Etranacogene Dezaparvovec (AMT-061) Form

Etranacogene dezaparvovec-drlb (Hemgenix®) is an adeno-associated virus (AAV) vector-based gene therapy. FDA Approved Indication(s)
Hemgenix is indicated for the treatment of adults with hemophilia B (congenital factor IX deficiency) who: • Currently use factor IX prophylaxis therapy, or • Have current or historical life-threatening hemorrhage, or • Have repeated, serious spontaneous bleeding episodes. 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.
All requests reviewed under this policy require medical director review. It is the policy of health plans affiliated with Centene Corporation® that Hemgenix is medically necessary when the following criteria are met:
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. Age ≥ 18 years;
   4. Member has severe or moderately severe hemophilia (defined as a factor IX level of ≤ 2%);
2. Member meets both of the following (a and b): a. Member has been adherent with use of a factor IX product (e.g., Alprolix®, Benefix®, Idelvion®, Ixinity®, Rebinyn®, Rixubis®) for routine prophylaxis for at least 12 months as assessed and documented by prescriber; b. Occurrence of at least one serious spontaneous bleeding event while on routine prophylaxis (see Appendix D);
   Prior authorization may be required

3. Member has been treated with factor IX product for a minimum of 150 exposure days (see Appendix D); Page 1 of 7

   CLINICAL POLICY Etranacogene Dezaparvovec-drlb

4. Member meets all of the following (a, b, and c): a. No previous documented history of a detectable factor IX inhibitor; b. Documentation of inhibitor level assay < 0.6 Bethesda units (BU) within the last 12 months; c. If member had an initial positive test result for factor IX inhibitor, member has documentation of a subsequent negative test within 2 weeks;
5. Member has had all of the following baseline liver assessments within the last 3 months (a, b, and c): a. Documentation of liver enzymes within normal limits (i.e., alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP] and total bilirubin); b. Documentation of normal hepatic ultrasound and elastography; c. If member has evidence of radiological liver abnormalities and/or sustained liver enzyme elevations, attestation from hepatologist that member is eligible for Hemgenix;
6. Member has not received prior gene therapy; 10. Member has documentation of AAV5 neutralizing antibody titer ≤ 1:678; 11. Dose does not exceed 2 x 1013 genome copies (gc) per kg.
   Approval duration: 3 months (1 dose only)
   B. Other diagnoses/indications (must meet 1 or 2):
7. 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
8. 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

9. Continued therapy will not be authorized as Hemgenix is indicated to be dosed one time only. Approval duration: Not applicable Page 2 of 7

   CLINICAL POLICY Etranacogene Dezaparvovec-drlb B. Other diagnoses/indications

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 2 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 AAV: adeno-associated virus ALP: alkaline phosphatase ALT: alanine aminotransferase AST: aspartate aminotransferase BU: Bethesda units ED: exposure day FDA: Food and Drug Administration gc: genome copies Appendix B: Therapeutic Alternatives
    This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization. Dosing Regimen Drug Name Dose Limit/ Maximum Dose Factor IX recombinant products for routine prophylaxis Alprolix®
    BeneFIX® Idelvion® Ixinity® Rebinyn® Rixubis® 50 IU/dL/kg IV once weekly or
    100 IU/dL/kg IV once every 10 days
    100 IU/kg IV once weekly 25-40 IU/kg IV every 7 days followed by 50-75 IU/kg IV every 14 days once well-controlled 40 to 70 IU/kg IV twice weekly 40 IU/kg IV once weekly 40-60 IU/kg IV twice weekly 100 IU/dL/kg/dose 100 IU/kg/dose 40 IU/kg/week 140 IU/kg/week 40 IU/kg/week 60 IU/kg/dose Page 3 of 7

    CLINICAL POLICY Etranacogene Dezaparvovec-drlb Appendix C: Contraindications/Boxed Warnings 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. • Exposure day (ED): An ED is a day on which a person with hemophilia has been infused with factor concentrate to treat or prevent a bleed. The number of EDs consists only of those days on which factor was infused. o 150 EDs of cumulative treatment increases the likelihood of immunologic stability – a decreased risk of producing inhibitors. Patients rarely develop inhibitors after 150 EDs. • In the clinical studies with Hemgenix, an unvalidated clinical trial assay was utilized to assess preexisting neutralizing anti-AAV5 antibodies. The subject sub-group with detectable preexisting neutralizing anti-AAV5 antibodies up to titers of 1:678 showed mean factor IX activity that was numerically lower compared to that subject sub-group without detectable preexisting neutralizing anti-AAV5 antibodies. Subjects, with and without preexisting neutralizing anti-AAV5 antibodies, demonstrated hemostatic protection. In one subject with a preexisting neutralizing anti-AAV5 antibody titer of 1:3212, no human factor IX expression was observed, and restart of the exogenous factor IX prophylaxis was needed for bleeding events.
    o Patients who intend to receive treatment with Hemgenix are encouraged to enroll in a study to measure pre-existing anti-AAV5 neutralizing antibodies by calling CSL Behring at 1-800-504-5434. The study evaluates the effect of pre-existing anti-AAV5 neutralizing antibodies on the risk of bleeding. V. Dosage and Administration
    Indication Hemophilia B Dosing Regimen Recommended dose: 2 x 1013 gc/kg of body weight by IV infusion Maximum Dose 2 x 1013 gc/kg VI. Product Availability
    Single-dose cell suspension: 10 to 48 single-use vials with a nominal concentration of 1 x 1013 gc/mL with each vial containing an extractable volume of ≥ 10 mL VII.