Selumetinib (Koselugo) Form

Selumetinib (Koselugo®) is a mitogen-activated protein kinase enzyme 1/2 inhibitor.
FDA Approved Indication(s)
Koselugo is indicated for the treatment of pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN). 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 Koselugo is medically necessary when the following criteria are met:
I. Initial Approval Criteria A. Neurofibromatosis Type 1 (must meet all):

1. Diagnosis of NF1;
   2. Prescribed by or in consultation with an oncologist or neurologist;
   3. Age between 2 and 18 years at start of therapy (see Appendix F);
   4. For Koselugo requests, member must use selumetinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
2. Member has body surface area ≥ 0.55 m2;
   
   6. Member has at least one inoperable and measurable PN, defined as a lesion ≥ 3 cm measured in one dimension;
3. Member meets one of the following (a or b):
   a. Positive genetic testing for NF1; b. Member has at least one other diagnostic criterion for NF1 (see Appendix D);
   8. Complete resection of PN is not considered to be feasible without substantial risk or morbidity (e.g., due to encasement of, or close proximity to, vital structures, invasiveness, or high vascularity of the PN);

4. Dose does not exceed both of the following (a and b):
   a. 100 mg per day;
   b. 4 capsules per day.
   Approval duration: 6 months
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   CLINICAL POLICY Selumetinib B. Off-Label NCCN Compendium Recommended Indications (must meet all):

5. Diagnosis of one of the following (a or b):
   a. Circumscribed glioma;
   b. Langerhans cell histiocytosis;
6. Prescribed by or in consultation with one of the following (a or b):
   a. For circumscribed glioma: an oncologist;
   b. For Langerhans cell histiocytosis: a hematologist or oncologist;
7. For circumscribed glioma, disease is recurrent or progressive;
   
   4. For Langerhans cell histiocytosis, failure of one of the following, unless clinically significant adverse effects are experienced or all are contraindicated (a or b): a. Cotellic® (cobimetinib); b. Mekinist® (trametinib);
      *Prior authorization may be required for Mekinist and Cotellic
8. Disease is positive BRAF fusion or BRAF V600E activating mutation;
   6. For Koselugo requests, member must use selumetinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
9. 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. 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
   C. 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.
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    CLINICAL POLICY Selumetinib II. Continued Therapy A. Neurofibromatosis Type 1 (must meet all):

12. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Koselugo for a covered indication and has received this medication for at least 30 days;
13. Member is responding positively to therapy as evidenced by decreased or maintained volume of PN(s) from baseline;
14. For Koselugo requests, member must use selumetinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
15. If request is for a dose increase, new dose does not exceed both of the following (a and b):
    a. 100 mg per day;
    b. 4 capsules per day.
    Approval duration: 12 months B. Off-Label NCCN Compendium Recommended Indications (must meet all):
16. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Koselugo for a covered indication and has received this medication for at least 30 days;
17. Member is responding positively to therapy;
    3. For Koselugo requests, member must use selumetinib, if available, unless contraindicated or clinically significant adverse effects are experienced;
18. 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. 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: 12 months C. Other diagnoses/indications (must meet 1 or 2):
19. 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

20. 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 Page 3 of 8

    CLINICAL POLICY Selumetinib 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 NF1: neurofibromatosis type 1
    PN: plexiform neurofibroma WHO: World Health Organization 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 Langerhans cell histiocytosis Cotellic® (cobimetinib) Mekinist® (trametinib) 60 mg (three tablets) PO QD for 21 days, then off for 7 days (28-day cycle) Various 60 mg/day Varies Appendix C: Contraindications/Boxed Warnings
    None reported Appendix D: Neurofibromatosis 1 Diagnostic Criterion
    • A: The diagnostic criteria for NF1 are met in an individual who does not have a parent diagnosed with NF1 if two or more of the following are present:
    o Six or more café-au-lait macules over 5 mm in greatest diameter in prepubertal individuals and over 15 mm in greatest diameter in postpubertal individuals o Freckling in axilla or inguinal region o Two or more neurofibromas of any type or one plexiform neurofibroma o Optic glioma o Two or more Lisch nodules
    o A distinctive bony lesion (sphenoid dysplasia, anterolateral bowing of the tibia, or pseudarthrosis of a long bone) o A heterozygous pathogenic NF1 variant with a variant allele fraction of 50% in apparently normal tissue such as white blood cells • B: A child of a parent who meets the diagnostic criteria specified in A merits a diagnosis of NF1 if one or more of the criteria in A are present Page 4 of 8

    CLINICAL POLICY Selumetinib Appendix E: Recommended Dosage Based on Body Surface Area Body Surface Area 0.55 – 0.69 m2
    0.70 – 0.89 m2
    0.90 – 1.09 m2
    1.10 – 1.29 m2
    1.30 – 1.49 m2
    1.50 – 1.69 m2
    1.70 – 1.89 m2
    ≥ 1.90 m2
    Recommended Dosage
    20 mg in the morning and 10 mg in the evening 20 mg twice daily 25 mg twice daily 30 mg twice daily 35 mg twice daily 40 mg twice daily 45 mg twice daily 50 mg twice daily Appendix F: General information
    • FDA approval was based on SPRINT II (NCT01362803): Phase II Stratum 1 clinical trial. Eligible patients were 2-18 years of age with NF1 who had inoperable PN. Study consisted of 50 children ages 2-18, median age 10.2 (3.5-17.4). V. Dosage and Administration
    Indication NF1 Dosing Regimen 25 mg/m2 PO BID
    Maximum Dose 100 mg/day VI. Product Availability
    Capsules: 10 mg, 25 mg VII.