Photo by Piotr Bodzek
Team performing surgery
AMSTERDAM—A recombinant factor IX Fc fusion protein (rFIXFc) can control bleeding among hemophilia B patients undergoing major surgery, according to data from the B-LONG study presented at ISTH 2013.
The goal of the phase 3 B-LONG study was to evaluate the safety, efficacy, and pharmacokinetics (PK) of rFIXFc among male patients with hemophilia B.
Previously released data from the study suggested rFIXFc can safely prevent bleeding in these patients, and the product stays in the body more than twice as long as the recombinant factor IX therapy BeneFIX.
At ISTH 2013, Jerry Powell, MD, of the University of California at Davis, presented an analysis of B-LONG data that demonstrated rFIXFc’s effects among hemophilia B patients who underwent major surgery (e-Poster PA 2.07-4).
The B-LONG study was sponsored by Biogen Idec and Sobi, the companies developing rFIXFc (also known as eftrenonacog alfa) as Alprolix.
The study included 123 male subjects with severe hemophilia B (≤2 IU/dL [2%] endogenous FIX). Patients were 12 years of age or older They had no current or previous FIX inhibitors and a history of 100 or more documented prior exposure days to FIX products.
Patients received rFIXFc in 1 of 4 treatment arms:
- Weekly prophylaxis starting at 50 IU/kg, with PK-driven dose adjustments (n=63)
- Individualized interval prophylaxis starting at 100 IU/kg every 10 days, with PK-driven interval adjustments (n=29)
- On-demand treatment at 20 IU/kg to 100 IU/kg (n=27)
- Perioperative management (n=12, including 8 from arms 1-3).
The patients who required major surgery were placed in arm 4. Investigators and surgeons decided upon treatment for these patients based on considerations of their rFIXFc PK profile, the type of planned surgery, and the patients’ clinical status.
The 12 patients underwent a total of 14 major surgeries, including arthroscopic meniscectomy of knee (n=1), arthroscopic ankle fusion (n=1), knee replacements (n=5), and other (n=7).
The investigators/surgeons rated hemostasis as “excellent” in 13 of the surgeries and “good” for 1 procedure.
The median estimated blood loss was 65.5 mL (range, 0.0 to 300.0 mL) during surgery and 0.0 mL (range, 0.0 to 500 mL) after surgery. None of the patients required blood transfusions during surgery, but 2 patients received transfusions postoperatively.
In most of the surgeries—85.7%—patients required a single injection of rFIXFc to maintain hemostasis during the operation. The median dose was 90.9 IU/kg per injection.
Most patients required 1 to 2 injections of rFIXFc the day before and the day of surgery. And most patients required 2 to 3 injections from days 1 to 3 after surgery. So the median rFIXFc consumption was 146.1 IU/kg on the day of surgery, 164.6 IU/kg from days 1 to 3 after surgery, and 277.1 IU/kg for days 4 to 14 after surgery.
A majority of patients—83.3% (10/12)—experienced 1 or more adverse events related to treatment. Three patients experienced 6 adverse events, but these were resolved, and investigators said they were unrelated to rFIXFc treatment.
Additional analyses of B-LONG data were presented at ISTH 2013, including an analysis of rFIXFc in the treatment of bleeding episodes and a PK analysis of rFIXFc.
