Valoctocogene roxaparvovec-rvox (Roctavian®) is a one-time gene replacement therapy for the prevention of bleeding episodes in adult individuals with severe hemophilia A, a genetic disease caused by the deficiency of clotting factor VIII (FVIII). Valoctocogene roxaparvovec-rvox (Roctavian) administration and follow-up requires a multidisciplinary team to provide adequate safety and access to care as necessary for recipients of gene therapy.

Valoctocogene roxaparvovec-rvox (Roctavian) is an adeno-associated virus (AAV) gene therapy composed of a recombinant AAV5 (rAAV5) vector containing a coagulation factor VIII complementary DNA driven by a liver-selective promoter. 

Valoctocogene roxaparvovec-rvox (Roctavian) may be considered medically necessary as a one-time infusion for individuals with hemophilia A when ALL of the following criteria are met:

• Individual is 18 years of age or older at the time of treatment decision; and
• Confirmed diagnosis of severe hemophilia A (i.e., less than 1 IU/dL clotting factor activity); and
• Prescribed by or in consultation with a hematologist or specialist with experience and expertise in the treatment of hemophilia A; and
• Individual has been on prophylactic FVIII replacement therapy and/or emicizumab (Hemlibra) for at least 12 months prior to receiving gene therapy; and
• Provider attestation that individual has been counseled regarding the risks of alcohol consumption and use of concomitant hepatotoxic medications after receiving valoctocogene roxaparvovec-rvox (Roctavian) and individual agrees to abstain from alcohol consumption for at least one (1) year following infusion; and
• Individual does not have ANY of the following:
  • Previous documented history of a detectable FVIII inhibitor (less than 0.6 Bethesda Units (BU), or less than 1.0 BU for laboratories with historical lower sensitivity cutoff for inhibitor detection of 1.0 BU); or
  • Detectable AAV5 antibodies as determined by an FDA approved companion diagnostic; or
  • Liver function levels (hepatic aminotransferases [ALT and AST], GGT, total bilirubin, and alkaline phosphatase) greater than 1.25 times the upper limit of normal or INR greater than 1.4; or
  • Significant hepatic fibrosis or cirrhosis (stage 3 or 4 on the Batts-Ludwig scale or equivalent); or
  • Individual does not have a contraindication to receiving corticosteroids or immunosuppressive agents in the event that they experience elevated ALT levels post infusion; or
    • Note: ALT levels should be monitored closely post-infusion; if ALT levels elevate >1.5 times the upper limit of normal, corticosteroids or alternative immunosuppressive agents should be initiated.
  • Positive HIV status; or
  • Chronic or active hepatitis B infection; or
  • Active hepatitis C infection; or
  • Other active or controlled chronic infection; or
  • History of arterial or recurrent or unprovoked venous thromboembolic events (e.g., non- hemorrhagic stroke, pulmonary embolism, myocardial infarction, arterial embolus); and
• Provider attestation of discontinuation of regular prophylactic therapy following appropriate timeframe for FVIII levels to reach therapeutic levels after steady state, after individual has received gene therapy; and
• Acute factor product utilized prior to receiving gene therapy to be maintained for treatment of on-demand bleeds or perioperative management; and
• The requesting physician shall provide continual clinical outcome information within a provider portal as requested by Highmark; and
• If the member changes providers, the member will notify Highmark of the member's new provider contact information. The member will allow Highmark the continuous ability to receive information pertaining to clinical outcomes of this therapy from the member's current and future providers. 

Note: Highmark's receipt of clinical outcome information shall not impact a member's eligibility, benefits, premiums, or cost-sharing obligations under the terms of the member's insurance contract.

Note: The safety and effectiveness of repeat administration of valoctocogene roxaparvovec-rvox (Roctavian) has not been evaluated. Therefore, coverage will be limited to once per lifetime.

The use of valoctocogene roxaparvovec-rvox (Roctavian) for any other indication is considered not medically necessary.

NOTE: In addition to the above criteria, product specific dosage and/or frequency limits may apply in accordance with the U.S. Food and Drug Administration (FDA)-approved product prescribing information, national compendia, Centers for Medicare and Medicaid Services (CMS) and other peer reviewed resources or evidence-based guidelines. Highmark may deny, in full or in part, reimbursement for utilization that does not fall within the applicable dosage and/or frequency limits.

Valoctocogene roxaparvovec-rvox (Roctavian) is typically an outpatient procedure which is only eligible for coverage as an inpatient procedure in special circumstances, including, but not limited to, the presence of a co-morbid condition that would require monitoring in a more controlled environment such as the inpatient setting.