TIBSOVO, Ivosidenib Form

Ivosidenib (Tibsovo®) is an isocitrate dehydrogenase-1 (IDH1) inhibitor. FDA Approved Indication(s) Tibsovo is indicated for the treatment of adult patients with a susceptible IDH1 mutation as detected by an FDA-approved test with: • Newly-diagnosed acute myeloid leukemia (AML), in combination with azacitidine or as monotherapy, in adults 75 years or old or who have comorbidities that preclude use of intensive induction chemotherapy • Relapsed or refractory AML
• Relapsed or refractory myelodysplastic syndromes (MDS) • Locally advanced or metastatic cholangiocarcinoma who have been previously treated 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 Tibsovo is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Acute Myeloid Leukemia (must meet all):

1. Diagnosis of AML;

   2. Prescribed by or in consultation with an oncologist or hematologist;
   3. Age ≥ 18 years;
   4. Member meets one of the following (a, b, or c): a. Disease is newly diagnosed, prescribed in combination with azacitidine or as monotherapy, and one of the following (i or ii): i. Age ≥ 75 years; ii. Medical justification supports inability to use intensive induction chemotherapy (see Appendices B and D for examples);
      b. Disease is relapsed or refractory; c. Age ≥ 60 years and one of the following (i or ii): i. Member is not a candidate for intensive induction therapy;
      ii. Used for post-induction therapy with previous lower-intensity therapy (see Appendix B for examples); *Prior authorization may be required. Page 1 of 9

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2. Presence of an IDH1 mutation;
   
   6. For Tibsovo requests, member must use generic ivosidenib, if available, unless contraindicated or clinically significant adverse effects are experienced;
3. Request meets one of the following (a or b): a. Dose does not exceed 500 mg (2 tablets) 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. Cholangiocarcinoma (must meet all):
4. Diagnosis of locally advanced or metastatic cholangiocarcinoma;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Disease is positive for an IDH1 mutation;
   5. Prescribed as a single agent for disease progression on or after systemic treatment;
   6. For Tibsovo requests, member must use generic ivosidenib, if available, unless contraindicated or clinically significant adverse effects are experienced;
5. Request meets one of the following (a or b): a. Dose does not exceed 500 mg (2 tablets) 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. Myelodysplastic Syndromes (must meet all):
6. Diagnosis of MDS;
   2. Prescribed by or in consultation with an oncologist or hematologist;
   3. Age ≥ 18 years;
   4. Member meets one of the following (a or b): a. Disease is relapsed or refractory; b. Disease progression, no response, or intolerance to prior systemic treatment;
7. Presence of an IDH1 mutation;
   
   6. For Tibsovo requests, member must use generic ivosidenib, if available, unless contraindicated or clinically significant adverse effects are experienced;

8. Request meets one of the following (a or b):
   a. Dose does not exceed 500 mg (2 tablets) 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 Page 2 of 9

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   D. Chondrosarcoma (off-label) (must meet all):

9. Diagnosis of conventional (grade 1-3) or dedifferentiated chondrosarcoma;
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Disease is positive for an IDH1 mutation;
   5. For Tibsovo requests, member must use generic ivosidenib, if available, unless contraindicated or clinically significant adverse effects are experienced;
10. Request meets one of the following (a or b): a. Dose does not exceed 500 mg (2 tablets) 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 E. Oligodendroglioma (off-label) (must meet all):
11. Diagnosis of recurrent or progressive oligodendroglioma;
    2. Prescribed by or in consultation with an oncologist;
    3. Age ≥ 18 years;
    4. Disease is positive for an IDH1 mutation;
    5. Prescribed as a single agent;
    6. For Tibsovo requests, member must use generic ivosidenib, if available, unless contraindicated or clinically significant adverse effects are experienced;
12. Request meets one of the following (a or b): a. Dose does not exceed 500 mg (2 tablets) 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 F. Other diagnoses/indications (must meet 1 or 2):

13. 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 Page 3 of 9

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14. 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):
15. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Tibsovo for a covered indication and has received this medication for at least 30 days;
16. Member is responding positively to therapy;
    3. For Tibsovo requests, member must use generic ivosidenib, 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 500 mg (2 tablets) 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):
17. 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

18. 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.
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    IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key AML: acute myeloid leukemia FDA: Food and Drug Administration IDH1: isocitrate dehydrogenase-1 MDS: myelodysplastic syndromes NCCN: National Comprehensive Cancer Network 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 Varies Varies Varies Varies cytarabine with idarubicin or daunorubicin cytarabine with idarubicin or daunorubicin or mitoxantrone gemcitabine+cisplatin,
    5-fluorouracil+ oxaliplatin, capecitabine+cisplatin, 5-fluoruracil, capecitabine, gemcitabine, FOLFOX (leucovorin, fluorouracil, oxaliplatin), FOLFIRI (leucovorin, fluorouracil, irinotecan), Stivarga® azacitidine, decitabine ± cedazuridine, lenalidomide, antithymocyte globulin ± cyclosporine ± eltrombopag, high- intensity chemotherapy regimens (e.g., idarubicin-, cytarabine-, fludarabine-, AML Age < 60 years: example of intensive induction therapy: cytarabine 100 – 200 mg/m2 continuous IV infusion x 7 days with idarubicin 12 mg/m2 IV or daunorubicin 60- 90 mg/m2 IV x 3 days AML Age ≥ 60 years: example of intensive induction therapy: cytarabine 100 – 200 mg/m2 continuous IV infusion x 7 days with idarubicin 12 mg/m2 IV or daunorubicin 60- 90 mg/m2 IV x 3 days or mitoxantrone 12 mg/m2 x 3 days Cholangiocarcinoma Varies MDS Varies Page 5 of 9

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    Drug Name Dosing Regimen Dose Limit/ Maximum Dose and topotecan-based regimens) 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): none reported • Boxed warning(s): differentiation syndrome in AML and MDS Appendix D: General Information Patient or disease state characteristics that may preclude use of intensive induction therapy include but are not limited to the following examples:
    • Limited functional status as indicated by an Eastern Cooperative Oncology Group (ECOG) performance status of ≥ 2 • Significant comorbidity (e.g., severe cardiac, hepatic, pulmonary or renal disease) • Adverse features (e.g. AML without favorable cytogenetics or molecular markers, therapy-related AML, antecedent hematologic disorder) V. Dosage and Administration
    Indication AML, cholangiocarcinoma, MDS Dosing Regimen 500 mg PO QD until disease progression or unacceptable toxicity Maximum Dose 500 mg/day For patients with AML or MDS without disease progression or unacceptable toxicity, continue Tibsovo for a minimum of 6 months to allow time for clinical response VI. Product Availability
    Tablet: 250 mg VII.