NPLATE, Romiplostim Form

Romiplostim (Nplate®) is a thrombopoietin receptor agonist. FDA Approved Indication(s) Nplate is indicated for the treatment of thrombocytopenia in: • Adult patients with immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. • Pediatric patients 1 year of age and older with ITP for at least 6 months who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. Nplate is indicated to increase survival in adults and in pediatric patients (including term neonates) acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome [HS-ARS]). Limitation(s) of use: • Nplate is not indicated for the treatment of thrombocytopenia due to myelodysplastic syndrome or any cause of thrombocytopenia other than ITP. • Nplate should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increases the risk for bleeding.
• Nplate should not be used in an attempt to normalize platelet counts.
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 Nplate is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Hematopoietic Syndrome of Acute Radiation Syndrome (must meet all):

1. Diagnosis of HS-ARS;
   2. Prescriber attestation that there has been suspected or confirmed exposure to radiation levels greater than 2 gray (Gy);

2. Prescribed by or in consultation with a hematologist;

   4. Dose does not exceed 10 mcg/kg. Approval duration: 4 weeks (1 dose only) Page 1 of 9

   CLINICAL POLICY Romiplostim B. Immune Thrombocytopenia (must meet all):

3. Diagnosis of ITP;
   2. Prescribed by or in consultation with a hematologist;
   3. Age ≥ 1 year;
   4. One of the following (a or b): a. Current (within the last 30 days) platelet count is < 30,000/µL; b. Member has an active bleed;
4. 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
5. Nplate is not prescribed concurrently with rituximab or another thrombopoietin receptor agonist (e.g., Promacta®, Doptelet®, Mulpleta®) or spleen tyrosine kinase inhibitor (e.g., Tavalisse™);
6. Dose does not exceed 10 mcg/kg per week. Approval duration: 6 months C. Recommended NCCN uses (off-label) (must meet all):
7. Diagnosis of one of the following (a or b): a. Myelodysplastic syndromes (MDS); b. Chemotherapy-induced thrombocytopenia (CIT);
8. Prescribed by or in consultation with an oncologist or hematologist;
   3. For MDS, member has both of the following (a and b): a. Lower-risk MDS (i.e., IPSS-R [Very Low, Low, Intermediate]); b. Severe or refractory thrombocytopenia following disease progression or no response to hypomethylating agents (e.g., azacitadine, decitabine), immunosuppressive therapy (e.g., Atgam®, cyclosporine), or clinical trial;
9. For CIT, both of the following (a and b): a. Age ≥ 18 years;
   b. Member has platelets < 100,000/µL for ≥ 3 weeks following the last chemotherapy administration and/or following delays in chemotherapy initiation related to thrombocytopenia;
10. Nplate is not prescribed concurrently with rituximab or another thrombopoietin receptor agonist (e.g., Promacta®, Doptelet®, Mulpleta®);
11. Request meets one of the following (a or b): a. Dose does not exceed 10 mcg/kg per week; b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN
    Approval duration: 6 months D. 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): Page 2 of 9

    CLINICAL POLICY Romiplostim 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.
    II. Continued Therapy A. Hematopoietic Syndrome of Acute Radiation Syndrome
14. Re-authorization is not permitted. Members must meet the initial approval criteria. Approval duration: Not applicable B. Immune Thrombocytopenia (must meet all):
    
    1. 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);
15. Member is responding positively to therapy (e.g., increase in platelet count from baseline, reduction in bleeding events);
16. Current (within the last 90 days) platelet count is < 400,000/µL;
    4. Nplate is not prescribed concurrently with rituximab or another thrombopoietin receptor agonist (e.g., Promacta, Doptelet, Mulpleta) or spleen tyrosine kinase inhibitor (e.g., Tavalisse™);
17. If request is for a dose increase, new dose does not exceed 10 mcg/kg per week. Approval duration: 12 months C. Recommended NCCN uses (off-label) (must meet all):
18. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Nplate for MDS or CIT and has received this medication for at least 30 days;
19. Member is responding positively to therapy;
    
    3. Nplate is not prescribed concurrently with rituximab or another thrombopoietin receptor agonist (e.g., Promacta®, Doptelet®, Mulpleta®);

20. If request is for a dose increase, request meets one of the following (a or b):* a. New dose does not exceed 10 mcg/kg per week; b. New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Page 3 of 9

    CLINICAL POLICY Romiplostim *Prescribed regimen must be FDA-approved or recommended by NCCN
    Approval duration: 12 months D. Other diagnoses/indications (must meet 1 or 2):

21. 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

22. 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 CIT: chemotherapy-induced thrombocytopenia FDA: Food and Drug Administration
    Gy: gray HS-ARS: hematopoietic syndrome of acute radiation syndrome IPSS-R: Revised International Prognostic Scoring System
    ITP: chronic immune thrombocytopenia MDS: myelodysplastic syndromes 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 Corticosteroids* dexamethasone
    ITP Oral dosage:
    Dosage must be individualized and is Page 4 of 9

    CLINICAL POLICY Romiplostim Drug Name Dosing Regimen Adults: Initially, 0.75 to 9 mg/day PO, given in 2 to 4 divided doses. Adjust according to patient response.
    Children and adolescents: 0.02 to 0.3 mg/kg/day PO or 0.6 to 9 mg/m2/day PO, given in 3 to 4 divided doses Intramuscular or intravenous dosage: Adults: Initially, 0.5 to 9 mg/day IV or IM, given in 2 to 4 divided doses. Adjust according to patient response. Children: 0.02 to 0.3 mg/kg/day or 0.6 to 9 mg/m2/day IV or IM given in 3-4 divided doses. Adjust according to patient response. methylprednisolone ITP Oral dosage:
    Adults: 4 to 48 mg/day PO in 4 divided doses. Adjust according to patient response. Children: 0.5 to 1.7 mg/kg/day PO in divided doses every 6 to 12 hours Intravenous dosage: Adults: 10 to 40 mg IV every 4 to 6 hours for up to 72 hours Children: 0.11 to 1.6 mg/kg/day IV in 3 or 4 divided doses. ITP Adults: Initially, 1 mg/kg PO once daily; however, lower doses of 5 mg/day to 10 mg/day PO are preferable for long-term treatment. Dose Limit/ Maximum Dose highly variable depending on the nature and severity of the disease, route of treatment, and on patient response. Dosage must be individualized and is highly variable depending on the nature and severity of the disease, route of treatment, and on patient response. Dosage must be individualized and is highly variable depending on the nature and severity of the disease, route of treatment, and on patient response. prednisone Immune globulins immune globulins (Carimune® NF, Flebogamma® DIF 10%, Gammagard® S/D, GammakedTM, Gamunex®-C, ITP Refer to prescribing information Refer to prescribing information Page 5 of 9

    CLINICAL POLICY Romiplostim Drug Name Dosing Regimen Dose Limit/ Maximum Dose Gammaplex®, Octagam® 10%, Privigen®) 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
    • MDS prognostic scoring system online calculator for IPSS-R: https://qxmd.com/calculate/calculator_109/mds-revised-international-prognostic-scoring- system-ipss-r
    V. Dosage and Administration
    Indication Dosing Regimen ITP The initial dose is 1 mcg/kg SC once weekly based on actual body weight. Adjust weekly dose by increments of 1 mcg/kg to achieve and maintain a platelet count ≥ 50,000/µL as necessary to reduce the risk for bleeding. Do not dose if platelet count is > 400,000/µL.
    10 mcg/kg administered once as a SC injection. Administer the dose as soon as possible after suspected or confirmed exposure to radiation levels greater than 2 gray (Gy).
    HS-ARS Maximum Dose 10 mcg/kg/week 10 mcg/kg
    VI. Product Availability
    Lyophilized powder in single-dose vials for injection: 125 mcg, 250 mcg, 500 mcg
    VII.