David Green, MD, PhD

Recombinant factor IX Fc fusion protein with prolonged half-life reduced infusion frequency.

In patients with severe hemophilia B, infusing factor IX concentrates twice a week can prevent spontaneous bleeding. However, infusions must be given intravenously, and venous access is often problematic. Reducing the frequency of infusions by prolonging the half-life of the clotting factor would simplify treatment.

To address the safety and efficacy of a long-acting construct of recombinant factor IX and the Fc domain of immunoglobulin G1 (rFIXFc), investigators conducted a manufacturer-sponsored, phase III, nonrandomized trial involving 123 males (age, ≥12) with severe hemophilia B. Pharmacokinetic data from 22 patients showed that the half-life of rFIXFc was significantly longer than that of rFIX (82.1 vs. 33.8 hours; P<0.001), as was the time to reach a factor IX level of 1 IU/dL (11.2 vs. 5.1 days).

Results were as follows:

• More than 90% of bleeding episodes resolved after one injection of rFIXFc; for those undergoing major surgery, hemostasis was rated good or excellent.
• For the 61 patients on weekly prophylaxis with rFIXFc (median weekly dose, 40.7 IU/kg), the annualized bleeding rate (ABR; the primary efficacy endpoint) was 3.1, and 23% had no bleeding.
• For the 29 patients assigned to adjusted-dose prophylaxis based on their post-dose nadir levels of rFIXFc, the ABR was 2.4, the median dosing interval was 13.8 days, and 42.3% had no bleeding.
• For the 27 patients on episodic treatment with rFIXFc, the ABR was 18.7.
• Adverse events were infrequent overall, and no patients developed thrombosis, serious hypersensitivity, or inhibitors.

Citation(s):

Powell JS et al. Phase 3 study of recombinant factor IX Fc fusion protein in hemophilia B. N Engl J Med 2013 Dec 12; 369:2313.