Last Review Date: 08/08/2023

Date of Origin: 08/08/2023

Dates Reviewed: 08/2023

1. Length of Authorization

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

2. Dosing Limits

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

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

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

• 44 vials one time only

3. Initial Approval Criteria

Coverage is provided in the following conditions:

Hemophilia A (Congenital Factor VIII Deficiency) † Ф ^1-12

• Patient is at least 18 years of age; AND
• Patient has severe hemophilia A (congenital factor VIII deficiency) diagnosed by a factor VIII activity level < 1 IU/dL (in the absence of exogenous factor VIII); 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
• Must not be administered concurrently with 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); AND
• Post administration monitoring of patient serum ALT levels will be 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 Factor VIII activity will be monitored periodically; AND
  • Patients with factor VIII activity levels >5 IU/dL should discontinue routine prophylactic exogenous factor VIII; OR
  • If Factor VIII activity levels decrease and/or if bleeding is not controlled, assess presence of factor VIII inhibitors and assess the need for hemostatic prophylaxis

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

† FDA Approved Indication(s); ‡ Compendium 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:

• J3590 – Unclassified biologics
• J1412 – Injection, valoctocogene roxaparvovec-rvox, per mL, containing nominal 2 × 10¹³ vector genomes; 1 billable unit  = 1 mL, containing nominal 2 × 10¹³ vector genomes (Effective 01/01/2024)

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 July 2023.
2. MASAC RECOMMENDATIONS CONCERNING PRODUCTS LICENSED FOR THE TREATMENT OF HEMOPHILIA AND OTHER BLEEDING DISORDERS. National Hemophilia Foundation. MASAC Document #263; August 2020. Available at: http://www.hemophilia.org. Accessed July 2023.
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 July 2023.
4. Annual Review of Factor Replacement Products. Oklahoma Health Care Authority Review Board. Updated April 2016. Accessed July 2023.
5. Graham A1, Jaworski K. Pharmacokinetic analysis of anti-hemophilic factor in the obese patient. Haemophilia. 2014 Mar;20(2):226-9.
6. Croteau SE1, Neufeld EJ. Transition considerations for extended half-life factor products. Haemophilia. 2015 May;21(3):285-8.
7. 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).
8. MASAC RECOMMENDATION CONCERNING PROPHYLAXIS. 2016 National Hemophilia Foundation. MASAC Document #241; February 2016. Available at: http://www.hemophilia.org. Accessed July 2023.
9. 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. Accessed July 2023.
10. 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.
11. Ozelo MC, et al. Valoctocogene roxaparvovec gene therapy for hemophilia A. N Engl J Med. 2022;386(11):1013-1025. doi:10.1056/NEJMoa2113708.
12. 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. Accessed November 17, 2022. https://icer.org/wp-content/uploads/2020/10/ICER_Hemophilia-A_Final-Report_112020.pdf

Appendix 1 – Covered Diagnosis Codes

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

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 Determination (NCD), Local Coverage Articles (LCAs) and Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. They can be found at: http://www.cms.gov/medicare-coverage-database/ search.aspx. Additional indications may be covered at the discretion of the health plan.

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