Last Review Date: 06/04/2024

Date of Origin: 08/08/2023

Dates Reviewed: 08/2023, 06/2024

1. Length of Authorization

Coverage will be provided for one dose and may not be renewed.

2. Dosing Limits

1. Quantity Limit (max daily dose) [NDC Unit]:

• Roctavian 2 x 10¹³ vg/mL single-dose vial: 44 vials one time only

2. Max Units (per dose and over time) [HCPCS Unit]:

• 352 billable units (352 mL) one time only

3. Initial Approval Criteria ^1-15

Coverage is provided in the following conditions:

Hemophilia A (Congenital Factor VIII Deficiency) † Ф

• Patient is at least 18 years of age; AND
• Patient has a diagnosis of severe hemophilia A (congenital factor VIII deficiency) as confirmed by a factor VIII activity level < 1 IU/dL; AND
• Evidence of any bleeding disorder NOT related to hemophilia A has been ruled out; AND
• Patient is on a stable dose of regularly administered exogenous factor VIII for the prevention and control of bleeding episodes; AND
• Patient does not have an active infection, either acute (such as acute respiratory infections or acute hepatitis) or uncontrolled chronic (such as chronic active hepatitis B); AND
• Patient is up to date with vaccinations prior to infusion and will avoid live vaccines while on immunosuppressive therapies; AND
• Patient does not have significant hepatic fibrosis (stage 3 or 4) or cirrhosis; AND
• Patient does not have a known hypersensitivity to mannitol: AND
• Patient has not received prior hemophilia AAV-vector–based gene therapy; AND
• Patient is adeno-associated virus serotype 5 (AAV5) antibody negative as determined by an FDA-approved or CLIA-compliant testv; AND
• Patient has been tested and found negative for active factor VIII inhibitors (i.e., results from a Bethesda assay or Bethesda assay with Nijmegen modification of less than 0.6 Bethesda Units (BU) on 2 consecutive occasions at least one week apart within the past 12 months) and is not receiving a bypassing agent (e.g., Feiba, NovoSeven RT, SevenFact, etc.); AND
• Patient will have post-administration monitoring of serum ALT levels performed according to the monitoring schedule outlined in the product labeling with corticosteroids (or other immunosuppressive therapy) administered in response to elevations; AND
• Patients with preexisting risk factors for hepatocellular carcinoma [e.g., patients with hepatitis C or B, non-alcoholic fatty liver disease (NAFLD), chronic alcohol consumption, non-alcoholic steatohepatitis (NASH), and advanced age] will have regular (e.g., annually) liver ultrasounds performed and will be tested for alpha-fetoprotein (AFP) elevations following administration; AND
• Patient will have factor VIII activity monitored according to the monitoring schedule outlined in the product labeling; AND
  • Patients with factor VIII activity levels >5 IU/dL will discontinue routine prophylactic exogenous factor VIII; OR
  • If the factor VIII activity levels decrease and/or if bleeding is not controlled, the patient will be assessed for the presence of factor VIII inhibitors and the need for hemostatic prophylaxis

v If confirmed using an immunotherapy assay-http://www.fda.gov/companiondiagnostics

† FDA Approved Indication(s); ‡ Compendia Recommended Indication(s); Ф Orphan Drug

4. Renewal Criteria ¹

Coverage cannot be renewed.

5. Dosage/Administration ¹

6. Billing Code/Availability Information

HCPCS code:

• J1412 – Injection, valoctocogene roxaparvovec-rvox, per mL, containing nominal 2 × 10¹³ vector genomes; 1 billable unit = 1 mL, containing nominal 2 × 10¹³ vector genomes

NDC:

• Roctavian 2 × 10¹³ vector genomes (vg) per mL – 8 mL single dose vial: 68135-0927-xx

7. References

1. Roctavian [package insert]. Novato, CA; BioMarin Pharm., LLC., June 2023. Accessed May 2024.
2. MASAC Recommendations Concerning Products Licensed for the Treatment of Hemophilia and Selected Disorders of the Coagulation System. National Hemophilia Foundation. MASAC Document #284; April 2024. Available at: https://www.bleeding.org/healthcare-professionals/guidelines-on-care/masac-documents/masac-document-284-masac-recommendations-concerning-products-licensed-for-the-treatment-of-hemophilia-and-selected-disorders-of-the-coagulation-system. Accessed May 2024.
3. Guidelines for the Management of Hemophilia. 3^rd Edition. World Federation of Hemophilia 2020. Available at: https://www1.wfh.org/publications/files/pdf-1863.pdf. Accessed May 2024.
4. Graham A1, Jaworski K. Pharmacokinetic analysis of anti-hemophilic factor in the obese patient. Haemophilia. 2014 Mar;20(2):226-9.
5. Croteau SE1, Neufeld EJ. Transition considerations for extended half-life factor products. Haemophilia. 2015 May;21(3):285-8.
6. Mingot-Castellano, et al. Application of Pharmacokinetics Programs in Optimization of Haemostatic Treatment in Severe Hemophilia a Patients: Changes in Consumption, Clinical Outcomes and Quality of Life. Blood. 2014 December; 124 (21).
7. MASAC Recommendation Concerning Prophylaxis for Hemophilia A and B with and without Inhibitors. National Hemophilia Foundation. MASAC Document #267 (Replaces Document #241); April 2022. Available at: https://www.bleeding.org/sites/default/files/document/files/267_Prophylaxis.pdf. Accessed May 2024.
8. Rayment R, Chalmers E, Forsyth K, et al. Guidelines on the use of prophylactic factor replacement for children and adults with Haemophilia A and B. B J Haem:190;5, Sep 2020. https://doi.org/10.1111/bjh.16704.
9. Peyvandi F, Palla R, Menegatti M, et al. Coagulation factor activity and clinical bleeding severity in rare bleeding disorders: results from the European Network of Rare Bleeding Disorders. J Thromb Haemost. 2012;10:615‐621.
10. Ozelo MC, et al. Valoctocogene roxaparvovec gene therapy for hemophilia A. N Engl J Med. 2022;386(11):1013-1025. doi:10.1056/NEJMoa2113708.
11. Rind DM, et al. Valoctocogene roxaparvovec and emicizumab for hemophilia A without inhibitors: effectiveness and value; final report. Institute for Clinical and Economic Review. Published November 20, 2020. https://icer.org/wp-content/uploads/2020/10/ICER_Hemophilia-A_Final-Report_112020.pdf
12. Mahlangu J, Kaczmarek R, von Drygalski A, et al. Two-year outcomes of valoctocogene roxaparvovec therapy for hemophilia A. N Engl J Med. 2023;388(8):694-705. doi: 10.1056/NEJMoa2211075.
13. Madan B, Ozelo MC, Raheja P, et al. Three-year outcomes of valoctocogene roxaparvovec gene therapy for hemophilia A. J Thromb Haemost. 2024 Apr 11:S1538-7836(24)00184-3. doi: 10.1016/j.jtha.2024.04.001.
14. MASAC Recommendations on Hemophilia Treatment Center Preparedness for Delivering Gene Therapy for Hemophilia. National Hemophilia Foundation. MASAC Document # 282 (Replaces Document #277). October 2023. Available at: https://www.bleeding.org/healthcare-professionals/guidelines-on-care/masac-documents/masac-document-282-masac-recommendations-on-hemophilia-treatment-center-preparedness-for-delivering-gene-therapy-for-hemophilia. Accessed May 2024.
15. Thornburg, C.D., Simmons, D.H., von Drygalski, A. Evaluating gene therapy as a potential paradigm shift in treating severe hemophilia. BioDrugs. 2023. DOI: 10.1007/s40259-023-00615-4

Appendix 1 – Covered Diagnosis Codes

Appendix 2 – Centers for Medicare and Medicaid Services (CMS)

The preceding information is intended for non-Medicare coverage determinations. Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determinations (NCDs) and/or Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. Local Coverage Articles (LCAs) may also exist for claims payment purposes or to clarify benefit eligibility under Part B for drugs which may be self-administered. The following link may be used to search for NCD, LCD, or LCA documents: https://www.cms.gov/medicare-coverage-database/search.aspx. Additional indications, including any preceding information, may be applied at the discretion of the health plan.

Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCA/LCD): N/A