Earlier today the first patient has been enrolled in the pivotal pediatric phase III study to evaluate the safety, efficacy and pharmacokinetics of recombinant fusion protein linking coagulation factor IX with recombinant albumin (rIX-FP) in previously treated children (up to age 11 years). The study site for this first enrollment is the Czech Republic.

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 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 while 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.

Phase I trial
Results of earlier studies presented at the Gesellschaft f?r Thrombose- und H?mostaseforschung e.V. (GTH) congress in Switzerland, showed that rIX-FP was well tolerated in all patients and lasted longer in the body, due to its prolonged half-life, compared with current Factor IX treatment options.

“Hemophilia B is a rare and serious bleeding disorder that prevents normal blood clotting and requires frequent infusion of Factor IX concentrates to restore clotting ability,” said Elena Santagostino, M.D., Ph.D., Professor in the Medical School of Clinical and Experimental Hematology at the University of Milan/IRCCS Maggiore Hospital. “The results of this study suggest that rIX-FP is a promising investigational agent for improvement of prophylactic and on-demand treatment for patients with hemophilia B.”

In this analysis, no serious adverse events (including no hypersensitivity reactions), presence of inhibitors to Factor IX, or antibodies to rIX-FP were reported. Terminal half-life (a measure of how long the drug lasts in the body) was more than five-times longer in comparison to values associated with current recombinant FIX therapy. Incremental recovery and area under the curve (a measure of total exposure to the drug) were also significantly improved in comparison to values associated with current recombinant FIX therapy.

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Follow-up trials
The decision to enroll patients in this trial was based on results from an innovative biodistribution study presented at the 54th American Society of Hematology (ASH) Annual Meeting, that supports rIX-FP long half-life data.

Results of an earlier phase I study evaluating recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in patients with severe hemophilia B showed that rIX-FP achieved a 91.57 hours terminal half-life, incremental recovery of 1.376 (IU/dL) / (IU/kg), and clearance of 0.75 mL/h/kg. This was an extension in half-life of 5.3 times that of the current recombinant FIX therapy.[1]

Commenting on the study initiation, Andrew Cutherbertson, Chief Scientist, CSL Limited, the trial?s sponsor developing rIX-FP through the Prolong-9FP clinical trial program for the prophylaxis and treatment of bleeding episodes which includes control and prevention of bleeding in surgical settings in patients with factor IX deficiency, said: “Developing safe and effective therapies to improve the lives of those affected by rare and serious bleeding disorders remains the key to our ongoing success in this therapeutic area. With each clinical milestone we meet, we draw closer to our goal of bringing another truly innovative new treatment option to patients.”

Tissue Distribution of rIX-FP
Study results presented late last years at the Annual meeting of the American Society of Hematology in Atlanta, demonstrated that the tissue distribution of rIX-FP was detectable five times longer in the tissues, including the bone. The extent and speed of onset of tissue penetration were similar for both rIX-FP and the study comparator product. “rIX-FP was detectable significantly longer than the study comparator product, though they both behave in essentially the same way in terms of speed of onset and tissue penetration,” said Stefan Schulte, M.D., Vice President of Research and Development at CSL Behring: “These results provide further evidence that rIX-FP is an extended half-life recombinant factor IX with the potential to reduce the number of injections needed in patients receiving prophylaxis from two or three injections per week with the study comparator product, to once weekly or significantly less frequently with rIX-FP. Further, they show that rIX-FP may have the potential to improve compliance and ease prophylaxis. This may, in turn, improve the quality of life for people with hemophilia B.”

Recruitment is currently underway for adult phase II/III and pediatric phase III trials, the final phase of the Prolong-9FP clinical trial program.

For more information:
[1] Santagostino E, Negrier C, Klamroth R, Tiede A, Pabinger-Fasching I, Voigt C, Jacobs I, Morfini M. Safety and pharmacokinetics of a novel recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in hemophilia B patients
Blood 2012 120:2405-2411; published ahead of print August 2, 2012, doi:10.1182/blood-2012-05-429688

Clinical trials
NCT01662531 – A Safety, Efficacy and Pharmacokinetics Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Children With Hemophilia B
NCT01496274 – A Safety and Efficacy Study of a Recombinant Fusion Protein Linking Coagulation Factor IX With Albumin (rIX-FP) in Patients With Hemophilia B
NCT01361126 – A Safety and Efficacy Study of a Recombinant Factor IX in Patients With Severe Hemophilia B
NCT01233440 – Safety and Pharmacokinetic Study of a Recombinant Coagulation Factor IX Albumin Fusion Protein in Subjects With Hemophilia B.

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