Aetna Commercial Clinical Policy

Aetna Valoctocogene Roxaparvovec-rvox (Roctavian) Form

Effective Date

10/02/2023

Last Reviewed

NA

Original Document

  Reference



Background for this Policy

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 10

    13

    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.

    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 (commercial), or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification . For Medicare Part B plans, call (866) 503-0857, or fax (844) 268-7263.

    Note

    : Site of Care Utilization Management Policy applies. For information on site of service for

    valoctocogene roxaparvovec-rvox (Roctavian)

    , see

    Utilization Management Policy on Site of Care for Specialty Drug Infusions

    .

    Prescriber Specialties

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

    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:

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

    • Aetna considers all other indications as experimental and investigational.

    Continuation of Therapy

    See Dosage and Administration information.