Advances that CSL Behring is making in developing innovative new technologies to meet the unmet therapeutic needs of patients with hemophilia A and B will be the topic of an oral presentation at an international medical congress on May 22, 2011. CSL Behring is a global biotherapeutics company specializing in plasma-derived and recombinant therapies and is a subsidiary of CSL Limited (ASX:CSL).
CSL627, a unique single chain recombinant factor VIII (rFVIII) studied for treatment of hemophilia A, will soon enter phase I clinical testing.
The structure of factor VIII (FVIII) is based on two linked protein chains—a heavy one and a light one. Under certain conditions, this structure can dissociate, resulting in the formation of separated, or "dissociated," FVIII chains. CSL627 uses a strong, covalent bond that connects the light and heavy chains, thereby creating a single-chain rFVIII.
In-house studies have shown that the molecular integrity of CSL627 is significantly increased using this single chain design, resulting in a homogenous product that may be more stable than currently available options. In addition, in-vitro studies have shown that CSL627 demonstrates a very strong affinity for von Willebrand factor (VWF) and a faster and more efficient binding to VWF than is demonstrated by wild-type FVIII. The FVIII/VWF complex plays an important role in the physiological activity and clearance of FVIII and has been shown to have an influence on the presentation of FVIII to the immune system.
"For more than 90 years, CSL Behring has been committed to providing safe and effective therapies to help improve the lives of patients and caregivers affected by hemophilia A and other rare bleeding disorders," said Dr. Andrew Cuthbertson, Chief Scientist CSL Limited. "Developing innovative therapeutic solutions to serious medical conditions is one important way to do that. Therefore, CSL Behring seeks to further expand its broad portfolio of products for the hemophilia community, starting with research into a single-chain rFVIII and other promising therapies."
The research leading to the initiation of the studies that CSL Behring is now conducting is the result of collaboration across the CSL Behring research sites in Marburg, Germany, in King of Prussia, PA, USA, and at facilities operated by CSL Limited in Melbourne, Australia.
CSL Behring is also at work on two recombinant fusion proteins (FP) linking coagulation factors with albumin. Both are in testing to demonstrate an extension of factor half life. One, rVIIa-FP (CSL689), is a recombinant factor VIIa albumin fusion protein for the treatment of patients with hemophilia A or B who have developed inhibitory antibodies. The other, rIX-FP (CSL654) is a recombinant fusion protein linking coagulation factor IX with albumin. It is currently recruiting for phase I studies.