Valoctocogene Roxaparvovec Form

Valoctocogene roxaparvovec-rvox (Roctavian™) is adeno-associated virus (AAV) vector-based gene therapy. FDA Approved Indication(s)
Valoctocogene roxaparvovec-rvox is indicated for the treatment of adults with severe hemophilia A (congenital factor VIII [FVIII] deficiency with FVIII activity < 1 IU/dL) without pre-existing antibodies to adeno-associated virus serotype 5 (AAV5) detected by an FDA-approved test. 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 Roctavian is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Congenital Hemophilia A (must meet all):
*Only for initial treatment dose; subsequent doses will not be covered.

1. Diagnosis of congenital hemophilia A;
2. Prescribed by or in consultation with a hematologist;
3. Age ≥ 18 years;
4. Member has severe hemophilia A (defined as pre-treatment FVIII level < 1% or activity < 1 IU/dL);
   5. Member meets both of the following (a and b): a. Member has been adherent with use of a FVIII product for routine prophylaxis for at least 12 months as assessed and documented by provider; b. Occurrence of at least one serious spontaneous bleeding event while on routine prophylaxis (see Appendix D); Prior authorization may be required
   6. Member has been treated with FVIII concentrates or cryoprecipitate for a minimum of 150 exposure days (EDs);
   7. Member meets both of the following (a and b): a. No previous documented history of a detectable FVIII inhibitor;
      b. Member has FVIII inhibitor level assay < 0.6 Bethesda units (BU) on 2 consecutive occasions at least one week apart within the last 12 months;

5. Member has no pre-existing antibodies to AAV5 as measured by an FDA-approved test; Page 1 of 7

   CLINICAL POLICY Valoctocogene Roxaparvovec-rvox

   9. Documentation of hepatic ultrasound and elastography or laboratory assessments for liver fibrosis within the last 3 months showing there is not significant hepatic fibrosis (stage 3 or 4) or cirrhosis;
   10. Attestation from hepatologist that member is eligible for Roctavian if any of the following (a, b, or c) baseline liver abnormalities, assessed within the last 3 months, are present: a. Radiological liver abnormalities; b. Liver function tests (LFTs) (i.e., alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyl transferase [GGT], alkaline phosphatase [ALP], total bilirubin) measuring ALT, AST, GGT, ALP and total bilirubin > 1.25 × upper limit of normal (ULN); c. International normalized ratio (INR) ≥ 1.4;
   11. Provider attestation of member’s ability to receive corticosteroids and/or other immunosuppressive therapy that may be required for an extended period and that the risks associated with immunosuppression are acceptable for the individual member;
   12. Member has not received prior gene therapy;
6. Provider attestation that alcohol abstinence education has been completed with the member; 14. Provider confirms that member will discontinue any use of hemophilia A prophylactic therapy within 4 weeks after administration of Roctavian; 15. Provider agrees to monitor the member according to the FDA-approved label (i.e., FVIII level tests, ALT monitoring and steroid treatment as appropriate); 16. Provider agrees to submit ALL of the following medical information after Roctavian administration upon plan request (a, b, and c): a. FVIII levels measured by the average of two consecutive chromogenic substrate assay or one stage assay measurements separated by one week; b. Documentation of all spontaneous bleeds after Roctavian administration (see Appendix D); c. Documentation of any resumed continuous hemophilia A prophylaxis and duration of prophylaxis; 17. Documentation of member’s body weight in kg;

7. Dose does not exceed a single IV infusion of 6 x 1013 vector genomes (vg) per kg.
   Approval duration: 3 months (1 dose only) B. Other diagnoses/indications (must meet 1 or 2):

   1. 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 Page 2 of 7

   CLINICAL POLICY Valoctocogene Roxaparvovec-rvox

   2. 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
   3. Continued therapy will not be authorized as Roctavian is indicated to be dosed one time only. Approval duration: Not applicable B. Other diagnoses/indications (must meet 1 or 2):
   4. 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
   5. 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 AAV: adeno-associated virus ALP: alkaline phosphatase ALT: alanine aminotransferase AST: aspartate aminotransferase BU: Bethesda unit ED: exposure day
      FDA: Food and Drug Administration FVIII: factor VIII GGT: gamma-glutamyl transferase INR: international normalized ratio LFT: liver function test ULN: upper limit of normal vg: vector genome WFH: World Federation of Hemophilia Page 3 of 7

   CLINICAL POLICY Valoctocogene Roxaparvovec-rvox Appendix B: Therapeutic Alternatives
   Drug Name Usual Dosing Regimen FVIII recombinant products for routine prophylaxis Advate®
   20-40 IU/kg IV every other day (3 to 4 times weekly) or every third day dosing regimen targeted to maintain FVIII trough levels ≥ 1% 40-55 IU/kg IV 2 times per week 20-50 IU/kg IV 2-3 times per week 50 IU/kg IV once weekly 50 IU/kg IV every 4 days 65 IU/kg IV twice weekly 25 IU/kg IV three times per week Adynovate® Afstyla® Altuviiio® Eloctate® Esperoct® Helixate FS®, Kogenate FS® Jivi® Kovaltry® NovoEight® 45-60 IU/kg every 5 days with further individual adjustment to less or more frequent dosing 20-40 IU/kg IV 2-3 times per week 20-50 IU/kg IV 3 times per week 60 IU/kg/dose 50 IU/kg/dose 60 IU/kg/dose Dose Limit/ Maximum Dose 40 IU/kg every other day 70 IU/kg/dose 50 IU/kg/dose 50 IU/kg/dose 65 IU/kg/dose 65 IU/kg 25 IU/kg/dose Nuwiq® Xyntha® Plasma-derived FVIII/von Willebrand factor complex for routine prophylaxis Wilate® 40 IU/kg/day 30-40 IU/kg IV every other day 30 IU/kg IV 3 times weekly
   20-40 IU/kg IV every 2 to 3 days 50 IU/kg/dose 30 IU/kg/dose Appendix C: Contraindications/Boxed Warnings • Contraindication(s): active infections, either acute or uncontrolled chronic; known significant hepatic fibrosis (stage 3 or 4), or cirrhosis; known hypersensitivity to mannitol • Boxed warning(s): none 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. • 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. Page 4 of 7

   CLINICAL POLICY Valoctocogene Roxaparvovec-rvox V. Dosage and Administration
   Indication Dosing Regimen Hemophilia A Recommended dose: 6 x 1013 vg/kg body weight as a single IV infusion
   Maximum Dose 6 x 1013 vg/kg body weight VI. Product Availability Single-dose cell suspension: nominal concentration of 2 × 1013 vg/mL with each vial containing an extractable volume of ≥ 8 mL
   VII.