Factor IX (Human, Recombinant) Form

The following are factor IX products requiring prior authorization: human – AlphaNine® SD, Mononine®; recombinant – Alprolix®, BeneFIX®, Idelvion®, Ixinity®, Rebinyn®, and Rixubis®.
FDA Approved Indication(s) Factor IX products are indicated for patients with hemophilia B (congenital factor IX deficiency or Christmas disease) for the following uses: • On-demand treatment and control of bleeding episodes o Adults and children: AlphaNine SD, Alprolix, BeneFIX, Idelvion, Ixinity (≥ 12 years), Mononine, Rebinyn, and Rixubis • Perioperative management of bleeding o Adults and children: Alprolix, BeneFIX, Idelvion, Ixinity (≥ 12 years), Rebinyn, and Rixubis • Routine prophylaxis to reduce the frequency of bleeding episodes
o Adults and children: Alprolix, BeneFIX, Idelvion, Ixinity (≥ 12 years), Rebinyn, and Rixubis
Limitation(s) of use: • AlphaNine SD, and Mononine contain low, non-therapeutic levels of factors II, VII, and X, and, therefore, are not indicated for the treatment of factor II, VII or X deficiencies. They are also not indicated for the reversal of coumarin anticoagulant-induced hemorrhage, nor in the treatment of hemophilia A patients with inhibitors to factor VIII. • Mononine is also not indicated in a hemorrhagic state caused by hepatitis-induced lack of production of liver dependent coagulation factors. • Alprolix, BeneFIX, Idelvion, Ixinity, Rebinyn, and Rixubis are not indicated for induction of immune tolerance in patients with hemophilia B. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that AlphaNine SD, Alprolix, BeneFIX, Idelvion, Ixinity, Mononine, Rebinyn, and Rixubis are medically necessary when the following criteria are met:
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CLINICAL POLICY Factor IX (Human, Recombinant) I. Initial Approval Criteria
A. Congenital Hemophilia B (must meet all):

1. Diagnosis of congenital hemophilia B (factor IX deficiency);
   2. Prescribed by or in consultation with a hematologist;
   3. For AlphaNine requests only: Age ≥ 17 years;
   4. For Ixinity requests only: Age ≥ 12 years;
   5. Request is for one of the following uses (a, b, or c): a. Control and prevention of bleeding episodes; b. Perioperative management; c. Routine prophylaxis to prevent or reduce the frequency of bleeding episodes;
   6. For routine prophylaxis requests: Request is for Alprolix, Benefix, Idelvion, Ixinity, Rebinyn, or Rixubis, and member meets one of the following (a, b, or c): a. Member has previously used factor IX for routine prophylaxis; b. Member has severe hemophilia (defined as factor level of < 1%); c. Member has experienced at least one serious spontaneous bleed (see Appendix D);
2. Documentation of member’s current body weight (in kg);
   8. Dose does not exceed the FDA approved maximum recommended dose for the relevant indication.
      Approval duration: 3 months for surgical/acute bleeding or 6 months for prophylaxis (12 months for prophylaxis for HIM Texas) B. Other diagnoses/indications (must meet 1 or 2):
3. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
4. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Congenital Hemophilia B (must meet all):

5. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; Page 2 of 11

   CLINICAL POLICY Factor IX (Human, Recombinant) b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);

   2. Member is responding positively to therapy;
   3. Documentation of member’s current body weight (in kg);
   4. If request is for a dose increase, new dose does not exceed the FDA approved maximum recommended dose for the relevant indication. Approval duration: 3 months for surgical/acute bleeding or 6 months for prophylaxis (12 months for prophylaxis for HIM Texas) B. Other diagnoses/indications (must meet 1 or 2):
6. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

7. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   III. Diagnoses/Indications for which coverage is NOT authorized:
   A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policy – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid, or evidence of coverage documents. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration Appendix B: Therapeutic Alternatives
   Not applicable Appendix C: Contraindications/Boxed Warnings
   • Contraindication(s):
   o All products except AlphaNine SD: known history of hypersensitivity reactions, including anaphylaxis, to the product or its excipients* Page 3 of 11

   CLINICAL POLICY Factor IX (Human, Recombinant) *Including mouse or hamster protein for BeneFix, Idelvion, Ixinity, Mononine, Rebinyn, and Rixubis o Rixubis: disseminated intravascular coagulation, signs of fibrinolysis • Boxed warning(s): none reported Appendix D: General Information • Serious bleeding episodes include bleeds in the following sites: intracranial; neck/throat; gastrointestinal; joints (hemarthrosis); muscles (especially deep compartments such as the iliopsoas, calf, forearm); or mucous membranes of the mouth, nose and genitourinary tract. • Spontaneous bleed is defined as a bleeding episode that occurs without apparent cause and is not the result of trauma. V. Dosage and Administration
   Drug Name Indication Dosing Regimen Factor IX, human (AlphaNine SD) Control and prevention of bleeding episodes Minor episodes: 20-30 IU/kg IV twice daily Moderate episodes: 25-50 IU/kg IV twice daily Major episodes: 30-50 IU/kg IV twice daily for at least 3-5 days, followed by 20 IU/kg IV twice daily Surgery: 50-100 IU/kg IV twice daily before surgery, followed by the same regimen for 7-10 days thereafter Minor episodes: 20-30 IU/kg IV every 24 hours Major trauma or surgery: 75 IU/kg IV every 18-30 hours Factor IX, human (Mononine) Control and prevention of bleeding episodes Factor IX, recombinant (Alprolix) Control and prevention of bleeding episodes, perioperative management Minor and moderate episodes: 30-60 IU/dL/kg IV every 48 hours if there is further evidence of bleeding after the first dose Page 4 of 11 Maximum Dose Bleeding episodes: 100 IU/kg/day Surgery: 200 IU/kg/day Minor episodes: 30 IU/kg/day Major trauma or surgery: 750 IU/kg/18 hours Bleeding episodes: 100 IU/dL/kg/dose Surgery: 100 IU/dL/kg/dose

   CLINICAL POLICY Factor IX (Human, Recombinant) Drug Name Indication Dosing Regimen Maximum Dose Major episodes: 80-100 IU/dL/kg IV initially; consider a repeat dose after 6-10 hours and then every 24 hours for the first 3 days. May extend to dosing every 48 hours or longer after the first 3 days Minor surgery: 50-80 IU/dL/kg IV initially followed by every 24-48 hours until bleeding stops and healing is achieved Major surgery: 60-100 IU/dL/kg IV initially; consider a repeat dose after 6-10 hours and then every 24 hours for the first 3 days. May extend to dosing every 48 hours or longer after the first 3 days 50 IU/dL/kg IV once weekly or 100 IU/dL/kg IV once every 10 days (start with 60 IU/kg once weekly for < 12 years) Minor episodes: 20-30 IU/dL/kg IV every 12-24 hours
   Moderate episodes: 25-50 IU/dL/kg IV every 12-24 hours Major episodes: 50-100 IU/dL/kg IV every 12-24 hours Surgery: 50-100 IU/dL/kg IV every 12-24 hours 100 IU/kg once weekly Minor and moderate episodes: 30-60 IU/dL/kg IV every 48-72 hours
   Major episodes: 60-100 IU/dL/kg IV every 48-72 hours 100 IU/dL/kg/dose 200 IU/dL/kg/day 100 IU/kg/dose Bleeding episodes: 100 IU/dL/kg/48 hours Factor IX, recombinant (BeneFIX) Routine prophylaxis Control and prevention of bleeding episodes, perioperative management Factor IX, recombinant (Idelvion) Routine prophylaxis Control and prevention of bleeding episodes, perioperative management Page 5 of 11

   CLINICAL POLICY Factor IX (Human, Recombinant) Drug Name Indication Dosing Regimen until bleeding stops and healing is achieved; maintenance dose is weekly Minor surgery: 50-80 IU/dL/kg IV every 48-72 hours until healing is achieved Major surgery: 60-100 IU/dL/kg IV every 48-72 hours until bleeding stops and healing is achieved; maintenance dose is 1-2 times per week ≥ 12 years of age: 25-40 IU/kg IV every 7 days followed by 50-75 IU/kg IV every 14 days once well-controlled < 12 years of age: 40-55 IU/kg IV every 7 days Minor episodes: 30-60 IU/dL/kg IV every 24 hours
   Moderate episodes: 40-60 IU/dL/kg IV every 24 hours Major episodes: 60-100 IU/dL/kg IV every 12-24 hours Minor surgery: 50-80 IU/dL/kg IV pre-operatively followed by 30-80 IU/dL/kg every 24 hours Routine prophylaxis Factor IX, recombinant (Ixinity) Control and prevention of bleeding episodes, perioperative management Maximum Dose Surgery: 80 IU/dL/kg/48 hours 55 IU/kg/week Bleeding episodes: 102 IU/dL/kg/dose Surgery: 81.6 IU/dL/kg/dose Major surgery: 60-80 IU/dL/kg IV pre-operatively followed by 40-60 IU/dL/kg IV every 8-24 hours for 1-3 days or 30-50 IU/dL/kg IV every 8-24 hours for 4-6 days or 20-40 IU/dL/kg IV every 8-24 hours for 7-14 days 40 to 70 IU/kg IV twice weekly 140 IU/kg/week Routine prophylaxis Page 6 of 11

   CLINICAL POLICY Factor IX (Human, Recombinant) Drug Name Indication Dosing Regimen Factor IX, recombinant (Rixubis) Control and prevention of bleeding episodes, perioperative management Routine prophylaxis Factor IX, recombinant, glycopegylated (Rebinyn) On-demand treatment and control of bleeding episodes Perioperative management of bleeding Minor episodes: 20-30 IU/dL/kg IV every 12-24 hours until healing is achieved Moderate episodes: 25-50 IU/dL/kg IV every 12-24 hours until bleeding stops and healing is achieved Major episodes: 50-100 IU/dL/kg IV every 12-24 hours until bleeding stops and healing is achieved Minor surgery: 30-60 IU/dL/kg IV every 24 hours until healing is achieved Major surgery: 80-100 IU/dL/kg IV every 8-24 hours until bleeding stops and healing is achieved ≥ 12 years of age: 40-60 IU/kg IV twice weekly < 12 years of age: 60-80 IU/kg IV twice weekly 40 IU/kg body weight for minor and moderate bleeds, and 80 IU/kg body weight for major bleeds. Additional doses of 40 IU/kg can be given Pre-operative dose of 40 IU/kg body weight for minor surgery, and 80 IU/kg body weight for major surgery. As clinically needed for the perioperative management of bleeding, repeated doses of 40 IU/kg (in 1-3 day intervals) within the first week after major surgery may be administered. Frequency may be extended to once weekly after the first week Page 7 of 11 Maximum Dose 100 IU/dL/kg/dose 80 IU/kg/dose 80 IU/kg/dose 80 IU/kg pre- operatively; 40 IU/kg/dose after surgery

   CLINICAL POLICY Factor IX (Human, Recombinant) Drug Name Indication Dosing Regimen Routine prophylaxis until bleeding stops and healing is achieved. 40 IU/kg body weight once weekly Maximum Dose 40 IU/kg/week VI. Product Availability
   Drug Name Factor IX, human (AlphaNine SD) Factor IX, human (Mononine) Factor IX, recombinant (Alprolix) Factor IX, recombinant (BeneFIX) Factor IX, recombinant (Idelvion) Factor IX, recombinant (Ixinity) Factor IX, recombinant (Rixubis) Factor IX, recombinant, glycopegylated (Rebinyn) Availability Vials: 500, 1,000, 1,500 IU Vials: 500, 1,000 IU Vials: 250, 500, 1,000, 2,000, 3,000, 4,000 IU Vials: 250, 500, 1,000, 2,000, 3,000 IU Vials: 250, 500, 1,000, 2,000, 3500 IU Vials: 250, 500, 1,000, 1,500, 2,000, 3,000 IU Vials: 250, 500, 1,000, 2,000, 3,000 IU Vials: 500, 1,000, 2,000, 3,000 IU VII.