WARSAW—Recombinant Fc fusion proteins can provide long-lasting protection from bleeding in patients with hemophilia A or B, according to data presented at the 6th Annual Congress of the European Association for Haemophilia and Allied Disorders.
Data from the phase 3 A-LONG study indicated that patients with hemophilia A could maintain low bleeding rates with once- to twice-weekly prophylactic injections of a recombinant factor VIII Fc fusion protein (rFVIIIFc, efmoroctocog alfa/Elocta, Eloctate).
Similarly, results of the phase 3 B-LONG study showed that patients with hemophilia B had low bleeding rates when they received prophylactic injections of a recombinant factor IX Fc fusion protein (rFIXFc, eftrenonacog alfa/Alprolix) every 1 to 2 weeks.
Both studies were sponsored by the companies developing these factors, Biogen Idec and Swedish Orphan Biovitrum (Sobi).
A-LONG data
In the A-LONG study, researchers evaluated the efficacy, safety, and pharmacokinetics of intravenous rFVIIIFc in 165 male patients aged 12 years and older. The team found that 98% of bleeding episodes were controlled by 1 or 2 injections of rFVIIIFc.
The factor was generally well-tolerated, and no inhibitors were detected. The most common adverse events (with an incidence of 5% or higher) were nasopharyngitis, arthralgia, headache, and upper respiratory tract infection.
The study also showed that rFVIIIFc stays in the body for 50% longer than Advate [antihemophilic factor (recombinant), plasma/albumin-free method], the most frequently used factor VIII therapy. The terminal half-life for rFVIIIFc was 19 hours, compared to 12 hours for Advate.
Additionally, the mean time for maintaining a clotting factor activity level associated with less bleeding (time to 1%) was approximately 5 days for rFVIIIFc, compared to 3.5 days for Advate. And the average rate at which rFVIIIFc was cleared from the body was 2.0 mL/hr/kg, compared with 3.0 mL/hr/kg for Advate.
In the study’s individualized prophylaxis arm, patients received rFVIIIFc at a median dosing interval of 3.5 days and a median weekly dose of 78 IU/kg to prevent bleeding, which compares favorably to the recommended dose for the standard of care. Nearly one-third of patients were able to achieve every-5-days dosing in this arm.
The A-LONG data were presented in the late-breaking oral abstract session and in poster 104, “Phase 3 clinical study of recombinant FC fusion factor FVIII (rFVIIIFc) demonstrated safety, efficacy, and improved pharmacokinetics (A-LONG).”
B-LONG data
In the B-LONG study, researchers evaluated the efficacy, safety, and pharmacokinetics of intravenous rFIXFc in 123 male patients aged 12 years and older. The team found that more than 90% of bleeding episodes were controlled by a single injection of rFIXFc.
rFIXFc was generally well-tolerated, and no inhibitors were detected. The most common adverse events (with an incidence of 5% or more) were nasopharyngitis, influenza, arthralgia, upper respiratory infection, hypertension, and headache.
One serious adverse event, obstructive uropathy in the setting of hematuria, may have been related to rFIXFc treatment. However, the patient continued to receive rFIXFc, and the event resolved with medical management.
The study also showed that rFIXFc stays in the body more than twice as long as BeneFIX [Coagulation Factor IX (Recombinant)], the only recombinant factor IX therapy currently approved for prophylactic use. The terminal half-life for rFIXFc was 82 hours, compared to 34 hours for BeneFIX.
In addition, the mean time for maintaining a normal clotting factor activity level (time to 1%) was 11 days for rFIXFc, compared to 5 days for BeneFIX. And the average rate at which rFIXFc was cleared from the body was 3.2 mL/hr/kg, compared with 6.3 mL/hr/kg for BeneFIX.
All patients in the individualized interval prophylaxis arm of the study were able to go at least 1 week between rFIXFc injections, and 50% could go 14 days or longer before needing another dose to prevent bleeding. The median weekly dose was 45 IU/kg, which is comparable to the recommended dose for the current standard of care.
The B-LONG data were presented in poster 115, “Safety, efficacy, and improved pharmacokinetics (PK) demonstrated in a phase 3 clinical trial of extended half-life recombinant FC fusion factor IX (B-LONG).”
