Ponatinib (Iclusig) Form

Ponatinib (Iclusig®) is a kinase inhibitor. FDA Approved Indication(s) Iclusig is indicated for the treatment of adult patients with: • Chronic phase chronic myeloid leukemia (CML) with resistance or intolerance to at least two prior kinase inhibitors.
• Accelerated phase, or blast phase chronic myeloid leukemia (CML) or Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) for whom no other tyrosine kinase inhibitor (TKI) therapy is indicated. • T315I-positive CML (chronic phase, accelerated phase, or blast phase) or T315I-positive Ph+ ALL. Limitation(s) of use: Iclusig is not indicated and is not recommended for the treatment of patients with newly diagnosed chronic phase CML. 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 Iclusig is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Chronic Myeloid Leukemia (must meet all):

1. Diagnosis of Ph+ (BCR-ABL1-positive) CML;
   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. Request is for chronic phase CML and member has experienced resistance, toxicity, or intolerance to prior therapy with two or more TKIs (e.g., imatinib, Bosulif®, Sprycel®, Tasigna®, Iclusig®); b. Request is for accelerated or blast phase CML for members whom no other TKI therapy is indicated; c. Member has BCR-ABL T315I mutation;

2. For brand Iclusig requests, member must use generic ponatinib, if available, unless contraindicated or clinically significant adverse effects are experienced; Page 1 of 8

   CLINICAL POLICY Ponatinib

3. Request meets one of the following (a or b): a. Dose does not exceed 45 mg 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. Acute Lymphoblastic Leukemia (must meet all):
   1. Diagnosis of Ph+ (BCR-ABL1-positive) ALL;
   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. Member has BCR-ABL T315I mutation; b. No other TKI therapy is indicated (e.g., imatinib, Bosulif®, Sprycel®, Tasigna®, Iclusig®);
4. For brand Iclusig requests, member must use generic ponatinib, 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 45 mg 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. Myeloid/Lymphoid Neoplasms (off-label) (must meet all):
6. Diagnosis of lymphoid, myeloid or mixed lineage neoplasms with eosinophilia and FGFR1 or ABL1 rearrangement in blast or chronic phase;
7. Prescribed by or in consultation with an oncologist or hematologist;
   3. Age ≥ 18 years;
   4. If disease is ABL1 rearrangement positive, one of the following (a or b): a. Member has contraindication, intolerance, or disease progression on imatinib; b. Request is for treatment associated with cancer for a State with regulations against step therapy in certain oncology settings (see Appendix D);
8. For brand Iclusig requests, member must use generic ponatinib, if available, unless contraindicated or clinically significant adverse effects are experienced;

9. 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 Page 2 of 8

   CLINICAL POLICY Ponatinib D. Other diagnoses/indications (must meet 1 or 2):

10. 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
11. 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):
12. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Iclusig for a covered indication and has received this medication for at least 30 days;
13. Member is responding positively to therapy;
    3. For brand Iclusig requests, member must use generic ponatinib, 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 45 mg 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):

14. 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: Page 3 of 8

    CLINICAL POLICY Ponatinib CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

15. 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 ALL: acute lymphoblastic leukemia
    CML: chronic myelogenous leukemia FDA: Food and Drug Administration TKI: tyrosine kinase inhibitor
    Ph+: Philadelphia chromosome-positive
    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 and may require prior authorization. Drug Name Dosing Regimen Dose Limit/ Maximum Dose 800 mg/day imatinib
    (Gleevec®)
    ALL: • Adult: 600 mg/day PO for relapsed / refractory Ph+ ALL • Pediatric: 340 mg/m2/day PO in combination with chemotherapy for newly diagnosed Ph+ ALL
    CML: • Adult: o 400-600 mg/day PO for chronic phase o 600-800 mg/day PO for accelerated phase or blast crisis (800 mg given as 400 BID) • Pediatric: 340 mg/m2/day PO for chronic phase
    Bosulif®
    (bosutinib) Sprycel®
    (dasatinib)
    MLNE: 100-400 mg PO QD [NCCN] 400 mg PO QD Adults: • Chronic phase: 100-140 mg/day PO • Accelerated, myeloid phase, or lymphoid blast phase: 140-180 mg/day PO
    Page 4 of 8 600 mg/day Adults: 180 mg/day

    Dose Limit/ Maximum Dose Adults: 600 mg/day CLINICAL POLICY Ponatinib Drug Name Dosing Regimen Adults: 300 mg PO BID Tasigna®
    (nilotinib)
    Iclusig®
    (ponatinib) Starting dose 45 mg PO QD 45 mg/day Appendix C: Contraindications/Boxed Warnings • Contraindication(s): none reported • Boxed warning(s): arterial occlusion, venous thromboembolism, heart failure, hepatotoxicity Appendix D: States with Regulations against Redirections in Certain Oncology Settings State Step Therapy Prohibited? Yes Yes FL GA IA LA NV OH PA TN TX Yes Yes Yes Yes Yes Yes Yes Notes For stage 4 metastatic cancer and associated conditions. For stage 4 metastatic cancer. Redirection does not refer to review of medical necessity or clinical appropriateness. For standard of care stage 4 cancer drug use, supported by peer- reviewed, evidence-based literature, and approved by FDA. For stage 4 advanced, metastatic cancer or associated conditions. Exception if “clinically equivalent therapy, contains identical active ingredient(s), and proven to have same efficacy. Stage 3 and stage 4 cancer patients for a prescription drug to treat
    the cancer or any symptom thereof of the covered person Applies to HIM requests only For stage 4 metastatic cancer and associated conditions For stage 4 advanced, metastatic cancer For advanced metastatic cancer and associated conditions For stage 4 advanced, metastatic cancer and associated conditions V. Dosage and Administration
    Indication Accelerated or blast phase CML and Ph+ ALL Chronic phase CML Dosing Regimen Starting dose 45 mg PO QD. Consider reducing the dose of Iclusig for patients with accelerated phase (AP) CML who have achieved a major cytogenetic response.
    Starting dosage is 45 mg PO QD with a reduction to 15 mg PO QD upon achievement of ≤1% BCR-ABL1. Patients with loss of response can re-escalate the dose of Iclusig to a previously tolerated dosage of 30 mg or 45 mg PO QD. Maximum Dose 45 mg/day
    45 mg/day
    Page 5 of 8

    CLINICAL POLICY Ponatinib VI. Product Availability
    Tablets: 10 mg, 15 mg, 30 mg, 45 mg VII.