CurrentmhnPolicy CP.PHAR.745

Dordaviprone (Modeyso) for diffuse midline glioma

Defines medical necessity criteria, dosing, and prior authorization requirements for Modeyso (dordaviprone) for members across Commercial, HIM, and Medicaid lines of business, focused on treatment of diffuse midline glioma with H3 K27M mutation. Applies to providers submitting requests for initial and continuation therapy.

Policy Summary

Payermhn

PolicyDordaviprone (Modeyso) for diffuse midline glioma

Policy CodePolicy CP.PHAR.745

Change TypeNo material changes

Effective DateDec 1, 2025

Next Review Date

Key ActionPrior authorization required; submit documentation confirming diagnosis of diffuse midline glioma with H3 K27M mutation, age ≥1 year, prior progression after therapy, oncologist involvement, and dosing within policy limits.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

1 yearmin patient age

12 monthsapproval duration

625 mg/weekmax adult dose

125 mgproduct strength

H3 K27Mrequired tumor mutation

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Coverage Criteria for Modeyso (dordaviprone)

Continuation Therapy — Covered when ALL of the following are met for Continuation/Renewal (Diffuse Midline Glioma)

Covered when ALL of the following are met for Continuation/Renewal (Diffuse Midline Glioma):

Continuation Approval: Diffuse Midline Glioma: 1. Currently receiving medication via Centene benefit, or documentation supports that member is currently receiving Modeyso for a covered indication and has received this medication for at least 30 days; 2. Member is responding positively to therapy; 3. For Modeyso requests, member must use dordaviprone, 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) New dose does not exceed policy-specified weekly dosing by adult or pediatric weight tiers (Adults: 625 mg/week; Pediatrics weight tiers: 10 to <12.5 kg = 125 mg/week; 12.5 to <27.5 kg = 250 mg/week; 27.5 to <42.5 kg = 375 mg/week; 42.5 to <52.5 kg = 500 mg/week; ≥ 52.5 kg = 625 mg/week); OR (b) New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).See dosing thresholds

Approval duration: 12 months

Population / Weight Tier	Once-weekly Dose	Product Strength Available
Pediatrics/Adults: ≥52.5 kg
625 mg once weekly
125 mg capsule

Non-FDA approved indications that are not specifically addressed in this policy are not authorized for coverage unless the provider supplies sufficient documentation of efficacy and safety in accordance with the applicable off‑label use policies (see referenced policies).

Requests for Modeyso (dordaviprone) to treat indications not listed in this policy will be considered not authorized if the provider does not submit adequate evidence per the referenced off‑label use policies; such uses are treated as not medically necessary when off‑label evidence is insufficient.

Coding and Dosing Summary

No CPT/HCPCS/ICD codes listedmixed

No codes listed

Maximum weekly dose (adults and pediatrics by weight)

Adults625 mg per week (maximum adult weekly dose)

Pediatric 10–<12.5 kg125 mg per week

Pediatric 12.5–<27.5 kg250 mg per week

Pediatric 27.5–<42.5 kg375 mg per week

Pediatric 42.5–<52.5 kg500 mg per week

Pediatric ≥52.5 kg625 mg per week

Prescriber / Prior Authorization Requirements

Prior Authorization

Prior authorization and required clinical information

Prior authorization is required. The provider must document: diagnosis of diffuse midline glioma, prescriber is or consulted with an oncologist, patient age ≥ 1 year, presence of H3 K27M mutation, disease progression following prior therapy (includes radiation and pharmacotherapies), and that the requested dose is within the policy's weekly dosing limits (adult or pediatric weight tiers) or supported by practice guidelines/peer‑reviewed literature. For continuation, documentation must show at least 30 days of prior Modeyso use and positive response to therapy.

Diagnosis: diffuse midline glioma with H3 K27M mutation
Prescribed by or in consultation with an oncologist
Age ≥ 1 year
Disease progressive following prior therapy (includes radiation; see Appendix B)
Dose does not exceed policy weekly limits by adult/pediatric weight tiers OR prescriber submits supporting guidelines/literature
Continuation: ≥30 days prior Modeyso use and evidence of positive response

Key Definitions and Regulatory Terms

Diffuse midline glioma — definition

DefinitionA glioma arising in midline structures characterized by the presence of an H3 K27M mutation and progressive disease following prior therapy.

Anatomic sites (examples)Midline structures of the central nervous system (per policy context).

Required disease statusProgressive disease after prior therapy (includes radiation therapy).

Accelerated approval — definition

DefinitionA regulatory designation in which approval is based on surrogate endpoints (e.g., response rate and duration of response); continued approval may be contingent on confirmatory trial(s).

Implication for coverageIndication granted under accelerated approval may require verification of clinical benefit in confirmatory trials for continued approval.

Line of Therapy / Treatment Setting

Salvage

Salvage: Indicated for patients with progressive disease following prior therapy (i.e., after prior therapy has failed).

Accelerated approval based on response; confirmatory trials may be required for continued approval.

Required Biomarker for Coverage

H3 K27M — biomarker requirement

Required biomarkerH3 K27M mutation

RoleRequired tumor mutation for the covered indication of diffuse midline glioma

DocumentationPrescription/authorization must document presence of H3 K27M mutation per coverage criteria.

Background and Clinical Context

Diffuse midline glioma with the H3 K27M mutation is an aggressive central nervous system tumor. Modeyso (dordaviprone) is indicated for treatment of adult and pediatric patients 1 year of age and older with diffuse midline glioma and progressive disease after prior therapy, and is provided under an accelerated approval pathway based on response rate and duration of response; continued approval may depend on confirmatory trials. The product is supplied as a 125 mg capsule and dosing is administered once weekly per policy weight tiers (maximum adult weekly dose 625 mg).

Policy Summary

Payermhn

PolicyDordaviprone (Modeyso) for diffuse midline glioma

Policy CodePolicy CP.PHAR.745

Change TypeNo material changes

Effective DateDec 1, 2025

Next Review Date

SourceLink

On This Page

Step Therapy

Therapeutic alternatives and product preference

Therapeutic alternatives are listed in Appendix B (examples include temozolomide, PCV, lomustine, carmustine, bevacizumab, etoposide, carboplatin, cisplatin for adults; temozolomide and lomustine for H3 K27‑altered pediatric diffuse midline glioma). The policy specifies that Modeyso (dordaviprone) should be used only if dordaviprone is available and not contraindicated or causing clinically significant adverse effects.

Appendix B lists preferred alternative pharmacotherapies and dosing varies by agent
Modeyso use requires dordaviprone if available unless contraindicated or significant adverse effects occur

Documentation Required

Required supporting documentation

Submit clinical documentation (e.g., office chart notes, laboratory results, or other clinical information) that demonstrates the member meets all approval criteria, including diagnosis, mutation status, prior therapies, oncologist involvement, dosing and response for continuation requests.

Office chart notes confirming diagnosis and oncologist involvement
Pathology/genetic testing showing H3 K27M mutation
Records of prior therapies and evidence of disease progression
For continuation: documentation of ≥30 days prior use and clinical response

Denial Risk

Non‑covered indications risk denial

Requests for indications not listed in this policy (non‑FDA approved indications) will be denied unless sufficient documentation of efficacy and safety is provided per the referenced off‑label use policies.

Off‑label requests must meet documentation requirements of CP.CPA.09 (Commercial), HIM.PA.154 (HIM), or CP.PMN.53 (Medicaid) or other evidence of coverage documents

Context in this policyModeyso's indication for diffuse midline glioma is approved under accelerated approval based on response rate and duration of response.