Avapritinib (Ayvakit) Form

Avapritinib (Ayvakit®) is a tyrosine kinase inhibitor. FDA Approved Indication(s) Ayvakit is indicated for the treatment of adults with: • Unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations • Advanced systemic mastocytosis (AdvSM), including aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL) Indolent Systemic Mastocytosis (ISM) • Limitation(s) of use: Ayvakit is not recommended for the treatment of patients with platelet counts of less than 50 X 109/L with AdvSM or ISM.
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 Ayvakit is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Gastrointestinal Stromal Tumor (must meet all):

1. Diagnosis of unresectable, recurrent, progressive, or metastatic GIST;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. For brand Ayvakit requests, member must use generic avapritinib, if available, unless contraindicated or clinically significant adverse effects are experienced;

2. One of the following (a or b): a. Documentation of a PDGFRA exon 18 D842V mutation; b. Member meets both of the following (i and ii): i. Documentation of a PDGFRA exon 18 mutation other than D842V; ii. Failure of imatinib, unless contraindicated or clinically significant adverse effects are experienced; Prior authorization may be required for imatinib
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   CLINICAL POLICY Avapritinib

3. Prescribed as single-agent therapy;
   7. Request meets one of the following (a or b): a. Dose does not exceed both of the following (i and ii):
      i. 300 mg per day;
      ii. 1 tablet per day; 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:
      Medicaid/HIM – 6 months Commercial – 12 months or duration of request, whichever is less B. Advanced Systemic Mastocytosis (must meet all):
   8. Diagnosis of one of the following (a, b, or c): a. ASM; b. SM-AHN; c. MCL;
4. Prescribed by or in consultation with an oncologist, allergist, or immunologist;
   
   3. Age ≥ 18 years;
   4. Prescribed as single-agent therapy;
   5. For brand Ayvakit requests, member must use generic avapritinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
5. Documentation of platelet count ≥ 50 x 109/L ( ≥ 50,000/mcL);
   7. Request meets one of the following (a or b): a. Dose does not exceed both of the following (i and ii):
      i. 200 mg per day;
      ii. 1 tablet per day; 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:
      Medicaid/HIM – 6 months Commercial – 12 months or duration of request, whichever is less C. Indolent Systemic Mastocytosis (must meet all):
6. Diagnosis of ISM;
   2. Prescribed by or in consultation with an oncologist, allergist, or immunologist;
   3. Age ≥ 18 years;
   4. Prescribed as single-agent therapy;
   5. For brand Ayvakit requests, member must use generic avapritinib, if available, unless contraindicated or clinically significant adverse effects are experienced;

7. Documentation of platelet count ≥ 50 x 109/L ( ≥ 50,000/mcL);

   7. Request meets one of the following (a or b):* a. Dose does not exceed both of the following (i and ii):
      i. 25 mg per day;
      ii. 1 tablet per day; Page 2 of 8

   CLINICAL POLICY Avapritinib 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:
   Medicaid/HIM – 6 months Commercial – 12 months or duration of request, whichever is less D. Myeloid/Lymphoid Neoplasm with Eosinophilia and Tyrosine Kinase Fusion Gene (off-label) (must meet all):

   1. Diagnosis of myeloid/lymphoid neoplasm with eosinophilia (MLNE) and FIP1L1- PDGFRA rearrangement;
8. Prescribed by or in consultation with a hematologist or oncologist;
   3. Age ≥ 18 years;
   4. For brand Ayvakit requests, member must use generic avapritinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
9. Member meets both of the following (a and b): a. Documentation of a PDGFRA D842V mutation;
   b. Failure of imatinib, unless contraindicated or clinically significant adverse effects are experienced; Prior authorization may be required for imatinib
10. Dose is within FDA maximum limit for any FDA-approved indication or 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:
    Medicaid/HIM – 6 months Commercial – 12 months or duration of request, whichever is less E. Other diagnoses/indications (must meet 1 or 2):
11. 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

12. 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.
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    CLINICAL POLICY Avapritinib II. Continued Therapy A. All Indications in Section I (must meet all):

13. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Ayvakit for a covered indication and has received this medication for at least 30 days;
14. Member is responding positively to therapy;
    3. For brand Ayvakit requests, member must use generic avapritinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
    4. If request is for a dose increase, request meets one of the following (a or b): a. New dose does not exceed any of the following (i, ii, or iii): i. GIST: 300 mg (1 tablet) per day; ii. AdvSM: 200 mg (1 tablet) per day; iii. ISM: 25 mg (1 tablet) per day b. New 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:
       Medicaid/HIM – 12 months
       Commercial – 12 months or duration of request, whichever is less B. 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 AdvSM: advanced systemic mastocytosis ASM: aggressive systemic mastocytosis Page 4 of 8

    CLINICAL POLICY Avapritinib FDA: Food and Drug Administration GIST: gastrointestinal stromal tumor
    ISM: indolent systemic mastocytosis MCL: mast cell leukemia MLNE: myeloid/lymphoid neoplasm with eosinophilia
    NCCN: National Comprehensive Cancer Network PDGFR: platelet-derived growth factor receptor SM-AHN: systemic mastocytosis with an associated hematological neoplasm
    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 800 mg/day imatinib mesylate (Gleevec®) GIST 400 mg PO QD up to 400 mg BID [FDA label] MLNE 100-400 mg PO QD [NCCN] 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 None reported V. Dosage and Administration
    Indication GIST AdvSM, including ASM, MCL, SM-AHN ISM Dosing Regimen 300 mg PO QD
    200 mg PO QD Maximum Dose 300 mg/day 200 mg/day 25 mg PO QD 25 mg/day VI. Product Availability
    Tablets: 25 mg, 50 mg, 100 mg, 200 mg, 300 mg VII.