ROCTAVIAN (valoctocogene roxaparvovec-rvox)

Roctavian (valoctocogene roxaparvovec-rvox)

Medical Administration – Intravenous

Diagnosis considered for coverage:

• Hemophilia A: Indicated for the treatment of adults with severe hemophilia A (congenital factor VIII deficiency with factor VIII activity < 1 IU/dL) without pre-existing antibodies to adeno-associated virus serotype 5 detected by an FDA-approved test.

Coverage Criteria:

For diagnosis of Hemophilia A:

• Diagnosis of severe Hemophilia A, AND
• Factor VIII (FVIII) assay baseline level of less than or equal to 1 IU/dL, AND
• Patient is 18 years of age or older, AND
• Patient does not have pre-existing immunity to the AAV5 capsid as detected by the FDA-approved companion diagnostic test, AND
• Patient does not have a history of inhibitors based on results from a modified Nijmegen Bethesda assay of less than 0.6 Bethesda Units (BU) on 2 consecutive occasions at least 1 week apart within the past 12 months, AND
• Treatment logs including both factor infusions and bleeding episodes confirming BOTH of the following:
  • Patient has been on prophylactic FVIII replacement therapy for at least 12 months
  • Patient has been treated/exposed to FVIII concentrates for a minimum 150 exposure days (EDs), AND
• One of the following:
  • Patient does not exhibit significant liver dysfunction as defined by abnormal elevation of ONE of the following:
    • alanine transaminase (ALT) greater than 1.25 times the upper limit of normal
    • aspartate aminotransferase (AST) greater than 1.25 times the upper limit of normal
    • gamma-glutamyl transferase (GGT) greater than 1.25 times the upper limit of normal 
    • alkaline phosphatase (ALP) greater than 1.25 times the upper limit of normal
    • bilirubin greater than 1.25 times the upper limit of normal
    • international normalized ratio (INR) greater than or equal to 1.4, OR
  • Patient has had a consultation with a hepatologist to assess eligibility for Roctavian, AND
• Patient does not have an active infection or any immunosuppressive disorder, AND
• Patient has never received valoctocogene roxaparvovec treatment in their lifetime, AND
• Prescribed by a hematologist affiliated with a comprehensive hemophilia treatment center (HTC), AND
• Prescriber attests that the patient has been counseled and has agreed to adhere to post-treatment monitoring and follow-ups with their hematologist and HTC

Dosing:

• The recommended dose of ROCTAVIAN is 6 × 1013 vector genomes per kilogram (vg/kg) body weight, administered as a single intravenous infusion. ROCTAVIAN is administered using an infusion pump at a rate of 1 mL/min, which can be increased every 30 minutes by 1 mL/min up to a maximum rate of 4 mL/min.
  • Calculating Dose in Milliliters (mL) and Number of Vials Required
    • Patient dose volume in mL:
      • Body weight in kg multiplied by 3 = dose in mL - The multiplication factor 3 represents the per kilogram dose (6 × 1013 vg/kg) divided by the amount of vector genomes per mL of the ROCTAVIAN suspension (2 × 1013 vg/mL).
    • Number of Roctavian vials to be thawed:
      • Patient dose volume (mL) divided by 8 = number of vials to be thawed (round up to next whole number of vials) - The division factor 8 represents the minimum volume of ROCTAVIAN extractable from a vial (8 mL).
• Example of Dose Volume and Number of Vials to be Thawed

• Roctavian can be administered only once.

Coverage Duration:

• 1 Time Authorization in Lifetime

Authorization is not covered for the following:

The use of this drug for indications not listed in this policy does not meet the coverage criteria established by the Western Health Advantage (WHA) Pharmacy and Therapeutics (P&T) Committee.

Additional Information: 

• The incidence rate of inhibitor development in patients with hemophilia A who have been previously treated for at least 150 EDs has been estimated to be approximately 2–5 per 1000 patient-years. 
• About 20% of the people with Hemophilia A in U.S are estimated to produce antibodies, which could make the ineligible for the AAV5-mediated gene therapy.

Policy Updates:

• 11/14/2023 – New policy approved by P&T.

References:

1. Pasi K.J., Rangarajan S, Mitchell N, et al. Multiyear follow-up of AAv5-hFVIII-SQ gene therapy for hemophilia A. New Eng J of Med. 2020;382:29-40.
2. Rangarajan S, Walsh L, Lester W, et al. AAV5–factor VIII gene transfer in severe hemophilia A. N Engl J Med 2017;377:2519-30. 
3. Hermans C, Astermark J, de Moerloose P. Exposure to factor VIII and prediction of inhibitor development: exposure days vs.danger days, or both?J Thromb Haemost 2012;10:2194.
4. Biomarin's Valrox, possible 1st gene therapy for hemophilia A, Under FDA priority review. Hemophilia News Today; February 2020. Available at: https://hemophilianewstoday.com/2020/02/24/biomarins-valrox-possible-first-gene-therapy-hemophila-a-under-fda-priority-review-marketing-application-accepted/
5. Per clinical consult with hematologist, May 29, 2020. 
6. Roctavian Prescribing Information. BioMarin Pharmaceutical Inc. Novato, CA. June 2023.