ModifiedmhnPolicy CP.PHAR.452

Tazemetostat (Tazverik)

Defines medical necessity and prior authorization criteria for tazemetostat (Tazverik) for epithelioid sarcoma and follicular lymphoma across Commercial, HIM, and Medicaid lines of business.

Policy Summary

Payermhn

PolicyTazemetostat (Tazverik) coverage criteria

Policy CodePolicy CP.PHAR.452

Change TypeDuration increased to 12 monthsNCCN-aligned criteria and redirect options updated

Effective DateMar 1, 2020

Next Review Date

Key ActionSubmit documentation (office notes, labs) showing EZH2 mutation status and prior therapy history to support authorization.

SourceLink

POLICY UPDATE CHANGES

Revised initial approval duration from 6 to 12 months.

Clarified that for EZH2-negative or unknown follicular lymphoma, relapsed/refractory disease with no satisfactory alternatives can be second-line therapy and added option for third-line and subsequent therapy; removed certain redirect options.

Added requirement that requests do not exceed health plan-approved quantity limit, if applicable.

1,600 mg/dayMax daily dose

800 mg PO BIDTypical dosing

12 monthsApproval duration

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12 moDuration revised

Coverage Criteria for Tazemetostat (Tazverik)

Initial Therapy - Epithelioid Sarcoma

Initial Approval Criteria — Epithelioid Sarcoma (must meet ALL):

Epithelioid Sarcoma initial

Diagnosis of epithelioid sarcoma (ES)
Prescribed by or in consultation with an oncologist
Age >= 16 years
For brand Tazverik requests, member must use generic tazemetostat if available unless contraindicated or clinically significant adverse effects are experienced
Disease is metastatic or locally advanced
Disease is not eligible for complete resection
Tumor demonstrates loss of INI1 (SMARCB1) gene expression via inactivation, deletion, or mutation
Tazemetostat is prescribed as monotherapy
Dose limits
- Dose does not exceed 1,600 mg (8 tablets) per day
- Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)

Initial Therapy - Follicular Lymphoma

Initial Approval Criteria — Follicular Lymphoma (must meet ALL):

Follicular Lymphoma initial

Diagnosis of follicular lymphoma (FL)
Prescribed by or in consultation with an oncologist or hematologist
Age >= 18 years
For brand Tazverik requests, member must use generic tazemetostat if available unless contraindicated or clinically significant adverse effects are experienced
Prior therapy and biomarker requirements
- If tumor is positive for EZH2 mutation: member has relapsed/refractory disease after >= 2 prior systemic therapies

Continuation Therapy

Continuation/Continuation Approval (All indications in Section I — must meet ALL):

Continuation therapy

Member currently receiving Tazverik via Centene benefit or documentation supports member has received Tazverik for at least 30 days for a covered indication
Member is responding positively to therapy
For brand Tazverik requests, member must use generic tazemetostat if available unless contraindicated or clinically significant adverse effects are experienced
Request does not exceed health plan-approved quantity limit, if applicable
Dose increase conditions

General coverage criteria

Covered when criteria per NCCN compendium and policy are met, with distinctions by EZH2 mutation status and prior therapies

General

Request meets an NCCN-aligned indication for tazemetostat and prescribed regimen is FDA-approved or recommended by NCCN
Documentation includes EZH2 mutation status (positive, negative, or unknown) and prior therapy history to justify line-of-therapy placement per NCCN-aligned criteria
Request does not exceed health plan-approved quantity limits
Initial approval duration for Commercial is 12 months (or duration of request, whichever is less); Medicaid/HIM initial approval duration is 12 months
For follicular lymphoma: if EZH2 mutation–positive, member must have relapsed/refractory disease after >= 2 prior therapies; if EZH2 mutation negative or unknown, relapsed/refractory disease with no satisfactory alternatives may be considered second-line or third-line and subsequent as specified

Non‑FDA approved indications that are not specifically addressed in this policy are not authorized unless the provider submits sufficient documentation demonstrating efficacy and safety consistent with the applicable off‑label use policies: CP.CPA.09 (Commercial), HIM.PA.154 (Health Insurance Marketplace), or CP.PMN.53 (Medicaid), or other evidence of coverage documents.

Per updates aligned with NCCN compendium changes, redirection to Copiktra, Zydelig, and Aliqopa as alternative agents for follicular lymphoma has been removed and is no longer recommended as redirect options.

Requests for use of tazemetostat outside the indications listed in this policy are considered not authorized/not covered unless the request is supported by the required off‑label documentation demonstrating efficacy and safety per the referenced off‑label use policies.

When state Medicaid coverage provisions conflict with the coverage provisions in this clinical policy, the state Medicaid coverage provisions take precedence for Medicaid members; refer to the applicable state Medicaid manual for details.

Dosing and Regimens

Regimen	Dose / Schedule	Maximum daily dose	Typical duration
Tazemetostat (Tazverik)
800 mg orally twice daily (800 mg PO BID)
1,600 mg/day
Until disease progression or unacceptable toxicity

Product Codes and Dosing Limits

Product availability / NDCNDC

NDC not listed

Tablet: 200 mg

Dosage Thresholds (Coding)

Maximum daily dose1,600 mg/day

Typical single-dose regimen800 mg PO twice daily (total 1,600 mg/day)

Tablet strength200 mg tablet

Provider Actions and Authorization Requirements

Prior Authorization

Prior Authorization and Duration

Prior authorization is required for Tazverik (tazemetostat). Initial approvals are limited to 12 months and must not exceed health plan‑approved quantity limits, if applicable. Commercial approvals are limited to 12 months or the duration of the request, whichever is less.

Initial approval duration: 12 months (Medicaid/HIM)
Commercial: 12 months or duration of request, whichever is less
Requests exceeding health plan‑approved quantity limits may be denied

Documentation Required

Clinical Rationale and Biomarker Status

Provider must submit documentation (such as office chart notes, pathology reports, and relevant laboratory results) that supports the member meets all approval criteria. Documentation should specifically include clinical rationale for use, EZH2 mutation testing results (positive, negative, or unknown), and prior therapy history to justify line‑of‑therapy placement or second/third‑line use.

Line-of-Therapy Rules

second-line | third-line

Line-of-therapy placement for follicular lymphoma (single top-level node):

FL line of therapy

EZH2 mutation–positive: relapsed/refractory after >= 2 prior therapies
See Appendix B for therapy examples; prior authorization may be required
EZH2 negative or unknown: relapsed/refractory disease with no satisfactory alternative treatment options for second-line OR third-line and subsequent therapy
Per NCCN-aligned policy updates

second-line | third-line and subsequent

Line-of-therapy placement (second-line, third-line and subsequent):

Line placement

Biomarker and Diagnostic Requirements

Biomarker requirement — EZH2 mutation

BiomarkerEZH2 mutation (enhancer of zeste homolog 2)

Role in coverageTumor EZH2 mutation–positive status determines requirement for ≥2 prior systemic therapies for FL eligibility

Test requirementDetected by an FDA‑approved test when used to define EZH2 mutation–positive FL indication

Biomarker requirement — INI1 (SMARCB1) loss

BiomarkerINI1 (SMARCB1) loss of expression

Role in coverageRequired demonstration of INI1 loss (inactivation, deletion, or mutation) for epithelioid sarcoma indication

Background

Tazemetostat (Tazverik) is an oral small‑molecule inhibitor of the histone methyltransferase EZH2. It is indicated for certain patients with epithelioid sarcoma and for relapsed/refractory follicular lymphoma under the conditions described in this policy. Typical dosing used in these indications is 800 mg PO twice daily with a maximum daily dose of 1,600 mg/day. Clinical use and line‑of‑therapy placement are guided by tumor biomarker status (for example, EZH2 mutation in follicular lymphoma and loss of INI1/SMARCB1 expression in epithelioid sarcoma) and by prior therapy history, consistent with NCCN recommendations and the policy's criteria.

Definitions and Abbreviations

Definition — EZH2

DefinitionEnhancer of zeste homolog 2 (EZH2)

AbbreviationEZH2

Clinical relevanceTargeted by tazemetostat; mutation status used to determine eligibility for relapsed/refractory FL

Definition — Epithelioid sarcoma

DefinitionEpithelioid sarcoma (ES)

Age requirementIndication includes adults and pediatric patients aged ≥16 years for metastatic or locally advanced ES not eligible for complete resection

Biomarker requirement

Revision History and Policy Changes

2025-10-17criteria_alignment_and_redirects

Aligned criteria with NCCN: removed Aliqopa as a redirection option for EZH2-negative/unknown follicular lymphoma and clarified that relapsed/refractory disease with no satisfactory alternatives may be considered second-line and added an option for third-line and subsequent therapy.

2025-10-13approval_duration_revisionLatest

Revised initial approval duration from 6 months to 12 months and added template requirement that requests not exceed health plan-approved quantity limits, if applicable.

Policy Summary

Payermhn

PolicyTazemetostat (Tazverik) coverage criteria

Policy CodePolicy CP.PHAR.452

Change TypeDuration increased to 12 monthsNCCN-aligned criteria and redirect options updated

Effective DateMar 1, 2020

Next Review Date

Key ActionSubmit documentation (office notes, labs) showing EZH2 mutation status and prior therapy history to support authorization.

SourceLink

On This Page

See Appendix B for examples of therapies; prior authorization may be required

If EZH2 mutation negative or unknown

Request is for second-line therapy for relapsed/refractory disease and no satisfactory alternative treatment options
Per NCCN supports use as second-line in this setting
Request is for third-line or subsequent therapy

Member does not have history of or current CNS metastases

Dose limits

Dose does not exceed 1,600 mg (8 tablets) per day
Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)

New dose does not exceed 1,600 mg (8 tablets) per day

New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence)

Aligned to NCCN compendium

Submit tumor EZH2 mutation status (positive, negative, or unknown)
Provide prior systemic therapy history and dates
Include rationale if used as second‑line therapy when EZH2 status is negative/unknown

Step Therapy

Prior Therapy Requirements (Follicular Lymphoma)

For follicular lymphoma, prior therapy requirements depend on EZH2 mutation status: if EZH2 mutation–positive, member must have relapsed/refractory disease after ≥ 2 prior systemic therapies. If EZH2 mutation status is negative or unknown, Tazverik may be used as second‑line therapy when member has relapsed/refractory disease and no satisfactory alternative treatment options, or for third‑line and subsequent therapy.

EZH2 mutation–positive: ≥ 2 prior therapies required
EZH2 negative/unknown: allowed as second‑line with relapsed/refractory disease and no satisfactory alternatives, or third‑line+
See Appendix B for examples of prior therapies

Denial Risk

Non‑Covered Non‑FDA Indications

If the requested indication is a non‑FDA approved use not addressed in this policy, the provider must submit sufficient documentation of efficacy and safety per the applicable off‑label use policies: CP.CPA.09 (commercial), HIM.PA.154 (health insurance marketplace), or CP.PMN.53 (Medicaid), or provide evidence of coverage documents. Requests for off‑label uses without adequate supporting evidence may be denied.

Refer to CP.CPA.09, HIM.PA.154, or CP.PMN.53 for off‑label documentation requirements
Provide peer‑reviewed literature or guideline support for proposed off‑label use

Step Therapy

Redirect / Step Options Updated

Redirect/step options and recommended alternative agents have been updated per NCCN changes. Previously listed redirect options such as Copiktra, Zydelig, and Aliqopa have been removed or updated; Aliqopa was removed for EZH2 negative/unknown in recent NCCN updates. Providers should follow current NCCN recommendations when considering alternative therapies and document rationale if redirecting to an alternative agent.

Copiktra and Zydelig removed as redirect options per NCCN
Aliqopa removed for EZH2 negative/unknown per 1Q 2025 update
Follow current NCCN compendium for acceptable alternatives

For EZH2 mutation–positive follicular lymphoma: requirement of >= 2 prior systemic therapies applies

For EZH2 mutation negative or unknown: relapsed/refractory disease with no satisfactory alternative treatment options may be considered second-line; additional option added for third-line and subsequent therapy

Removed Aliqopa as redirection option per NCCN; aligned to compendium updates

Must be documented in tumor for initial approval of ES

Biomarker requirement — EZH2 (duplicate)

BiomarkerEZH2 (enhancer of zeste homolog 2)

InterpretationEZH2 mutation–positive FL requires ≥2 prior systemic therapies; negative/unknown status changes line-of-therapy placement

DocumentationClinical documentation should include EZH2 mutation status to support eligibility per policy

Tumor must demonstrate loss of INI1 (SMARCB1) expression for coverage

Definition — Follicular lymphoma

DefinitionFollicular lymphoma (FL)

Age requirementIndication applies to adults aged ≥18 years for relapsed or refractory FL

Line-of-therapy noteEZH2 mutation–positive FL requires ≥2 prior systemic therapies; EZH2 negative/unknown may be second-line if no satisfactory alternatives or third-line and subsequent

EZH2 mutation status — impact on eligibility and prior-therapy requirements

Use of EZH2 mutation statusDetermines required number of prior therapies for FL: EZH2 mutation–positive requires ≥2 prior systemic therapies

Negative or unknown statusIf EZH2 mutation is negative or unknown, use may be second-line for relapsed/refractory disease with no satisfactory alternatives or third-line and subsequent therapy

DocumentationProvider must submit documentation supporting EZH2 mutation status and prior therapy history to justify line-of-therapy placement