Enasidenib (Idhifa) Form

Enasidenib (Idhifa®) is an isocitrate dehydrogenase-2 (IDH2) inhibitor. FDA Approved Indication(s) Idhifa is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an IDH2 mutation as detected by an FDA-approved test. 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 Idhifa 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. Prescribed as single-agent therapy;
   5. Member meets one of the following (a or b): a. Disease is relapsed or refractory; b. Idhifa is prescribed in members age ≥ 60 years and one of the following (i or ii); i. Used for induction therapy when member is not a candidate for intensive induction therapy or declines intensive therapy;
      ii. Used for post-induction therapy with previous lower-intensity therapy (see Appendix B for examples);Prior authorization may be required.
2. Presence of an IDH2 mutation;
   
   7. For Idhifa requests, member must use generic enasidenib, 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 both of the following (i and ii): i. 100 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.
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   CLINICAL POLICY
   Enasidenib Approval duration:
   Medicaid/HIM – 6 months Commercial – 12 months or duration of request, whichever is less B. Other diagnoses/indications (must meet 1 or 2):

4. 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
5. 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. Acute Myeloid Leukemia (must meet all):
6. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Idhifa for AML and has received this medication for at least 30 days;
7. Member is responding positively to therapy;
   3. For Idhifa requests, member must use generic enasidenib, 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 both of the following (i and ii): i. 100 mg per day; ii. 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):

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): Page 2 of 6

   CLINICAL POLICY
   Enasidenib 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.
   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 AML: acute myeloid leukemia FDA: Food and Drug Administration IDH2: isocitrate dehydrogenase-2 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 cytarabine with idarubicin or daunorubicin cytarabine with idarubicin or daunorubicin or mitoxantrone 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 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 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. Page 3 of 6

   CLINICAL POLICY
   Enasidenib Appendix C: Contraindications/Boxed Warnings • Contraindication(s): none reported • Boxed warning(s): differentiation syndrome. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution. V. Dosage and Administration Indication AML Dosing Regimen 100 mg PO QD
   VI. Product Availability Tablets: 50 mg, 100 mg Maximum Dose 100 mg/day VII.