Important Safety Information and Indication
  • BeneFix, Coagulation Factor IX (Recombinant), is contraindicated in patients who have manifested life-threatening, immediate hypersensitivity reactions, including anaphylaxis, to the product or its components, including hamster protein.
  • Hypersensitivity reactions, including anaphylaxis, have been reported with BeneFix. Closely monitor patients for signs and symptoms of acute anaphylaxis, particularly during the early phases of initial exposure to the product. Immediately discontinue the administration of the product and initiate appropriate treatment if symptoms occur.
  • Patients may develop hypersensitivity to hamster (CHO) protein as BeneFix contains trace amounts.
  • BeneFix has been associated with the development of thromboembolic complications, including patients receiving continuous infusion through a central venous catheter. The safety and efficacy of BeneFix administration by continuous infusion have not been established.
  • Neutralizing antibodies (inhibitors) have been reported following the administration of BeneFix. If expected plasma factor IX activity levels are not attained, or if the patient presents with an allergic reaction, or if bleeding is not controlled following an expected dose of BeneFix, perform an assay that measures factor IX inhibitor concentration.
  • The most common adverse reactions (>5%) from clinical trials were nausea, injection site reaction, injection site pain, headache, dizziness and rash.

Indication

BeneFix, Coagulation Factor IX (Recombinant), is a human blood coagulation factor indicated in adult and pediatric patients with hemophilia B (congenital factor IX deficiency or Christmas disease) for the control and prevention of bleeding episodes and peri-operative management.

Limitations of use:

BeneFix is NOT indicated for:

  • treatment of other factor deficiencies (eg, factors II, VII, VIII and X),
  • treatment of hemophilia A patients with inhibitors to factor VIII,
  • reversal of coumarin-induced anticoagulation,
  • treatment of bleeding due to low levels of liver-dependent coagulation factors.

Please see Full Prescribing Information for BeneFix.

Reference

  • 1. Center for Biologics Evaluation and Research, US Food and Drug Administration, US Department of Health and Human Services. CBER Approval Letter, Coagulation Factor IX (Recombinant), Genetics Institute, Inc. http://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/
    ucm057039.htm. Published February 11, 1997. Accessed November 14, 2016.

Reference

  • 1. Center for Biologics Evaluation and Research, US Food and Drug Administration, US Department of Health and Human Services. CBER Approval Letter, Coagulation Factor IX (Recombinant), Genetics Institute, Inc. http://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/
    ucm057039.htm. Published February 11, 1997. Accessed November 14, 2016.

Reference

  • 1. Center for Biologics Evaluation and Research, US Food and Drug Administration, US Department of Health and Human Services. CBER Approval Letter, Coagulation Factor IX (Recombinant), Genetics Institute, Inc. http://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/
    ucm057039.htm. Published February 11, 1997. Accessed November 14, 2016.

Reference

  • 1. Center for Biologics Evaluation and Research, US Food and Drug Administration, US Department of Health and Human Services. CBER Approval Letter, Coagulation Factor IX (Recombinant), Genetics Institute, Inc. http://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/
    ucm057039.htm. Published February 11, 1997. Accessed November 14, 2016.

Efficacy and Safety Data

BeneFix — a recombinant Factor IX with data to support bleed prevention in previously untreated patients (PUPs)

84.3% of PUPs had no spontaneous bleeds within 48 hours of receiving a preventive infusion of BeneFix.2†

  • 32 PUPs were administered BeneFix for routine prevention of bleeding.2†
  • 5 out of 32 patients did have early spontaneous bleeding.2†

Includes patients who received routine infusions to prevent spontaneous bleeding and intermittent administration.2

Bleed control in PUPs

94.1% of responses were rated excellent or good in PUPs receiving an initial infusion for on-demand treatment.2‡

  • 2.9% rated moderate.2
  • 1.0% rated none.2
  • 2.0% were not rated.3
  • All bleeding episodes were controlled.3

1505 infusions were given for on-demand treatment of 997 hemorrhages. Mean dose per infusion was 75.58 IU/kg ± 42.47 IU/kg. Mean duration of exposure was 26.72 ± 26.41 days.3

Rating scale: Four-point scale based on comparison with previously-used plasma-derived (pd) FIX product: excellent (as much and as rapid an improvement as the best pdFIX-related responses), good (as much and as rapid an improvement as most pdFIX-related responses), moderate (not as good as most pdFIX-related responses), or no response (no improvement).3

Safety profile—supported by clinical trials




2 out of 63 PUPs developed high-titer (>5 BU/dL) inhibitors in clinical trials.2,3

  • Both PUPs with high-titer inhibitors were withdrawn from the study.2,3
  • Incidence of factor IX inhibitor is consistent with reports of hemophilia B patients treated with plasma-derived factor IX or previously treated patients (PTPs) treated with recombinant factor IX.3
  • Fifty-six patients received a total of 5032 infusions (mean 89.86 ± 74.04) for a mean duration of exposure of 86.75 ± 71.73 days.3

Adverse reactions (<5%) reported for PUPs

Adverse Reaction Number of Patients
Hives 3 (4.8%)
Dyspnea 2 (3.2%)
Injection site reaction 1 (1.6%)
Chills 1 (1.6%)
Rash 1 (1.6%)

§Adverse reactions were reported within 72 hours of an infusion of BeneFix.2

Study description: A multicenter, open-label, single-cohort study consisting of a core phase and an extension phase. In the core phase, patients received recombinant factor IX (rFIX) for: (1) on-demand treatment in response to any bleeding episode, (2) routine prophylaxis for prevention of bleeding episodes, or (3) surgical prophylaxis. Patients who completed the core phase were allowed to enter the extension phase to receive rFIX for up to 1 additional year, at the discretion of the investigator and after prior written authorization from the sponsor.2,3

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Bleed prevention in previously treated patients (PTPs)

93.1% of preventive regimen responses were rated excellent or effective by HCPs2||

  • 4.3% rated inadequate2
  • 2.6% response not provided2

||2985 infusions were given 2 to 3 times per week. Average dose of 40.3 IU/kg; range 13–78 IU/kg.2,4

Rating scale: Responses were assessed once every 3 months by the investigator using a 3-point scale: excellent (no spontaneous bleeding of any kind, no change in dosing regimen necessary), effective (no spontaneous musculoskeletal bleeding, no change in dosing regimen necessary), or inadequate (inadequate prevention of bleeding requiring a change in dosing regimen).4

Bleed control in PTPs

92.5% of bleeds were treated successfully with 1 or 2 on-demand infusions

  • 80.9% of bleeds were controlled with a single infusion2
  • All 1796 bleeds were controlled with on-demand infusions of BeneFix4
  • Based on 2758 infusions administered4

Fifty-five PTPs received on-demand treatment with BeneFix for bleeding episodes.2

Safety in PTPs—low inhibitor formation



1 out of 65 patients developed a low-titer transient inhibitor.2#

Most common adverse reactions (frequency >5%) were2:

Adverse Reaction Number of Patients
Headache 7 (10.8%)
Dizziness 5 (7.7%)
Injection site reaction 5 (7.7%)
Nausea 4 (6.2%)
Injection site pain 4 (6.2%)
Rash 4 (6.2%)

#At study completion (approximately 15 months after inhibitor detection), the patient had normal factor IX recovery pharmacokinetics. Patient populations across these studies represented different hemophilia severities, prior factor IX replacement treatment histories, and ages.2,4

Study description: A 20-center international trial was conducted in PTPs with severe or moderate (≤5 IU/dL factor IX activity) hemophilia B. Participants received recombinant factor IX for pharmacokinetic studies, treatment of or prophylaxis against hemorrhage, or surgical hemostasis, and were assessed at 3-month intervals for 2 years.4

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Effective hemostasis in surgical procedures

In a subset analysis of PTPs and PUPs, 95.5% of responses rated excellent or good in both PTPs and PUPs receiving BeneFix and undergoing surgery2††

  • 1.5% were rated moderate, 3.0% of responses were not provided2

28 PTPs underwent 36 surgeries2

  • 23 (63.9%) were major surgeries2
  • 13 (36.1%) were minor surgeries, including 7 minor dental procedures5

23 PUPs underwent 30 surgeries2

  • 28 were minor surgeries2
  • 2 were hernia repairs2

Dental and minor procedures2

  • 92% of responses rated excellent or good in PTPs during dental procedures2
  • 96% of responses rated excellent or good in PUPs during minor procedures2

Rating scale: Efficacy was graded by subjective assessment of response to surgery by the subject and by the physician, in consultation with the surgeon. The response was rated excellent if the response was as satisfactory, with as much and as rapid an improvement as the best responses with other FIX products for similar bleeds or procedures; good if the response was as satisfactory, with as much and as rapid an improvement as most responses with other FIX products for similar bleeds or procedures; moderate if the response was less than satisfactory and not as good as most responses seen with other FIX products when used for similar bleeding episodes or similar procedures; or no response if no improvement at all was observed.5


††Study descriptions:
PTPs: A multicenter, international trial was conducted in PTPs with severe or moderate (≤5 IU/dL factor IX activity) hemophilia B. Participants received recombinant factor IX (rFIX) for pharmacokinetic studies, treatment of or prophylaxis against hemorrhage, or surgical hemostasis, and were assessed at 3-month intervals for 2 years.4

PUPs: A multicenter, open-label, single-cohort study consisting of a core phase and an extension phase. In the core phase, patients received rFIX for: (1) on-demand treatment in response to any bleeding episode, (2) routine prophylaxis for prevention of bleeding episodes, or (3) surgical prophylaxis. Patients who completed the core phase were allowed to enter the extension phase to receive rFIX for up to 1 additional year, at the discretion of the investigator and after prior written authorization from the sponsor.2,3


BeneFix is available in hundreds of institutions nationwide.6

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