Interim Phase II/III and III findings presented today by CSL Behring at the World Federation of Hemophilia (WFH) 2014 Congress demonstrate an improved pharmacokinetic (PK) profile of recombinant fusion protein linking coagulation factor IX with recombinant albumin (rIX-FP) among hemophilia B patients of all age groups. These findings suggest an improvement in hemophilia B treatment by allowing a prolonged routine prophylaxis treatment interval of 14 days or potentially longer, compared to the current standard of two to three times per week. Data were presented during an oral session at the WFH Congress in Melbourne, Australia. CSL Behring is a subsidiary of CSL Limited (CSL: ASX), a biopharmaceutical company with headquarters in Melbourne, Australia.
“Patients with hemophilia B and treating physicians are eager for innovative products that are able to decrease the dosing frequency while being effective and reliable in the prevention or treatment of bleeding episodes,” said Elena Santagostino, MD, Ph.D., and lead investigator of this study. “Our interim PK data from two Phase III studies, combined with the Phase I and I/II results, demonstrate that rIX-FP has the potential to satisfy this unmet need by offering a longer dosing interval and fewer injections.”
“This data provides further encouragement to our ongoing efforts to bring forward to hemophilia patients an improved treatment option that will improve their quality of life,” said Charmaine Gittleson, CSL Behring Senior Vice President of Clinical Research and Development. “We look forward to completing this study and moving into the next steps with this promising clinical candidate.”
The interim pharmacokinetic results from the two phase III trials were based on the analysis of pharmacokinetic samples over the course of 14 days in 68 severe hemophilia B patients, ages from 1 to 61 years. A single dose of 50 IU/kg rIX-FP gave a mean FIX activity level above 3% at 14 days in all age ranges. In a paired comparison, the PK profile of rIX-FP demonstrated a 30 to 40 percent greater incremental recovery and greater than five times longer half-life, along with over five-fold larger area under the curve (AUC) and slower clearance compared with patients’ previous plasma-derived and recombinant FIX products.
About the Phase II/III and III Study
The Phase II/III (patients age 12 to 61 years) and Phase III (patients age 1 to 11 years) studies are open-label, multicenter, safety and efficacy studies of rIX-FP in previously treated patients with severe hemophilia B (FIX ≤ 2%). The studies are part of CSL Behring’s PROLONG - 9FP clinical developmental program.
The Phase II/III is a crossover study, designed to compare the change in frequency of spontaneous bleeding events between on-demand and weekly prophylaxis regimen in patients previously receiving only on-demand treatment and the number of patients developing inhibitors against factor IX as primary outcome measures. In addition, the study is also designed to compare multiple prophylaxis regimens of different treatment intervals, including 7-day and 14-day intervals. This study is ongoing since December 2011.
The Phase III primary outcome measures are PK parameters of rIX-FP and the number of subjects developing inhibitors against factor IX. All patients received weekly prophylaxis regimen. This study is ongoing since September 2012.
More information about study design can be found at www.clinicaltrials.gov.
CSL Behring engineered rIX-FP to extend the half-life of factor IX through genetic fusion with recombinant albumin. CSL Behring selected albumin as the ideal recombinant genetic fusion partner for its coagulation factor proteins due to its long physiological half-life. In addition, albumin has been shown to have a good tolerability profile, low potential for immunogenic reactions and a well-known mechanism of clearance compared to some other technologies. The cleavable linker connecting recombinant factor IX and recombinant albumin has been specifically designed to preserve the native function of the coagulation factor in the fusion protein, while benefiting from recombinant albumin’s long physiological half-life.
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. 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 people with hemophilia deficiency 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. CSL Behring is a subsidiary of CSL Limited (CSL: ASX), a biopharmaceutical company with headquarters in Melbourne, Australia. For more information, visit www.cslbehring.com.
Sheila A. Burke
Director, Communications & Public Relations
Worldwide Commercial Operations