Description

Valoctocogene roxaparvovec-rvox (e.g., Roctavian) is an AAV5 based gene therapy vector, designed to introduce a functional copy of a transgene encoding the B-domain deleted SQ form of human coagulation factor VIII (hFVIII[1]SQ). Transcription of this transgene occurs within the liver, using a liver-specific promoter, which results in the expression of hFVIII-SQ. The expressed hFVIII-SQ replaces the missing coagulation factor VIII needed for effective hemostasis.

Policy

Roctavian is proven and MEDICALLY NECESSARY for the treatment of Hemophilia A (factor VIII Deficiency) when all of the following criteria are met:

• • Patient is 18 years of age or older; and
  • Diagnosis of severe hemophilia A; and
  • Documentation of endogenous factor VIII levels less than 1% of normal factor VIII (< 0.01 IU/mL, < 1 IU/dL); and
  • One of the following:
  • Patient is currently receiving chronic prophylactic Hemlibra (emicizumab) therapy;

(All prophylactic therapy must be discontinued 5 posts (23 weeks) post administration)

• • Both of the following:
    1. Patient currently uses factor VIII prophylaxis therapy; and
    2. Patient has had a minimum of 150 exposure days to a factor VIII agent;

(All prophylactic therapy must be discontinued 23 weeks post administration)

• • Patient has been determined to be an appropriate candidate for Roctavian by the Hemophilia Treatment Center based on willingness to adhere to initial and long-term monitoring and management; and
  • Patient does not have a history of inhibitors to factor VIII greater than or equal to 0.6 Bethesda units [BU]; and
  • Patient does not screen positive for active factor VIII inhibitors as defined as greater than or equal to 0.6 Bethesda units [BU] prior to administration of Roctavian; and
  • Patient does not have pre-existing immunity to the AAV5 capsid as detected by the FDA-approved companion diagnostic test AAV5 DetectCDx™; and
  • Liver health assessments including enzyme testing [alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin)] and hepatic ultrasound and elastography are performed to rule out radiological liver abnormalities and/or sustained liver enzyme elevations; and
  • One of the following:
    1. Patient is not HIV positive; or
    2. Patient is HIV positive and is virally suppressed with anti-viral therapy (i.e., < 200 copies of HIV per mL) and
  • The patient’s hepatitis B surface antigen is negative; and
  • One of the following:
    1. Patient’s hepatitis C virus (HCV) antibody is negative; or
    2. Patient’s HCV antibody is positive, and the patient’s HCV RNA is negative and
  • The patient is not currently using antiviral therapy for hepatitis B or C; and
  • Patient has not previously received treatment with Roctavian or other gene therapy product for the treatment of hemophilia A in the patient’s lifetime; and
  • Prescriber attests that the patient’s ALT and factor VIII activity will be monitored weekly for at least 26 weeks following administration of Roctavian and regularly thereafter per the monitoring schedule recommended in the prescribing information; and
  • Prescriber attests that counseling has been provided to the patient to abstain from consuming alcohol for at least one year following administration of Roctavian and regarding how much alcohol may be acceptable for the patient in the longer term; and
  • Roctavian dosing is in accordance with the United States Food and Drug Administration approved labeling; and
  • Authorization will be issued for no more than one single-use intravenous infusion per lifetime.

References

1. Roctavian [package insert]. Novato, CA: Biomarin Pharmaceuticals Inc, June 2023
2. Curry MP, Afdhal NH.(2023) Noninvasive assessment of hepatic fibrosis: Overview of serologic and radiographic tests. In: UpToDate, Runyon BA, (Ed), UpToDate, Waltham, MA, 2023.
3. Hoots WK, Shapiro AD.(2023) Inhibitors in hemophilia: Mechanisms, prevalence, diagnosis, and eradication. . In: UpToDate, Leung LLK, Mahoney DHS (Ed), UpToDate, Waltham, MA, 2023.
4. Mahlangu J, Kaczmarek R, von Drygalski A, et al.(2023) Two-Year Outcomes of Valoctocogene Roxaparvovec Therapy for Hemophilia A. N Engl J Med. Feb 23 2023; 388(8): 694-705. PMID 36812433
5. Ozelo, M. C., Mahlangu, J., Pasi, K.J., et al.(2023) Valoctocogene Roxaparvovec Gene Therapy for Hemophilia A. N Engl J Med. 386(11), 1013–1025.
6. Pasi KJ, Rangarajan S, Mitchell N, et al.(2020) Multiyear Follow-up of AAV5-hFVIII-SQ Gene Therapy for Hemophilia A. N Engl J Med. 2020;382:29-40.
7. Rangarajan S, Walsh L, Lester W, et al.(2017) AAV5-factor VIII Gene Transfer in Severe Hemophilia A. N Engl J Med. 2017;377:2519-2530.
8. Single-Arm Study To Evaluate The Efficacy and Safety of Valoctocogene Roxaparvovec in Hemophilia A Patients (BMN 270301). Clinicaltrials.gov website https://clinicaltrials.gov/study/NCT03370913. Accessed October 25, 2023.
9. 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.
10. Guidelines for the Management of Hemophilia. 3rd Edition. World Federation of Hemophilia 2020. Available at: https://www1.wfh.org/publications/files/pdf-1863.pdf. Accessed July 2023.
11. Annual Review of Factor Replacement Products. Oklahoma Health Care Authority Review Board. Updated April 2016. Accessed July 2023.
12. Graham A1, Jaworski K. Pharmacokinetic analysis of anti-hemophilic factor in the obese patient. Haemophilia. 2014 Mar;20(2):226-9.
13. Croteau SE1, Neufeld EJ. Transition considerations for extended half-life factor products. Haemophilia. 2015 May;21(3):285-8.
14. 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).
15. MASAC RECOMMENDATION CONCERNING PROPHYLAXIS. 2016 National Hemophilia Foundation. MASAC Document #241; February 2016. Available at: http://www.hemophilia.org. Accessed July 2023.
16. 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.
17. 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.
18. 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

Coding Section

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community and other nonaffiliated technology evaluation centers, reference to federal regulations, other plan medical policies, and accredited national guidelines.

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