Centene Selumetinib (Koselugo) Coverage Update

Coverage Criteria for Selumetinib (Koselugo)

inv-01: Initial Approval — Neurofibromatosis Type 1

Covered when ALL of the following are met

NF1 initial: 1. Diagnosis of neurofibromatosis type 1 (NF1); 2. Prescribed by or in consultation with an oncologist or neurologist; 3. Age ≥ 1 year; 4. For Koselugo requests, member must use selumetinib, if available, unless contraindicated or clinically significant adverse effects are experienced; 5. Member's body surface area meets one of the following: a) request for capsules: ≥ 0.55 m2; b) request for oral granules: ≥ 0.4 m2; 6. Member has at least one inoperable and measurable plexiform neurofibroma (PN) defined as a lesion ≥ 3 cm in one dimension; 7. Member meets one of the following: a) positive genetic testing for NF1; b) at least one other diagnostic criterion for NF1 (see Appendix D); 8. Complete resection of PN is not considered feasible without substantial risk or morbidity; 9. If request is for oral granules, documentation supports that member has difficulty swallowing whole capsules; 10. Request does not exceed health plan‑approved quantity limit, if applicable; 11. Dose does not exceed both of the following: a) 50 mg/m2 (up to a maximum of 100 mg) per day; b) 4 capsules or 14 oral granules per day.

Approval duration: 12 months

inv-02: Initial Approval — Off-Label NCCN Compendium Recommended Indications

Covered when ALL of the following are met

Off-label initial: 1. Diagnosis of one of the following: a) Circumscribed glioma that is either i) positive for BRAF fusion or BRAF V600E activating mutation or ii) NF‑1 mutated; b) Pleomorphic xanthoastrocytoma (PXA); c) Langerhans cell histiocytosis (LCH) with one of: i) MAP kinase pathway mutation; ii) no detectable/actionable mutation; iii) provider attestation that testing is not available; iv) Koselugo prescribed for LCH‑associated abnormal CNS imaging/neurodegeneration (LACI/ND). 2. Prescribed by or in consultation with an appropriate specialist: oncologist for circumscribed glioma or PXA; hematologist or oncologist for LCH. 3. Prescribed as a single agent. 4. For circumscribed glioma or PXA, disease is recurrent or progressive. 5. For LCH in patients age ≥ 18 years, failure of cobimetinib (Cotellic) or trametinib (Mekinist) is required unless contraindicated or clinically significant adverse effects are experienced. 6. For Koselugo requests, member must use selumetinib, if available, unless contraindicated or clinically significant adverse effects are experienced. 7. If request is for oral granules, documentation supports difficulty swallowing whole capsules. 8. Request does not exceed health plan‑approved quantity limit, if applicable. 9. Request meets one of the following: a) Dose does not exceed both i) 50 mg/m2 (up to a maximum of 100 mg) per day and ii) 4 capsules or 14 oral granules per day; b) Dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use with prescriber‑provided supporting evidence. Prescribed regimen must be FDA‑approved or recommended by NCCN.

Approval duration: 12 months

inv-03: Continuation/renewal — Neurofibromatosis Type 1

Covered when ALL of the following are met

NF1 continuation: 1. 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; 2. Member is responding positively to therapy as evidenced by decreased or maintained volume of PN(s) from baseline; 3. For Koselugo requests, member must use selumetinib, if available, unless contraindicated or clinically significant adverse effects are experienced; 4. If request is for oral granules, documentation supports that member has difficulty swallowing whole capsules; 5. Request does not exceed health plan‑approved quantity limit, if applicable; 6. If request is for a dose increase, new dose does not exceed both: a) 50 mg/m2 (up to a maximum of 100 mg) per day; b) 4 capsules or 14 oral granules per day.

Approval duration: 12 months

inv-04: Continuation/renewal — Off-Label NCCN Indications

Covered when ALL of the following are met

Off-label continuation: 1. 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; 2. 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; 4. If request is for oral granules, documentation supports that member has difficulty swallowing whole capsules; 5. Request does not exceed health plan‑approved quantity limit, if applicable; 6. If request is for a dose increase, request meets one of the following: a) new dose does not exceed both i) 25 mg/m2 (up to a maximum of 100 mg) per day and ii) 4 capsules or 14 oral granules per day; b) new dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use with prescriber‑provided supporting evidence. Prescribed regimen must be FDA‑approved or recommended by NCCN.

Approval duration: 12 months

inv-05: Off‑label NCCN compendium recommended indications (selected extracts)

Policy updated to cover select NCCN off‑label indications with specified conditions

Langerhans cell histiocytosis (LCH): Covered when MAP kinase pathway positive or when no detectable/actionable mutation is present unless testing is unavailable; for adults, prior trial and failure of cobimetinib or trametinib is required for certain cases; selumetinib dosing must not exceed 50 mg/m2 per day based on BID dosing; request must not exceed health plan‑approved quantity limits; initial approval duration for LCH maintenance extended to 12 months; option added for use in LACI/ND.dose <= 50 mg/m2/day; initial approval 12 months

Circumscribed glioma: Pleomorphic xanthoastrocytoma (PXA) and NF‑1 mutated circumscribed glioma are coverable; BRAF fusion or BRAF V600E activating mutation applicability is specified for circumscribed glioma only.

Pediatric formulation: Oral granules available with pediatric extension to age ≥ 1 year and require body surface area ≥ 0.4 m2 per PI.BSA >= 0.4 m2

Requests for uses that are non‑FDA approved and are not specifically addressed in this policy are excluded from coverage unless the provider submits sufficient documentation of efficacy and safety in accordance with the plan’s off‑label use policies (see CP.CPA.09 for Commercial, HIM.PA.154 for Health Insurance Marketplace, and CP.PMN.53 for Medicaid) or the member’s evidence‑of‑coverage documents.

Koselugo (selumetinib) must be prescribed as a single agent. Combination therapy with other systemic anticancer agents is not authorized under this policy unless explicit coverage criteria are later added.

Uses that are not listed in this policy and for which the provider does not supply adequate supporting evidence per the plan’s off‑label use policies will be considered not authorized and are subject to denial.

Prior versions of this policy limited coverage for glioma to World Health Organization grade 1; that restriction has been removed. The current policy language was updated to add select circumscribed glioma diagnoses (including pleomorphic xanthoastrocytoma and NF‑1 mutated circumscribed glioma) as coverable indications per NCCN compendium recommendations.

Initial Therapy Requirements

inv-25: Initial therapy — Initial approval criteria for FDA and NCCN-based off-label uses are detailed and must be fully met.

Initial approval requirements for FDA and NCCN-based off-label uses — all elements below must be met

Initial therapy nodes: See specific initial approval criteria for NF1 and Off‑Label NCCN indications: required diagnosis confirmation, specialist prescribing/consultation, age/BSA minima, measurable/inoperable disease criteria for NF1, prior therapy failure requirements for adult LCH, single‑agent prescribing, requirement to use selumetinib when available, formulation‑specific swallowing documentation for oral granules, adherence to dose limits (50 mg/m2 up to 100 mg/day and/or 4 capsules or 14 oral granules per day) unless supported by guidelines/literature, and requests must not exceed health plan‑approved quantity limits.

Authorization limits: Approval duration for initial authorizations: 12 months; dose and quantity limits per product form apply; prescribed regimen must be FDA‑approved or NCCN‑recommended for off‑label uses.Approval duration: 12 months

inv-26: Initial therapy — Initial authorization requirements and limits updated

Continuation and Renewal Requirements

inv-27: Continuation therapy — Continuation criteria require documented prior use and clinical benefit.

Continuation criteria require documented prior use and clinical benefit

Continuation nodes: Continuation requests must document current therapy via Centene benefit or at least 30 days of prior selumetinib use, evidence of clinical benefit (for NF1: decreased or maintained PN volume; for off‑label: responding positively to therapy), use of selumetinib if available, formulation‑specific swallowing documentation for oral granules when applicable, and that request does not exceed health plan‑approved quantity limits. Any dose increase must meet the policy dose limits or be supported by practice guidelines/peer‑reviewed literature with prescriber evidence.

inv-28: Continuation therapy for LCH — Continuation approvals and durations updated for maintenance use

Continuation approvals and durations updated for maintenance use

Continuation for LCH maintenance: Continuation approval aligns with initial approval updates for LCH: requests must remain within plan‑approved quantity limits and dosing limits (≤ 50 mg/m2/day based on BID dosing). Initial and continuation approval durations for maintenance LCH are 12 months.

Step Therapy / Prior Treatment Requirements

Step	Requirement	Notes
1	Trial and documented failure of cobimetinib (Cotellic) or trametinib (Mekinist)	Applies to adults with Langerhans cell histiocytosis (LCH); required unless both agents are contraindicated or clinically significant adverse effects are experienced

Prior agent	Required for	Supporting detail / exceptions
Cobimetinib (Cotellic)	Adult LCH prior to selumetinib	Failure of cobimetinib required unless clinically significant adverse effects or contraindication; prior authorization for cobimetinib may be required
Trametinib (Mekinist)	Adult LCH prior to selumetinib	Failure of trametinib required unless clinically significant adverse effects or contraindication; applies only to adults per policy update

Dosing, Formulation & Coding Minimums

Body Surface Area minimums

Capsules (minimum BSA)≥ 0.55 m2

Oral granules (minimum BSA)≥ 0.4 m2

Source guidanceBSA cutoffs used to determine recommended dosing tables for capsules and oral granules per Appendices E and F.

Minimum body surface area for oral granules

Minimum BSA for oral granules>= 0.4 m2

Pediatric applicabilityOral granules added with pediatric extension to age ≥ 1 year; BSA requirement applies per PI.

Dosage reference

Provider Actions and Documentation Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required. Provider must submit documentation (such as office chart notes, lab results, or other clinical information) supporting that the member has met all applicable approval criteria.

Prior authorization required for Koselugo (selumetinib).
Provider must document that all approval criteria are met and submit supporting clinical information (office notes, labs, test results).

Denial Risk

Non‑Covered Indications

Requests for non–FDA approved indications that are not addressed in this policy will be denied unless there is sufficient documentation of efficacy and safety per the applicable off‑label use policies (CP.CPA.09 for commercial, HIM.PA.154 for Health Insurance Marketplace, CP.PMN.53 for Medicaid) or evidence of coverage documents.

Quantity Limits and Dose

Koselugo (selumetinib) — daily quantity

Daily quantity (capsules)4 capsules per day

Daily quantity (oral granules)14 oral granules per day

Approval contextQuantity limits apply to both FDA and NCCN-based off-label indications per policy dosing limits.

Plan quantity limit

Quantity limit policyRequests must not exceed the health plan–approved quantity limit; plan‑approved limit applies.

Dose vs quantityQuantity limits (4 capsules or 14 granules/day) apply in addition to per‑day mg/m2 dose limits (≤50 mg/m2/day up to 100 mg/day).

Definitions and Diagnostic Criteria

Selumetinib mechanism

Mechanism of actionMitogen-activated protein kinase enzyme 1/2 (MEK1/2) inhibitor

Drug classMEK inhibitor

Product nameSelumetinib (Koselugo)

Neurofibromatosis type 1 (NF1) diagnostic criteria

Key diagnostic features (examples)Six or more café‑au‑lait macules, axillary/inguinal freckling, two or more neurofibromas or one plexiform neurofibroma

Other diagnostic featuresOptic glioma, two or more Lisch nodules, distinctive bony lesion (e.g., sphenoid dysplasia), NF1 pathogenic variant

Background

Selumetinib is a mitogen‑activated protein kinase (MEK1/2) inhibitor approved for adults and children aged ≥ 1 year with symptomatic, inoperable plexiform neurofibromas associated with neurofibromatosis type 1. The policy also incorporates select NCCN‑recommended off‑label indications under specified conditions (see coverage criteria).

OpenPayer

Selumetinib (Koselugo) coverage

Coverage Criteria for Selumetinib (Koselugo)

Initial Therapy Requirements

Continuation and Renewal Requirements

Step Therapy / Prior Treatment Requirements

Dosing, Formulation & Coding Minimums

Provider Actions and Documentation Requirements

Quantity Limits and Dose

Definitions and Diagnostic Criteria

Background