our results support previous observations that virus-inactivated, human plasma-derived coagulation factor concentrates have an excellent safety profile [7][8][9][10][11][12]. Although only 36 patients received Beriate ® P during the 10-years of observation in this study, over 27 million IUs of the product were administered without transmission of viruses or the development of inhibitors in PTPs or the PUP.…”

“…Another landmark study has demonstrated the safety of a pasteurized FVIII concentrate with regard to hepatitis in patients with haemophilia and no previous infusions [9]. Data from other study groups [11,12] have confirmed the safety of virus-inactivated plasmaderived coagulation factor concentrates.…”

Pharmacokinetics of plasma-derived and recombinant factor IX - implications for prophylaxis and on-demand therapy

“…In spite of this, a recent survey in Italy indicated that the two species of FIX are used in similar doses with similar outcome . There are no comparative studies on regular prophylaxis, but the investigated doses of rFIX tend to be higher than the originally studied and traditionally recommended ones of pdFIX. Based on PK calculations, the average dose needed with rFIX to obtain a 1 IU dL −1 (1%) trough level of FIX coagulant activity (FIX:C) has been estimated to be about twice that of pdFIX .…”

Research in haemophilia B – approaching the request for high evidence levels in a rare disease

“…Information on 31 selected JA concerning 35 studies on HB and/or FIX is provided in Table . Overall 21 published studies (60.0%) were related to FIX, of which 17 (48.6%) were on safety, efficacy and/or pharmacokinetics of different FIX products , two studies on dosing , one on allergic reactions and one on use of FIX worldwide . HB was the focus of seven studies, of which three studies compared features of HA or FVII deficiency to HB, two studies on correlation between genotype and phenotype of HB , one registry on incidence of inhibitors, allergic and anaphylactic reactions and one study on the global prevalence of HB .…”