HEMLIBRA, Emicizumab-kxwh Form

Emicizumab-kxwh (Hemlibra®) is a bispecific factor IXa- and factor X-directed antibody.
FDA Approved Indication(s) Hemlibra is indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients ages newborn and older with hemophilia A (congenital factor VIII [FVIII] deficiency) with or without FVIII inhibitors.
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 Hemlibra is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Congenital Hemophilia A With Inhibitors (must meet all):

1. Prescribed for routine prophylaxis of bleeding episodes in patients with congenital hemophilia A (FVIII deficiency);
2. Prescribed by or in consultation with a hematologist;
   3. Member has inhibitor level ≥ 5 Bethesda units (BU);
   4. Provider confirms that member will discontinue any use of bypassing agents or FVIII products as prophylactic therapy while on Hemlibra (on-demand usage may be continued);
3. Documentation of member’s current body weight (in kg);
   6. Dose does not exceed 3 mg/kg per week during the first four weeks of therapy, followed by either 1.5 mg/kg per week, 3 mg/kg once every two weeks, or 6 mg/kg once every four weeks thereafter. Approval duration: 6 months (12 months for HIM Texas) B. Congenital Hemophilia A Without Inhibitors (must meet all):
4. Prescribed for routine prophylaxis of bleeding episodes in patients with congenital hemophilia A (FVIII deficiency);

5. Prescribed by or in consultation with a hematologist; Page 1 of 7

   CLINICAL POLICY Emicizumab-kxwh

6. Member meets one of the following (a or b):
   a. Failure of a FVIII product (e.g., Advate®, Adynovate®, Eloctate®) used for routine prophylaxis as assessed and documented by prescriber (see Appendix D), unless clinically significant adverse effects are experienced or all are contraindicated;
   *Prior authorization is required for FVIII products b. Member has poor venous access, does not tolerate frequent venous access, or has central line or port placement;
7. For members who are new to Hemlibra therapy and have not previously used FVIII products for routine prophylaxis: member meets one of the following (a or b): a. Member has severe hemophilia (defined as FVIII level of < 1%); b. Member has experienced at least one serious spontaneous bleed (see Appendix D);
8. Provider confirms that member will discontinue any use of FVIII products as prophylactic therapy while on Hemlibra (on-demand usage may be continued);
9. Documentation of member’s current body weight (in kg);
   7. Dose does not exceed 3 mg/kg per week during the first four weeks of therapy, followed by either 1.5 mg/kg per week, 3 mg/kg once every two weeks, or 6 mg/kg once every four weeks thereafter. Approval duration: 6 months (12 months for HIM Texas) C. Other diagnoses/indications (must meet 1 or 2):
10. 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
11. 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 A With or Without Inhibitors (must meet all):

12. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; 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; Page 2 of 7

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13. Provider confirms that member has discontinued any use of bypassing agents (if member has inhibitors) or FVIII products as prophylactic therapy while on Hemlibra (on-demand usage may be continued);
14. Documentation of member’s current body weight (in kg);
    5. If request is for a dose increase, new dose does not exceed 3 mg/kg per week during the first four weeks of therapy, followed by either 1.5 mg/kg per week, 3 mg/kg once every two weeks or 6 mg/kg once every four weeks thereafter.
       Approval duration: 6 months (12 months for HIM Texas) B. Other diagnoses/indications (must meet 1 or 2):
15. 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

16. 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 policies – 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 aPCC: activated prothrombin complex concentrate BU: Bethesda unit FDA: Food and Drug Administration Appendix B: Therapeutic Alternatives Not applicable FEIBA: factor eight inhibitor bypassing activity FVIII: factor VIII Appendix C: Contraindications/Boxed Warnings • Contraindication(s): none reported • Boxed warning(s): thrombotic microangiopathy and thromboembolism.
    Page 3 of 7

    CLINICAL POLICY Emicizumab-kxwh Appendix D: General Information • The elimination half-life of Hemlibra is 27.8 ± 8.1 days. Therefore, the “on-demand” use of Hemlibra for the treatment of acute bleeding episodes is inappropriate. • There is insufficient data to support the use of Hemlibra for the treatment of hemophilia B either with or without inhibitors. • There is potential for thrombotic microangiopathy and thrombotic events when used concurrently with FEIBA > 100 U/kg/day for 24 hours or more. Additional monitoring is recommended with concomitant use of the two agents. Discontinuation of FEIBA and suspended dosing of Hemlibra is recommended if symptoms occur. • The World Federation of Hemophilia recommends starting primary prophylaxis before the second clinically evident large joint bleed, and before 3 years of age, to prevent future bleeding episodes and the resulting complications. • Examples of member responding positively to therapy may include: reduction in number of all bleeds over time, reduction in number of joint bleeds over time, or reduction in number of target joint bleeds over time. • There are no strict criteria for failing FVIII product for routine prophylaxis; however, the following reasons are acceptable to fulfill the criteria: o Prescriber has documented clinical criteria which support his or her assessment that the member has failed FVIII therapy; o Clinically significant bleeding, hemarthroses, life-threatening bleeding episodes, joint swelling, upcoming surgery/procedure not responding to current therapy, or other clinical assessment as determined by prescriber. • 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. • A spontaneous bleed is defined as a bleeding episode that occurs without apparent cause and is not the result of trauma. V. Dosage and Administration Indication Routine prophylaxis of bleeding episodes Dosing Regimen Loading dose of 3 mg/kg SC weekly for four weeks, followed by a maintenance dose of 1.5 mg/kg SC weekly or 3 mg/kg once every two weeks or 6 mg/kg once every four weeks
    Maximum Dose 3 mg/kg/week for the first 4 weeks, followed by 1.5 mg/kg/week thereafter VI. Product Availability
    Single-dose vials for injection: 12 mg/0.4 mL, 30 mg/mL, 60 mg/0.4 mL, 105 mg/0.7 mL, 150 mg/mL, 300 mg/2 mL Page 4 of 7

    CLINICAL POLICY Emicizumab-kxwh VII.