CSL Behring, a leader in the plasma protein therapeutics industry, has presented data which showed that clinical efficacy of a once-weekly dosing regimen of recombinant fusion protein linking coagulation Factor IX with albumin (rIX-FP). These results were presented during an oral session at the International Society on Thrombosis and Haemostasis (ISTH) congress in Amsterdam.

CSL Behring, in collaboration with its parent company, CSL Limited is developing rIX-FP for the prophylaxis and treatment of bleeding episodes in patients with haemophilia B as part of the PROLONG-9FP clinical study programme.

"Haemophilia B is characterized by factor IX deficiency, which prevents normal blood clotting. People with this condition require factor IX infusions two to three times a week to achieve a significant reduction in bleeding," said Professor Uri Martinowitz, director of the Institute of Thrombosis and Hemostasis and the Israeli National Haemophilia Centre at Chaim Sheba Medical Centre in Tel Hashomer, Israel. "This trial showed that less frequent infusions were needed with CSL Behring’s investigational rIX-FP compared to currently available FIX products used on-demand or prophylactically to prevent or treat bleeding episodes."

The trial enrolled 17 haemophilia B patients, 13 of whom received weekly prophylactic treatment for approximately 11 months, and four of whom received on-demand treatment only when bleeding occurred. All prophylaxis patients maintained weekly treatment for the entire study, with mean and median annualized spontaneous bleeding rates of 1.26 and 1.13, respectively. All bleeding was treated successfully with two or fewer infusions of rIX-FP, with 95.3 per cent of events treated with a single infusion.

Following a single infusion of 25 IU/kg rIX-FP, the mean FIX activity level was 3.8 per cent and 2.7 per cent above baseline at day 7 and 14, respectively, and the half-life (time taken for half of the treatment to be eliminated or metabolized) of rIX-FP was 94 hours.

"We are very encouraged by these results demonstrating efficacy of a once-weekly infusion of our investigational rIX-FP, as we selected albumin as the ideal genetic fusion partner for our recombinant Factor IX due to its inherently long half-life and good tolerability profile," said Dr Stefan Schulte, vice president of Research and Development, CSL Behring. "We look forward to advancing rIX-FP in clinical trials as we are committed to developing recombinant factor therapies that have the potential to improve compliance and ease prophylaxis. This may, in turn, improve the quality of life for people with haemophilia B."

The phase I/II study was an open-label, multi-centre, clinical study of rIX-FP in previously treated patients with severe haemophilia B (FIX = 2%), and part of CSL Behring’s PROLONG - 9FP clinical developmental programme.

The objectives of the study were to evaluate the prevention of bleeding episodes during once weekly prophylaxis and to assess the hemostatic efficacy of rIX-FP for the treatment of bleeding, in addition to safety and pharmacokinetic (PK) assessments. The study consisted of a 10 to 14 day PK evaluation period, and a three to 12 month safety and efficacy evaluation period, during which patients received either on-demand or prophylaxis treatment.

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 an inherited bleeding disorder characterized by prolonged or spontaneous bleeding, especially into the muscles and joints. 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 haemophilia A, or classic haemophilia, in which the clotting factor VIII is either deficient or defective.

CSL Behring is a leader in the plasma protein therapeutics industry and 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.