A Recombinant Factor IX Albumin Fusion Protein for Hemophilia B

Patients with severe factor IX deficiency (levels ≤2%) have recurrent hemarthroses associated with progressive joint destruction and crippling. This outcome can be prevented by twice-weekly intravenous injections of factor IX concentrate. A current goal in treatment is to reduce the frequency of injections using concentrates formulated to prolong the half-life of factor IX.

To that end, investigators have conducted an industry-sponsored, international, prospective, nonrandomized, open-label, phase III study of a recombinant factor IX albumin fusion protein (rIX-FP) that has a half-life more than four times longer than that of native factor IX. Forty patients were given doses of 35 to 50 IU/kg every 7 days for 26 weeks, and those without spontaneous bleeding for 1 month were given 75 IU/kg every 14 days. Another 23 patients received on-demand treatment with rIX-FP for a variety of bleeding episodes.

Results were as follows:

• Trough levels of factor IX levels were 20 IU/dL with 40 IU/kg weekly and 12 IU/dL with 75 IU/kg every 2 weeks.

• Patients switching from on-demand treatment to prophylaxis decreased their median annualized bleeding rate from 15.43 to 0; the 14-day prophylaxis regimen was noninferior to the 7-day regimen during ≥12 weeks of treatment.

• Hemostatic efficacy of treatment for bleeding episodes was rated by investigators as excellent or good in 94.1% of bleeding episodes; fewer than 10% of bleeds required a second injection.

• No safety concerns were observed; no patients developed inhibitors.