Pharmacokinetic drug evaluation of recombinant factor VIII for the treatment of hemophilia A

ABSTRACT

Introduction: The prevention of bleeding by prophylactic factor replacement is the recommended approach for the treatment of severe hemophilia. Prophylaxis should be individualized to provide the best clinical benefit to each patient. Therefore, a pharmacokinetic approach is crucial.

Areas covered: This review aims to concisely describe the basic principles of pharmacokinetics of FVIII, the role of population pharmacokinetic, the available different recombinant FVIII concentrates and the new extended half-life FVIII molecules with possible improvement in hemophilia A treatment.

Expert opinion: Pharmacokinetic is a useful tool to predict the outcome of replacement therapy, even though a large inter-individual variability exists, becauseof several factors: age, weight, von Willebrand factor level, blood group, active bleed, presence of inhibitors to FVIII, FVIII concentrate. Among the different recombinant FVIII concentrates pharmacokinetic differences are minor and clinically not significant. The extended half-life FVIII products brings only moderate advances, as half life extension is limited to 1.5–1.8-fold in comparison to that of native FVIII. Thus, infusions could be done every fourth, rarely fifth day to ensure a safe through level and a significant benefit can be offered only to patients treated every other day or three times weekly.

KEYWORDS:

• Clearance
• extended half-life concentrates
• hemophilia A
• pharmacokinetics
• population pharmacokinetics
• prophylaxis
• recombinant FVIII concentrates
• trough level

Article highlights

• Individualized prophylaxis is the recommended standard of treatment for severe hemophilia.

• Individual PK assessment and PopPK are useful tools to predict the outcome of replacement therapy

• FVIII PK analysis is characterized by a large inter-individual variability

• Several rFVIII concentrates are available and pharmacokinetic differences are clinically not significant

• The rFVIII EHL concentrates show a limited HL extension to 1.5-1.8-fold in comparison to that of native FVIII

This box summarizes key points contained in the article.

Declaration of interest

G Castaman participated into Advisory boards for Bayer, Shire, Sobi, Pfizer, CSL Behring, Novo Nordisk, Kedrion. S Linari participated into Advisory boards for Bayer, Sobi, Pfizer, Novo Nordisk. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper is not funded.