TURALIO, Pexidartinib HCl Form

Pexidartinib (Turalio®) is a tyrosine kinase inhibitor with strong selective activity against colony stimulating factor 1 receptor (CSF1R). FDA Approved Indication(s) Turalio is indicated for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery. 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 Turalio is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Tenosynovial Giant Cell Tumor (must meet all):

1. Diagnosis of TGCT (also known as giant cell tumor of the tendon sheath [GCT-TS] or pigmented villonodular synovitis [PVNS]);
   2. Prescribed by or in consultation with an oncologist;
   3. Age ≥ 18 years;
   4. Disease is associated with severe morbidity or functional limitations and is not amenable to improvement with surgery;
2. For brand Turalio requests, member must use generic pexidartinib, 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. 500 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 6

   CLINICAL POLICY Pexidartinib B. Histiocytic Neoplasms (off-label) (must meet all):

4. Diagnosis of histiocytic neoplasms (Erdheim-Chester disease, Rosai-Dorfman disease, Langerhans cell histiocytosis);
5. Prescribed by or in consultation with an oncologist or hematologist;
   
   3. Age ≥ 18 years;
   4. Disease is CSF1R mutation positive;
   5. For brand Turalio requests, member must use generic pexidartinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
6. 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 C. Other diagnoses/indications (must meet 1 or 2):
7. 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
8. 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):
9. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Turalio for a covered indication and has received this medication for at least 30 days;

10. Member is responding positively to therapy;

    3. For brand Turalio requests, member must use generic pexidartinib, 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. 500 mg per day; ii. 4 capsules per day;
       Page 2 of 6

    CLINICAL POLICY Pexidartinib 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):

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.
    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 CSF1R: colony stimulating factor 1 receptor FDA: Food and Drug Administration Appendix B: Therapeutic Alternatives
    Not applicable GCT-TS: giant cell tumor of the tendon sheath
    PVNS: pigmented villonodular synovitis
    TGCT: tenosynovial giant cell tumor Appendix C: Contraindications/Boxed Warnings • Contraindication(s): none reported • Boxed warning(s): hepatotoxicity o Turalio is available only through a restricted program called the Turalio Risk Evaluation and Mitigation Strategy (REMS) Program (additional information available at: www.turalioREMS.com). Page 3 of 6

    CLINICAL POLICY Pexidartinib V. Dosage and Administration
    Indication Dosing Regimen TGCT 250 mg PO BID with a low-fat meal (approximately 11 to 14 grams of total fat) until disease progression or unacceptable toxicity Maximum Dose 500 mg/day Reduce the dose of Turalio if used concomitantly with moderate/strong CYP3A inhibitors or UGT inhibitors VI. Product Availability
    Capsule: 125 mg VII.