By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Medical Director, Pharmacy, Northern California Kaiser Permanente, and Assistant Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA.
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved the first coagulation factor-albumin fusion protein to treat patients with hemophilia B. The new product is a recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP), which extends the half-life of factor IX up to a mean of 118 hours.1 It is the second factor IX fusion protein after coagulation factor IX Fc fusion protein (rFIXFc). Coagulation factor-albumin fusion protein is marketed as Idelvion.
rIX-FP is indicated for on-demand control and prevention of bleeding episodes, perioperative management of bleeding, or routine prophylaxis to prevent or reduce the frequency of bleeding episodes in children and adults with hemophilia B (congenital factor IX deficiency).1
The dose and duration of treatment are individualized based on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient’s clinical condition, age, and recovery of factor IX.1 Coagulation factor IX albumin fusion protein is available as a lyophilized powder in 250, 500, 1000, or 2000 IU.
This product currently has the longest elimination half-life of any factor IX product.
Hypersensitivity reactions, including anaphylaxis, are possible, and development of neutralizing antibodies may occur.1 The most common adverse event reported was headache.
The safety and efficacy of rIX-FP were evaluated in three different settings: on-demand treatment of bleeding episodes, perioperative management of major and minor procedures, and routine prophylaxis. Overall treatment efficacy (excellent and good) for on-demand control and prevention of bleeding episodes was 94%, with 94% requiring one injection. Excellent response was defined as pain relief and/or unequivocal improvement in objective signs of bleeding and no additional infusion required to achieve hemostasis. Good response was defined as pain relief and/or improvement in signs of bleeding at approximately 8 hours after the first infusion but possibly requiring a second infusion. In perioperative management of bleeding, rIX-FP was evaluated in various major and minor surgical procedures. In 11 of 15 surgeries, hemostatic response was rated as excellent, one rated good, and three minor surgeries received no rating. In routine prophylaxis, rIX-FP dosed weekly resulted in an 89% reduction in the annualized spontaneous and traumatic bleeding rate compared to on-demand treatment.1,2 Subjects treated with both weekly and 14-day intervals had annualized spontaneous bleeding rates of 0.28 and 1.07, respectively. The overall efficacy appears similar to that reported for other factor IX recombinant products.3,4
Hemophilia B is a rare, inherited bleeding disorder. Patients experience repeated episodes of potentially serious bleeding episodes. The new coagulation factor-albumin fusion protein offers a product with good efficacy and a longer half-life. This allows for a slightly longer interval for routine prophylaxis to every 7 to 14 days compared to 7 to 10 for rFIXFc (elimination half-life of 87 hours) and much longer than earlier recombinant factor IX (approximately 27 hours for Rixubis, and dosing twice a week). The cost for each IU of rIX-FP is $4.25 compared to $2.85 for rFIXFc and $1.46 for Rixubis.
- Idelvion Prescribing Information. CSL Behring, March 2016.
- Santagostino E, et al. Long acting recombinant coagulation factor IX albumin fusion protein (rIX-FP) in hemophilia B: Results of a phase 3 trial. Blood Jan 11, 2016. [Epub ahead of print].
- Alprolix Prescribing Information. Biogen, February 2016.
- Rixubis Prescribing Information. Baxter HealthCare, September 2014.