Antithymocyte Globulin (Atgam, Thymoglobulin) Form

Antithymocyte globulin (Thymoglobulin®, Atgam®) is an immunoglobulin G. FDA Approved Indication(s) Atgam is indicated for: • The management of allograft rejection in renal transplant patients; when administered with conventional therapy at the time of rejection, Atgam increases the frequency of resolution of the acute rejection episode • The treatment of moderate-to-severe aplastic anemia in patients unsuitable for bone marrow transplantation. Limitation(s) of use: The usefulness of Atgam has not been demonstrated in patients with aplastic anemia who are suitable candidates for bone marrow transplantation or in patients with aplastic anemia secondary to neoplastic disease, storage disease, myelofibrosis, Fanconi’s syndrome, or in patients known to have been exposed to myelotoxic agents or radiation.
Thymoglobulin is indicated for the prophylaxis and treatment of acute rejection in patients receiving a kidney transplant. Thymoglobulin is used in conjunction with concomitant immunosuppression. 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 Atgam and Thymoglobulin are medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Kidney Transplant Rejection (must meet all):

1. Member has received or is scheduled for a kidney transplant;
   2. If request is for prophylaxis of acute rejection, request is for Thymoglobulin;
   3. Prescribed by or in consultation with a nephrologist, transplant specialist, or hematologist/oncologist;

2. Age ≥ 18 years;

   5. Prescribed in combination with conventional therapy for transplant rejection (see Appendix D);
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   CLINICAL POLICY Antithymocyte Globulin

3. Dose does not exceed one of the following (a or b): a. For Atgam: 15 mg/kg per day; b. For Thymoglobulin: 1.5 mg/kg per day. Approval duration:
   7 days for Thymoglobulin for prophylaxis of acute rejection (7 doses) 14 days for Thymoglobulin for treatment of acute rejection (14 doses) Up to 42 days for Atgam (21 doses) B. Aplastic Anemia (must meet all):
4. Diagnosis of moderate to severe aplastic anemia;
   2. Request is for Atgam;
   3. Prescribed by or in consultation with a hematologist;
   4. Age ≥ 18 years;
   5. Prescribed in combination with cyclosporine;
   6. Dose does not exceed 20 mg/kg per day. Approval duration: Up to 42 days (21 doses) C. 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.
   II. Continued Therapy A. All Indications in Section I (must meet all):

7. Member meets one of the following (a, b, or c): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Documentation supports that member is currently receiving Atgam or Thymoglobulin for kidney transplant rejection and has received this medication for at least 30 days;
   c. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B); Page 2 of 7

   CLINICAL POLICY Antithymocyte Globulin

8. Member is responding positively to therapy;
   3. For Thymoglobulin for prophylaxis of acute rejection, member has not received more than both of the following (a and b):
      a. 7 days of total treatment duration;
      b. 7 doses of Thymoglobulin;
9. For Thymoglobulin for treatment of acute rejection, member has not received more than both of the following (a and b):
   a. 14 days of total treatment duration;
   b. 14 doses of Thymoglobulin;
10. For Atgam, member has not received more than both of the following (a and b):
    a. 42 days of total treatment duration;
    b. 21 doses of Atgam;
11. If request is for a dose increase, new dose does not exceed (a or b): a. For Atgam (i or ii): i. For treatment of acute rejection: 15 mg/kg per day; ii. For aplastic anemia: 20 mg/kg per day; b. For Thymoglobulin for treatment or prophylaxis of acute rejection: 1.5 mg/kg per day. Approval duration: Up to a total treatment duration of: 7 days for Thymoglobulin for prophylaxis of acute rejection (7 doses) 14 days for Thymoglobulin for treatment of acute rejection (14 doses) 42 days for Atgam (21 doses) B. Other diagnoses/indications (must meet 1 or 2):
12. 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

13. 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. Page 3 of 7

    CLINICAL POLICY Antithymocyte Globulin IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration 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.
    Dosing Regimen Drug Name Dose Limit/ Maximum Dose See dosing regimen cyclosporine Aplastic Anemia Adults: 12 mg/kg PO QD
    Children: 15 mg/kg 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. Appendix C: Contraindications/Boxed Warnings • Contraindication(s):
    o Atgam: anaphylactic reaction during prior administration of Atgam or any other equine gamma globulin preparation o Thymoglobulin:
     Patients with history of allergy or anaphylactic reaction to rabbit proteins or to any product excipients  Patients who have active acute or chronic infections that contraindicate any additional immunosuppression • Boxed warning(s):
    o Atgam: anaphylaxis o Thymoglobulin: immunosuppression Appendix D: General Information • The current standard first-line treatment for aplastic anemia is equine antithymocyte globulin (Atgam) combined with cyclosporine (off-label use). • Conventional therapy for transplant rejection include: calcineurin inhibitors (tacrolimus, cyclosporine), antimetabolite (mycophenolate, azathioprine), corticosteroid (prednisone) V. Dosage and Administration
    Drug Name Antithymocyte globulin
    (Atgam) Indication Aplastic anemia Treatment of acute renal transplant rejection Dosing Regimen 10 to 20 mg/kg IV QD for 8 to 14 days. Additional alternate-day therapy up to a total of 21 doses may be given. 10 to 15 mg/kg IV QD for 14 days. Additional alternate-day therapy up to Maximum Dose 20 mg/kg/dose 15 mg/kg/dose Page 4 of 7

    CLINICAL POLICY Antithymocyte Globulin Drug Name Indication Antithymocyte globulin (Thymogobulin) Prophylaxis of acute renal transplant rejection Treatment of acute renal transplant rejection Dosing Regimen a total of 21 doses may be given. 1.5 mg/kg IV QD for 4 to 7 days Maximum Dose 1.5 mg/kg/dose 1.5 mg/kg IV QD for 7 to 14 days 1.5 mg/kg/dose VI. Product Availability
    Drug Name Antithymocyte globulin (Thymoglobulin) Antithymocyte globulin (Atgam) Availability Vial, powder for solution: 25 mg Ampule: 250 mg/5 mL VII.