In data presented at the ASH 49th annual meeting recombinant factor VIIa-albumin fusion protein seen as first step toward more convenient
treatment option for hemophilia patients with inhibitors
ATLANTA, Dec. 10 /PRNewswire/ -- CSL Behring today announced the results of a pre-clinical study that show for the first time it is feasible to genetically fuse Factor VIIa (FVIIa) to human albumin, prolonging the half- life of this therapeutic protein while retaining its biologic activity. In the study, which was presented at the American Society of Hematology 49th Annual Meeting and Exposition, the half-life of recombinant VIIa-albumin fusion protein (rVIIa-FP) was shown to be extended 6-to-9 fold compared to wild type rFVIIa. Additionally, rVIIa-FP demonstrated a biologic activity comparable to wild type rFVIIa.
Recombinant factor VIIa (rFVIIa) may be used to control bleeding episodes in hemophilia patients with inhibitors. These patients develop an immune response that inhibits the substituted clotting factor from stopping a bleeding episode. However, rFVIIa has a short half-life of approximately 2.5 hours. This necessitates multiple injections, which are inconvenient for both physicians and patients, particularly during surgical intervention.
"A major unmet need in hematology is improving the pharmacokinetic parameters of coagulation factors, such as half-life, while retaining full hemostatic activity," said Dr. Stefan Schulte, Head Pre-clinical R&D, CSL Behring GmbH and lead investigator of the study. "The pharmacological properties of rVIIa-FP seen in our study could one day facilitate a single dosing regimen of one injection per bleeding event, as well as significantly reduce the number of injections hemophilia patients with inhibitors need during surgical interventions."
Recombinant VIIa-FP represents CSL Behring's initial corporate foray into research with recombinant coagulation product technology.
"CSL Behring is pleased to be at the forefront of this exciting development in hemophilia treatment, which is consistent with our mission to improve the lives of patients with bleeding disorders," said Dr. Andrew Cuthbertson, Chief Scientific Officer at CSL Ltd., parent company of CSL Behring. "By increasing convenience and compliance, rVIIa-FP has the potential to benefit hemophilia patients with inhibitors and the physicians who treat those patients. We look forward to continuing our research and accumulating additional data to validate the results seen in our pre-clinical study of this molecule."
Today's Presentation: Study Design
Genetic fusion to albumin is an efficient way to extend the half-life of small proteins, but so far it has not been successfully used for the half-life extension of complex proteins. In the presented proof-of-principle study, rVIIa-FP was generated by genetic engineering, expressed in mammalian cell culture, purified and characterized. The rVIIa-FP displayed full biological activity and 6 to 9-fold extended half-life compared to either Novoseven(R)(1), a recombinant FVIIa, or rVIIa control protein in a pre-clinical rat model. The superior pharmacological properties of the rVIIa-FP could facilitate a single dosing regimen of one injection per bleeding event for treatment of hemophilia inhibitor patients.
About Hemophilia with Inhibitors
In some patients with hemophilia, the immune system produces an antibody that blocks the action of the substituted coagulation factor and prevents clot formation. This antibody is known as an inhibitor, and its presence makes treatment of bleeding episodes more difficult. The reason inhibitors develop is unknown, although people with hemophilia have the greatest risk for developing an inhibitor during childhood. The incidence of inhibitors is highest among those with severe hemophilia, followed by moderate and mild deficiency. The risk of inhibitor development is higher if someone in the patient's family also has an inhibitor, and is more frequent among African Americans.(2)
About CSL Behring
CSL Behring is a global leader in the protein biotherapeutics industry.
Passionate about saving and improving the quality of patients' lives, CSL
Behring manufactures and markets a range of safe and effective
plasma-derived and recombinant products and related services. The company's
therapies are used in the treatment of rare diseases such as immune
deficiency disorders, hemophilia, von Willebrand disease, other bleeding
disorders and inherited emphysema. Other products are used for the
prevention of hemolytic diseases in the newborn, in cardiac surgery, organ
transplantation and in the treatment of burns. The company also operates
one of the world's largest plasma collection networks, ZLB Plasma. CSL
Behring is a subsidiary of CSL Limited, a biopharmaceutical company with
headquarters in Melbourne, Australia. For more information, visit
Contacts: Sheila A. Burke Jeff Hoyak
Director, Communications & Public Relations MCS Public Relations
Worldwide Commercial Operations, CSL Behring +1-908-884-6753
(1) NovoSeven is a registered trademark of Novo Nordisk Health Care AG.
(2) National Hemophilia Foundation website http://www.hemophilia.org
|SOURCE CSL Behring|
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