The Safety and Efficacy History of B-domainless Factor VIII

Mannucci P M.  The Safety and Efficacy History of B-domainless Factor VIII.  Journal of Coagulation Disorders, July 2010; 2(2):  7-9

REVIEW ARTICLE

Pier M. Mannucci

Affiliation: A. Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Medicine and Medical Specialties,
IRCCS Ca` Granda Foundation Maggiore Hospital and University of Milan, Italy


ABSTRACT

Hemophilia A is the predominant cause of an overall burden of hemophilia that affects one in every 5000 males worldwide. Management of hemophilia A revolves around replacement therapy, and introduction of recombinant factor VIII (rFVIII) was a major milestone in this field. First generation rFVIII, which used animal-derived proteins, was followed by second generation products such as B-domain-deleted rFVIII (ReFacto). ReFacto was comparable to full-length rFVIII in its pharmacokinetics, efficacy, safety, hemostatic activity and immunogenicity. The overall hemostatic efficacy of ReFacto was rated good or excellent in 95% of patients without prior treatment history and in more than 99% of patients who were either treated earlier or underwent surgery. Third generation rFVIII such as the plasma/albumin-free Advate were introduced to minimize viral contamination of biological products; however, these were not completely free from biological contamination, as one of the steps in the purification process involved monoclonal antibody derived from mouse hybridoma cell lines. In order to address this issue, a novel product, ReFacto AF has been introduced. ReFacto AF is completely free from biological contamination as it involves no animal- or human-derived raw materials in either the culture or purification process. ReFacto AF is comparable to the original ReFacto in its pharmacokinetic and pharmacodynamic properties as it has similar structural integrity and stability. ReFacto AF also has adverse event profile comparable to ReFacto and other rFVIII products, without any evidence of neoantigenicity. Ongoing long term trials may provide more insight into the efficacy and safety of ReFacto AF in patients with hemophilia A.

Keywords: Coagulation disorder, factor VIII, hemophilia, ReFacto, rFVIII

Correspondence: P. M. Mannucci, A. Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Medicine and Medical Specialties
and Scientific Direction, IRCCS Ca` Granda Foundation Maggiore Hospital and University of Milan, Milan, Italy. Phone :
39-02-55035422;
Fax :
39-02-50320723. Email : pmmannucci@libero.it