Hemophilia Factor IX Products - NC Standard

Commercial Policy

Version Date: April 2024

Restricted Product(s)

Extended Half-life Products

Alprolix®
Idelvion®
Rebinyn®

Standard Half-life Products

BeneFIX®
Ixinity®
Rixubis®
AlphaNine SD®
Profilnine SD®

FDA Approved Use

Agent	Indication	Dosage
Alprolix® [Coagulation Factor IX (recombinant), Fc Fusion protein]	Adult and pediatric patient with hemophilia B for: On-demand treatment and control of bleeding episodes Perioperative management of bleeding Routine prophylaxis to reduce the frequency of bleeding episodes Limitations of Use: Alprolix is not indicated for induction of immune tolerance in patients with hemophilia B	Control and prevention of bleeding episodes: One unit/kg body weight will raise the Factor IX level by 1 unit/dL in adults and children greater than or equal to 6 years old. One unit/kg body weight will raise the Factor IX level by 0.6 units/dL in children less than 6 years old. Perioperative management: Dose (units) = body weight (kg) x desired factor IX rise (units/dL or % of normal) x 0.5 - 0.8 (units/kg per units/dL); frequency based on type of surgery Routine Prophylaxis: Children (< 12 years of age): Dose (units) = 60 units/kg once weekly ≥12 years of age: Dose (units) = 50 units/kg once weekly or 100 units/kg once every 10 days. Regimen may be individually adjusted to less or more frequent dosing based on bleeding episodes. Dose should be titrated to patient’s clinical response.
BeneFIX® [Coagulation Factor IX (Recombinant)]	Adult and pediatric patient with hemophilia B for: Control and prevention of bleeding episodes Perioperative management of bleeding Routine prophylaxis to reduce the frequency of bleeding episodes Limitations of Use: BeneFIX is not indicated for the treatment of other factor deficiencies (e.g., factors II, VII, VIII, and X), hemophilia A patients with inhibitors to factor VIII, reversal of coumarin-induced anticoagulation, and bleeding due to low levels of liver-dependent coagulation factors.	Control and prevention of bleeding episodes: Dose (units) = Body Weight (kg) x Desired Factor IX rise (units/dL or % of normal) x reciprocal of observed recovery (units/kg per units/dL); frequency based on type of bleed Routine Prophylaxis: Dose (units) = 100 units/kg once weekly Regimen may be individually adjusted to less or more frequent dosing based on bleeding episodes. Dose should be titrated to patient’s clinical response.
Idelvion® [Coagulation Factor IX (recombinant), Albumin Fusion Protein (rIX-FP)	Adult and pediatric patient with Hemophilia B (congenital Factor IX deficiency) for: On-demand treatment and control of bleeding episodes Perioperative management of bleeding Routine prophylaxis to reduce the frequency of bleeding episodes Limitations of Use: Idelvion is not indicated for immune tolerance induction in patients with Hemophilia B.	Control and prevention of bleeding episodes: One unit/kg body weight will raise the Factor IX level by 1.3 unit/dL in adults and adolescents One unit/kg body weight will raise the Factor IX level by 1 unit/dL in children less than 12 years old Perioperative management: Dose (units) = Body Weight (kg) x Desired Factor IX rise (units/dL or % of normal) x reciprocal of observed recovery (units/kg per units/dL); frequency based on type of bleed Routine Prophylaxis: Children (< 12 years of age): Dose (units) = 40-55 units/kg every 7 days ≥12 years of age: Dose (units) = 25-40 units/kg every 7 days or 50-75 units/kg every 14 days for well-controlled patients. Regimen may be individually adjusted to less or more frequent dosing based on bleeding episodes. Dose should be titrated to patient’s clinical response.
Ixinity® [Coagulation Factor IX (Recombinant)	Adults and pediatric patient with hemophilia B for: On-demand treatment and control of bleeding episodes Perioperative management of bleeding Routine prophylaxis to reduce the frequency of bleeding episodes Limitations of Use: Ixinity is not indicated for induction of immune tolerance in patients with hemophilia B.	Control and prevention of bleeding episodes: Dose (units) = Body Weight (kg) x Desired Factor IX rise (units/dL or % of normal) x reciprocal of observed recovery (units/kg per units/dL); frequency based on type of bleed One unit/kg body weight will raise the Factor IX level by 0.98 unit/dL Perioperative management: Dose (units) = Body Weight (kg) x Desired Factor IX rise (units/dL or % of normal) x reciprocal of observed recovery (units/kg per units/dL); frequency based on type of bleed Routine Prophylaxis: Dose (units) = 40-70 units/kg twice weekly
Rebinyn® [Coagulation Factor IX (Recombinant), GlycoPEGylated]	Adult and pediatric patient with hemophilia B for: On-demand treatment and control of bleeding episodes Perioperative management of bleeding Routine prophylaxis to reduce the frequency of bleeding episodes Limitations of Use: Rebinyn is not indicated for immune tolerance induction in patients with hemophilia B.	Control and prevention of bleeding episodes: Dose (units) = 40 units/kg for minor and moderate bleeds, 80 units/kg for major bleeds Perioperative management: Pre-operative dose (units) = 40 units/kg for minor surgery and 80 units/kg for major surgery; frequency based on type of bleed/surgery Routine Prophylaxis: Dose (units) = 40 units/kg once weekly
Rixubis® [Coagulation Factor IX (Recombinant)]	Adult and pediatric patient with hemophilia B for: Control and prevention of bleeding episodes Perioperative management of bleeding Routine prophylaxis to reduce the frequency of bleeding episodes Limitations of Use: Rixubis is not indicated for induction of immune tolerance in patients with Hemophilia B.	Control and prevention of bleeding episodes: One unit/kg body weight will raise the Factor IX level by 0.9 unit/dL in adults and children greater than or equal to 12 years old. One unit/kg body weight will raise the Factor IX level by 0.7 unit/dL in children less than 12 years old Perioperative management: Dose (units) = Body Weight (kg) x Desired Factor IX rise (units/dL or % of normal) x reciprocal of observed recovery (units/kg per units/dL); frequency based on type of bleed Routine Prophylaxis: Children (< 12 years of age): Dose (units) = 60-80 units/kg twice weekly ≥12 years of age: Dose (units) = 40-60 units/kg twice weekly
AlphaNine SD® [Coagulation Factor IX (Human)]	Patient with Factor IX deficiency due to hemophilia B for: Control and prevention of bleeding episodes Limitations of Use: AlphaNine SD is not indicated for the treatment of Factor II, VII or X deficiencies. AlphaNine SD is not indicated for the reversal of coumarin anticoagulant-induced hemorrhage, nor in the treatment of hemophilia A patients with inhibitors to Factor VIII.	Dose (units) = Body Weight (kg) x Desired Factor IX rise (units/dL or % of normal) x 1 unit/kg; frequency based on type of bleed Minor hemorrhage: Dose (units) = 20-30 units/kg twice daily until hemorrhage stops which is typically 1-2 days. Moderate hemorrhage: Dose (units) = 25-50 units/kg twice daily until healing has been achieved which is typically 2-7 days. Major hemorrhage: Dose (units) = 30-50 units/kg twice daily until healing has been achieved and may require treatment for up to 10 days. Surgery: Dose (units) = 50-100 units/kg twice daily until healing has been achieved which is typically 7-10 days.
Profilnine® SD (Factor IX complex)	Patient with Factor IX deficiency due to hemophilia B for: Control and prevention of bleeding episodes Limitations of Use: Profilnine SD contains non-therapeutic levels of factor VII and is not indicated for use in the treatment of VII deficiency	Factor IX level of each patient should be monitored frequently during replacement therapy. Mild to moderate hemorrhages may usually be treated with a single administration sufficient to raise the plasma Factor IX level to 20 to 30 percent. Infusions are generally required daily. More serious hemorrhage, the patient's plasma Factor IX level should be raised to 30 to 50 percent. Infusions are generally required daily. Surgery in patients with Factor IX deficiency requires that the Factor IX level should be raised to 30 to 50 percent for at least one week following operation. Dental extractions, the Factor IX level should be raised to 50 percent immediately prior to the procedure; additional Factor IX Complex may be given if bleeding recurs.

Criteria for Approval of Factor IX Products

The patient has been diagnosed with Hemophilia B; AND
The factor product has been prescribed in consultation with a specialist in hemophilia; AND
Treatment dosing details have been provided for review, as highlighted below (medical record documentation required):
1. Patient age and current weight
2. Severity of factor deficiency and factor activity level [i.e. Mild (>5-40%) vs. Moderate (≥1 to ≤5%) vs. Severe (<1%)]
3. Bleeding history
4. Inhibitor status
5. Current trough and target trough levels when applicable
6. Actual prescribed dose and frequency
7. Mode of treatment (i.e. prophylaxis vs. on-demand bleeding vs. peri-operative dosing); AND
For patients with normal factor activity level, there is documentation of history of 2 or more spontaneous bleeds into joints; AND
One of the following:
1. The patient is being treated prophylactically; OR
2. The patient is being treated on demand for bleeding; OR
3. The patient will be receiving peri-operative dosing; AND
The requested quantity (dose) does NOT exceed the program quantity limit defined by BOTH of the following:
1. The requested dose is within the FDA labeled dosing; AND
2. The requested quantity (number of doses) is appropriate based on intended use (e.g., prophylaxis, on-demand); OR
3. The prescriber has provided clinical rational for exceeding the defined program quantity limit (dose and/or number of doses) including BOTH of the following (medical record documentation required):
  1. Pharmacokinetic (PK) testing results demonstrate that increased dose/frequency are supported; AND
  2. Patient is not a suitable candidate for use of another factor product or anti-hemophilic product within FDA labeled dosing; AND
The patient will not be treated concurrently with another factor IX product; AND
The prescribed dosing and quantity for the requested factor product is appropriate based on intended use and FDA labeling; AND
For formularies that exclude (non-formulary) the requested medication, Non-formulary Exception Criteria applies.

Duration of Approval:

On-demand bleeds or Perioperative dosing: 90 days
Prophylaxis: 365 days
On-demand with Prophylaxis: 365 days for both therapies

Quantity Limitations

Quantity limitations apply to brand and associated generic products.

Therapy Regimen	Quantity with allowed variance	Allowed variance
Prophylaxis	Standard dosing for 28 days of therapy	5% or less
On Demand	3 doses per 28 days or as indicated per provider’s order for specific incident or procedure	5% or less
Perioperative	Per provider’s order for specific incident or procedure	5% or less

Quantity Limit Exception Criteria

The quantity (dose) requested is for documented titration purposes at the initiation of therapy (authorization for a 90 day titration period); AND
The prescribed dose cannot be achieved using a lesser quantity of a higher strength; AND
The quantity (dose) requested does not exceed the maximum FDA labeled dose, when specified, or to the safest studied dose per the manufacturer’s product insert; OR
If the quantity (dose) requested exceeds the maximum FDA labeled dose, when specified, or to the safest studied dose per the manufacturer’s product insert, then the prescriber must submit documentation in support of therapy with a higher dose for the intended diagnosis (submitted documentation must include medical records which reflect the length of time the requested dose has been used, and what other medications and doses have been tried and failed) in addition to BOTH of the following
1. Pharmacokinetic (PK) testing results demonstrate that increased dose/frequency are supported (medical record documentation required); AND
2. Patient is not a suitable candidate for use of another factor product or anti-hemophilic product within FDA labeled dosing (medical record documentation required)

Duration of Approval:

On-demand bleeds or Perioperative dosing: 90 days
Prophylaxis: 365 days

References

All information referenced is from FDA package insert unless otherwise noted below.

Policy Implementation/Update Information

Criteria and treatment protocols are reviewed annually by the Blue Cross NC P&T Committee, regardless of change. This policy is reviewed in Q2 annually.

April 2024: Criteria update: Updated Ixinity indication to include adults and pediatric patients.
December 2022: Criteria update: Removed Bebulin and Mononine from criteria as these products are discontinued. Added expanded indication for Ixinity for on demand treatment.
August 2022: Criteria change: Updated Rebinyn for FDA expanded indication of routine prophylaxis to reduce the frequency of bleeding episodes.
June 2022: Criteria update: Clarified quantity limitations chart and separated out on demand and perioperative therapy regimens.
April 2022: Criteria change: Added dosage for FDA approved indications. Added assessment of quantity limits.
October 2020. Original utilization management criteria issued.

Disclosures:

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