Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A.
(2014) Blood — Vol. 123, n° 3, p. 317-325 (2014)
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- This phase 3 pivotal study evaluated the safety, efficacy, and pharmacokinetics of a recombinant FVIII Fc fusion protein (rFVIIIFc) for prophylaxis, treatment of acute bleeding, and perioperative hemostatic control in 165 previously treated males aged ≥12 years with severe hemophilia A. The study had 3 treatment arms: arm 1, individualized prophylaxis (25-65 IU/kg every 3-5 days, n = 118); arm 2, weekly prophylaxis (65 IU/kg, n = 24); and arm 3, episodic treatment (10-50 IU/kg, n = 23). A subgroup compared recombinant FVIII (rFVIII) and rFVIIIFc pharmacokinetics. End points included annualized bleeding rate (ABR), inhibitor development, and adverse events. The terminal half-life of rFVIIIFc (19.0 hours) was extended 1.5-fold vs rFVIII (12.4 hours; P < .001). Median ABRs observed in arms 1, 2, and 3 were 1.6, 3.6, and 33.6, respectively. In arm 1, the median weekly dose was 77.9 IU/kg; approximately 30% of subjects achieved a 5-day dosing interval (last 3 months on study). Across arms, 87.3% of bleeding episodes resolved with 1 injection. Adverse events were consistent with those expected in this population; no subjects developed inhibitors. rFVIIIFc was well-tolerated, had a prolonged half-life compared with rFVIII, and resulted in low ABRs when dosed prophylactically 1 to 2 times per week.
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Mahlangu, J., Powell, J. S., Ragni, M. V., Chowdary, P., Josephson, N. C., Pabinger, I., Hanabusa, H., Gupta, N., Kulkarni, R., Fogarty, P., Perry, D., Shapiro, A., Pasi, K. J., Apte, S., Nestorov, I., Jiang, H., Li, S., Neelakantan, S., Cristiano, L. M., et al. (2014). Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A. Blood, 123(3), 317-325. https://doi.org/10.1182/blood-2013-10-529974 (Original work published 2014)