King of Prussia, — CSL Behring has dosed the first patient in Part 3 of its AFFINITY clinical trial program, which is now in phase III. AFFINITY is an open-label, non-randomized, multi-center study evaluating the efficacy, safety and pharmacokinetics of its novel investigational recombinant coagulation single-chain factor VIII (rVIII-SingleChain) for the treatment of hemophilia A. The patient was dosed in Vienna, Austria and had a successful major surgery.
The CSL Behring rVIII-SingleChain is a novel recombinant single-chain Factor VIII design that uses a strong, covalent bond that has been shown to improve the stability and half-life of factor VIII (FVIII). A recombinant factor therapy option with a longer half-life could provide a longer dosing interval, leading to less frequent injections. This may have the potential to improve compliance and ease prophylaxis, improving the quality of life for people with hemophilia A.
“We are proud and excited that this recombinant coagulation factor development program is progressing into Phase III clinical studies and look forward to sharing the clinical trial results for our novel rVIII-SingleChain molecule with the hemophilia community in the future,” said Russell Basser, M.D., CSL Senior Vice President, Global Clinical Research & Development. “As part of our ongoing commitment to the hemophilia community, we are developing and investigating innovative recombinant factor therapies for the treatment of both hemophilia A and B that have the potential to offer patients and caregivers significant advances in treatment and convenience of factor infusion.” CSL Behring, in collaboration with its parent company, CSL Limited (asx:CSL), is developing rVIII-SingleChain through the AFFINITY clinical trial program.
About the AFFINITY Phase I/III Study The Phase I/III study is an open-label, multi-center trial that examines the crossover safety, efficacy and pharmacokinetics of recombinant coagulation single-chain factor VIII compared with recombinant human antihemophilic factor VIII (octocog alpha).
In Part 1 of the study, 27 subjects received a single infusion of 50 IU/kg body weight (b.w.) of octocog alfa followed by a single infusion of 50 IU/kg b.w. rVIII-SingleChain. Results of Part 1 of the study will be presented at the 2013 International Society on Thrombosis and Haemostasis in Amsterdam, Netherlands on 2 July. In Parts 2 and 3 of the study, subjects will receive infusions of rVIII-SingleChain to prevent and treat bleeding (if required), at a dose and frequency determined by their study doctor (based on the subject’s underlying bleeding phenotype). More information about the study design can be found at www.clinicaltrials.gov.
Recombinant FVIII molecules so far available consist of a heavy and a light chain. Under certain conditions, these chains can dissociate, resulting in the formation of separated, or “dissociated,” rFVIII chains that are not hemostatically active. The CSL Behring rVIII-SingleChain uses a strong, covalent bond that connects the light and heavy chains, thereby creating a stable single chain rFVIII.
In-house studies have shown that the molecular integrity of rVIII-SingleChain is significantly increased using the single-chain design, resulting in a homogenous product that is more stable than currently available FVIII products. In addition, in-vitro studies have shown that rVIII-SingleChain demonstrates a strong affinity for von Willebrand factor (VWF), resulting in a faster and more efficient binding to VWF. 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.
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, USA, and at laboratories operated by CSL Limited in Melbourne, Australia.
About Hemophilia Hemophilia is a congenital bleeding disorder characterized by prolonged or spontaneous bleeding, especially into the muscles, joints, or internal organs. In nearly all cases, it affects only males. The disease is caused by deficient or defective blood coagulation proteins known as factor VIII or IX (FIX). The most common form of the disease is hemophilia A, or classic hemophilia, in which the clotting factor VIII is either deficient or defective. Hemophilia B is characterized by deficient- or defective factor IX. Hemophilia A affects approximately 1 in 5,000 to 10,000 people. Hemophilia B affects approximately 1 in 25,000 to 50,000 people. The recommended treatment for patients who are factor deficient is to treat by replacement factor therapy.
About CSL Behring CSL Behring is a leader in the plasma protein therapeutics industry. Committed to saving lives and improving the quality of life for people with rare and serious diseases, the company manufactures and markets a range of plasma-derived and recombinant therapies worldwide.
CSL Behring therapies are used around the world to treat coagulation disorders including hemophilia and von Willebrand disease, primary immune deficiencies, hereditary angioedema and inherited respiratory disease, and neurological disorders in certain markets. The company’s products are also used in cardiac surgery, organ transplantation, burn treatment and to prevent hemolytic diseases in the newborn. CSL Behring operates one of the world’s largest plasma collection networks, CSL Plasma.