PREVYMIS, Letermovir Form

Letermovir (Prevymis®) is a cytomegalovirus (CMV) DNA terminase complex inhibitor. FDA Approved Indication(s) Prevymis is indicated for:
• Prophylaxis of CMV infection and disease in adult CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant (HSCT) • Prophylaxis of CMV disease in adult kidney transplant recipients at high risk (Donor CMV seropositive/Recipient CMV seronegative [D+/R-]) 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 Prevymis is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Prophylaxis of CMV Infection in Adult CMV-Seropositive Recipients of an Allogeneic HSCT (must meet all):

1. Member has received or is scheduled to receive allogeneic HSCT;
2. Member is CMV-seropositive;
3. Prescribed by or in consultation with an oncology, hematology, infectious disease, or transplant specialist;
   4. Age ≥ 18 years;
4. If request is for IV Prevymis, documentation supports inability to use oral therapy;

5. At the time of request, member is not receiving any of the following contraindicated agents:
   a. Pimozide or ergot alkaloids; b. Cyclosporine co-administered with pitavastatin or simvastatin;

   7. If request is for prophylaxis beyond 100 days post-transplantation, both of the following (a and b): a. Member is at risk for late CMV infection and disease (see Appendix D); b. Prevymis is prescribed up to day 200 post-HSCT;
   8. Dose does not exceed any of the following (a or b):
      a. 480 mg per day; b. If co-administered with cyclosporine: 240 mg per day. Page 1 of 8

   CLINICAL POLICY Letermovir Approval duration: Through Day 100 post-transplantation (or through Day 200 post-transplantation if at risk for late CMV infection and disease) B. Prophylaxis of CMV in Adult Kidney Recipients at High Risk (must meet all):

   1. Member has received or scheduled to receive an allograft kidney transplant from a CMV-seropositive donor;
6. Member is CMV-seronegative;
7. Prescribed by or in consultation with a nephrologist or transplant specialist;
8. Age ≥ 18 years;
9. If request is for IV Prevymis, documentation supports inability to use oral therapy;
10. At the time of request, member is not receiving any of the following contraindicated agents:
    a. Pimozide or ergot alkaloids; b. Cyclosporine co-administered with pitavastatin or simvastatin;
    7. Dose does not exceed any of the following (a or b):
       a. 480 mg per day;
       b. If co-administered with cyclosporine: 240 mg per day. Approval duration: Through Day 200 post-transplantation C. Other diagnoses/indications (must meet 1 or 2):
    8. 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
    9. 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. All Indications in Section I (must meet all):
    10. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Prevymis for a covered indication and has received this medication for at least 30 days;
    11. Member is responding positively to therapy;

11. One of the following (a or b):
    a. For HSCT, one of the following (i or ii):
    Page 2 of 8

    CLINICAL POLICY Letermovir i. Member has not received Prevymis therapy beyond 100 days post- transplantation; ii. Member is at risk for late CMV infection and disease (see Appendix D) and has not received Prevymis therapy beyond 200 days post-transplantation; b. Kidney transplant: Member has not received Prevymis therapy beyond 200 days post-transplantation;

    4. If request is for a dose increase, new dose does not exceed any of the following (a or b):
       a. 480 mg per day;
       b. If co-administered with cyclosporine: 240 mg per day.
       Approval duration: Through Day 100 (for HSCT) or Day 200 (for kidney transplant or HSCT at risk for late CMV infection and disease) post-transplantation B. Other diagnoses/indications (must meet 1 or 2):
    5. 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
    6. 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 CMV: cytomegalovirus
       FDA: Food and Drug Administration D+: donor CMV seropositive
       Appendix B: Therapeutic Alternatives
       Not applicable HSCT: hematopoietic stem cell transplant
       R+: seropositive recipients R-: recipient CMV seronegative Page 3 of 8

    CLINICAL POLICY Letermovir Appendix C: Contraindications/Boxed Warnings • Contraindication(s): patients receiving any of the following - pimozide, ergot alkaloids, pitavastatin and simvastatin when co-administered with cyclosporine • Boxed warning(s): none reported Appendix D: General Information • Prophylaxis strategy against early CMV replication (i.e., < 100 days after HSCT) for allogeneic recipients involves administering prophylaxis to all allogeneic recipients at risk throughout the period from engraftment to 100 days after HSCT. o CMV prophylaxis has been studied using a variety of agents, including ganciclovir, valganciclovir, foscarnet, acyclovir, and valacyclovir. • Preemptive strategy targets antiviral treatment to those patients who have evidence of CMV replication after HSCT. • Positive response to therapy may be demonstrated if there is no evidence of CMV viremia. • The 2021 American Society for Transplantation and Cellular Therapy Guideline for prevention of CMV infection after HCT states that primary prophylaxis in CMV- seropositive adult allogeneic recipients with alternative agents such as valganciclovir, ganciclovir, or foscarnet is generally not recommended. • Examples of risk factors for late CMV infection and disease include, but are not limited to, the following:
    o HLA-related (sibling) donor with at least one mismatch at one of the following three HLA-gene loci: HLA-A, -B or –DR;
    o Haploidentical donor;
    o Unrelated donor with at least one mismatch at one of the following four HLA-gene loci: HLA-A, -B, -C and -DRB1;
    o Use of umbilical cord blood as stem cell source;
    o Use of ex vivo T-cell-depleted grafts;
    o Receipt of anti-thymocyte globulin;
    o Receipt of alemtuzumab;
    o Use of systemic prednisone (or equivalent) at a dose of ≥1 mg/kg of body weight per day V. Dosage and Administration
    Indication Prophylaxis of CMV infection in adult CMV- seropositive recipients [R+] of an allogeneic HSCT Prophylaxis of CMV disease in adult kidney transplant recipients at high risk (Donor CMV Dosing Regimen 480 mg administered once daily PO or as an IV infusion over 1 hour through 100 days post-transplant.
    If co-administered with cyclosporine, the dosage of should be decreased to 240 mg once daily. 480 mg administered once daily PO or as an IV infusion over 1 hour through 200 days post-transplant.
    Maximum Dose 480 mg (or 240 mg when co-administered with cyclosporine) per day 480 mg (or 240 mg when co-administered with cyclosporine) per day Page 4 of 8

    CLINICAL POLICY Letermovir Indication seropositive/Recipient CMV seronegative [D+/R-] Dosing Regimen If co-administered with cyclosporine, the dosage of should be decreased to 240 mg once daily. Maximum Dose VI. Product Availability
    • Tablets: 240 mg, 480 mg
    • Single-dose vials: 240 mg/12 mL, 480 mg/24 mL
    VII.