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Thromb Haemost 2013; 110(05): 931-939
DOI: 10.1160/TH13-03-0213
Review Article
Schattauer GmbH

Extending the pharmacokinetic half-life of coagulation factors by fusion to recombinant albumin

Hubert J. Metzner
1   CSL Behring GmbH, Marburg, Germany
,
Steven W. Pipe
2   Departments of Pediatrics and Pathology, University of Michigan Medical Center, Ann Arbor, Michigan, USA
,
Thomas Weimer
1   CSL Behring GmbH, Marburg, Germany
,
Stefan Schulte
1   CSL Behring GmbH, Marburg, Germany
› Author Affiliations Financial support: This article was financially supported by CSL Behring, Germany.
Further Information

Publication History

Received: 12 March 2013

Accepted after major revision: 17 July 2013

Publication Date:
01 December 2017 (online)

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Summary

The prophylactic treatment of haemophilia B and the management of haemophilia A or B with inhibitors demand frequent administrations of coagulation factors due to the suboptimal half-lives of the products commercially available and currently in use, e.g. recombinant factor IX (rFIX) and recombinant factor VIIa (rFVIIa), respectively. The extension of the half-lives of rFIX and rFVIIa could allow for longer intervals between infusions and could thereby improve adherence and clinical outcomes and may improve quality of life. Albumin fusion is one of a number of different techniques currently being examined to prolong the half-life of rFIX and rFVIIa. Results from a phase I clinical trial demonstrated that the recombinant fusion protein linking FIX to albumin (rIX-FP) has a five-times longer half-life than rFIX, and preclinical studies with the recombinant fusion protein linking FVIIa to albumin (rVIIa-FP) suggest that rVIIa-FP possesses a significantly extended half-life versus rFVIIa. In this review, we describe albumin fusion technology and examine the recent progress in the development of rIX-FP and rVIIa-FP.

keywords

Coagulation factor IX - coagulation factor VIIa - half-life extension - albumin fusion
 

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