Valoctocogene Roxaparvovec-rvox (Roctavian)

Number: 1037

Table Of Contents

Applicable CPT / HCPCS / ICD-10 Codes


Scope of Policy

This Clinical Policy Bulletin addresses valoctocogene roxaparvovec-rvox (Roctavian) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification: 

Precertification of valoctocogene roxaparvovec-rvox (Roctavian) is required of all Aetna participating providers and members in applicable plan designs. For precertification of valoctocogene roxaparvovec-rvox (Roctavian), call (866) 752-7021, or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification.  

Note: Unless member's health plan has elected not to require, gene and cellular therapies must be administered at an Aetna Institutes® Gene Based, Cellular and Other Innovative Therapy (GCIT®) Network. For valoctocogene roxaparvovec-rvox (Roctavian), see Aetna Institutes® GCIT Designated Centers.  

  1. Prescriber Specialties

    This medication must be prescribed by or in consultation with a hematologist.

  2. Criteria for Initial Approval

    Hemophilia A

    Aetna considers valoctocogene roxaparvovec-rvox (Roctavian) medically necessary for one dose total for treatment of severe hemophilia A when all of the following criteria are met:

    1. Member must be 18 years of age or older; and 
    2. Member has severe disease with factor VIII activity levels less than or equal to 1 IU/dL; and
    3. Absence of pre-existing antibodies to AAV5 was confirmed by an FDA-approved test (e.g., AAV5 DetectCDX™); and
    4. Member does not have prior or active factor VIII inhibitors (inhibitor titer must be less than 0.6 Bethesda Units [BU]); and
    5. Member has not received treatment with the requested medication previously.

    Aetna considers all other indications as experimental, investigational, or unproven.

  3. Continuation of Therapy

    See Dosage and Administration information.

  4. Related Policies

    1. CPB 0131 - Clotting Factors

Dosage and Administration

Valoctocogene roxaparvovec-rvox is supplied as Roctavian suspension for intravenous infusion and has a nominal concentration of 2 x 1013 vg valoctocogene roxaparvovec-rvox per mL, each vial contains an extractable volume of not less than 8 mL (16 × 1013 vg).

Roctavian is for one-time single-dose intravenous use only.

  • Perform baseline testing to select patients, including testing for pre-existing antibodies to adeno-associated virus serotype 5 (AAV5), factor VIII inhibitor presence, and liver health assessments.
  • The recommended dose of Roctavian is 6 × 1013 vector genomes (vg) per kg of body weight.
  • Start the infusion at 1 mL/min. If tolerated, the rate may be increased every 30 minutes by 1 mL/min up to a maximum rate of 4 mL/min.

Refer to full prescribing information for Roctavian for preparation and administration instructions.

Source: BioMarin Pharmaceutical; 2023


CPT Codes / HCPCS Codes / ICD-10 Codes

Code Code Description

Other CPT codes related to the CPB:

AAV5 Detect CDX –no specific code
85335 Factor inhibitor test
85240 Clotting; factor VIII (AHG), 1-stage
85730 Thromboplastin time, partial (PTT); plasma or whole blood
85732 Thromboplastin time, partial (PTT); substitution, plasma fractions, each
96365 - 96368 Intravenous infusion

HCPCS codes covered if selection criteria are met:

Valoctocogene roxaparvovec-rvox (Roctavian) –no specific code

Other HCPCS codes related to the CPB:

J7182 Injection, factor viii, (antihemophilic factor, recombinant), (novoeight), per iu
J7185 Injection, factor viii (antihemophilic factor, recombinant) (xyntha), per i.u
J7186 Injection, antihemophilic factor viii/von willebrand factor complex (human), per factor viii i.u
J7188 Injection, factor viii (antihemophilic factor, recombinant), (obizur), per i.u
J7190 Factor viii (antihemophilic factor, human) per i.u
J7191 Factor viii (antihemophilic factor (porcine)), per i.u
J7192 Factor viii (antihemophilic factor, recombinant) per i.u., not otherwise specified
J7204 Injection, factor viii, antihemophilic factor (recombinant), (esperoct), glycopegylated-exei, per iu
J7205 Injection, factor viii fc fusion protein (recombinant), per iu
J7207 Injection, factor viii, (antihemophilic factor, recombinant), pegylated, 1 i.u
J7208 Injection, factor viii, (antihemophilic factor, recombinant), pegylated-aucl, (jivi), 1 i.u
J7209 Injection, factor viii, (antihemophilic factor, recombinant), (nuwiq), 1 i.u
J7210 Injection, factor viii, (antihemophilic factor, recombinant), (afstyla), 1 i.u
J7211 Injection, factor viii, (antihemophilic factor, recombinant), (kovaltry), 1 i.u
S9345 Home infusion therapy, anti-hemophilic agent infusion therapy (e.g., factor viii); administrative services, professional pharmacy services, care coordination, and all necessary supplies and equipment (drugs and nursing visits coded separately), per diem

ICD-10 codes covered if selection criteria are met:

D66 Hereditary factor VIII deficiency


U.S. Food and Drug Administration (FDA)-Approved Indications 

  • Roctavian is indicated for the treatment of adults with severe hemophilia A (congenital factor VIII deficiency with factor VIII activity < 1 IU/dL) without antibodies to adeno-associated virus serotype 5 (AAV5) detected by an FDA-approved test.

Valoctocogene roxaparvovec-rvox is available as Roctavian (BioMarin Pharmaceutical Inc) and is an adeno-associated virus (AAV) vector-based gene therapy product. It is derived from naturally occurring adeno-associated virus and is produced using Sf9 insect cells and recombinant baculovirus technology. Roctavian is designed to introduce a functional copy of a transgene encoding the B-domain deleted SQ form of human coagulation factor VIII (hFVIIII-SQ). The expression of the B-domain deleted recombinant human factor VIII under the control of a liver-specific promoter results in the replacement of missing coagulation factor VIII required for effective hemostasis (BioMarin Pharmaceutical; 2023).

According to the prescribing information, Roctavian carries the following contraindications:

  • Active infections, either acute or uncontrolled chronic.
  • Known significant hepatic fibrosis (stage 3 or 4), or cirrhosis.
  • Known hypersensitivity to mannitol.

Per the prescribing information, Roctavian carries the following warnings and precautions:

  • Infusion-related reactions: Infusion reactions, including hypersensitivity reactions and anaphylaxis, have occurred. Monitor during and for at least 3 hours after Roctavian administration. If symptoms occur, slow or interrupt administration and give appropriate treatment. Restart infusion at slower rate once symptoms resolve. Discontinue infusion for anaphylaxis.
  • Hepatotoxicity: Monitor alanine aminotransferase (ALT) weekly for at least 26 weeks and institute corticosteroid treatment in response to ALT elevations as required. Continue to monitor ALT until it returns to baseline. Monitor factor VIII activity levels since ALT elevation may be accompanied by a decrease in factor VIII activity. Monitor for and manage adverse reactions from corticosteroid use.
  • Thromboembolic events: Thromboembolic events may occur in the setting of elevated factor VIII activity above the upper limit of normal (ULN). Factor VIII activity above ULN has been reported following Roctavian infusion. Evaluate for risk factors for thrombosis including cardiovascular risk factors prior to and after Roctavian use and advise patients accordingly.
  • Monitoring laboratory tests: Monitor for factor VIII activity and factor VIII inhibitors.
  • Malignancy: Monitor for hepatocellular malignancy in patients with risk factors for hepatocellular carcinoma (e.g., hepatitis B or C, non-alcoholic fatty liver disease, chronic alcohol consumption, non-alcoholic
    steatohepatitis, advanced age). Perform regular liver ultrasound (e.g., annually) and alpha-fetoprotein testing following administration.

Per the prescribing information, Roctavian carries the following adverse reactions:

  • Most common adverse reactions (incidence ≥ 5%): Nausea, fatigue, headache, infusion-related reactions, vomiting, and abdominal pain.
  • Most common laboratory abnormalities (incidence ≥ 10%): ALT, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), factor VIII activity levels, gamma-glutamyl
    transferase (GGT) and bilirubin > ULN.

On June 29, 2023, the U.S. Food and Drug Administration approved valoctocogene roxaparvovec-rvox (Roctavian), an adeno-associated virus vector-based gene therapy for the treatment of adults with severe hemophilia A without pre-existing antibodies to adeno-associated virus serotype 5 detected by an FDA-approved test. The FDA approval was based on supporting data from the GENEr8-1 study (FDA, 2023).

In the GENEr8-1 study, a prospective, phase 3, open-label, single-dose, single-arm, multinational trial, Ozelo and colleagues (2022) evaluated the efficacy and safety of valoctocogene roxaparvovec-rvox (Roctavian) in 134 adult males (18 years of age and older) with severe hemophilia A. Patients receiving prior prophylactic factor VIII replacement therapy, but not emicizumab, were enrolled in this study. Only patients without detectable, pre-existing antibodies to AAV5 capsid were eligible for Roctavian therapy. The AAV5 DetectCDx™ total antibody assay (i.e., the FDA-approved test for selection for Roctavian therapy) was used to screen the presence of pre-existing antibodies to AAV5 capsid. Patients received a single intravenous dose of 6.x 1013 vg/kg body weight of Roctavian and entered a follow-up period of 5 years. The primary efficacy end point was a non-inferiority (NI) test of the difference in annualized bleeding rate (ABR) in the efficacy evaluation period (EEP) following Roctavian administration compared with ABR during the baseline period in the rollover population. Efficacy was determined from the results of a cohort of 112 patients followed up for at least 3 years after Roctavian treatment. Compared to their baseline, patients experienced an average ABR reduction of 52% after receiving Roctavian, or roughly 2.6 bleeds/year, through to the end of a median three years of follow-up. Their baseline ABR while receiving routine FVIII prophylaxis was about 5.4 bleeds/year (FDA, 2023). Among this cohort of 112 patients, the mean annualized rates of factor VIII concentrate use and treated bleeding after week 4 had decreased after infusion by 98.6% and 83.8%, respectively (p<0.001 for both comparisons). An increase in alanine aminotransferase levels occurred in 115 of 134 individuals (85.8%) and were managed with immune suppressants. Other most common adverse events included headache (38.1%), nausea (37.3%), and elevations in aspartate aminotransferase levels (35.1%). No development of factor VIII inhibitors or thrombosis was noted in any of the participants. 


The above policy is based on the following references:

  1. BioMarin Pharmaceutical Inc. Roctavian (valoctocogene roxaparvovec-rvox) suspension for intravenous infusion. Prescribing Information. Novato, CA: BioMarin Pharmaceutical; revised June 2023.
  2. Ozelo MC, Mahlangu J, Pasi KJ, et al. Valoctocogene roxaparvovec Gene therapy for hemophilia A. N Engl J Med. 2022;386(11):1013-1025.
  3. U.S. Food and Drug Administration (FDA). FDA approves first gene therapy for adults with severe hemophilia A. FDA News Release. Silver Spring, MD: FDA; June 29, 2023.