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

​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.

MEDICALLY NECESSARY

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 antagonists compared with other brands. The company has designated the following as its preferred product for members who are treatment-naïve:
  • First line:
    • Any bevacizumab product
  • Second line:
    • ​Ranibizumab (Lucentis®)
    • Ranibizumab-nuna (ByoovizTM)
    • Ranibizumab-eqrn (Cimerli®)

These products are less costly and at least as likely to produce equivalent therapeutic results as the non-preferred products, which include, but are not limited to, Beovu®, Eylea®, Eylea® High Dose (HD), Susvimo®, Vabysmo®​, and related biosimilars.​


According to the US Food and Drug Administration (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. ​

NON-PREFERRED PRODUCTS*    
For individuals who meet the medical necessity criteria below, use of non-preferred products (which include Beovu, Eylea, Eylea HD, ​Susvimo, Vabysmo, and ​any biosimilars ​to non-preferred products) is considered medically necessary and, therefore, covered when the individual has a documented contraindication, or documented nonresponse, to ​any bevacizumab product and at least one other preferred product.​​

*The use of non-preferred products that do not meet either of these instances are considered not medically necessary and, therefore, not covered.

NOTE: Use of non-preferred 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.​

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 NON-PREFERRED 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 NON-PREFERRED PRODUCTS sections above: 
  • Neovascular (wet or exudative) AMD
  • DME
  • DR​
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 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
  • DME
  • DR
  • Macular edema following RVO
  • Neovascular (wet) AMD
  • Neovascular glaucoma
  • 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 NON-PREFERRED PRODUCTS sections above:
  • Neovascular (wet or exudative) AMD
  • 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 NON-PREFERRED PRODUCTS sections above:
  • Neovascular (wet or exudative) AMD
  • DME​
  • Macular edema following 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 NON-PREFERRED PRODUCTS sections above: 
  • Neovascular (wet or exudative) AMD
  • Macular edema following RVO
  • DME
  • DR
  • 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 NON-PREFERRED PRODUCTS sections above:
  • Diagnosed with neovascular (wet or exudative) AMD and requires VEGF antagonist treatment every month                    
  • Documented response to at least two intravitreal injections of a non-preferred product (e.g., Beovu, Eylea, Eylea HD, Vabysmo, and related biosimilars) within the last 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

For individuals receiving their first course of VEGF antagonists, use of non-preferred products is considered not medically necessary and, therefore, not covered unless the individual has a documented contraindication or nonresponse to a preferred​ bevacizumab product first, then a ranibizumab product second, because more cost-effective alternatives are available.

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.

​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

BLACK BOX WARNINGS  

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

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, the intravitreal injection of 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 the medical benefits of the Company’s products when the medical necessity criteria listed in the medical policy are met.

However, services 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:
  • Wet age-related macular degeneration (AMD): 2 mg every 4 weeks (monthly) for the first 3 months, followed by one 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 3 months. Although not as effective as the recommended every-8-week dosing regimen, individuals may also be treated with one dose every 12 weeks after 1 year of effective therapy.​ Individuals should be evaluated regularly.​
  • Diabetic macular edema (DME) and diabetic retinopathy in individuals with DME: every 4 weeks (monthly) for the first 5 months, followed by one 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).
  • Macular edema following retinal vein occlusion (RVO): every 4 weeks
  • Retinopathy of prematurity: treatment is initiated with a single 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:
  • Wet AMD: 8 mg every 4 weeks (monthly) for the first 3 months, followed by one intravitreal injection every 8 to 16 weeks.
  • DME: 8 mg every 4 weeks (monthly) for the first 3 months, followed by one intravitreal injection once every 8 to 16 weeks.
  • Diabetic retinopathy: 8 mg every 4 weeks (monthly) for the first 3 months, followed by one intravitreal injection once every 8 to 12 weeks.
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: 
  • Wet AMD: ​once monthly (approximately every 25–31 days) for the first three doses, followed by one injection every 8 to 12 weeks thereafter.
  • DME:​ ​every 6 weeks (approximately every 39–45 days) for the first five doses, followed by one 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:
  • Wet AMD: 
    • 6 mg 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. ​
  • Diabetic macular edema:  
    • One of the following regimens:
      • 1) 6 mg 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 every 4 weeks for the first six doses, followed by 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 months.
  • ​​​​Macular edema following RVO: 6 mg 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, no more than once monthly per affected eye for treatment of wet AMD, macular edema following RVO, diabetic macular edema, diabetic retinopathy, and myopic choroidal neovascularization (mCNV).

Although less effective, treatment for AMD may begin with three monthly doses 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. Individuals should be evaluated regularly. 
 
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. 

Monthly dosing for up to 3 months is the recommendation for the treatment of mCNV; individuals may be retreated, if needed.
 
RANIBIZUMAB (SUSVIMO) OCULAR IMPLANT   ​
Ranibizumab (Susvimo) is a surgically placed intravitreal ocular implant that is filled with ranibizumab. It is designed to continuously deliver ranibizumab 2 mg​ via the ocular implant over 24 weeks (approximately 6 months), then a refill procedure is performed every 24 weeks. Supplemental treatment with 0.5-mg intravitreal ranibizumab injection may be administered in the affected eye while the Susvimo​ implant is in place and if clinically necessary.

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

Aflibercept (Eylea) was approved by the 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 diabetic retinopathy (DR).

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.
​
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​.
​​
​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.
​
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), in which 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 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 RVO, 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 whereas 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.​

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 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 the treatment of neovascular (wet) AMD 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

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Aflibercept injection (Eylea®) [prescribing information]. Tarrytown, NY: Regeneron Pharmaceuticals, Inc.; 12/2023. Available at: http://hcp.eylea.us/. Accessed August 26, 2024.

Aflibercept HD injection (Eylea® HD​) [prescribing information]. Tarrytown, NY: Regeneron Pharmaceuticals, Inc.; 12/2023. Available at: http://hcp.eylea.us/. Accessed August 26, 2024.

Aflibercept-abzv (EnzeevuTM​) [prescribing information]. Princeton, NJ: Sandoz Inc; 08/2024. Available at: https://prod.cms.us.sandoz.com/sites/spare37_sandoz_com/files/Media Documents/ENZEEVU_PI_2024_2.pdf. Accessed August 26, 2024.

Alagöz C, Alagöz N, Özkaya A, et al. Intravitreal bevacizumab in the treatment of choroidal neovascular membrane due to angioid streaks. Retina. 2015;35(10):2001-2010. 

American Academy of Ophthalmology Ophthalmic Technology Assessment. Safety and efficacy of anti-vascular endothelial growth factor therapies for neovascular age-related macular degeneration: a report by the American Academy of Ophthalmology. 2019:126(1):55–63. Available at: https://www.aaojournal.org/article/S0161-6420(18)32031-1/fulltext. Accessed August 26, 2024.

American Academy of Ophthalmology. What is macular degeneration? 11/13/2023. Available at: https://www.aao.org/eye-health/diseases/amd-macular-degeneration. Accessed August 26, 2024. 

American Academy of Ophthalmology. Diabetic retinopathy: causes, symptoms, treatment. 11/27/2023. Available at: https://www.aao.org/eye-health/diseases/what-is-diabetic-retinopathy. Accessed August 26, 2024.

American Academy of Ophthalmology. What is a retinal vein occlusion? 02/02/2024. Available at: https://www.aao.org/eye-health/diseases/retinal-vein-occlusion-3. Accessed August 26, 2024.

American Academy of Ophthalmology. Treat-and-extend-strategy: is there a consensus? EyeNet Magazine. 01/01/2016. Available at: https://www.aao.org/eyenet/article/treat-extend-strategy-is-there-consensus. Accessed August 26, 2024.

American Hospital Formulary Service (AHFS). Aflibercept (Eylea®). Drug Information 2024 [Lexicomp Online Web site]. 03/11/2024. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed August 26, 2024.

American Hospital Formulary Service (AHFS). Bevacizumab (Avastin®). Drug Information 2024. [Lexicomp Online Web site]. 03/11/2024. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed August 26, 2024. 

American Hospital Formulary Service (AHFS). Brolucizumab-dbll (Beovu®). Drug Information 2024. [Lexicomp Online Web site]. 03/11/24. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed August 26, 2024.

American Hospital Formulary Service (AHFS). Faricimab (Vabysmo®). Drug Information 2024. [Lexicomp Online Web site]. 08/02/2024. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed August 26, 2024.

American Hospital Formulary Service (AHFS). Ranibizumab (Lucentis®​). Drug Information 2024. [Lexicomp Online Web site]. 03/11/2024. Available at: http://online.lexi.com/lco/action/home [via subscription only]. Accessed August 26, 2024.

Arevalo JF, Garcia-Amaris RA. Intravitreal bevacizumab for diabetic retinopathy. Curr Diabetes Rev. 2009;5:39-46.

Arevalo JF, Wu L, Sanchez JG, et al. Intravitreal bevacizumab (avastin) for proliferative diabetic retinopathy: 6-months follow-up. Eye. 2009;23(1):117-123.

Artunay O, Yuzbasioglu E, Rasier R, et al. Combination treatment with intravitreal injection of ranibizumab and reduced fluence photodynamic therapy for choroidal neovascularization secondary to angioid streaks: preliminary clinical results of 12-month follow-up. Retina. 2011;31(7):1279-1286.

Artunay O, Yuzbasioglu E, Rasier R, et al. Intravitreal bevacizumab in treatment of idiopathic persistent central serous chorioretinopathy: a prospective, controlled clinical study. Curr Eye Res. 2010;35(2):91-98.

Avery RL, Pearlman J, Pieramici DJ, et al. Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy. Ophthalmology. 2006;113(10):1695.e1-e15. 

Battaglia Parodi M, Iacono P, La Spina C, et al. Intravitreal bevacizumab for nonsubfoveal choroidal neovascularization associated with angioid streaks. Am J Ophthalmol. 2014;157(2):374-377.e2.

Berk Ergun S, Toklu Y, Cakmak HB, et al. The effect of intravitreal bevacizumab as a pretreatment of vitrectomy for diabetic vitreous hemorrhage on recurrent hemorrhage. Semin Ophthalmol. 2015;30(3):177-180.

Bevacizumab injection (Avastin®​) [prescribing information]. South San Francisco, CA: Genentech, Inc.; 09/2022. Available at: https://www.avastin.com/hcp.html. Accessed August 26, 2024.

Bevacizumab-adcd injection (Vegzelma®​) [prescribing information]. Jersey City, NJ: Celltrion, Inc.; 02/2023. Available at: https://vegzelma.com. Accessed August 26, 2024.

Bevacizumab-awwb injection (Mvasi®​) [prescribing information]. Thousand Oaks, CA: Amgen Inc.; 02/2023. Available at: https://www.mvasi.com/hcp. Accessed August 26, 2024.  

Bevacizumab-bvzr injection (Zirabev®​) [prescribing information]. New York, NY: Pfizer Inc.; 02/2023. Available at: https://www.zirabev.com/. Accessed August 26, 2024.​​​

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Company Benefit Contracts.

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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 August 26, 2024.  

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 August 26, 2024.

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 August 26, 2024.

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 August 26, 2024.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Ranibizumab (SusvimoTM). Prescribing information. [FDA Web site]. 04/18/2022. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed August 26, 2024.  

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 August 26, 2024.  

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Ranibizumab-nuna (ByoovizTM). Prescribing information. [FDA Web site]. 10/03/2023. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/. Accessed August 26, 2024. 

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.

Virgili G, Parravano M, Menchini F, Brunetti M. Antiangiogenic therapy with anti-vascular endothelial growth factor modalities for diabetic macular oedema. Cochrane Database Syst Rev. 2012;12: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.

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 August 26, 2024.

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.

Coding

CPT Procedure Code Number(s)
N/A
ICD - 10 Procedure Code Number(s)
N/A
ICD - 10 Diagnosis Code Number(s)
​N/A​
HCPCS Level II Code Number(s)

MEDICALLY NECESSARY

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, 10mg

THE FOLLOWING CODES ARE USED TO REPRESENT AFLIBERCEPT-ABZV (ENZEEVUTM), AFLIBERCEPT-AYYH (PAVBLUTM), AFLIBERCEPT-JBVF (YESAFILITM), AFLIBERCEPT-MRBB (AHZANTIVETM), AFLIBERCEPT-YSZY (OPUVIZTM), AND BEVACIZUMAB-TNJN (AVZIVI®)​

C9399 Unclassified drugs or biologics

J3590 Unclassified biologics​

Revenue Code Number(s)
N/A



Coding and Billing Requirements

Policy History

Revisions From 08.00.74x:
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 (EnzeevuTM) 08/07/2024
Aflibercept-ayyh (Pavblu​TM) 08/23/2024
Aflibercept-jbvf (YesafiliTM) 05/20/2024
Aflibercept-mrbb (Ahzantive​TM) 06/28/2024
Aflibercept-yszy (Opuviz​TM) 05/20/2024

Revisions From 08.00.74w:
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 terminated (no longer valid codes)​ and removed from the policy:
C9161 Injection, aflibercept hd, 1 mg​​

Revisions From 08.00.74v:
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 08.00.74u:
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 08.00.74t:
​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 08.00.74s:
09/18/2023​
This 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.

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 08.00.74r:
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 ​08.00.74q:
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 08.00.74p:
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 08.00.74o:
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.


​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: 

​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​


Avastin and 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


Revisions From 08.00.74n:
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.

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 08.00.74m:
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.

Effective 10/05/2017 this policy has been updated to the new policy template format.
1/1/2025
1/6/2025
08.00.74
Medical Policy Bulletin
Commercial
No