Health Net tazemetostat Coverage Update

Coverage Criteria

Initial Therapy — Epithelioid Sarcoma

Initial Approval — Epithelioid Sarcoma (covered when ALL of the following are met):

ES Initial: 1) Diagnosis of epithelioid sarcoma; 2) Prescribed by or in consultation with an oncologist; 3) Patient is >= 16 years of age; 4) Disease is metastatic or locally advanced and not eligible for complete resection; 5) Tumor demonstrates loss of INI1 (SMARCB1) gene expression through inactivation, deletion, or mutation; 6) Tazemetostat is prescribed as monotherapy; 7) Request meets one of the following: a) dose does not exceed 1,600 mg (8 tablets) per day, or b) dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence); 8) For brand Tazverik requests, member must use generic tazemetostat if available unless contraindicated or clinically significant adverse effects are experienced.

Prescribed regimen must be FDA‑approved or recommended by NCCN

Initial Therapy — Follicular Lymphoma

Initial Approval — Follicular Lymphoma (covered when ALL of the following are met):

FL Initial: 1) Diagnosis of follicular lymphoma; 2) Prescribed by or in consultation with an oncologist or hematologist; 3) Age >= 18 years; 4) One of the following: a) Tumor positive for EZH2 mutation: relapsed/refractory disease after >= 2 prior systemic therapies (see Appendix B for examples); alternatively, request may be for second‑line therapy if member has relapsed/refractory disease and no satisfactory alternative treatment options; b) If EZH2 mutation status is negative or unknown: request is for third‑line and subsequent therapy OR, when relapsed/refractory disease and no satisfactory alternative options exist, may be considered as second‑line per NCCN; 5) Member does not have a history of or current CNS metastases; 6) Request meets one of the following: a) dose does not exceed 1,600 mg (8 tablets) per day; or b) dose is supported by practice guidelines or peer‑reviewed literature for the relevant off‑label use (prescriber must submit supporting evidence); 7) For brand Tazverik requests, member must use generic tazemetostat if available unless contraindicated or clinically significant adverse effects are experienced.

Prescribed regimen must be FDA‑approved or recommended by NCCN

Continuation / Renewal — Continued Therapy

Continued Therapy (all indications in Section I must meet all):

Continued Therapy: 1) Member is currently receiving tazemetostat via the Centene benefit with documentation showing at least 30 days of therapy; 2) Member is responding positively to therapy; 3) If request is for a dose increase, the new dose must not exceed 1,600 mg (8 tablets) per day or must be supported by practice guidelines or peer‑reviewed literature (prescriber must submit supporting evidence); 4) For brand Tazverik requests, member must use generic tazemetostat if available unless contraindicated or clinically significant adverse effects are experienced.

Approval durations specified by line of business

Indication- and mutation-status-based coverage

Policy coverage is governed by NCCN compendium recommendations and differs by EZH2 mutation status and prior therapies.

FL EZH2 mutation-positive: Use of tazemetostat for follicular lymphoma with EZH2 mutation‑positive disease requires prior therapies as specified by NCCN (e.g., relapsed/refractory after >= 2 prior systemic therapies); redirection options have been updated per NCCN.per NCCN

See full policy for exact number and types of prior therapies and required documentation

FL EZH2 mutation-negative or unknown: For EZH2 mutation‑negative or unknown follicular lymphoma, tazemetostat may be considered for relapsed/refractory disease when no satisfactory alternative treatment exists; policy clarifies availability as second‑line in that context and includes third‑line and subsequent therapy options per NCCN updates; certain redirection options (e.g., Aliqopa, Copiktra, Zydelig) have been removed as NCCN recommendations changed.per NCCN

Documentation should support EZH2 mutation status, prior therapies, and rationale when alternatives are lacking.

Coverage is not authorized for non‑FDA approved indications that are not specifically addressed in this policy unless the provider supplies sufficient documentation of efficacy and safety in accordance with the applicable off‑label use policy for the member's line of business (Commercial: CP.CPA.09; Health Insurance Marketplace: HIM.PA.154; Medicaid: CP.PMN.53). Refer to the referenced off‑label use policies for the type and amount of clinical evidence required to support authorization.

Per the most recent annual reviews and NCCN compendium alignment, Copiktra and Zydelig have been removed as redirect (alternative) options for follicular lymphoma; additionally, Aliqopa has been removed as a redirection option for EZH2 negative/unknown disease. These redirection updates reflect NCCN guideline changes and were applied during policy annual review.

Requests for tazemetostat for non‑FDA approved indications that lack sufficient supporting evidence per the applicable off‑label use policy are considered not covered. Providers must follow and document compliance with the off‑label use policy requirements (see CP.CPA.09, HIM.PA.154, CP.PMN.53) to support any request for such uses.

Although not restated verbatim in this section, the policy's redirection rules and alignment with NCCN imply that when NCCN no longer recommends a product as an alternative or redirect, coverage for tazemetostat in that context may be denied or the request redirected to NCCN‑preferred therapies. Providers should expect denial or redirection when NCCN guidance does not support the requested use or when previously acceptable redirect options have been removed.

Initial Therapy

Initial Therapy — Initial therapy requirements per indication

Initial therapy requirements per indication

Initial ES: See Initial Therapy — Epithelioid Sarcoma criteria set.

Dose: 800 mg PO BID; maximum 1,600 mg/day (8 tablets)

Initial FL: See Initial Therapy — Follicular Lymphoma criteria set.

Dose: 800 mg PO BID; maximum 1,600 mg/day (8 tablets)

Initial therapy (referenced) — Initial therapy criteria referenced to NCCN

Initial therapy criteria referenced to NCCN

Initial therapy context: Policy references initial therapy requirements consistent with the NCCN Compendium; EZH2 mutation status determines acceptable lines of therapy and prior‑therapy requirements.

Continuation / Renewal

Continuation Therapy — Continuation therapy requirements

Continuation therapy requirements

Continuation: Member has received tazemetostat for at least 30 days via the benefit with documentation; member is responding to therapy; dose limits apply; generic substitution required when available unless contraindicated or significant adverse effects.

See approval durations by line of business

Continuation/approval duration — Approval duration and continuation considerations

Approval duration and continuation considerations

Commercial continuation duration: Revised approval duration for Commercial line of business: up to 12 months or duration of request, whichever is less.12 months

Applied during annual review; Medicaid/HIM approval duration noted separately in policy (12 months)

Step Therapy & Prior Lines

Step	Requirement / Description
[{"text":"For follicular lymphoma (FL)","status":""},{"text":"Prior lines of therapy referenced to Appendix B examples; if tumor is EZH2 mutation‑positive, member must have relapsed/refractory disease after 2 prior systemic therapies (see Appendix B for examples of prior therapies). Prescribed regimen must be FDA‑approved or recommended by NCCN.","status":""}]
[{"text":"EZH2 mutation-positive specific","status":""},{"text":"Requirement: 2 prior therapies for relapsed/refractory FL. Appendix B lists therapeutic alternatives (e.g., bendamustine + rituximab/Gazyva; CHOP + rituximab/Gazyva; CVP + rituximab/Gazyva; lenalidomide + rituximab; single‑agent rituximab/Gazyva) that illustrate prior therapy options.","status":""}]
Dose limitation	Dose must not exceed 1,600 mg/day (8 tablets).

EZH2 mutation status	Number / type of prior therapies required (per NCCN guidance)
[{"text":"Positive","status":""},{"text":"Relapsed/refractory disease after 2 prior systemic therapies (per NCCN); prior therapy examples provided in Appendix B. Prior authorization may be required to document prior therapies and NCCN alignment.","status":""}]
Negative or Unknown	Use restricted to third‑line and subsequent therapy, OR may be used as second‑line when member has relapsed/refractory disease and provider documents no satisfactory alternative treatment and NCCN supports second‑line use in that context. Redirection to Aliqopa removed per 1Q 2025 updates.
General notes	Number and specific types of required prior therapies vary by EZH2 mutation status and are governed by NCCN compendium recommendations; see full policy for exact step definitions and required documentation. Annual reviews updated redirection options (e.g., Copiktra and Zydelig removed previously).

Coding & Dosage

Maximum daily dose

Maximum daily dose1,600 mg/day (maximum of 8 tablets of 200 mg)

Typical dosing regimen800 mg orally twice daily until disease progression or unacceptable toxicity

Dose exceptionsHigher or alternative doses only if supported by practice guidelines or peer‑reviewed literature with prescriber submission

Tazemetostat (Tazverik) — quantity limits

Quantity limit8 tablets (200 mg) per day

Tablet strength200 mg per tablet

Equivalent daily dose

Provider Actions & Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for requests for tazemetostat (Tazverik). Requests must demonstrate that the member meets the diagnosis and clinical criteria in this policy and any applicable age and prescriber specialty requirements. Requests submitted without required information may be delayed or denied.

Prior authorization required for all lines of business where benefit coverage applies.
Prescriptions must be written by or in consultation with an oncologist or hematologist.

Prior Authorization

Prior Authorization — Tazemetostat (Tazverik) Specifics

Prior authorization requests for tazemetostat must document the indication and supporting clinical details consistent with the policy and current NCCN recommendations for follicular lymphoma (FL). For FL, the request must indicate the patient's EZH2 mutation status (positive, negative, or unknown) and whether the disease is relapsed or refractory.

If EZH2 mutation-positive: member must have relapsed/refractory disease after ≥ 2 prior therapies, unless request is for second-line therapy when there are no satisfactory alternative treatment options (in which case document rationale).

Definitions

Definition: EZH2

TermEZH2: enhancer of zeste homolog 2

ContextEZH2 is the molecular target relevant to tazemetostat use in follicular lymphoma

Use in policyEZH2 mutation status guides eligibility for tazemetostat in FL per NCCN-referenced criteria

Definition: ES

AbbreviationES: epithelioid sarcoma

PopulationIndication includes metastatic or locally advanced ES not eligible for complete resection (patients >=16 years)

Policy relevance

Background

Tazemetostat (Tazverik) is an EZH2 (methyltransferase) inhibitor with FDA‑recognized indications that include treatment of epithelioid sarcoma and certain cases of relapsed or refractory follicular lymphoma. Dosing for both indications is typically 800 mg orally twice daily (tablets are available as 200 mg), with a maximum daily dose of 1,600 mg/day (8 tablets). Approvals based on accelerated pathways are supported by response‑rate data; confirmatory evidence requirements and NCCN compendium recommendations are referenced in the full policy.

OpenPayer

Clinical Policy: Tazemetostat (Tazverik)