Hope for hemophiliacs

New research into subcutaneous factor replacement therapy could offer IV alternative

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SOUTH SAN FRANCISCO, Calif.—New research conducted by Catalyst Biosciences Inc. has shown positive results in advanced preclinical development of subcutaneous dosing of a next-generation coagulation factor IX variant used in the treatment of hemophilia B. A recent study of CB 2679D/ISU304 indicated a positive pharmacokinetic profile based on bioavailability, potency, time to maximal concentration and half-life. These findings signify an ability to dose CB 2679D/ISU304 subcutaneously while achieving steady-state levels of procoagulant activity that moved hemophilia B mice from the severe range to the mild range.
“We believe that [for hemophiliacs], while stopping bleeding is good, preventing bleeding is better. Our strategy for doing this is by developing a clotting factor that can be injected subcutaneously which will enhance the treatment, and lives, of [affected] individuals,” asserts Dr. Nassim Usman, president and CEO of Catalyst Biosciences.
Hemophilia is a rare but serious bleeding disorder that can cause spontaneous bleeding episodes and prolonged bleeding times that can be life-threatening following injury or trauma. Affecting about 20,000 Americans and nearly 400,000 people worldwide, it is caused by a genetic lack of blood-clotting proteins, known as factor VIII for hemophilia A, or factor IX in hemophilia B. Hemophilia patients are treated with a replacement therapy of key coagulant proteins which currently have significant limitations regarding potency and duration of efficacy. Existing interventions must be administered intravenously with a high frequency, causing struggle to access peripheral veins in home treatment, or necessitating medical intervention or use of an IV port, especially in children.
“The leading recombinant human factor IX on the market for treating acute bleeding episodes in hemophilia B patients is dosed intravenously, which is not optimal for people who predominantly take these medicines at home. Also, it has a short half-life and is therefore not ideal for prophylactic treatment,” says Usman.
CB 2679D/ISU304 has been shown to have a significantly higher potency than existing factor IX products that cannot be dosed intravenously to achieve consistent factor IX levels to prevent life-threatening episodes. Researchers tested CB 2679D/ISU304 in both hemophilia B and wild-type mice, with factor IX antigen and activity being measured. The study found that the highly specific activity of subcutaneous CB 2679D/ISU304 increased factor IX antigens, with a potency nearly 17 times greater than the existing factor IX intervention when injected subcutaneously.
Catalyst, in conjunction with its partner ISU Abxis, is preparing to launch a Phase 1/2 proof-of-concept clinical trial in individuals with hemophilia B in early 2017. The trial will follow European guidance for developing a factor IX agent to determine what proportion of CB 2679D/ISU304 dosed intravenously becomes measurable in blood compared with intravenous dosing. According to a company spokesperson, the trial will treat for six consecutive days and determine the peak activity level and trough activity levels in patients. The expectation is that patient activity levels will increase over time because subsequent injections would be done before CB 2679D/ISU304 is eliminated from the blood.
“Quite simply, a therapy that could be given more easily at home would provide more convenience, and one that could be taken prophylactically to avoid bleeding episodes would be even more ideal,” concludes Usman.
Catalyst is wholly focused on novel medicines to address hematology indications. In addition to this research on factor IX applications, the company specializes in hemostasis that assists in facilitating surgery for individuals with hemophilia. They are also developing a coagulant factor VIIa variant known as CB 813d that has successfully completed a Phase 1 clinical trial in patients with severe hemophilia A and B, and those who develop inhibitors that impact efficacy of current factor-replacement therapies.

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