Pacritinib (Vonjo) Form

Pacritinib (Vonjo™) is a kinase inhibitor. FDA Approved Indication(s) Vonjo is indicated for the treatment of adults with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis (MF) with a platelet count below 50 × 109/L. This indication is approved under accelerated approval based on spleen volume reduction. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). 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 Vonjo is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Myelofibrosis (must meet all):

1. Diagnosis of primary or secondary (post-polycythemia vera or post-essential thrombocythemia) MF;

2. Member meets one of the following (a or b):
   a. Documentation of a recent (within the last 30 days) platelet count of < 50 × 109/L and one of the following (i, ii or ii):
   i. Disease is intermediate-risk; ii. Disease is high-risk; iii. Both of the following (a and b): a) Disease is lower-risk (see Appendix D); b) Failure of ruxolitinib, peginterferon alfa-2a, or hydroxyurea (see Appendix B), unless clinically significant adverse effects are experienced or all are contraindicated; *Prior authorization may be required for hydroxyurea, peginterferon alfa-2a, and ruxolitinib b. Documentation of recent (within the last 30 days) platelet count of ≥ 50 x 109/L and all of the following (i, ii, and iii): i. Disease is higher-risk;
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   CLINICAL POLICY Pacritinib ii. Member is not a candidate for allogenic hematopoietic stem cell transplantation;
   iii. Failure of ruxolitinib or fedratinib (see Appendix B), unless clinically significant adverse effects are experienced or both are contraindicated;

3. Prescribed by or in consultation with a hematologist or oncologist;
   4. Age ≥ 18 years;
   5. For Vonjo requests, member must use pacritinib, 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: 6 months B. Other diagnoses/indications (must meet 1 or 2):
5. 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
6. 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. Myelofibrosis (must meet all):
7. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Vonjo for a covered indication and has received this medication for at least 30 days;
8. Member is responding positively to therapy;
   3. For Vonjo requests, member must use pacritinib, if available, unless contraindicated or clinically significant adverse effects are experienced;

9. 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; Page 2 of 6

   CLINICAL POLICY Pacritinib 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: 12 months B. 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.
    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
    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 Jakafi® (ruxolitinib) Pegasys® (peginterferon alfa-2a)* hydroxyurea (Droxia®, Hydrea®) Varies Inrebic® (fedratinib) 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 Varies 180 mcg SC once weekly 400 mg PO daily Dose Limit/ Maximum Dose 20 mg twice daily 180 mcg/week Varies 400 mg/day Page 3 of 6

    CLINICAL POLICY Pacritinib *Off label
    Appendix C: Contraindications/Boxed Warnings • Contraindication(s): concomitant use of strong CYP3A4 inhibitors or inducers • Boxed warning(s): none Appendix D: General Information • The Dynamic International Prognostic Scoring System (DIPSS) was used in the pivotal trial for Vonjo (Persist-2) to determine disease risk. The scoring system and risk group stratification is provided below.
    Prognostic Variable Points 0 ≤ 65 ≤ 25 ≥ 10 < 1 No 2 < 10 1

    65 25 ≥ 1 Yes Age (years) White blood cell count (x109/L) Hemoglobin (g/dL) Precent peripheral blood blast Constitutional symptoms (Yes or No) Risk Group Low Intermediate-1 (INT-1) Intermediate-2 (INT-2) High Points 0 1 or 2 3 or 4 5 or 6 • The NCCN Myelofibrosis v3.2022 guideline stratifies risk for myelofibrosis into two categories, lower- and higher-risk. The categories include the following grading scales: mutation-enhanced IPSS for age ≤ 70 (MIPSS-70), mutation and karyotype-enhanced IPSS (MIPSS-70+ version 2.0) DIPSS, DIPSS-Plus and Myelofibrosis secondary to PV and ET-prognostic model (MYSEC-PM). The risk group with corresponding points scale is provided below. Please refer to the guidelines for additional details on the prognostic variables for each grading scale.
    Risk Group Lower-risk Higher-risk Points MIPSS-70 ≤ 3 MIPSS-70+ version 2.0: ≤ 3 DIPSS-Plus: ≤ 1 DIPSS: ≤ 2 MYSEC-PM: < 14 MIPSS-70 ≥ 4 MIPSS-70+ version 2.0: ≥ 4 DIPSS-Plus: > 1 DIPSS: > 2 MYSEC-PM: ≥ 14 Page 4 of 6

    CLINICAL POLICY Pacritinib V. Dosage and Administration
    Indication MF Dosing Regimen 200 mg PO BID Maximum Dose 400 mg/day VI. Product Availability
    Capsule: 100 mg VII.