CurrentBlue Cross Blue Shield - TennesseePolicy N/A

Aflibercept Products (intravitreal) coverage criteria

Coverage policy for Eylea and listed biosimilars/brands for ophthalmologic indications (e.g., diabetic retinopathy, DME, wet AMD, RVO macular edema, ROP) including authorization durations and dosing limits; applies to BlueCross BlueShield of Tennessee members and providers.

Policy Summary

PayerBlue Cross Blue Shield - Tennessee

PolicyAflibercept Products (intravitreal) coverage criteria

Policy CodePolicy N/A

Change TypeNo material change

Effective DateN/A

Next Review DateN/A

Key ActionObtain prior authorization and document clinical response for continuation requests.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

6initial auth (months)

12continuation auth (months)

2 mgcommon dose

8 mgEylea HD dose

TN §56-7-2352state mandate

6/30/26

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Coverage Criteria for Aflibercept Products

inv-01: Indication criteria

Covered when ALL of the following are met

Covered indications: Treatment is for an FDA-approved indication or a compendial use listed in the policy (diabetic retinopathy, diabetic macular edema, neovascular (wet) age-related macular degeneration, macular edema following retinal vein occlusion, retinopathy of prematurity for Eylea and biosimilars; Enzeevu limited to wet AMD).

All other indications are considered experimental/investigational and not medically necessary.

inv-02: Authorization durations

Authorization durations

Initial authorization duration: Authorization may be granted for 6 months for diabetic macular edema, diabetic retinopathy, neovascular (wet) age-related macular degeneration, macular edema following retinal vein occlusion, and retinopathy of prematurity (Eylea and biosimilars only).6 months

Continuation authorization: Authorization of 12 months may be granted for continued treatment when member demonstrates a positive clinical response (e.g., improvement or maintenance in best corrected visual acuity or visual field, or reduction in rate of vision decline).12 months

Documentation of clinical response required for reauthorization.

inv-03: Dosing and quantity limits

Dosing / quantity limits by product and indication

Standard intravitreal dosing (most products): Initial: 2 mg per affected eye every 4 weeks for specified loading doses (commonly 3 or 5 doses depending on product/indication). Maintenance: 2 mg per affected eye every 4 weeks (approximately every 25 days, monthly).2 mg q4w

Product-specific variations described below.

Eylea HD dosing: Eylea HD initial: 8 mg per affected eye every 4 weeks (+/- 7 days) for the first 3 (or 3–5 for some indications) doses. Maintenance: 8 mg per affected eye every 8 to 16 weeks (+/- 7 days); may be dosed as frequently as every 4 weeks (+/- 7 days) to maintain response.8 mg

Higher-dose regimen is specific to Eylea HD.

Retinopathy of prematurity dosing (Eylea): Eylea for ROP: 0.4 mg per affected eye; may be repeated up to a total of 3 doses, at least 10 days apart.

All indications not listed as FDA-approved or included as compendial uses in this policy are considered experimental/investigational and not medically necessary. The FDA‑approved indications for Eylea and the listed aflibercept products are limited to diabetic retinopathy, diabetic macular edema, neovascular (wet) age-related macular degeneration, macular edema following retinal vein occlusion, and retinopathy of prematurity (Eylea and biosimilars); Enzeevu is indicated for neovascular (wet) AMD. Use outside these listed indications will be denied as investigational.

This policy is written to comply with Tennessee Code Annotated §56-7-2352. Per that statute, off‑label uses of FDA‑approved drugs may be considered for coverage only when the off‑label indication is recognized by one of the statutorily recognized standard reference compendia or is supported in the published peer‑reviewed medical literature; documentation meeting those requirements must be provided for consideration of coverage.

Use of aflibercept products for indications other than those explicitly listed as FDA‑approved or recognized compendial uses in this policy is considered not medically necessary. Requests for treatment of unlisted indications will be reviewed and are expected to be denied unless the indication meets the compendial or peer‑reviewed literature criteria required by state statute.

Provider Requirements, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization and Step Therapy Required

Prior authorization is required for the listed aflibercept products. Some agents may also require step therapy per the insurer's Step Therapy Requirements for Provider Administered Specialty Medications; see the Step Therapy Guide at https://www.bcbst.com/docs/providers/Comm_BC_PAD_Step_Therapy_Guide.pdf. Quantity and dosing limits apply as specified in the policy (initial and maintenance intravitreal dosing regimens and maximum dosing intervals).

Prior authorization required for listed aflibercept products (Eylea, Eylea HD, Ahzantive, Enzeevu, Eydenzelt, Opuviz, Pavblu, Yesafili).
Some agents may require step therapy — follow insurer Step Therapy Requirements for Provider Administered Specialty Medications.

Documentation Required

Off‑Label Use Documentation Requirement

Off‑label uses will be considered only when the use is recognized in a statutorily recognized compendium or in published peer‑reviewed medical literature consistent with Tennessee law. Providers must supply documentation demonstrating the off‑label indication is supported by one of these sources.

Definitions and Special Notes

Retinopathy of Prematurity (ROP) — coverage limitation

Policy limitationCoverage for retinopathy of prematurity (ROP) is limited to Eylea and its biosimilars only.

Affected productsEylea and listed biosimilars (policy notes Eylea specifically for ROP).

Non-covered alternativesOther aflibercept brands (e.g., Enzeevu) are not listed for ROP and are considered not medically necessary for this indication.

Covered indications

Covered usesFDA‑approved indications are covered when approval criteria are met (e.g., diabetic retinopathy, diabetic macular edema, neovascular (wet) AMD, macular edema following retinal vein occlusion, and ROP for Eylea/biosimilars).

Compendial uses

Background

Aflibercept products (Eylea and the listed biosimilars/brands) are intravitreal vascular endothelial growth factor (VEGF) inhibitors indicated for treatment of retinal vascular diseases. FDA‑approved indications in this class include diabetic retinopathy, diabetic macular edema, neovascular (wet) age‑related macular degeneration, macular edema following retinal vein occlusion, and retinopathy of prematurity (Eylea and biosimilars). Enzeevu is indicated for neovascular (wet) AMD. Coverage is limited to these FDA‑approved and recognized compendial uses when the policy criteria are met.

Policy Summary

PayerBlue Cross Blue Shield - Tennessee

PolicyAflibercept Products (intravitreal) coverage criteria

Policy CodePolicy N/A

Change TypeNo material change

Effective DateN/A

Next Review DateN/A

Key ActionObtain prior authorization and document clinical response for continuation requests.

SourceLink

On This Page

0.4 mg up to 3 doses

Specific to ROP and limited to Eylea and biosimilars as indicated in the policy.

Product-specific initial/maintenance examples: Examples by product: Ahzantive, Eydenzelt, Eylea, Opuviz, Pavblu, Yesafili, Enzeevu — most list initial intravitreal 2 mg per eye for loading (3 months or 5 doses depending on product) and maintenance 2 mg every ~25 days; Enzeevu indicated for wet AMD with initial 2 mg every 4 weeks for first 3 months and maintenance 2 mg every 4 weeks.varies by product (see policy text)

Refer to product-specific entries for exact loading dose counts and indication-specific schedules.

Coverage for off‑label indications requires documentation that the use is listed in a statutorily recognized compendium or peer‑reviewed literature per Tennessee Code Annotated Section 56-7-2352.
Reference compendia include sources such as NCCN, Drugdex, and AHFS — cite the specific compendium or literature with the request.

Denial Risk

Non‑Covered Indications

Indications not listed as FDA‑approved for the specific aflibercept product or not supported by compendia/published literature are considered experimental/investigational and may be denied.

All other indications beyond the FDA‑approved or compendial uses are considered experimental/investigational and not medically necessary.
If submitting for a non‑covered indication, include supporting evidence; absence of acceptable support may result in denial.

Documentation Required

Continuation Therapy Documentation

For continuation/reauthorization requests, documentation must show a positive clinical response to therapy (for example, improvement or maintenance in best corrected visual acuity [BCVA] or visual field, or reduction in rate of vision decline). Authorization may be granted for up to 12 months when criteria are met.

Reauthorization: demonstrate improvement or maintenance in BCVA or visual field, or other objective evidence of benefit.
Authorization of up to 12 months may be granted for continued treatment when positive response is documented.

Note

Reference Documentation

Providers should reference standard compendia and published sources when documenting clinical rationale, dosing, or off‑label support. Common references include NCCN Guidelines®, Drugdex (Micromedex), and AHFS Drug Information.

Acceptable reference sources: NCCN, Drugdex (Micromedex), AHFS — cite specific guidance used.
Tennessee statutory requirements require compendial or peer‑reviewed support for off‑label coverage decisions.

Step Therapy

Provider Action Checklist

Providers must follow the policy's dosing and quantity limits and include all required documentation with prior authorization requests to avoid delays or denials.

Include diagnosis, dosing regimen (initial and maintenance schedule), affected eye(s), and objective response measures when requesting authorization.
Ensure submitted dose and frequency do not exceed the policy's specified maximum dosing regimens.

Compendial uses listed in the policy are considered covered when the policy's approval criteria are satisfied.

Not medically necessaryAll other indications not listed as FDA‑approved or compendial uses are considered experimental/investigational and not medically necessary.

Reference compendia

Statutory compendia requirementTennessee Code Annotated Section 56-7-2352 requires off‑label coverage when the use is recognized in a statutorily recognized standard reference compendium or in peer‑reviewed medical literature.

Examples of recognized compendiaExamples cited in the policy: NCCN Clinical Practice Guidelines in Oncology, Drugdex (Micromedex), and The American Hospital Formulary Service (AHFS) Drug Information.

Use in documentationProviders should reference these standard compendia when documenting off‑label or compendial uses and when supporting dosing, contraindications, precautions, and monitoring.