Rixubis® (coagulation factor IX [recombinant], nonacog gamma, BAX326), manufactured by Baxter Healthcare, is an antihemophilic factor used as on-demand treatment to control episodes of bleeding in adults and children with hemophilia B. It is also used to manage perioperative bleeding and for routine prophylaxis to minimize the frequency of episodes of bleeding. The use of Rixubis to induce immune tolerance in patients with hemophilia B is not recommended. Stringent methods of virus removal and purification are used during the manufacture of Rixubis, and its activated factor IX activity is minimal, so that the risk for thrombogenesis in humans is greatly reduced.1,2 

Rixubis has been licensed in the United States (2013), Europe (2014), and South Korea (2015) for the prevention and treatment of episodes of bleeding as well as routine prophylaxis in patients with hemophilia B.3 Single-use vials contain 250, 500, 1000, 2000, or 3000 IU of Rixubis in the form of a white or nearly white lyophilized powder.4 

Hemophilia B is an inherited disease of blood coagulation in which mutations in the F9 gene cause a deficiency of clotting factor IX. Primarily males are affected. Roughly 3300 individuals in the United States have hemophilia B. The disease can cause significant bleeding, particularly in the joints.5

Mechanism of Action

Clotting factor IX is required for effective hemostasis. Patients with hemophilia B have a deficiency of factor IX and a prolonged activated partial thromboplastin time (aPTT). Rixubis, a factor IX concentrate, boosts plasma levels of factor IX, temporarily correcting the coagulation abnormality and normalizing the aPTT.6 

Get full prescribing information on Rixubis at MPR

Efficacy in Trials and Trial Results

The goal of NCT01174446, the pivotal phase I/III study, was to compare the pharmacokinetic attributes of Rixubis with those of nonacog alfa. Another goal was to explore its safety and efficacy, as well as the health-related quality of life of previously treated patients aged 12 to 65 years with severe hemophilia B (factor IX levels <1%) or moderately severe hemophilia B (factor IX levels ≤2%).7 

A calculated preventive infusion dose (40-75 IU/kg) was administered to 96.7% of the participants, and 89.2% of them maintained the scheduled dosing frequency. During the 6 months of twice-weekly Rixubis prophylaxis, the overall median annualized bleeding rate (ABR) was 1.99. The overall mean ABR (4.20 ± 5.75) was substantially lower than the ABR in the 276 patients who had used on-demand therapy (plasma-derived factor IX or recombinant factor IX) in 12 previous studies (20.0 ± 39.4).7 

Rixubis had a good safety profile in the pivotal study. Severe allergic reactions, anaphylaxis, thrombotic events, and other treatment-related serious adverse effects and deaths were not noted. Factor IX inhibitors or treatment-related antibodies did not develop in any of the patients. Adverse effects that were not serious, including dysgeusia and extremity pain, were observed in a few cases. Thrombogenic markers were elevated in some patients, but this was considered to be due to sampling technique or recent bleeding.7 

In September 2014, after positive results from a clinical trial (NCT01488994) in 23 children with moderate to severe hemophilia B, the US Food and Drug Administration approved Rixubis for use in children, following approval for use in adults. All of the children were 12 years old at the time, and they were given Rixubis twice a week for 6 months. In this age group, the therapy was also found to be safe and efficacious.8

Warnings, Precautions, and Adverse Reactions

Rixubis can cause hypersensitivity reactions, including allergies and anaphylaxis. It should be discontinued in such cases and emergency treatment provided. Chinese hamster ovary (CHO) protein, which is present in tiny amounts in Rixubis, can cause hypersensitivity.1,9

The induction of immune tolerance has been linked to nephrotic syndrome in patients with hemophilia B.1 Ribuxis neutralizing antibodies or inhibitors may develop. A factor IX inhibitor concentration assay should be done if the intended plasma levels of factor IX are not achieved, or if bleeding cannot managed with an appropriate dose.1

The use of products containing factor IX has been linked to the development of thromboembolic events.1

Common adverse reactions, observed in more than 1% of individuals in clinical trials, include dysgeusia, extremity pain, and a positive furin antibody test result.4 

Interference of human coagulation factor IX (rDNA) products with other medications has not been reported.10

References

  1. RIXUBIS (coagulation factor ix- recombinant kit. DailyMed. Updated August 6, 2020. Accessed December 26, 2021.
  2. Windyga J, Solano Trujillo MH, Hafeman AE. BAX326 (RIXUBIS): a novel recombinant factor IX for the control and prevention of bleeding episodes in adults and children with hemophilia B. Ther Adv Hematol. 2014;5(5):168-180. doi:10.1177/2040620714550573
  3. Choi EJ, Hwang TJ, Choi YM, et al. Safety and effectiveness of Rixubis in patients with hemophilia B: a real-world, prospective, postmarketing surveillance study in South Korea. Blood Res. 2020;55(4):246-252. doi:10.5045/br.2020.2020225.
  4. RIXUBIS (coagulation factor IX [recombinant]), Prescribing information. Revised September 2014. Accessed December 26, 2021.
  5. Zornoza L. FDA approves Baxter’s Rixubis, first recombinant coagulation factor IX for hemophilia B | RAPS. News release. Regulatory Affairs Professionals Society. June 28, 2013.
  6. Rixubis-pm-en.pdf (takeda.com). Product monograph including patient medication information. Revised March 12, 2021. Accessed December 26, 2021.
  7. Windyga J, Lin VW, Epstein JD, et al. Improvement in health-related quality of life with recombinant factor IX prophylaxis in severe or moderately severe haemophilia B patients: results from the BAX326 Pivotal Study. Haemophilia. 2014;20(3):362-368. doi:10.1111/hae.12315
  8. Urasinski T, Stasyshyn O, Andreeva T, et al. Recombinant factor IX (BAX326) in previously treated paediatric patients with haemophilia B: a prospective clinical trial. Haemophilia. 2015;21(2):196-203. doi:10.1111/hae.12548
  9. Dosing, administration & storage information about RIXUBIS. Accessed December 26, 2021.
  10. RIXUBIS, nonacog gamma. Summary of product characteristics. Accessed December 26, 2021.

Reviewed by Hasan Avcu, MD, on 12/30/2021.

READ MORE ON