DOPTELET, Avatrombopag Maleate Form

Avatrombopag (Doptelet®) is a thrombopoietin (TPO) receptor agonist. FDA Approved Indication(s) Doptelet is indicated for the treatment of: • Thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo a procedure. • Thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. 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 Doptelet is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Thrombocytopenia with Chronic Liver Disease (must meet all):

1. Diagnosis of chronic liver disease;
   2. Prescribed by or in consultation with a hematologist, hepatologist, or gastroenterologist;
2. Age ≥ 18 years;
   
   4. Recent (within the past 14 days) platelet count is < 50 x 109/L;
   5. Member is scheduled to undergo a medical or dental procedure within the next 30 days;
3. Dose does not exceed (a or b): a. For platelet count < 40 x 109/L, both of the following (i and ii):
   i. 60 mg per day for a total of 5 days; ii. 3 tablets per day for a total of 5 days; b. For platelet count of 40 to < 50 x 109/L, both of the following (i and ii):
   i. 40 mg per day for a total of 5 days; ii. 2 tablets per day for a total of 5 days. Approval duration: 14 days (no more than 5 total days of treatment) B. Chronic Immune Thrombocytopenia (must meet all):

4. Diagnosis of chronic ITP; Page 1 of 7

   CLINICAL POLICY Avatrombopag

5. Prescribed by or in consultation with a hematologist;
   3. Age ≥ 18 years;
   4. Current (within 30 days) platelet count < 30,000/µL or member has an active bleed;
   5. Member meets one of the following (a or b): a. Failure of a systemic corticosteroid;
      b. Member has intolerance or contraindication to systemic corticosteroids, and failure of an immune globulin, unless contraindicated or clinically significant adverse effects are experienced (see Appendix B); *Prior authorization may be required for immune globulins
6. Doptelet is not prescribed concurrently with rituximab or another TPO receptor agonist (e.g., Promacta®, Nplate®);
7. Dose does not exceed both of the following (a and b): a. 40 mg per day; b. 2 tablets per day. Approval duration: 6 months 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. Thrombocytopenia with Chronic Liver Disease
10. Re-authorization is not permitted. Members must meet the initial approval criteria. Approval duration: Not applicable B. Chronic Immune Thrombocytopenia (must meet all):

11. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. 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 Avatrombopag

12. Member is responding positively to therapy (e.g., increase in platelet count from baseline, reduction in bleeding events);
13. Doptelet is not prescribed concurrently with rituximab or another TPO receptor agonist (e.g., Promacta, Nplate);
14. If request is for a dose increase, new dose does not exceed both of the following (a and b): a. 40 mg per day; b. 2 tablets per day. Approval duration: 12 months C. Other diagnoses/indications (must meet 1 or 2):
15. 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

16. 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 ASH: American Society of Hematology FDA: Food and Drug Administration ITP: immune thrombocytopenia
    TPO: thrombopoietin 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.
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    CLINICAL POLICY Avatrombopag Dose Limit/ Maximum Dose Highly variable depending on the nature and severity of the disease, route of treatment, and on patient response Drug Name Dosing Regimen Chronic immune thrombocytopenia Corticosteroids dexamethasone Oral dosage: Initially, 0.75 to 9 mg/day PO in 2 to 4 divided doses. Adjust according to patient response methylprednisolone prednisone Intramuscular or intravenous dosage: Initially, 0.5 to 9 mg/day IV or IM in 2 to 4 divided doses. Adjust according to patient response Oral dosage: 4 to 48 mg/day PO, administered in 4 divided doses. Adjust according to patient response Intravenous:10-40 mg IV Initially, 1 mg/kg PO QD; however, lower doses of 5 mg/day to 10 mg/day PO are preferable for long-term treatment Refer to prescribing information Refer to prescribing information Immune globulins Immune globulins (e.g., Carimune® NF, Flebogamma® DIF 10%, Gammagard® S/D, Gammaked™, Gamunex®-C, Gammaplex®, Octagam® 10%, Privigen®, etc.) 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. Examples of corticosteroids/immunosuppressive agents provided are not all inclusive
    Appendix C: Contraindications/Boxed Warnings None reported Appendix D: General Information • Examples of chronic liver disease include: alcoholic liver disease, chronic viral hepatitis (e.g., hepatitis B and C), and nonalcoholic steatohepatitis. • Definitions of acute v. chronic ITP: o Per an International Working Group consensus panel of ITP experts, ITP is defined as newly diagnosed (diagnosis to 3 months), persistent (3 to 12 months from diagnosis), or chronic (lasting for more than 12 months). Although not formally validated, these definitions are supported and used by the American Society of Hematology (ASH). Page 4 of 7

    CLINICAL POLICY Avatrombopag • Per the 2019 ASH guidelines, response to treatment was defined by the following: o A response is defined as a platelet count ≥ 30,000/µL and a greater than 2-fold increase in platelet count from baseline measured on 2 occasions > 7 days apart and the absence of bleeding. o A failure is defined as a platelet count < 30,000/µL or a less than 2-fold increase in platelet count from baseline or the presence of bleeding. Platelet count must be measured on 2 occasions more than a day apart. V. Dosage and Administration
    Indication Thrombocytopenia with chronic liver disease Chronic ITP Dosing Regimen Platelet count < 40 x 109/L: 60 mg PO QD for a total of 5 days Maximum Dose See regimen Platelet count of 40 to < 50 x 109/L: 40 mg PO QD for a total of 5 days Initiate at 20 mg PO QD and titrate to maintain platelet count ≥ 50 x109/L 40 mg/day VI. Product Availability
    Tablet: 20 mg VII.