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Recombinant Factor VIII Fc fusion protein effective in severe hemophilia A
A novel recombinant Factor VIII Fc fusion protein with a prolonged half-life was associated with low bleeding rates in patients with severe hemophilia A, according to phase 3 study results.
The regimen, which reduced injection frequency compared with recombinant Factor VIII, also appeared well tolerated.
The open-label, multicenter, partially randomized study included 165 males aged 12 years or older (median age, 30 years) with previously treated hemophilia A.
Patients received one of three treatment regimens: 25 IU/kg to 65 IU/kg individualized prophylaxis of recombinant Factor VIII Fc fusion protein (rFVIIIFc) every 3 to 5 days (n=118); 65 IU/kg weekly prophylaxis (n=24); and 10 IU/kg to 50 IU/kg episodic treatment (n=23).
Annualized bleeding rates, inhibitor development and adverse events served as endpoints.
The median weekly dose was 77.9 IU/kg in the individualized prophylaxis arm, and 30% of patients achieved a 5-day dosing interval within the last 3 months of the study.
The median annualized bleeding rate was highest in the episodic treatment arm (33.6), followed by the weekly prophylaxis arm (3.6) and the individualized prophylaxis arm (1.6).
Among all patients, 87.3% of bleeding episodes resolved after one treatment.
Researchers also compared pharmacokinetics of rFVIIIFc with recombinant Factor VIII in a subgroup of patients.
Results showed the terminal half-life of rFVIIIFc was 1.5-fold greater than that of recombinant Factor VIII (19 hours vs. 12.4 hours; P˂.001).
Adverse events occurred in 80 patients (684%) assigned to individualized prophylaxis, 18 (75%) assigned to weekly prophylaxis and 10 (43.5%) assigned to episodic treatment.
The most common adverse events — which were consistent with those expected for the patient population, according to researchers — were nasopharyngitis, arthralgia, upper respiratory tract infection and headache. No patients developed inhibitors.
“This study demonstrates that recombinant Factor VIII Fc was well tolerated and efficacious in the prevention and treatment of bleeding events, including in the setting of major surgery, in adolescents and adults with severe hemophilia A,” the researchers wrote. “Thus, recombinant Factor VIII Fc offers the potential for an injection frequency reduced up to 50% compared with existing Factor VIII therapeutic regimens, an improvement in treatment burden that may increase compliance with prophylaxis among patients with hemophilia A.”
Disclosure: The researchers report advisory, speakers’ bureau, employment and consultant roles with, research funding, travel grants and honoraria from, and equity ownership in Amgen, Baxter Healthcare, Bayer, Biogen Idec, Bristol-Myers Squibb, CSL Behring, GlaxoSmithKline, Grifols, Inspiration, Merck, Novo Nordisk, OctaPharma, Pfizer and Tacere Benitec.