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Intravitreal Injection of Vascular Endothelial Growth Factor (VEGF) Antagonists, VEGF Biosimilars, and Combination VEGF/Angiopoietin-2 (Ang-2) Inhibitors
MA08.073v

Policy

In the absence of coverage criteria from applicable Medicare statutes, regulations, NCDs, LCDs, CMS manuals, or other Medicare coverage documents, this policy uses internal coverage criteria developed by the Company in consideration of peer-reviewed medical literature, clinical practice guidelines, and/or regulatory status.​
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The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

COMPANY-DESIGNATED PREFERRED PRODUCTS

Although there are many brands of vascular endothelial growth factor (VEGF) antagonists and VEGF/Angiopoietin-2 (Ang-2) inhibitors​ on the market for the treatment of vascular diseases of the eye, there is no reliable evidence of the superiority of any one brand of VEGF antagonist compared with other brands. The Company has designated bevacizumab (all brands) as its LEVEL 1 PREFERRED PRODUCTS, followed by ranibizumab (Lucentis, Byooviz, Cimerli), as its LEVEL 2 PREFERRED PRODUCTS. The COMPANY-DESIGNATED PREFERRED PRODUCTS are less costly and at least as likely to produce equivalent therapeutic results as the COMPANY-DESIGNATED NONPREFERRED PRODUCTS.

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COMPANY-DESIGNATED PREFERRED PRODUCTS (LEVEL 1)

Bevacizumab (all brands)

 

COMPANY-DESIGNATED PREFERRED PRODUCTS (LEVEL 2)*

Ranibizumab (Lucentis®, Byooviz®, Cimerli®)

 

COMPANY-DESIGNATED NONPREFERRED PRODUCTS (LEVEL 3)**

Aflibercept (Ahzantive®, Enzeevu®, Eydenzelt®, Eylea®, Eylea HD®, OpuvizTM, Pavblu®, Yesafili®)


Brolucizumab (Beovu®)


Ranibizumab (Nufymco®, Susvimo®)


Faricimab (Vabysmo®)

 

*In order to be eligible to receive coverage of a Level 2 preferred product, the individual must have documentation of a contraindication, intolerance (e.g., as documented per the US Food and Drug Administration [FDA] labeling), or inadequate response to a Level 1 preferred product. An inadequate response is determined after administering at least three (3) monthly injections at doses in accordance with FDA labeling.​

According to the FDA, “a biosimilar is a biological product that has no clinically meaningful differences from the existing FDA-approved reference product. All biosimilar products meet the FDA’s rigorous standards for approval for the indications described in the product labeling. Once a biosimilar has been approved by the FDA, the safety and effectiveness of these products have been established, just as they have been for the reference product.” Coverage of a biosimilar product as an alternate to a reference product is not considered a form of step therapy by the Company. ​

COMPANY-DESIGNATED NONPREFERRED PRODUCTS**    

Use of the COMPANY-DESIGNATED NONPREFERRED VEGF PRODUCTS (Level 3) is eligible for coverage only for individuals who are currently receiving, or have previously received, a COMPANY-DESIGNATED NONPREFERRED PRODUCT for the specified indication.

If the individual has not previously received the COMPANY-DESIGNATED NONPREFERRED VEGF PRODUCT to treat the specified indication, the nonpreferred product is eligible for coverage when the individual has documentation of a contraindication, intolerance (e.g., as documented per the FDA labeling), or inadequate response to BOTH​ the Company-designated Level 1 AND ​Level 2 preferred products. An inadequate response is determined after administering at least three (3) monthly injections at doses in accordance with FDA labeling.

** See the Not Medically Necessary section below.

NOTE: Use of nonpreferred product samples administered by the professional provider will not meet coverage criteria for the exception. Additional clinical information demonstrating medical necessity of the desired medication must be submitted by the requesting provider ​for review.​

MEDICALLY NECESSARY​

Initial Therapy

AFLIBERCEPT (EYLEA) AND RELATED BIOSIMILARS
The intravitreal injection of VEGF antagonist aflibercept (Eylea) and related biosimilars are considered medically necessary and, therefore, covered for individuals who have the following conditions AND meet the requirements listed in the COMPANY-DESIGNATED PREFERRED PRODUCTS and NONPREFERRED PRODUCTS sections above:
  • Neovascular (wet or exudative) age-related macular degeneration (AMD)
  • Macular edema following retinal vein occlusion (RVO)
  • Diabetic macular edema ​(DME)
  • Diabetic retinopathy ​(DR)
  • Retinopathy of prematurity (ROP) 
AFLIBERCEPT HD (EYLEA HD) AND RELATED BIOSIMILARS​
The intravitreal injection of VEGF antagonist aflibercept HD (Eylea HD) and related biosimilars are considered medically necessary and, therefore, covered for individuals who have the following conditions AND meet the requirements listed in the COMPANY-DESIGNATED PREFERRED PRODUCTS and NONPREFERRED PRODUCTS sections above: 
  • ​Neovascular (wet or exudative) age-related macular degeneration (AMD)​
  • Diabetic macular edema ​(DME)​
  • Diabetic retinopathy ​(DR)​​
  • ​Macular edema following retinal vein occlusion (RVO)​
BEVACIZUMAB (AVASTIN) AND RELATED BIOSIMILARS 
The intravitreal injection of VEGF antagonist bevacizumab (Avastin) and related biosimilars are considered medically necessary and, therefore, covered for vascular diseases of the eye including but not limited to ANY ​of the following:
  • Choroidal neovascularization due to angioid streaks, central serous chorioretinopathy, choroidal rupture or trauma, idiopathic choroidal neovascularization, multifocal choroiditis, pathologic myopia, presumed ocular histoplasmosis syndrome, uveitis
  • Diabetic macular edema ​(DME)​
  • ​Diabetic retinopathy ​(DR)​
  • Macular edema following retinal vein occlusion (RVO)​
  • Neovascular (wet or exudative) age-related macular degeneration (AMD)​
  • Neovascular glaucoma
  • Retinopathy of prematurity (ROP)
BROLUCIZUMAB-DBLL (BEOVU) AND RELATED BIOSIMILARS 
The intravitreal injection of VEGF antagonist brolucizumab-dbll (Beovu) and related biosimilars are considered medically necessary and, therefore, covered for individuals who have the following conditions AND meet the requirements listed in the COMPANY-DESIGNATED PREFERRED PRODUCTS and NONPREFERRED PRODUCTS sections above:
  • Neovascular (wet or exudative) age-related macular degeneration (AMD)​
  • Diabetic macular edema ​(DME)​​
FARICIMAB-SVOA (VABYSMO) AND RELATED BIOSIMILARS  
The intravitreal injection of faricimab-svoa (Vabysmo) and related biosimilars are considered medically necessary and, therefore, covered for individuals who have the following conditions AND meet the requirements listed in the COMPANY-DESIGNATED PREFERRED PRODUCTS and NONPREFERRED PRODUCTS sections above:
  • Neovascular (wet or exudative) age-related macular degeneration (AMD)​
  • Diabetic macular edema ​(DME)​
  • Macular edema following retinal vein occlusion (RVO)​
RANIBIZUMAB (LUCENTIS) AND RELATED BIOSIMILARS 
The intravitreal injection of VEGF antagonist ranibizumab (Lucentis) and related biosimilars are considered medically necessary and, therefore, covered for individuals who have the following conditions AND meet the requirements listed in the COMPANY-DESIGNATED PREFERRED PRODUCTS and NONPREFERRED PRODUCTS sections above: 
  • Neovascular (wet or exudative) age-related macular degeneration (AMD)​
  • Macular edema following retinal vein occlusion (RVO)​
  • ​​Diabetic macular edema ​(DME)​
  • Diabetic retinopathy ​(DR)​
  • Retinopathy of prematurity (ROP)​ ​
  • Choroidal neovascularization due to angioid streaks, central serous chorioretinopathy, choroidal rupture or trauma, idiopathic choroidal neovascularization, multifocal choroiditis, pathologic myopia, presumed ocular histoplasmosis syndrome, uveitis
​RANIBIZUMAB (SUSVIMO) OCULAR IMPLANT
The intravitreal ocular implant ranibizumab (Susvimo) is considered medically necessary and, therefore, covered for individuals who meet all of the following criteria AND meet the requirements listed in the COMPANY-DESIGNATED PREFERRED PRODUCTS and NONPREFERRED PRODUCTS sections above:
  • Diagnosed with ONE of the following:
    • Neovascular (wet or exudative) age-related macular degeneration (AMD)​
    • Diabetic macular edema ​(DME)​
    • Diabetic retinopathy ​(DR)​ 
  • Requires VEGF antagonist treatment every month   
  • Meets the conditions listed under the COMPANY-DESIGNATED PREFERRED PRODUCTS and NONPREFERRED PRODUCTS​ sections above
  • Documented response to at least two intravitreal injections of a nonpreferred product (e.g., brolucizumab-dbll [Beovu)], aflibercept [Eylea)], aflibercept HD [Eylea HD], faricimab-svoa [Vabysmo], and related biosimilars) within the past 6 months ​
Continuation Therapy   

VEGF antagonists and VEGF/Ang-2 inhibitors are considered medically necessary and, therefore, covered for the continuation therapy when the individual meets ALL of the following: 
  • ​Individual has met the medical necessity criteria for Initial Therapy    
  • Medical records show BOTH of the following:
    • Documented improvement or stabilization in visual acuity
    • The professional provider orders continued treatment with the requested drug
NOT MEDICALLY NECESSARY

The use of nonpreferred products that do not meet the conditions listed under the COMPANY-DESIGNATED PREFERRED PRODUCTS and COMPANY-DESIGNATED NONPREFERRED PRODUCTS sections above are considered not medically necessary and, therefore, not covered since they are more costly than the preferred products that are at least as likely to produce equivalent therapeutic results. 

EXPERIMENTAL/INVESTIGATIONAL

All other uses of aflibercept (Eylea), ​aflibercept HD (Eylea HD), bevacizumab (Avastin), brolucizumab-dbll (Beovu), faricimab-svoa (Vabysmo), ranibizumab (Lucentis​, Susvimo), and related biosimilars are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the medical policy on off-label coverage for prescription drugs and biologics.

The use of more than one VEGF antagonist product and/or combination VEGF/angiopoietin-2 (Ang-2) inhibitor product in the same eye, in a concurrent and/or alternating manner, is considered experimental/investigational and, therefore, not covered because the use is not supported by professional medical practice guidelines or a review of the currently published peer-reviewed literature.

​REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.​​

Guidelines

There is no Medicare coverage determination addressing intravitreal injection of vascular endothelial growth factor (VEGF) antagonists, VEGF biosimilars, and combination VEGF/Angiopoietin-2 (Ang-2) inhibitors; therefore, the Company policy is applicable.

BLACK BOX WARNINGS

Refer to the specific manufacturer's prescribing information for any applicable Black Box Warnings for ranibizumab (Susvimo).
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BENEFIT APPLICATION

Subject to the terms and conditions of the applicable Evidence of Coverage, the intravitreal injection of aflibercept (Eylea), bevacizumab (Avastin), brolucizumab-dbll (Beovu), faricimab-svoa (Vabysmo), ranibizumab (Lucentis, Susvimo), and related biosimilars are covered under the medical benefits of the Company’s Medicare Advantage products when the medical necessity criteria listed in the medical policy are met.

Certain drugs are available through either the member's medical benefit (Part B benefit) or pharmacy benefit (Part D benefit), depending on how the drug is prescribed, dispensed, or administered. This medical policy only addresses instances when aflibercept (Eylea), aflibercept high dose (HD) (Eylea HD),​ bevacizumab (Avastin), brolucizumab-dbll (Beovu), faricimab-svoa (Vabysmo), ranibizumab (Lucentis, Susvimo), and related biosimilars are covered under a member's medical benefit (Part B benefit). It does not address instances when aflibercept (Eylea), bevacizumab (Avastin), brolucizumab-dbll (Beovu), ​faricimab-svoa (Vabysmo), ranibizumab (Lucentis, Susvimo), and related biosimilars are covered under a member’s pharmacy benefit (Part D benefit).

However, drugs that are identified in this policy as not medically necessary are not eligible for coverage or reimbursement by the Company.​

ADMINISTRATION GUIDELINES FROM THE PRODUCTS' PACKAGE INSERT​S

AFLIBERCEPT (EYLEA) 
Aflibercept (Eylea) is supplied as a single-dose vial or single-dose prefilled syringe and is administered only by ophthalmic intravitreal injection as follows:
  • Neovascular (wet or exudative) age-related macular degeneration (AMD): 2 mg intravitreal injection every 4 weeks (monthly) for the first 3 months, followed by 2 mg intravitreal injection once every 8 weeks. Additional efficacy was not demonstrated in most individuals when dosing every 4 weeks compared to every 8 weeks; however, some individuals may need dosing every 4 weeks after the first 3 months. Although not as effective as the recommended every-8-week dosing regimen, individuals may also be treated with a 2 mg dose every 12 weeks after 1 year of effective therapy​
  • Macular edema following retinal vein occlusion (RVO): 2 mg intravitreal injection every 4 weeks​
  • Diabetic macular edema (DME): 2 mg intravitreal injection ​4 weeks (monthly) for the first 5 months, followed by a 2 mg intravitreal injection every 8 weeks. Additional efficacy was not demonstrated in most individuals when dosing every 4 weeks compared to every 8 weeks; however, some individuals may need dosing every 4 weeks after the first 20 weeks (5 months)
  • Diabetic retinopathy (DR): 2 mg intravitreal injection every 4 weeks (monthly) for the first 5 months, followed by a 2 mg intravitreal injection every 8 weeks. Additional efficacy was not demonstrated in most individuals when dosing every 4 weeks compared to every 8 weeks; however, some individuals may need dosing every 4 weeks after the first 20 weeks (5 months)​
  • Retinopathy of prematurity: the recommended dose is a 0.4 mg treatment initiated with a single intravitreal injection per eligible eye and may be given bilaterally on the same day. Injections may be repeated in each eye but should be at least 10 days after the previous injection
AFLIBERCEPT HD (EYLEA HD) AND RELATED BIOSIMILARS​
Aflibercept (Eylea) is supplied as a single-dose vial and is administered only by ophthalmic intravitreal injection as follows:
  • Neovascular (wet or exudative) AMD: 8 mg intravitreal injection every 4 weeks (monthly) for the first 3 months, followed by 8 mg intravitreal injection every 8 to 16 weeks thereafter. Some individuals do not maintain a response with extended dosing intervals after successful response to the three initial monthly doses and may benefit from resuming every 4 weeks (monthly) dosing. Extended dosing intervals (8mg every 20 weeks) may be considered after one year of successful response based on visual and anatomic outcomes 
  • DME: 8 mg intravitreal injection every 4 weeks (monthly) for the first 3 months, followed by 8 mg intravitreal injection once every 8 to 16 weeks thereafter. Some individuals do not maintain a response with extended dosing intervals after successful response to the 3 initial monthly doses and may benefit from resuming every 4 weeks (monthly) dosing. Extended dosing intervals (8mg every 20 weeks) may be considered after one year of successful response based on visual and anatomic outcomes
  • DR: 8 mg intravitreal injection every 4 weeks (monthly) for the first 3 months, followed by 8 mg intravitreal injection once every 8 to 12 weeks thereafter. Some individuals do not maintain a response with extended dosing intervals after successful response to the three initial monthly doses and may benefit from resuming every 4 weeks (monthly) dosing
  • ​Macular edema following RVO: 8 mg intravitreal injection every 4 weeks (monthly) for the first 3 to 5 doses, followed by 8 mg via intravitreal injection once every 8 weeks thereafter. Some individuals do not maintain a response with extended dosing intervals after successful response to the three initial monthly doses and may benefit from resuming every 4 weeks (monthly) dosing​
BROLUCIZUMAB-DBLL (BEOVU) 
Brolucizumab-dbll (Beovu) is supplied as a single-dose vial or single-dose prefilled syringe and is administered only by ophthalmic intravitreal injection as follows:
  • Neovascular (wet or exudative) AMD: 6 mg intravitreal injection once monthly (approximately every 25–31 days) for the first three doses, followed by 6 mg injection every 8 to 12 weeks thereafter​
  • ​DME:​ ​6 mg intravitreal injection every 6 weeks (approximately every 39–45 days) for the first five doses, followed by 6 mg injection every 8 to 12 weeks​ thereafter​
FARICIMAB-SVOA (VABYSMO)
Faricimab-svoa (Vabysmo) is supplied as a single-dose vial and is administered only by ophthalmic intravitreal injection, as follows:
  • Neovascular (wet or exudative) AMD: 
    • 6 mg intravitreal injection every 4 weeks (monthly) for the first 4 months, followed by optical coherence tomography and visual acuity evaluations 8 and 12 weeks later to inform whether to give a 6 mg dose on ONE of the following three regimens:
      • Weeks 28 and 44
      • Weeks 24, 36, and 48
      • Weeks 20, 28, 36, and 44 ​
    • Additional efficacy was not demonstrated in most individuals when dosing every 4 weeks compared to every 8 weeks; however, some individuals may need dosing every 4 weeks after the first four doses
  • DME:  
    • ONE of the following regimens:
      • 1) 6 mg intravitreal injection every 4 weeks (monthly) for at least four doses. If after at least four doses, resolution of edema based on the central subfield thickness (CST) of the macula as measured by optical coherence tomography is achieved, then modify the interval by extensions of up to 4-week-interval increments or reductions of up to 8-week-interval increments based on CST and visual acuity evaluations
      • 2) 6 mg intravitreal injection every 4 weeks for the first six doses, followed by 6 mg dose intervals of every 8 weeks. 
    • ​Additional efficacy was not demonstrated in most individuals when dosing every 4 weeks compared to every 8 weeks; however, some individuals may need dosing every 4 weeks after the first 4 m​onths
  • ​​​​Macular edema following RVO: 6 mg intravitreal injection administered every 4 weeks for 6 months (after 6 months, the frequency is individualized based on clinical response, but would not be administered more frequently than every 4 weeks)
RANIBIZUMAB (LUCENTIS) AND RELATED BIOSIMILARS
Ranibizumab (Lucentis) is supplied in a single-dose vial or single-dose prefilled syringe and is administered only by ophthalmic intravitreal injection, 0.5 mg intravitreal injection no more than once monthly per affected eye for treatment of neovascular (wet or exudative) AMD, macular edema following RVO, DME, DR, and myopic choroidal neovascularization (mCNV).
  • Neovascular (wet or exudative) AMD:
    • ONE of the following regimens:
      • 0.5 mg intravitreal injection once monthly
      • Although not as effective, individuals may be treated with 0.5 mg intravitreal injection monthly for 3 months followed by less frequent dosing. In the 9 months after the three initial monthly doses, less frequent dosing with four to five doses on average is expected to maintain visual acuity while monthly dosing may be expected to result in an additional average one- to two-letter gain of visual acuity
      • Although less effective, treatment for AMD may be reduced to one injection every 3 months after the first four injections if monthly injections are not feasible. Compared to continued monthly dosing, dosing every 3 months over the next 9 months will lead to an approximate five-letter (one-line) loss of visual acuity benefit, on average. Individuals should be evaluated regularly.
  • Macular edema following RVO: 0.5 mg intravitreal injection monthly
  • DME: 0.5 mg intravitreal injection monthly
  • DR: 0.5 mg intravitreal injection monthly​
  • Myopic choroidal neovascularization (mCNV): 0.5 mg intravitreal injection monthly for up to 3 months. Individuals may be re-treated if needed.​
RANIBIZUMAB (SUSVIMO) OCULAR IMPLANT   ​
Ranibizumab (Susvimo) is a surgically placed intravitreal ocular implant that is filled with ranibizumab to treat both neovascular (wet or exudative) AMD and DME.
  • Neovascular (wet or exudative) AMD: 2 mg continuously delivered via the ocular implant with refills administered every 24 weeks (approximately 6 months)
  • DME: 2 mg continuously delivered via the ocular implant with refills administered every 24 weeks (approximately 6 months)
  • DR: 2 mg continuously delivered via the ocular implant with refills administered every 36 weeks (approximately 9 months)
  • Supplemental treatment with ranibizumab injection: 0.5 mg intravitreal injection may be administered in the affected eye while the implant is in place and if clinically necessary​
US FOOD AND DRUG ADMINISTRATION STATUS

Aflibercept (Eylea) was approved by the US Food and Drug Administration (FDA) on November 18, 2011, for treatment of neovascular (wet) AMD. Supplemental approvals for aflibercept (Eylea) have since been issued by the FDA.

Aflibercept HD (Eylea HD) was approved by the FDA on August 18, 2023, for the treatment of individuals with neovascular (wet) AMD (nAMD), DME, and DR. ​Supplemental approvals for aflibercept HD (Eylea HD) have since been issued​​​​ by the FDA.

The initial approval for the use of bevacizumab (Avastin) was granted by the FDA on February 26, 2004. Supplemental approvals have since been issued by the FDA. The FDA has issued subsequent approvals for biosimilar products.
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Brolucizumab-dbll (Beovu) was approved by the FDA on October 7, 2019, for the treatment of neovascular (wet) AMD. Supplemental approvals for brolucizumab-dbll (Beovu)​ have since been issued by the FDA.

Faricimab-svoa (Vabysmo) was approved by the FDA on January 28, 2022, for the treatment of neovascular (wet) AMD and DME.​ ​Supplemental approvals for faricimab-svoa (Vabysmo) have since been issued by the FDA.

Ranibizumab (Lucentis) was approved by the FDA on June 30, 2006, for the treatment of neovascular (wet) AMD. Supplemental approvals for ranibizumab (Lucentis) have since been issued by the FDA. The FDA has issued subsequent approvals for biosimilar products.

Ranibizumab (Susvimo) was approved by the FDA on October 22, 2021, for the treatment of neovascular (wet) AMD in individuals who have previously responded to at least two intravitreal injections of a VEGF inhibitor​. The product was voluntarily removed from the market by the manufacturer, but returned to the market in 2025. Subsequent approvals for ranibizumab (Susvimo) ​​have since been issued by the FDA.
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​PEDIATRIC USE
The safety and effectiveness of aflibercept (Eylea) have been demonstrated in two clinical studies of pre-term infants with ROP.

The safety and effectiveness of aflibercept HD (Eylea HD) have not been established in the pediatric population.​

The safety and effectiveness of bevacizumab (Avastin), brolucizumab-dbll (Beovu), faricimab-svoa (Vabysmo), ranibizumab (Lucentis, Susvimo), and related biosimilars have not been established in the pediatric population.​​​

Description

Vascular endothelial growth factor (VEGF) is a secreted protein that selectively binds and activates its receptors, which are located primarily on the surface of vascular endothelial cells. VEGF stimulates new blood vessel formation. Overexpression of VEGF can induce abnormal neovascularization and increase vascular permeability and inflammation.
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Neovascularization results in the growth of abnormal blood vessels behind the retina and contributes to the progression of neovascular (wet) age-related macular degeneration (AMD), also known as exudative AMD. Wet AMD occurs when the abnormal blood vessels under the macula leak blood and fluid, leading to vision loss.

Other ocular conditions where VEGF plays a role includes retinal vein occlusion (RVO) where the normal blood flow through a retinal vein becomes blocked, causing edema and hemorrhaging in the retina that can lead to vision loss. RVO is classified according to whether the central retinal vein (CRVO) or one of its branches is obstructed. Diabetic macular edema (DME) is a condition associated with diabetes and causes blurred vision, severe vision loss, and sometimes blindness. Diabetic retinopathy may occur with or without DME and is classified as nonproliferative or proliferative, depending on the severity of the disease. Choroidal neovascularization occurs when abnormal blood vessels begin growing in the choroid (the area beneath the retina) and move into subretinal space and leak blood and fluid, leading to vision loss.

Aflibercept (Eylea) is ​a VEGF antagonist administered via ophthalmic intravitreal injection that received US Food and Drug Administration (FDA) approval in 2011 for the treatment of neovascular (wet) AMD. Since that time, multiple related biosimilars have also received FDA approval. Aflibercept (Eylea) and related biosimilars act as a soluble decoy receptor that binds VEGF-A and placental growth factor (PIGF), a second growth factor that initiates the formation of new blood vessels. Aflibercept (Eylea) received supplemental approvals from the FDA in September 2012 for use in the treatment of macular edema following central retinal vein occlusion (CRVO), in July 2014 for use in the treatment of DME, in October 2014 for use in the treatment of macular edema following branch retinal vein occlusion, and in March 2015 and May 2019 for expanded use in the treatment of diabetic retinopathy. In February 2023, the FDA approved its use for retinopathy of prematurity (ROP).

Aflibercept high dose (HD) (Eylea HD) is a VEGF inhibitor administered via ophthalmic intravitreal injection that received FDA approval in 2023 for the treatment of neovascular (wet) AMD, DME, and diabetic retinopathy. The high-dose formulation contains 8 mg of active ingredient while the low-dose formulation contains 2 mg of active ingredient. The high-dose formulation has the same mechanism of action as the low-dose formulation. After the first three doses, the interval of administration can be increased depending on the response to the injection.​ In November 2025, the FDA approved its use for retinal vein occlusion (RVO).​

Bevacizumab (Avastin) and related biosimilars are a recombinant humanized monoclonal immunoglobulin G1 (IgG1) antibody derived from the same monoclonal antibody as ranibizumab (Lucentis) that binds to and inhibits the biologic activity of human VEGF. Bevacizumab (Avastin) and related biosimilars are​ administered via ophthalmic intravitreal injection.   

Brolucizumab-dbll (Beovu) is a recombinant humanized VEGF inhibitor that binds to the three major isoforms of VEGF-A, thereby preventing interaction with receptors VEGFR-1 and VEGFR-2. By inhibiting VEGF-A, brolucizumab suppresses endothelial cell proliferation, neovascularization, and vascular permeability. Brolucizumab-dbll (Beovu) is administered via ophthalmic intravitreal injection. Brolucizumab-dbll (Beovu) received FDA approval on October 7, 2019, for the treatment of neovascular (wet) AMD. In May 2022, brolucizumab-dbll (Beovu) received FDA approval for the treatment of DME. 
​
Faricimab-svoa (Vabysmo) is administered via ophthalmic intravitreal injection. Faricimab-svoa (Vabysmo) is a humanized bispecific IgG1 antibody that binds both VEGF-A and angiopoietin-2 (Ang-2). By inhibiting VEGF-A, the drug suppresses endothelial cell proliferation, neovascularization, and vascular permeability. By inhibiting Ang-2, the drug is thought to promote vascular stability and desensitize blood vessels to the effects of VEGF-A. Faricimab-svoa (Vabysmo) was approved by the FDA on January 28, 2022, for the treatment of neovascular (wet) AMD and DME. Faricimab-svoa (Vabysmo) was approved by the FDA on October 26, 2023, for the treatment of macular edema following RVO.  ​  ​

Ranibizumab (Lucentis) and related biosimilars are VEGF-A antagonists. Ranibizumab (Lucentis) and related biosimilars work by binding to and inhibiting the action of VEGF-A, a substance that binds to certain cells to stimulate new blood vessel formation and growth (e.g., angiogenesis, neovascularization). When VEGF-A binds to ranibizumab (Lucentis), it cannot stimulate neovascularization. 
  • Ranibizumab (Lucentis) is also administered via ophthalmic intravitreal injection. Ranibizumab (Lucentis) received FDA approval in 2006 for the treatment of neovascular (wet) AMD. Ranibizumab (Lucentis) received supplemental approvals from the FDA in June 2010 for use in the treatment of macular edema following retinal vein occlusion (RVO) and in August 2012 for use in the treatment of DME. In February 2015, ranibizumab (Lucentis) received FDA approval for use in the treatment of diabetic retinopathy in individuals with DME; in April 2017, the approval was modified to include those without DME. Also, in January 2017, ranibizumab (Lucentis) was FDA approved for the treatment of myopic choroidal neovascularization (mCNV). Multiple biosimilars have also received FDA approval.​
  • Ranibizumab (Susvimo) is also administered via ophthalmic intravitreal injection. Ranibizumab (Susvimo) was approved by the FDA on October 22, 2021, for use in the treatment of neovascular (wet) AMD in individuals who have previously responded to at least two intravitreal injections of a VEGF inhibitor.​ In February 2025, ranibizumab (Susvimo) received FDA approval for use in the treatment of diabetic macular edema in individuals who have previously responded to at least two intravitreal injections of a VEGF inhibitor. In May 2025, ranibizumab (Susvimo) received FDA approval for use in the treatment of diabetic retinopathy in individuals who have previously responded to at least two intravitreal injections of a VEGF inhibitor.
OFF-LABEL INDICATIONS

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.​​

References

Ababneh OH, Yousef YA, Gharaibeh AM, et al. Intravitreal bevacizumab in the treatment of diabetic ocular neovascularization. Retina. 2013;33(4):748-755.

 

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Evidence of Coverage.

 

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Schmidt-Erfurth U, Eldem B, Guymer R, et al. Efficacy and safety of monthly versus quarterly ranibizumab treatment in neovascular age-related macular degeneration: the EXCITE study. Ophthalmology. 2011;118(5):831-839.

 

Schmidt-Erfurth U, Kaiser PK, Korobelnick JF, et al. Intravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six-week results of the VIEW studies. Ophthalmology. 2014;121(1):193-201.

 

Schmidt-Erfurth U, Lang GE, Holz FG, et al. Three-year outcomes of individualized ranibizumab treatment in patients with diabetic macular edema: the RESTORE extension study. Ophthalmology. 2014;121(5):1045-1053.

 

Semeraro F, Morescalchi F, Russo A, et al. Central serous chorioretinopathy: pathogenesis and management. Clin Ophthalmol. 2019;13:2341-2352.

 

Shah M, Amoaku WMK. Intravitreal ranibizumab for the treatment of choroidal neovascularisation secondary to angioid streaks. Eye (Lond). 2012;26(9):1194-1198.

 

Shah SU, Shields CL, Bianciotto CG, et al. Intravitreal bevacizumab at 4-month intervals for prevention of macular edema after plaque radiotherapy of uveal melanoma. Ophthalmology. 2014;121(1):269-275.

 

Sharma A, Hafeez Faridi M, Kumar N, et al. Immunogenicity and efficacy after switching from original ranibizumab to a ranibizumab biosimilar: real-world data. Eye (Lond). 2020;34(6):1008-1009.

 

Sharma A, Kumar N, Parachuri N, et al. Biosimilars for retinal diseases: an update. Am J Ophthalmol. 2021;224:36-42.

 

Sharma A, Parachuri N, Kumar N, et al. The Port Delivery System with ranibizumab-journey of mitigating vitreous hemorrhage. Eye (Lond). 2022;36(3):488-489.

 

Simha A, Aziz K, Braganza A, et al. Anti-vascular endothelial growth factor for neovascular glaucoma. Cochrane Database Syst Rev. 2020;2:CD007920.

 

Singer MA, Awh CC, Sadda SV, et al. HORIZON: an open-label extension trial of ranibizumab for choroidal neovascularization secondary to age-related macular degeneration. Ophthalmology. 2012;119(6):1175-1183.

 

Soheilian M, Garfami KH, Ramezani A, et al. Two-year results of a randomized trial of intravitreal bevacizumab alone or combined with triamcinolone versus laser in diabetic macular edema. Retina. 2012;32(2):314-321.

 

Soheilian M, Ramezani A, Obudi A, et al. Randomized trial of intravitreal bevacizumab alone or combined with triamcinolone versus macular photocoagulation in diabetic macular edema. Ophthalmology. 2009;116(6):1142-1150.

 

Solomon SD, Chew E, Duh EJ, et al. Diabetic retinopathy: a position statement by the American Diabetes Association. Diabetic Care. 2017;40:412-418.

 

Solomon SD, Lindley K, Vedula SS, et al. Anti-vascular endothelial growth factor for neovascular age-related macular degeneration. Cochrane Database Syst Rev. 2014;8:CD005139.

 

Solomon SD, Lindsley K, Vedula SS, et al. Anti-vascular endothelial growth factor for neovascular age-related macular degeneration. Cochrane Database Syst Rev. 2019;3:CD005139.

 

Stahl A, Lepore D, Fielder A, et al. Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): an open-label randomised controlled trial. Lancet. 2019;394(10208):1551-1559.

 

Stahl A, Sukgen EA, Wu WC, et al. Effect of intravitreal aflibercept vs laser photocoagulation on treatment success of retinopathy of prematurity: the FIREFLEYE randomized clinical trial. JAMA. 2022;328(4):348-359.

 

Staurenghi G, Feltgen N, Arnold JJ, et al. Impact of baseline diabetic retinopathy severity scale scores on visual outcomes in the VIVID-DME and VISTA-DME studies. Br J Ophthalmol. 2018;102(7):954-958.

 

Thach AB, Yau L, Hoang C, Tuomi L. Time to clinically significant visual acuity gains after ranibizumab treatment for retinal vein occlusion: BRAVO and CRUISE trials. Ophthalmology. 2014;121(5):1059-1066.

 

Troutbeck R, Bunting R, van Heerdon A, et al. Ranibizumab therapy for choroidal neovascularization secondary to non-age-related macular degeneration causes. Clin Experiment Ophthalmol. 2012;40(1):67-72.

 

Tufail A, Patel PJ, Egan C, et al; ABC Trial Investigators. Bevacizumab for neovascular age related macular degeneration (ABC Trial): multicentre randomised double masked study. BMJ. 2010;340:c2459.

 

UpToDate® LexidrugTM. Aflibercept/aflibercept HD (Eylea®, Eylea® HD, Pavblu®). [UpToDate Lexidrug Web site]. 01/23/2026. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed February 5, 2026.

 

UpToDate® LexidrugTM. Bevacizumab (Alymsys®, Avastin®, Jobevne®, Mvasi®, Vegzelma®, Zirabev®). [UpToDate Lexidrug Web site]. 01/16/2026. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed February 5, 2026.

 

UpToDate® LexidrugTM. Brolucizumab (Beovu®). [UpToDate Lexidrug Web site]. 01/09/2026. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed February 5, 2026.

 

UpToDate® LexidrugTM. Faricimab (Vabysmo®). [UpToDate Lexidrug Web site]. 01/02/2026. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed February 5, 2026.

 

UpToDate® LexidrugTM. Ranibizumab (Byooviz®, Cimerli®, Lucentis®, Susvimo®). [UpToDate Lexidrug Web site]. 02/04/2026. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed February 5, 2026.

 

US Food and Drug Administration (FDA). Biosimilars. [FDA Web site].  03/01/2023. Available at: https://www.fda.gov/drugs/therapeutic-biologics-applications-bla/biosimilars. Accessed February 5, 2026.

 

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Aflibercept (Eylea®). Prescribing information. [FDA Web site]. 10/10/2024. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed February 5, 2026.

 

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Aflibercept HD (Eylea® HD). Prescribing information. [FDA Web site]. 04/02/2026. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed April 5, 2026.

 

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Aflibercept-abzv (Enzeevu®). Prescribing information. [FDA Web site]. 02/10/2025. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed February 5, 2026.

 

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Aflibercept-ayyh (Pavblu®). Prescribing information. [FDA Web site]. 08/23/2024. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed February 5, 2026.

 

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Aflibercept-boav (Eydenzelt®). Prescribing information. [FDA Web site]. 10/02/2025. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed February 5, 2026.

 

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Aflibercept-jvbf (Yesafili®). Prescribing information. [FDA Web site]. 01/13/2026. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed February 5, 2026.

 

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Aflibercept-mrbb (Ahzantive®). Prescribing information. [FDA Web site]. 06/28/2024. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed February 5, 2026.

 

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Aflibercept-yszy (OpuvizTM). Prescribing information. [FDA Web site]. 08/25/2025. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed February 5, 2026.

 

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Bevacizumab (Avastin®). Prescribing information. [FDA Web site]. 09/18/2022. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed February 5, 2026.

 

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Bevacizumab-adcd (Vegzelma®). Prescribing information. [FDA Web site]. 09/27/2022. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed February 5, 2026.

 

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Bevacizumab-awwb (Mvasi®). Prescribing information. [FDA Web site]. 02/17/2023. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed February 5, 2026.

 

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Bevacizumab-bvzr (Zirabev®). Prescribing information. [FDA Web site]. 08/28/2024. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed February 5, 2026.

 

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Bevacizumab-maly (Alymsys®). Prescribing information. [FDA Web site]. 04/13/2022. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed February 5, 2026.

 

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Bevacizumab-nwgd (JobevneTM). Prescribing information. [FDA Web site]. 04/09/2025. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed February 5, 2026.

 

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Bevacizumab-tnjn (Avzivi®). Prescribing information. [FDA Web site]. 12/06/2023. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed February 5, 2026.

 

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Brolucizumab-dbll (Beovu®). Prescribing information. [FDA Web site]. 07/29/2024. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed February 5, 2026.

 

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Faricimab (Vabysmo®). Prescribing information. [FDA Web site]. 07/03/2024. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed February 5, 2026.

 

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Ranibizumab (Lucentis®). Prescribing information. [FDA Web site]. 02/15/2024. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed February 5, 2026.

 

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Ranibizumab (Susvimo®). Prescribing information. [FDA Web site]. 09/05/2025. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed February 5, 2026.

 

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Ranibizumab-eqrn (Cimerli®). Prescribing information. [FDA Web site]. 05/21/2024. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed February 5, 2026.

 

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Ranibizumab-leyk (Nufymco®). Approval letter. [FDA Web site]. 12/18/2025. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed February 5, 2026.

 

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Ranibizumab-nuna (Byooviz®). Prescribing information. [FDA Web site]. 11/12/2025. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed February 5, 2026.

 

VanderVeen DK, Melia M, Yang MB, et al. Anti-Vascular endothelial growth factor therapy for primary treatment of type I retinopathy of prematurity; a report by the American Academy of Ophthalmology. Ophthalmology. 2017;124(5):619-633.

 

Virgili G, Parravano M, Evans JR, et al. Anti-vascular endothelial growth factor for diabetic macular oedema: a network meta-analysis. Cochrane Database Syst Rev. 2018;10;CD007419.

 

Wakabayashi T, Oshima Y, Sakaguchi H, et al. Intravitreal bevacizumab to treat iris neovascularization and neovascular glaucoma secondary to ischemic retinal diseases in 41 consecutive cases. Ophthalmology. 2008;115(9):1571-1580, 1580.e1-e3.

 

Wallace DK, Dean TW, Hartnett ME, et al.; Pediatric Eye Disease Investigator Group. A dosing study of bevacizumab for retinopathy of prematurity: late recurrences and additional treatments. Ophthalmology. 2018;125(12):1961-1966.

 

Weber ML, Heier JS. Choroidal neovascularization secondary to myopia, infection and inflammation. Dev Ophthalmol. 2016;55:167-175.

 

Wells JA, Glassman AR, Ayala AR, et al.; Diabetic Retinopathy Clinical Research Network. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema: two-year results from a comparative effectiveness randomized clinical trial. Ophthalmology. 2016;123(6):1351-1359.

 

Wolf S, Balciuniene VJ, Laganovska G, et al.; RADIANCE Study Group. RADIANCE: a randomized controlled study of ranibizumab in patients with choroidal neovascularization secondary to pathologic myopia. Ophthalmology. 2014;121(3):682-692.e1-e2.

 

Woo SJ, Bradvica M, Vajas A, et al. Efficacy and safety of the aflibercept biosimilar SB15 in neovascular age-related macular degeneration: a phase 3 randomized clinical trial. JAMA Ophthalmol. 2023;141(7):668-676.

 

Woo SJ, Veith M, Hamouz J, et al. Efficacy and safety of a proposed ranibizumab biosimilar product vs a reference ranibizumab product for patients with neovascular age-related macular degeneration: a randomized clinical trial. JAMA Ophthalmol. 2021;139(1):68-76.

 

Wykoff C. Regeneron presents positive data from PANORAMA trial. Healio Ocular Surgery News; 2/14/2019. Available at: https://www.healio.com/news/ophthalmology/20190214/regeneron-presents-positive-data-from-panorama-trial. Accessed February 5, 2026.

 

Wykoff CC, Le RT, Khurana RN, et al. Outcomes with as-needed aflibercept and macular laser following the phase III VISTA DME trial: ENDURANCE 12-month extension study. Am J Ophthalmol. 2017;173:56-63.

 

Wycoff CC, Marcus DM, Midena E, et al. Intravitreal aflibercept injection in eyes with substantial vision loss after laser photocoagulation for diabetic macular edema: subanalysis of the VISTA and VIVID randomized clinical trials. JAMA Ophthalmol. 2017;135(2):107-114.

 

Wykoff CC, Shah C, Dhoot D, et al. Longitudinal retinal perfusion status in eyes with diabetic macular edema receiving intravitreal aflibercept or laser in VISTA study. Ophthalmology. 2019;126(8):1171-1180.

 

Yadav NK, Bharghav M, Vasudha K, Shetty KB. Choroidal neovascular membrane complicating traumatic choroidal rupture managed by intravitreal bevacizumab. Eye (Lond). 2009;23(9):1872-1873.

 

Yang J, Manson DK, Marr BP, Carvajal RD. Treatment of uveal melanoma: where are we now? Ther Adv Med Oncol. 2018;10:1758834018757175.

 

Yeh S, Kim SJ, Ho AC, et al. Therapies for macular edema associated with central retinal vein occlusion: a report by the American Academy of Ophthalmology. Ophthalmology. 2015;122(4):769-778.

 

Ziemssen F, Schlottman PG, Lim JI, et al. Initiation of intravitreal aflibercept injection treatment in patients with diabetic macular edema: a review of VIVID-DME and VISTA-DME data. Int J Retina Vitreous. 2016;2:16.​

Coding

CPT Procedure Code Number(s)
N/A
ICD - 10 Procedure Code Number(s)
N/A
ICD - 10 Diagnosis Code Number(s)

Report the most appropriate diagnosis code in support of medically necessary criteria as listed in the policy.​​

HCPCS Level II Code Number(s)
C9257 Injection, bevacizumab, 0.25 mg
J0177 Injection, aflibercept hd, 1 mg
J0178 Injection, aflibercept, 1 mg
J0179 Injection, brolucizumab-dbll, 1 mg
J2777 Injection, faricimab-svoa, 0.1 mg
J2778 Injection, ranibizumab, 0.1 mg
J2779 Injection, ranibizumab, via intravitreal implant (susvimo), 0.1 mg
J9035 Injection, bevacizumab, 10 mg
Q5107 Injection, bevacizumab-awwb, biosimilar (mvasi), 10 mg
Q5118 Injection, bevacizumab-bvzr, biosimilar (zirabev), 10 mg
Q5124 Injection, ranibizumab-nuna, biosimilar (byooviz), 0.1 mg 
Q5126 Injection, bevacizumab-maly, biosimilar (alymsys), 10 mg
Q5128 Injection, ranibizumab-eqrn (cimerli), biosimilar, 0.1 mg
Q5129 Injection, bevacizumab-adcd (vegzelma) biosimilar, 10 mg
​Q5147 Injection, aflibercept-ayyh (pavblu) biosimilar, 1 mg
Q5149 Injection, aflibercept-abzv (enzeevu) biosimilar, 1 mg
Q5150 Injection, aflibercept-mrbb (ahzantive) biosimilar, 1 mg
Q5153 Injection, aflibercept-yszy (opuviz) biosimilar, 1 mg
Q5155 Injection, aflibercept-jbvf (yesafili) biosimilar, 1 mg
Q5160 Injection, bevacizumab-nwgd (jobevne), biosimilar 10 mg​

THE FOLLOWING CODES ARE USED TO REPRESENT AFLIBERCEPT-BOAV (EYDENZELT)​​​, BEVACIZUMAB-TNJN (AVZIVI) ​AND RANIBIZUMAB-LEYK (NUFYMCO)

C9399 Unclassified drugs or biologics
J3590 Unclassified biologics
Revenue Code Number(s)
N/A

​

Coding and Billing Requirements

Policy History

Revisions From MA08.073v:
08/03/2026This version of the policy will become effective 08/03/2026.

The following policy criteria have been added to this policy:

An inadequate response is determined after administering at least three (3) monthly injections at doses in accordance with FDA labeling.

The following drug was added to this policy as medically necessary ​in accordance with the US Food and Drug Administration:

Ranibizumab-leyk (Nufymco®​)​

Revisions From MA08.073u:
01/01/2026
​This version of the policy will become effective 01/01/2026.
 
​The Company-designated preferred and non-preferred products section was revised to add names of biosimilars (Ahzantive, Enzeevu, Eydenzelt, Opuviz, Pavblu, Yesafili).

The following new indication was added to aflibercept HD (Eylea HD):
macular edema following retinal vein occlusion (RVO)​

The indications for ranibizumab (Susvimo) were revised to add diabetic macular edema ​(DME) and diabetic retinopathy ​(DR) in accordance with the US Food and Drug Administration (FDA) labeling.

​The following HCPCS code has been added to this policy:
Q5160 Injection, bevacizumab-nwgd (jobevne), biosimilar 10 mg

Revisions From MA08.073t:
10/01/2025
​This version of the policy will become effective 10/01/2025.
 
Inclusion of a policy in a Code Update memo does not imply that a full review of
the policy was completed at this time.
 
The following HCPCS code has been added to this policy:
Q5155 Injection, aflibercept-jbvf (yesafili), biosimilar, 1 mg​

​Revisions From MA08.073s:
07/01/2025This version of the policy will become effective 07/01/2025.
Inclusion of a policy in a Code Update memo does not imply that a full review of
the policy was completed at this time.

The following HCPCS code has been added to this policy:
Q5153 Injection, aflibercept-yszy (opuviz), biosimilar, 1 mg

Revisions From MA08.073r:
04/01/2025This version of the policy will become effective 04/01/2025.
Inclusion of a policy in a Code Update memo does not imply that a full review of
the policy was completed at this time.

The following HCPCS codes have been added to this policy:
Q5147 Injection, aflibercept-ayyh (pavblu), biosimilar, 1 mg
Q5149 Injection, aflibercept-abzv (enzeevu), biosimilar, 1 mg
Q5150 Injection, aflibercept-mrbb (ahzantive), biosimilar, 1 mg​​

Revisions From MA08.073q:
01/01/2025This version of the policy will become effective 01/01/2025 

First line and second line Company-Designated Preferred Products were added to the policy:
  • First line:
    • Any bevacizumab product
  • Second line:
    • Ranibizumab (Lucentis®)
    • Ranibizumab-nuna (ByoovizTM)
    • Ranibizumab-eqrn (Cimerli®)
Ranibizumab (Lucentis) was removed​ from the list of Non-Preferred Products.

The following drugs have been added​​ to the policy in accordance with the US Food and Drug Administration (FDA):

Aflibercept-abzy (Enzeevu​​TM) 08/07/2024
Aflibercept-ayyh (PavbluTM) 08/23/2024
Aflibercept-jbvf (YesafiliTM) 05/20/2024
Aflibercept-mrbb (AhzantiveTM) 06/28/2024
Aflibercept-yszy (Opuviz​TM​) 05/20/2024​

Revisions From MA08.073p:
04/01/2024
This version of the policy will become effective 04/01/2024.

The following drug has been added to the policy in accordance with the US Food and Drug Administration (FDA) (12/06/2023):
Bevacizumab-tnjn (Avzivi)

The following HCPCS codes were added to the policy:
C9399 Unclassified drugs or biologicals to represent bevacizumab-tnjn (Avzivi)​
J3590 unclassified biologics to represent bevacizumab-tnjn (Avzivi)​​​
J0177 Injection, aflibercept hd, 1 mg

The following HCPCS code has been termed (no longer valid codes)​and removed from the policy:
C9161 Injection, aflibercept hd, 1 mg​

Revisions From MA08.073o:
02/26/2024
This version of the policy will become effective 02/26/2024.

The following indication for faricimab-svoa ​(Vabysmo) has been added to this policy in accordance with the US Food and Drug Administration (FDA) (10/26/2023):

Macular edema following retinal vein occlusion (RVO)

Revisions From MA08.073n:
01/02/2024
The policy will become effective 01/02/2024.
Inclusion of a policy in a Code Update memo does not imply that a full review of
the policy was completed at this time.

The following HCPCS code has been added to this policy:
C9161 Injection, aflibercept hd, 1 mg

The following HCPCS code has been removed from this policy:
C9399 Unclassified drugs​ or biologicals​

Revisions From MA08.073m:
​01/01/2024
​Effective 01/01/2024 this policy applies to New Jersey Medicare Advantage (MA) lines of business.
​10/16/2023
This version of the policy will become effective 10/16/2023

Aflibercept high dose (HD) (Eylea HD) and related biosimilars were added to the policy in accordance with US Food and Drug Administration (FDA) labeling (08/18/2023)

The following HCPCS codes have been added to the policy:
  • C9399 Unclassified drugs or biologicals
  • J3590 Unclassified biologics​

Revisions From MA08.073l:
09/18/2023This version of the policy will become effective 09/18/2023.
​
This policy has been updated to communicate the Company's coverage position for the newly FDA-approved products: faricimab-svoa (Vabysmo) and intravitreal ocular implant ranibizumab (Susvimo).

There was clarification that the Company has designated bevacizumab as its preferred product for members who are treatment-naïve. 

The following indication for aflibercept (Eylea) has been added to this policy in accordance with the US Food and Drug Administration (FDA) (02/08/2023):
Retinopathy of prematurity

The following indication for bevacizumab (Avastin) and related biosimilars and ranibizumab (Lucentis) and related biosimilars has been added to this policy in accordance with clinical trials and peer-reviewed literature:
Retinopathy of prematurity

Continuation Therapy criteria were added as a policy criterion.​

Due to the retired Novitas LCA, the following criterion was removed from Eylea, bevacizumab, Beovu, and Lucentis: "Other retinal diseases, including ischemic retinal vein occlusions, and for decreasing the vascularity of proliferative diabetic retinopathy prior to vitreous surgery". These indications are covered under indications from the FDA labeling.

The following HCPCS codes have been added to this policy:
  • J2777 Injection, faricimab-svoa, 0.1 mg
  • ​J2779 Injection, ranibizumab, via intravitreal implant (Susvimo), 0.1 mg
The following HCPCS code has been removed from this policy, since it is no longer manufactured and has been withdrawn from market​: ​: 
  • ​J2503 Injection, pegaptanib sodium, 0.3 mg​​

Revisions From MA08.073k:
04/01/2023

This version of the policy will become effective 04/01/2023


Inclusion of a policy in a Code Update memo does not imply that a full review of
the policy was completed at this time.


The following HCPCS codes have been removed from this policy:

C9399  Unclassified drugs or biologicals​

J3590   Unclassified biologics​


The following HCPCS codes have been added to this policy:


Q5128 Injection, ranibizumab-eqrn (cimerli), biosimilar, 0.1 mg​​

Q5129 Injection, bevacizumab-adcd (vegzelma), biosimilar, 10 mg


Revisions From ​MA08.073j:
01/01/2023​
This version of the policy will become effective 01/01/2023​.

This policy has been updated to communicate the Company's coverage position for the newly FDA-approved products: bevacizumab-adcd (Vegzelma), ranibizumab-eqrn (Cimerli), bevacizumab-maly (Alymsys). 

Brolucizumab-dbll (Beovu) coverage was added for a new indication for diabetic macular edema (DME)​, in alignment with the FDA-approval.

​​The following HCPCS codes have been added to this policy:

Q5126 Injection, bevacizumab-maly, biosimilar, (alymsys), 10 mg​

​THE FOLLOWING CODES ARE USED TO REPRESENT ​ranibizumab-eqrn (Cimerli), bevacizumab-adcd (Vegzelma):
C9399  Unclassified drugs or biologicals
J3590  Unclassified biologics 
​

All of the ICD-10 CM codes have been removed from this policy, since they are informational.​​


Revisions From MA08.073i:
04/01/2022​
This version of the policy will become effective 04/01/2022.

The following HCPCS code has been added to this policy:
Q5124 Injection, ranibizumab-nuna, biosimilar, (byooviz), 0.1 mg

Revisions From MA08.073h:
04/12/2021​This policy has been updated to communicate the Company's coverage position for ​the following:


Clarify the Medical Necessity of non-preferred products when the product was initiated prior to 01/01/2020 and the individual is currently receiving the product or has previously received a non-preferred product for vascular diseases of the eye. 


Clarify the use of non-preferred product samples; additional clinical information demonstrating medical necessity of the desired medication must be submitted by the requesting provider for review.


The following indication for Beovu has been added as Medically Necessary, and is in alignment with Novitas:
  • Other retinal diseases, including ischemic retinal vein occlusions, and for decreasing the vascularity of proliferative diabetic retinopathy prior to vitreous surgery

​Macugen has been withdrawn from the market and is no longer eligible for reimbursement. 

The following HCPCS code has been revised from Medically Necessary to Not Eligible ​for Reimbursement: 

​J2503 Injection, pegaptanib sodium, 0.3 mg


​The following ICD-10 DM codes have been added to this policy: ​

Beovu:

H35.82     Retinal ischemia

H35.89     Other specified retinal disorders

 

Eylea:

H34.8110 - H34.8190 Central retinal vein occlusion, with macular edema

H34.8111 - H34.8191 Central retinal vein occlusion, with retinal neovascularization 

H34.8310 - H34.8390 Tributary (branch) retinal vein occlusion, with macular edema

H34.8311 - H34.8391 Tributary (branch) retinal vein occlusion, with retinal neovascularization​

H35.82     Retinal ischemia

H35.89     Other specified retinal disorders

 

Avastin & Lucentis:

H20.011- H20.019 Primary iridocyclitis

H20.021 - H20.029 Recurrent acute iridocyclitis

H20.031 - H20.039 Secondary infectious iridocyclitis

H20.041 - H20.049 Secondary noninfectious iridocyclitis

H20.052 - H20.059 Hypopyon

H20.10 - H20.13 Chronic iridocyclitis

H20.20 - H20.23 Lens-induced iridocyclitis

H20.811 - H20.819 Fuchs' heterochromic cyclitis

H20.821 - H20.829 Vogt-Koyanagi syndrome

H35.82     Retinal ischemia

H35.89     Other specified retinal disorders ​


Revisions From MA08.073g:
04/27/2020This version of the policy will become effective 04/27/2020.

This policy has been updated to communicate the Company's coverage position for brolucizumab-dbll (Beovu®) and bevacizumab-bvzr (ZirabevTM), in accordance with US Food and Drug Administration (FDA) prescribing information. An additional indication has been added for Avastin® and related biosimilars in accordance with Novitas Solutions, Inc.

The following HCPCS codes have been added to this policy:

J0179 Injection, brolucizumab-dbll, 1 mg
Q5118 Injection, bevacizumab-bvcr, biosimilar, (Zirabev), 10 mg

Revisions From MA08.073f:
01/01/2020This version of the policy will become effective 01/01/2020. This policy was updated to:
  • change policy title to "Intravitreal Injection of Vascular Endothelial Growth Factor (VEGF) Antagonists and Related Biosimilars"
  • include Avastin® and incorporate the company's designation of Avastin® and related biosimilars as its preferred product.
  • revise the 'Medically Necessary' criteria for Lucentis and Eylea to indicate both vascular endothelial growth factor (VEGF) antagonists are covered for individuals with non-proliferative and proliferative diabetic retinopathy with and without diabetic macular edema.
The following ICD10 codes have been added to the policy for Lucentis only: E08.3521, E08.3522, E08.3523, and E08.3529.

Applicable diagnosis codes have been added to the policy due to criteria changes for Eylea and Avastin.

Revisions From MA08.073e:
10/30/2017This policy was updated to include a new FDA-labeled indication for Lucentis® for the treatment of non-proliferative and proliferative diabetic retinopathy in individuals with or without diabetic macular edema.

Note: on 05/03/2018 the following ICD-10 codes were removed from Attachment A for Lucentis, Eylea, and Macugen: H34.00, H34.01, H34.02, H34.03, H34.10, H34.11, H34.12, H34.13, H34.211, H34.212, H34.213, H34.219, H34.231, H34.232, H34.233, H34.239, H34.8112, H34.8122, H34.8132, H34.8192, H34.821, H34.822, H34.823, H34.829, H34.8312, H34.8322, H34.8392, H35.89, H36

Note: on 05/22/2018 the following ICD-10 code was removed from Attachment A for Lucentis and Eylea: H34.8332.

Revisions From MA08.073d:
10/01/2017This policy has been identified for the ICD-10 CM code update, effective 10/01/2017.

The following ICD-10 CM codes have been added to this policy for Lucentis® only:
H44.2A1 Degenerative myopia with choroidal neovascularization, right eye
H44.2A2 Degenerative myopia with choroidal neovascularization, left eye
H44.2A3 Degenerative myopia with choroidal neovascularization, bilateral eye
H44.2A9 Degenerative myopia with choroidal neovascularization, unspecified eye
H44.2B1 Degenerative myopia with macular hole, right eye
H44.2B2 Degenerative myopia with macular hole, left eye
H44.2B3 Degenerative myopia with macular hole, bilateral eye
H44.2B9 Degenerative myopia with macular hole, unspecified eye
H44.2C1 Degenerative myopia with retinal detachment, right eye
H44.2C2 Degenerative myopia with retinal detachment, left eye
H44.2C3 Degenerative myopia with retinal detachment, bilateral eye
H44.2C9 Degenerative myopia with retinal detachment, unspecified eye
H44.2D1 Degenerative myopia with foveoschisis, right eye
H44.2D2 Degenerative myopia with foveoschisis, left eye
H44.2D3 Degenerative myopia with foveoschisis, bilateral eye
H44.2D9 Degenerative myopia with foveoschisis, unspecified eye
H44.2E1 Degenerative myopia with other maculopathy, right eye
H44.2E2 Degenerative myopia with other maculopathy, left eye
H44.2E3 Degenerative myopia with other maculopathy, bilateral eye
H44.2E9 Degenerative myopia with other maculopathy, unspecified eye

Revisions From MA08.073c:
03/28/2017This policy has been updated to reflect the FDA-approved prescribing information for Eylea®.

The coding table has been updated to reflect the Policy's covered indications; as such, the following codes have been removed from this policy:

The following ICD-10 codes have been removed from the policy for EYLEA® & MACUGEN® & LUCENTIS®:
E08.3521, E08.3522, E08.3523, E08.3529, E08.3531, E08.3532, E08.3533, E08.3539, E08.3541, E08.3542, E08.3543, E08.3549, E08.3551, E08.3552, E08.3553, E08.3559, E09.3521, E09.3522, E09.3523, E09.3529, E09.3531, E09.3532, E09.3533, E09.3539, E09.3541, E09.3542, E09.3543, E09.3549, E09.3551, E09.3552, E09.3553, E09.3559, E10.3521, E10.3522, E10.3523, E10.3529, E10.3531, E10.3532, E10.3533, E10.3539, E10.3541, E10.3542, E10.3543, E10.3549, E10.3551, E10.3552, E10.3553, E10.3559, E11.3521, E11.3522, E11.3523, E11.3529, E11.3531, E11.3532, E11.3533, E11.3539, E11.3541, E11.3542, E11.3543, E11.3549, E11.3551, E11.3552, E11.3553, E11.3559, E13.3521, E13.3522, E13.3523, E13.3529, E13.3531, E13.3532, E13.3533, E13.3539, E13.3541, E13.3542, E13.3543, E13.3549, E13.3551, E13.3552, E13.3553, E13.3559, H34.11, H34.12, H34.13, H34.231, H34.232, H34.233, H34.8112, H34.8122, H34.8132, H34.8192, H34.821, H34.822, H34.823, H34.8312, H34.8322, H34.8332, H34.8392, H35.3113, H35.3114, H35.3123, H35.3124, H35.3133, H35.3134, H35.3193, H35.3194

The following ICD-10 codes have been removed from the policy for LUCENTIS® only:
H21.1X1, H21.1X2, H21.1X3

Revisions From MA08.073b:
10/01/2016This policy has been identified for the ICD-10 code update, effective 10/01/2016.

The following ICD-10 code has been added to this policy:
H34.8110, H34.8111, H34.8112, H34.8120, H34.8121, H34.8122, H34.8130, H34.8131, H34.8132, H34.8190, H34.8191, H34.8192, H34.8310, H34.8311, H34.8312, H34.8320, H34.8321, H34.8322, H34.8330, H34.8331, H34.8332, H34.8390, H34.8391, H34.8392, H35.3113, H35.3114, H35.3123, H35.3124, H35.3133, H35.3134, H35.3193, H35.3194, H35.3210, H35.3211, H35.3212, H35.3213, H35.3220, H35.3221, H35.3222, H35.3223, H35.3230, H35.3231, H35.3232, H35.3233, H35.3290, H35.3291, H35.3292, H35.3293, E08.3211, E08.3212, E08.3213, E08.3219, E08.3311, E08.3312, E08.3313, E08.3319, E08.3411, E08.3412, E08.3413, E08.3419, E08.3511, E08.3512, E08.3513, E08.3519, E08.3521, E08.3522, E08.3523, E08.3529, E08.3531, E08.3532, E08.3533, E08.3539, E08.3541, E08.3542, E08.3543, E08.3549, E08.3551, E08.3552, E08.3553, E08.3559, E09.3211, E09.3212, E09.3213, E09.3219, E09.3311, E09.3312, E09.3313, E09.3319, E09.3411, E09.3412, E09.3413, E09.3419, E09.3511, E09.3512, E09.3513, E09.3519, E09.3521, E09.3522, E09.3523, E09.3529, E09.3531, E09.3532, E09.3533, E09.3539, E09.3541, E09.3542, E09.3543, E09.3549, E09.3551, E09.3552, E09.3553, E09.3559, E10.3211, E10.3212, E10.3213, E10.3219, E10.3311, E10.3312, E10.3313, E10.3319, E10.3411, E10.3412, E10.3413, E10.3419, E10.3511, E10.3512, E10.3513, E10.3519, E10.3521, E10.3522, E10.3523, E10.3529, E10.3531, E10.3532, E10.3533, E10.3539, E10.3541, E10.3542, E10.3543, E10.3549, E10.3551, E10.3552, E10.3553, E10.3559, E11.3211, E11.3212, E11.3213, E11.3219, E11.3311, E11.3312, E11.3313, E11.3319, E11.3411, E11.3412, E11.3413, E11.3419, E11.3511, E11.3512, E11.3513, E11.3519, E11.3521, E11.3522, E11.3523, E11.3529, E11.3531, E11.3532, E11.3533, E11.3539, E11.3541, E11.3542, E11.3543, E11.3549, E11.3551, E11.3552, E11.3553, E11.3559, E13.3211, E13.3212, E13.3213, E13.3219, E13.3311, E13.3312, E13.3313, E13.3319, E13.3411, E13.3412, E13.3413, E13.3419, E13.3511, E13.3512, E13.3513, E13.3519, E13.3521, E13.3522, E13.3523, E13.3529, E13.3531, E13.3532, E13.3533, E13.3539, E13.3541, E13.3542, E13.3543, E13.3549, E13.3551, E13.3552, E13.3553, E13.3559

The following ICD-10 codes have been deleted from this policy:
H34.811, H34.812, H34.813, H34.831, H34.832, H34.833, H35.31, H35.32, E08.321, E08.331, E08.341, E08.351, E09.321, E09.331, E09.341, E09.351, E10.321, E10.331, E10.341, E10.351, E11.321, E11.331, E11.341, E11.351, E13.321, E13.331, E13.341, E13.351

Revisions From MA08.073a:
07/15/2015This policy has been updated to communicate the Medical Necessity of the new FDA-labeled indications for aflibercept (Eylea®) for the treatment of diabetic macular edema and macular edema following branch retinal vein occlusion. The administration guidelines of aflibercept (Eylea®) were also updated.

The Medical Necessity of a new FDA-labeled indication for ranibizumab (Lucentis®) and aflibercept (Eylea®) was included for the treatment of non-proliferative and proliferative diabetic retinopathy in individuals with diabetic macular edema.

The Medical Necessity of an off-label indication for ranibizumab (Lucentis®) was also included.
  • Choroidal neovascularization due to angioid streaks, central serous chorioretinopathy, choroidal rupture or trauma, idiopathic choroidal neovascularization, multifocal choroiditis, pathologic myopia, and presumed ocular histoplasmosis syndrome, uveitis
Language regarding off-label indications have been updated.

Revisions From MA08.073:
01/01/2015This is a new policy.​​

8/3/2026
8/3/2026
MA08.073
Medical Policy Bulletin
Medicare Advantage
No
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Independence Blue Cross is a subsidiary of Independence Health Group, Inc. — independent licensees of the Blue Cross and Blue Shield Association, serving the health insurance needs of Philadelphia and southeastern Pennsylvania.