Hemophilia

BeneFIX, or coagulation factor IX (recombinant), is a human coagulation factor used to treat adults and children with hemophilia B. BeneFIX is indicated for the on-demand control of episodes of bleeding, routine prophylaxis, and surgical management. The drug was initially approved by the US Food and Drug Administration in 1997.¹

Hemophilia B (also known as Christmas disease) is a rare genetic bleeding disorder characterized by a deficiency of clotting factor IX (FIX). Mutations in the F9 gene, located on the X chromosome, are responsible for the development of this disease.² Without sufficient and functional levels of FIX, the flow of blood from wounds is not effectively controlled, so that affected persons bleed for a longer time than is normal.^2,3 

Cases of hemophilia B can range from mild to severe. In mild disease, bruises and bleeding may develop following surgical procedures or trauma, whereas severe cases are characterized by frequent and spontaneous episodes of bleeding. Bleeding into muscles and joints can affect movement and function, causing pain. The joints may become permanently damaged.²

Mechanism of Action and Use of BeneFIX

Replacing absent or defective FIX is important to establish proper blood clotting and prevent further complications of hemophilia B. Currently, various treatment options are available, such as plasma-derived factor IX concentrates, fresh frozen plasma, and recombinant FIX.² 

The active ingredient in BeneFIX is a purified form of coagulation FIX produced by recombinant DNA technology.¹ It does not contain animal or human protein and is not derived from human blood, so that risk for the transmission of blood-borne viral infection is avoided.^1,2 The structure and function of the recombinant protein of BeneFIX are similar to those of endogenous FIX, and its structure is identical to that of the Ala¹⁴⁸ allelic form of FIX. Thus, the administration of BeneFIX temporarily replaces FIX and restores proper hemostasis.¹

BeneFIX is formulated as a sterile and lyophilized powder and is available in single-use vials containing between 250 and 3000 IU of recombinant FIX. The dose and duration of treatment will depend on the severity of the disease, age of the patient, and level of bleeding. For long-term prophylaxis, the recommended dose is 100 IU/kg once a week.¹

Get full prescribing information for BeneFIX at MPR

Contraindications and Warnings

BeneFIX is contraindicated in patients who have experienced life-threatening hypersensitivity reactions to the product or to any of its components. The administration of BeneFIX has been associated with thromboembolic events and the development of neutralizing antibodies (inhibitors).¹ 

Efficacy and Safety in Clinical Trials

The efficacy of BeneFIX has been evaluated in previously treated and previously untreated patients.⁴ A multicenter, international, open-label, single-cohort trial comprising a core and an extension phase was conducted to determine the efficacy of BeneFIX in previously untreated patients.⁴ Data from an evaluation of the on-demand use of BeneFIX for episodes of bleeding in 54 previously untreated patients who received an initial infusion indicated that all episodes of bleeding were controlled and that 94.1% of the responses were rated “excellent” or “good.”^1,5 According to the data, a single infusion of BeneFIX was sufficient to control 75% of the bleeds.⁵ Evaluation of the safety of BeneFIX revealed that inhibitors developed in 2 of 63 previously untreated patients.^1,5 

The efficacy and safety of BeneFIX in previously treated patients presenting with severe or moderate hemophilia were evaluated in an international trial conducted at 20 centers.⁶ The use of BeneFIX for treatment, prophylaxis, and surgical management was studied. The responses to an initial on-demand infusion of BeneFIX in previously treated patients were reported as “excellent” or “good” in 90.9% of cases. A single infusion of BeneFIX was able to control 80.9% of the episodes of bleeding effectively.⁶

Adverse reactions frequently reported during the trials include hives, dyspnea, injection-site reaction, rash, nausea, headache, and chills.¹ 

References

1. Prescribing information. BeneFIX, Coagulation factor IX (recombinant). Pfizer; 2021. Accessed December 11, 2021.

2. Hemophilia B. National Organization for Rare Disorders (NORD). Accessed December 11, 2021.

3. Hemophilia B. National Hemophilia Foundation. Accessed December 11, 2021.

4. On-demand bleed control. Pfizer. Accessed December 11, 2021.

5. Shapiro AD, Ragni MV, Lusher JM, et al. Safety and efficacy of monoclonal antibody purified factor IX concentrate in previously untreated patients with hemophilia B. Thromb Haemost. 1996;75(1):30-35

6. Roth DA, Kessler CM, Pasi KJ, Rup B, Courter SG, Tubridy KL. Recombinant Factor IX Study Group. Human recombinant factor IX: safety and efficacy studies in hemophilia B patients previously treated with plasma-derived factor IX concentrates. Blood. 2001;98(13):3600-3606. doi:10.1182/blood.v98.13.3600

Reviewed by Hasan Avcu, MD, on 12/13/2021.

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Diana Diez Gaspar, PharmD, PhD

Diana earned her PhD and PharmD with distinction in the field of Medicinal and Pharmaceutical Chemistry at the Universidade do Porto. She is an accomplished oncology scientist with 10+ years of experience in developing and managing R&D projects and research staff directed to the development of small proteins fit for medical use.