Efficacy and Safety Data

PUPs

Indicated for bleed control^† and prevention^‡ in PUPs²

94.1% of responses were rated excellent or good in PUPs receiving an initial infusion of BeneFix for on-demand treatment²

2.9% were rated moderate, 1% were rated as no response, 2% were not rated^2,3
1505 infusions were given for on-demand treatment of 997 hemorrhages³
All bleeding episodes were controlled³

75% of bleeds were controlled after 1 infusion with BeneFix³

14.9% were controlled after 2 infusions
5.4% were controlled after 3 infusions
2.4% were controlled after 4 infusions
2.2% were controlled after >4 infusions

In the same study,^‡ 84.3% of PUPs did not have spontaneous bleeding within 48 hours of their last infusion.²

Bleed control rating scale: Efficacy was rated by the caregiver or investigator using a 4-point scale based on a comparison with previously used plasma-derived factor IX (pdFIX) products for similar bleeds or procedures: 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).^3,4

^†Study included 54 evaluable patients; median dose 62.7 IU/kg (8.2-292).³
^‡Study included 32 evaluable patients; mean dose (± SD) 73.3 IU/kg (±33.1).²

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Both PUPs with high-titer inhibitors were withdrawn from the study^2,3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 pdFIX or previously treated patients (PTPs) treated with recombinant factor IX³
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 days³

Adverse reactions (<5%) reported for PUPs^2,§

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, international, 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

PTPs

Indicated for bleed control^|| and prevention^¶in PTPs²

90.9% of responses were rated excellent or good in PTPs receiving an initial infusion of BeneFix for on-demand treatment⁴

7.1% were rated as moderate, 0.7% were rated as no response, 1.3% were not rated⁴
2758 infusions were given for on-demand treatment of 1796 hemorrhages⁴
All bleeding episodes were controlled⁴

80.9% of bleeds were controlled after 1 infusion with BeneFix⁴

11.6% were controlled after 2 infusions
3.6% were controlled after 3 infusions
1.8% were controlled after 4 infusions
2.1% were controlled after >4 infusions

In the same study,^¶ 63% of PTPs did not have spontaneous bleeding within 48 hours of their last infusion.²

^||Study included 55 evaluable patients; median dose 42.8 IU/kg (range: 6.5-224.6 IU/kg).⁴
^¶Study included 19 evaluable patients; mean dose 40.3 IU/kg (range: 13-78 IU/kg).⁴

Bleed control rating scale: Efficacy was rated by the caregiver or investigator using a 4-point scale based on a comparison with previously used pdFIX products for similar bleeds or procedures: 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).⁴

Safety in PTPs—low inhibitor formation

1 out of 65 patients developed a low-titer transient inhibitor in clinical trials including children and adults.^2,#

Most common adverse reactions (>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 rFIX 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 rFIX for pharmacokinetic studies, treatment of or prophylaxis against hemorrhage, or surgical hemostasis, and were assessed at 3-month intervals for 2 years.⁴

Surgery

Management of hemostasis in surgical procedures

In a subset analysis, 95.5% of responses were 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 surgeries^2,**

23 (63.9%) were major surgeries⁵
13 (36.1%) were minor surgeries, including 7 minor dental procedures⁵

23 PUPs underwent 30 surgeries^2,††

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

Surgical management 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 rFIX 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 rFIX products for similar bleeds or procedures; moderate if the response was less than satisfactory and not as good as most responses seen with other rFIX products when used for similar bleeding episodes or similar procedures; or no response if no improvement at all was observed.^3,4

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 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, international, 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

^**In the PTP surgery subjects, the median increase in circulating factor IX activity was 0.7 IU/dL per IU/kg infused (range 0.3-1.2 IU/dL mean 0.8 ± 0.2 IU/dL per IU/kg).²

^††In the PUP surgery subjects, the mean dose per infusion was 89.87 ± 51.95 IU/kg, and mean duration of treatment was 5.09 ± 3.96 days.³

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Important Safety Information

Important Safety Information and Indication

BeneFix 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.

References

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://wayback.archive-it.org/7993/20170723024338/https://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/ucm057039.htm. Published February 11, 1997. Accessed September 10, 2019.

2. BeneFix [prescribing information]. New York, NY: Pfizer Inc.; 2019.

3. Edwards J, Kirby N. Recombinant coagulation factor IX (BeneFix). In: Walsh G, Murphy B, eds. Biopharmaceuticals, an Industrial Perspective. Dordrecht, the Netherlands: Kluwer Academic Publishers; 1999:73-108.

4. Data on file. Pfizer Inc., New York, NY.

References

2. BeneFix [prescribing information]. New York, NY: Pfizer Inc.; 2019.

3. Shapiro AD, Di Paola J, Cohen A, et al; for Recombinant Factor IX Study Group. The safety and efficacy of recombinant human blood coagulation factor IX in previously untreated patients with severe or moderately severe hemophilia B. Blood. 2005;105(2):518-525.

4. Roth DA, Kessler CM, Pasi KJ, Rup B, Courter SG, Tubridy KL; for 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.

5. Ragni MV, Pasi KJ, White GC, Giangrande PL, Courter SG, Tubridy KL; and Recombinant FIX Surgical Study Group. Use of recombinant factor IX in subjects with haemophilia B undergoing surgery. Haemophilia. 2002;8(2):91-97.

6. Data on file. Pfizer Inc., New York, NY.

References

2. BeneFix [prescribing information]. New York, NY: Pfizer Inc.; 2019.

References

2. BeneFix [prescribing information]. New York, NY: Pfizer Inc.; 2019.

References

2. US National Institutes of Health. Clinical Trials Registry website. http://www.clinicaltrials.gov. Accessed September 10, 2019.

3. Summary of Basis for Approval: Coagulation Factor IX (Recombinant). US Food and Drug Administration website. http://wayback.archive-it.org/
7993/20170723024341/https://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM058970.pdf. Accessed September 10, 2019.

4. Data on file. Pfizer Inc., New York, NY.

References

2. Adamson S, Charlebois T, O'Connell B, Foster W. Viral safety of recombinant factor IX. Semin Hematol. 1998;35(2)(suppl 2):22-27.

3. Harrison S, Adamson S, Bonam D, et al. The manufacturing process for recombinant factor IX. Semin Hematol. 1998;35(2)(suppl 2):4-10.

4. Edwards J, Kirby N. Recombinant coagulation factor IX (BeneFIX). In: Walsh G, Murphy B, eds. Biopharmaceuticals, an Industrial Perspective. Dordrecht, the Netherlands: Kluwer Academic Publishers; 1999:73-108.

5. Data on file. Pfizer Inc., New York, NY.

6. BeneFix [prescribing information]. New York, NY: Pfizer Inc.; 2019.

Important Safety Information and Indication

Indication

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Efficacy and Safety Data

PUPs

Indicated for bleed control† and prevention‡ in PUPs2

†Study included 54 evaluable patients; median dose 62.7 IU/kg (8.2-292).3‡Study included 32 evaluable patients; mean dose (± SD) 73.3 IU/kg (±33.1).2

Safety profile—supported by clinical trials

Adverse reactions (<5%) reported for PUPs2,§

PTPs

Indicated for bleed control|| and prevention¶ in PTPs2

||Study included 55 evaluable patients; median dose 42.8 IU/kg (range: 6.5-224.6 IU/kg).4¶Study included 19 evaluable patients; mean dose 40.3 IU/kg (range: 13-78 IU/kg).4

Safety in PTPs—low inhibitor formation

Most common adverse reactions (>5%) were2:

Surgery

Management of hemostasis in surgical procedures

Clinical Information

Support & Services

Flexibility for your patients

Important Safety Information

Important Safety Information and Indication

Indication

References

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Indicated for bleed control^† and prevention^‡ in PUPs²

^†Study included 54 evaluable patients; median dose 62.7 IU/kg (8.2-292).³
^‡Study included 32 evaluable patients; mean dose (± SD) 73.3 IU/kg (±33.1).²

Adverse reactions (<5%) reported for PUPs^2,§

Indicated for bleed control^|| and prevention^¶in PTPs²

^||Study included 55 evaluable patients; median dose 42.8 IU/kg (range: 6.5-224.6 IU/kg).⁴
^¶Study included 19 evaluable patients; mean dose 40.3 IU/kg (range: 13-78 IU/kg).⁴

Most common adverse reactions (>5%) were²: