INREBIC, Fedratinib HCl Form

Fedratinib (Inrebic®) is a kinase inhibitor.
FDA Approved Indication(s) Inrebic is indicated for the treatment of adult patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera (post-PV) or post-essential thrombocythemia (post-ET)) myelofibrosis (MF). Policy/Criteria Provider must submit documentation (including 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 Inrebic is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Myelofibrosis (must meet all):

1. Diagnosis of intermediate-2 or high-risk primary MF, post-PV MF, or post-ET MF;
   2. Prescribed by or in consultation with a hematologist or oncologist;
   3. Age ≥ 18 years;
   4. Documentation of a recent (within the last 30 days) thiamine level of ≥ 70 nmol/L (3 mcg/dL);
2. Documentation of a recent (within the last 30 days) platelet count of ≥ 50,000/mcL;
   6. Failure of Jakafi®, unless contraindicated or clinically significant adverse effects are experienced; *Prior authorization may be required for Jakafi
3. For brand Inrebic requests, member must use generic fedratinib, if available, unless contraindicated or clinically significant adverse effects are experienced;

4. Request meets one of the following (a or b): a. Dose does not exceed both of the following (i and ii): i. 400 mg per day; ii. 4 capsules 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 1 of 7

   CLINICAL POLICY Fedratinib B. Myeloid/Lymphoid Neoplasms with Eosinophilia and Janus Kinase 2 arrangement (off-label) (must meet all):

   1. Diagnosis of myeloid or lymphoid neoplasm with eosinophilia and Janus kinase 2 arrangement;
5. Documentation that disease is in the chronic or blast phase;
   3. Prescribed by or in consultation with a hematologist or oncologist;
   4. Age ≥ 18 years;
   5. Documentation of a recent (within the last 30 days) thiamine level of ≥ 70 nmol/L (3 mcg/dL);
6. Documentation of a recent (within the last 30 days) platelet count of ≥ 50,000/mcL;
   7. Failure of Jakafi, unless contraindicated or clinically significant adverse effects are experienced; *Prior authorization may be required for Jakafi
7. For brand Inrebic requests, member must use generic fedratinib, 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 both of the following (i and ii): i. 400 mg per day; ii. 4 capsules 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. Other diagnoses/indications (must meet 1 or 2):
9. 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

10. 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): Page 2 of 7

    CLINICAL POLICY Fedratinib

11. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Inrebic for a covered indication and has received this medication for at least 30 days;
12. Member is responding positively to therapy;
    3. For brand Inrebic requests, member must use generic fedratinib, 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. 400 mg per day; ii. 4 capsules 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):
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

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.
    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 FDA: Food and Drug Administration MF: myelofibrosis NCCN: National Comprehensive Cancer Network Post-ET: post-essential thrombocythemia Page 3 of 7

    CLINICAL POLICY Fedratinib Post-PV: post-polycythemia vera Appendix B: Therapeutic Alternatives Drug Name Dosing Regimen Dose Limit/ Maximum Dose 50 mg/day Jakafi (ruxolitinib) 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. MF: 5 mg to 25 mg PO BID Appendix C: Contraindications/Boxed Warnings • Contraindication(s): none reported
    • Boxed warning(s): serious and fatal encephalopathy, including Wernicke’s Appendix D: General Information • NCCN recommendations for the initial treatment of intermediate-2 or high-risk MF include the use of Jakafi® and Inrebic as a category 1 recommendation after clinical trial therapies and allogeneic hematopoietic cell transplantation.
    • The Inrebic Prescribing Information and NCCN guidelines for myeloproliferative neoplasms recommend a baseline platelet count of ≥ 50,000/mcL before initiation of Inrebic. The Jakafi Prescribing Information also recommends the same baseline platelet count for Jakafi, but NCCN guidelines include support for use of Jakafi for low- or intermediate-1 risk MF without regard to baseline platelet counts.
    • Examples of positive response to therapy for myelofibrosis include: reduction in spleen • size or improvement in symptoms such as pruritus, fatigue, night sweats, bone pain since initiation of therapy. Intermediate-2 or high-risk disease is defined as having two or more of the following risk factors:
    o Age > 65 o Constitutional symptoms (weight loss greater than 10 percent from baseline and/or unexplained fever, or excessive sweats persisting for more than 1 month) o Hemoglobin less < 10 g/dL o White blood cell count ≥ 25 x109/L o Peripheral blood blasts ≥ 1 % o Platelets < 100 x 109/L o Red Cell Transfusion o Unfavorable karyotype (i.e., complex karyotype or sole or two abnormalities that include trisomy 8, -7/7q-, i(17q),-5/5q-, 12p-, inv(3), or 11q23 rearrangement) V. Dosage and Administration
    Indication MF Dosing Regimen 400 mg PO QD VI. Product Availability
    Capsule: 100 mg Maximum Dose 400 mg/day Page 4 of 7

    CLINICAL POLICY Fedratinib VII.