Review of Data for Monoclonal Antibody-purified Plasma-derived Factor IX

European Oncology & Haematology, 2011;7(4):257-262

Abstract:

Haemophilia B is attributed to a mutation in the gene that produces coagulation factor IX (FIX), resulting in FIX deficiency. Treatment of haemophilia B currently consists of replacing the deficient FIX by intravenous administration of exogenous FIX. There are two major treatment strategies: prophylactic FIX administration (to prevent recurrent bleeding episodes in patients), and on-demand FIX administration (to control existing bleeding in patients when it occurs). Prothrombin complex concentrates (PCCs), which were initially used to treat haemophilia B patients, have been available for approximately 40 years. However, PCCs have been largely replaced by highly purified plasma-derived FIX and recombinant FIX, which have benefited from improvements in purification and viral inactivation, reduction or elimination methods. Monoclonal antibody-purified plasma-derived FIX (MAb pd-FIX) has been extensively evaluated in clinical trials and has proved to be safe and efficacious for surgical prophylaxis and for on-demand and prophylactic treatment in previously untreated and previously treated patients. While intermittent dosing is the conventional method of administration, MAb pd-FIX is also suitable for continuous intravenous infusion; this dosing method has been shown to result in normal haemostasis in patients with haemophilia B. This article reviews the data available for MAb pd-FIX.

Acknowledgements: Editorial support was funded by CSL Behring LLC and provided by Touch Medical Communications.
Support: The publication of this article was funded by CSL Behring LLC. The views and opinions expressed are those of the authors and not necessarily those of CSL Behring LLC.
Keywords: Factor IX (FIX), haemophilia B, plasma-derived factor IX, monoclonal antibody-purified plasma-derived factor IX (MAb pd-FIX)
Disclosure: Massimo Morfini has acted as a paid consultant for Bayer, Novo Nordisk and Pfizer, and has served on advisory boards for, and received a fee as invited speaker from, Baxter and CSL Behring. Wolfhart Kreuz has received research support from Abbott, Baxter, Bayer, Biotest, Boehringer Ingelheim, CSL Behring, Grifols, Intersero, Janssen, Jerini, Novo Nordisk, Octapharma, Pfizer and Shire; he has received meeting sponsorship from Baxter, has served on advisory boards for Baxter, Bayer, Biotest, CSL Behring, Novo Nordisk, Octapharma, Pfizer and Viropharma, and has received travel grants from Baxter, Bayer, Biotest, CSL Behring, Octapharma and Viropharma.
Received: September 19, 2011 Accepted October 31, 2011 Citation European Oncology & Haematology, 2011;7(4):257-262
Correspondence: Massimo Morfini, Agenzia per l’Emofilia, Azienda Ospedaliero Universitaria Careggi, Viale GB Morgagni 85, 50134 Florence, Italy. E: Massimo Morfini (massimo.morfini@unifi.it) or Wolfhart Kreuz (w.kreuz@gmx.de)

Haemophilia B is an X-linked recessive coagulation disorder with an estimated incidence of 1 in 60,000 people.1,2 It is characterised by repeated bleeding, particularly into the joints and muscles, which can initiate a cascade of events leading to destruction of the synovium due to synovitis, breakdown of cartilage, development of fibrosis and, eventually, severe and disabling arthropathy.3–6 Pain associated with joint bleeding and arthropathy can have a significant impact on the patient’s quality of life (QoL).7,8 Muscle bleeding represents a major problem in the haemophiliacs owing to the increased risk of life-threatening bleeding. Some recent studies have suggested that haemophilia B may be a less severe form of the disease than haemophilia A because, at the same degree of disease severity (indicated by the baseline level of clotting factor), there appeared to be less joint damage and fewer bleeds over time in haemophilia B than in haemophilia A.9–11 However, to date, there are no large-scale studies to support this view.
Haemophilia B is attributed to a mutation in the gene coding for coagulation factor IX (FIX), resulting in FIX deficiency. Treatment of haemophilia B currently consists of replacing the deficient FIX by intravenous administration of exogenous FIX. There are two major treatment strategies:
  • prophylactic FIX administration (see Table 1),12 either as primary or secondary prophylaxis – to prevent recurrent bleeding episodes in patients – reinforced by short-term anticipatory prophylaxis, for example, for preventing uncontrolled bleeding in those patients undergoing surgery; and
  • on-demand FIX administration – to control existing bleeding in patients when it occurs.13,14

Currently available FIX concentrates include the human plasma-derived FIX (pd-FIX) concentrates and one recombinant FIX (rFIX) (see Table 2). Two prothrombin complex concentrates (PCCs), Bebulin® VH and Profilnine® SD, are also approved for treating haemophilia B. While they have been available for approximately 40 years, PCCs have since been largely replaced by highly purified pd-FIX (HP-FIX) and rFIX, which have benefited from improvements in purification and viral inactivation, reduction or elimination methods. HP-FIX concentrates include monoclonal antibody (MAb)-purified pd-FIX (MAb pd-FIX; Mononine®, CSL Behring) and ion-exchange chromatography purified pd-FIX (Alphanine® SD, Alpha). This article will focus on the efficacy, safety and pharmacokinetic profile of the MAb pd-FIX concentrate, which has been approved in the US since 1992 and in Europe from 1993 onwards for the prevention and control of bleeding in haemophilia B patients.
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Keywords: Factor IX (FIX), haemophilia B, plasma-derived factor IX, monoclonal antibody-purified plasma-derived factor IX (MAb pd-FIX)