Cabotegravir (Apretude), Cabotegravir/Rilpivirine (Cabenuva) Form

Cabotegravir (Apretude™) is a human immunodeficiency virus type-1 (HIV-1) integrase strand transfer inhibitor (INSTI). Cabotegravir/rilpivirine (Cabenuva®) is a 2-drug co-packaged product of cabotegravir and rilpivirine, an HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI). FDA Approved Indication(s) Apretude is indicated in at-risk adults and adolescents weighing at least 35 kg for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection. Individuals must have a negative HIV-1 test prior to initiating Apretude (with or without an oral lead-in with oral cabotegravir) for HIV-1 PrEP. Cabenuva is indicated as a complete regimen for the treatment of HIV-1 infection in adults and adolescents 12 years of age and older and weighing at least 35 kg to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 ribonucleic acid (RNA) < 50 copies/mL) on a stable antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine.
Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Apretude and Cabenuva are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. HIV-1 Infection (must meet all):

1. Request is for Cabenuva;
2. Diagnosis of HIV-1 infection;
3. Prescribed by or in consultation with an infectious disease or HIV specialist;
4. Age ≥ 12 years;
5. Member weighs ≥ 35 kg;

6. Documentation of adherence to a stable oral antiretroviral regimen for HIV-1 for ≥ 3 months;

   7. Documentation of sustained virologic suppression as evidenced by HIV-1 RNA viral load < 50 copies/mL for ≥ 3 months; Page 1 of 8

   CLINICAL POLICY Cabotegravir, Cabotegravir/Rilpivirine

   8. Member has no history of treatment failure (see Appendix D);
7. Member has no known or suspected resistance to either cabotegravir or rilpivirine;
8. Dose does not exceed (a or b):
   a. Monthly schedule: 600 mg cabotegravir and 900 mg rilpivirine (1 kit of 2 vials) initiation dose, followed by 400 mg cabotegravir and 600 mg rilpivirine (1 kit of 2 vials) every month thereafter; A initiation dose may be repeated if member misses more than 2 monthly scheduled continuation injections b. Every 2-month schedule: 600 mg cabotegravir and 900 mg rilpivirine (1 kit of 2 vials) 1 month apart for 2 consecutive months (initial dose), followed by 600 mg cabotegravir and 900 mg rilpivirine (1 kit of 2 vials) every 2 months thereafter.
   Approval duration:
   Medicaid/HIM – 6 months
   Commercial – 6 months or to the member’s renewal date, whichever is longer B. Pre-exposure HIV Prophylaxis (must meet all):
   1. Request is for Apretude;
9. Member is HIV-negative has no signs or symptoms of acute HIV infection;
10. Member is considered at high risk for acquiring HIV and meets one of the following (a, b, or c): a. Engaging in sexual activity with an HIV-1 infected partner; b. Engaging in sexual activity and one or more of the following:
    Inconsistent or no condom use;
    i. ii. Diagnosis of sexually transmitted infections in the past 6 months;
    iii. Exchange of sex for commodities;
    iv. Incarceration; v. Not in a monogamous partnership;
    vi. Partner of unknown HIV status with any of the preceding risk factors; c. Use of illicit injection drugs;
    4. Member weighs ≥ 35 kg;

11. Member must instead use emtricitabine/tenofovir disoproxil fumarate (generic Truvada), unless contraindicated, clinically significant adverse effects are experienced, or member has bone/renal co-morbidities or risk factors (see Appendix E);

    6. Dose does not exceed a 600 mg intramuscular injection given 1 month apart for 2 consecutive months (initial dose), followed by single 600 mg intramuscular injection given every 2 months thereafter.
       Approval duration:
       Medicaid/HIM – 12 months (7 injections)
       Commercial – 6 months or to the member’s renewal date, whichever is longer C. Other diagnoses/indications (must meet 1 or 2):
    7. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: Page 2 of 8

    CLINICAL POLICY Cabotegravir, Cabotegravir/Rilpivirine CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

    2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
       II. Continued Therapy A. HIV-1 Infection (must meet all):
    3. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Cabenuva for a covered indication and has received this medication for at least 30 days;
    4. Request is for Cabenuva;
12. Member is responding positively to therapy;
13. If request is for a dose increase, new dose does not exceed (a, b, or c): a. 400 mg cabotegravir and 600 mg rilpivirine (1 kit of 2 vials) every month; b. 600 mg cabotegravir and 900 mg rilpivirine (1 kit of 2 vials) every 2 months;
    c. If member has missed injections (> 2 injections if on monthly schedule or just one injection if on every 2-month schedule) as evidenced by claims history, both of the following (i and ii):
    i. Provider attestation that member remains an appropriate candidate for therapy; ii. Follow recommended dosing schedule for missed injections. Approval duration:
    Medicaid/HIM – 12 months
    Commercial – 6 months or to the member’s renewal date, whichever is longer B. Pre-exposure HIV Prophylaxis (must meet all):
    
    1. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Apretude for a covered indication and has received this medication for at least 30 days;
    2. Request is for Apretude;
14. Member is responding positively to therapy;

15. If request is for a dose increase, new dose does not exceed a single 600 mg intramuscular injection given every 2 months.
    Approval duration:
    Medicaid/HIM – 12 months (6 injections)
    Commercial – 6 months or to the member’s renewal date, whichever is longer Page 3 of 8

    CLINICAL POLICY Cabotegravir, Cabotegravir/Rilpivirine C. Other diagnoses/indications (must meet 1 or 2):

    1. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
    2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
       III. Diagnoses/Indications for which coverage is NOT authorized:
       A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents.
       IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration HBV: hepatitis B virus HIV-1: human immunodeficiency virus type 1
       INSTI: integrase strand transfer inhibitor NNRTI: non-nucleoside reverse transcriptase inhibitor NRTI: nucleos(t)ide reverse transcriptase inhibitor
       PI: protease inhibitor
       PrEP: pre-exposure prophylaxis RNA: ribonucleic acid Appendix B: Therapeutic Alternatives
       This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
       Drug Name Dosing Regimen Dose Limit/ Maximum Dose Refer to prescribing information emtricitabine and tenofovir disoproxil fumarate (Truvada®) PrEP: One tablet (200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate) PO QD Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Page 4 of 8

    CLINICAL POLICY Cabotegravir, Cabotegravir/Rilpivirine Appendix C: Contraindications/Boxed Warnings • Contraindication(s):
    o Apretude: unknown or positive HIV-1 status, previous hypersensitivity reaction to cabotegravir o Cabenuva: previous hypersensitivity reaction to cabotegravir or rilpivirine; coadministration with uridine diphosphate (UDP)-glucuronosyl transferase (UGT)1A1 and/or cytochrome P450(CYP)3A4 enzyme induction drugs for which significant decreases in cabotegravir and/or rilpivirine plasma concentrations may occur, which may result in loss of virologic response. • Boxed warning(s):
    o Apretude: risk of drug resistance with use of Apretude for HIV-1 PrEP in undiagnosed HIV-1 infection o Cabenuva: none reported Appendix D: General Information
    Per the Department of Health and Human Services Antiretroviral Guidelines: • Evaluation of virologic failure should include assessment of adherence, drug-drug and drug-food interactions, drug tolerability, HIV RNA, and CD4 T lymphocyte cell count trends over time, treatment history, and prior and current drug-resistance testing results. • Virologic failure is defined as the inability to achieve or maintain suppression of viral replication to HIV RNA level < 200 copies/mL. Patients with levels persistently above 200 copies/mL, especially > 500 copies/mL, often develop drug resistance. • Panel’s recommendation: Cabenuva can be used, after optional oral lead-in therapy, to replace an existing oral antiviral regimen in people with HIV with sustained viral suppression for 3 to 6 months (optimal duration is not defined), who have good adherence and engagement in care, no baseline resistance to either medication, no prior virologic failures (AI recommendation).
    Appendix E: Examples of Bone/Renal Co-morbidities and Risk Factors
    Examples include, but are not limited to: • Bone disease: osteoporosis, osteopenia, receiving chronic corticosteroids or other therapies known to decrease bone density (e.g., aromatase inhibitors, androgen deprivation therapy, doxorubicin, cyclophosphamide), frail/underweight. • Renal disease: chronic kidney disease, estimated creatinine clearance < 60 mL/min, albuminuria, family history of kidney disease, diabetes, receiving nephrotoxic medications. V. Dosage and Administration
    Drug Name Indication Dosing Regimen Apretude HIV-1 PrEP Initiation A single 600 mg IM gluteal injection given 1 month apart for 2 consecutive months (on the last day of an oral lead-in if used or within 3 days)
    Continuation
    Maximum Dose 600 mg every 2 months Page 5 of 8

    CLINICAL POLICY Cabotegravir, Cabotegravir/Rilpivirine Drug Name Indication Dosing Regimen Maximum Dose Cabenuva HIV-1 infection
    600 mg IM gluteal injection every 2 months
    Prior to initiating treatment, oral lead-in dosing may be considered to assess the tolerability of cabotegravir and rilpivirine with the recommended dosage used for approximately 1 month.
    400 mg cabotegravir and 600 mg rilpivirine every month Monthly Dosing Schedule
    Initiate with 600 mg cabotegravir and 900 mg rilpivirine IM on the last day of current antiretroviral therapy or oral lead-in and continue with IM injections of 400 mg cabotegravir and 600 mg rilpivirine every month thereafter. OR 600 mg cabotegravir and 900 mg rilpivirine every 2 months
    Every 2-Month Dosing Schedule
    Initiate with 600 mg cabotegravir and 900 mg rilpivirine IM on the last day of current antiretroviral therapy or oral lead-in for 2 consecutive months then continue with IM injections every 2 months thereafter.
    VI. Product Availability
    Drug Apretude Cabenuva Availability
    Single-dose vial: 600 mg/3 mL (200 mg/mL) Injectable suspension kits: • Cabenuva 400 mg/600 mg kit: cabotegravir 400 mg/2 mL (200 mg/mL) vial / rilpivirine 600 mg/2mL (300 mg/mL) vial • Cabenuva 600 mg/900 mg kit: cabotegravir 600 mg/3 mL (200 mg/mL) vial / rilpivirine 900 mg/3mL (300 mg/mL) vial VII.