Intravitreal Angiogenesis Inhibitors

POLICY NUMBER

L.5.01.569

Alymsys (bevacizumab-maly)

Avastin (bevacizumab)

Beovu (brolucizumab)

Byooviz (ranibizumab-nuna)

Cimerli (ranibizumab-eqrn)

Eylea (aflibercept)

Eylea HD (aflibercept)

Izervay (avacincaptad pegol)

Lucentis (ranibizumab)

Mvasi (bevacizumab-awwb)

Susvimo (ranibizumab)

Vabysmo (faricimab-svoa)

Vegzelma (bevacizumab-adcd)

Zirabev (bevacizumab-bvzr)

Please perform a formulary drug search on your patient’s member ID to ensure the prescription drug is covered under their benefit plan. The medication(s) in this medical policy may not be covered under a specific member’s benefit plan.

DESCRIPTION

Vascular endothelial growth factor (VEGF) is a secreted protein that selectively binds and activates its receptors located primarily on the surface of vascular endothelial cells. It induces angiogenesis and increases vascular permeability and inflammation, which has been implicated in the pathogenesis of a variety of ocular vascular conditions. Intravitreal injection of drugs that inhibit VEGF can limit progression of exudative AMD and stabilize, or reverse, visual loss.

A number of anti-VEGF molecules have been developed that can limit the destructive effects of choroidal neovascularization associated with age-related macular degeneration (AMD) and for the treatment of disorders of retinal circulation (e.g., diabetic macular edema [DME], diabetic retinopathy, macular edema following retinal vein occlusion, retinopathy of prematurity [ROP]). In a systematic review of 16 randomized trials (6,347 participants) evaluating VEGF inhibitors, outcomes for bevacizumab and ranibizumab were similar and both improved visual acuity, as well as morphologic parameters, compared with placebo. In light of the significant difference in cost between bevacizumab and ranibizumab or aflibercept, use of bevacizumab is increasingly being administered in the United States.

Related medical policies -

• Photodynamic Therapy for Choroidal Neovascularization

• Transpupillary Thermotherapy for Treatment of Choroidal Neovascular Conditions

• Intraocular Radiotherapy for Age-Related Macular Degeneration

• Biosimilar Medications

POLICY

Prior authorization is required for Byooviz (ranibizumab-nuna), Eylea (aflibercept) or Lucentis (ranibizumab).

The use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements.

Avastin (bevacizumab), Mvasi (bevacizumab-awwb), and Zirabev (bevacizumab-bvzr) are considered medically necessary for the following indications:

• neovascular (wet) age-related macular degeneration;

• choroidal neovascularization due to angioid streaks, central serous chorioretinopathy, choroidal rupture or trauma, idiopathic choroidal neovascularization, multifocal choroiditis, pathologic myopia, presumed ocular histoplasmosis syndrome, and uveitis;

• diabetic macular edema;

• diabetic retinopathy;

• macular edema following central retinal vein occlusion;

• macular edema following branch retinal vein occlusion; AND

• retinopathy of prematurity.

Byooviz (ranibizumab-nuna), Eylea (aflibercept) or Lucentis (ranibizumab) may be considered medically necessary when ALL of the following criteria are met:

1. The individual is ≥18 years of age;

2. ONE of the following:

   1. The request is for Byooviz (ranibizumab-nuna) or Lucentis (ranibizumab), and the individual has a documented diagnosis of ONE of the following:

      1. neovascular (wet) age-related macular degeneration;

      2. macular edema following retinal vein occlusion;

      3. diabetic macular edema;

      4. diabetic retinopathy; OR

      5. myopic choroidal neovascularization; OR

   2. The request is for Eylea (aflibercept) and ONE of the following:

      1. BOTH of the following:

         1. The individual has a documented diagnosis of ONE of the following:

            1. neovascular (wet) age-related macular degeneration;

            2. macular edema following retinal vein occlusion;

            3. diabetic macular edema; OR

            4. diabetic retinopathy; AND

         2. Treatment with ranibizumab or a ranibizumab biosimilar has been ineffective, not tolerated, or contraindicated; OR

      2. The individual has a documented diagnosis of retinopathy of prematurity in preterm neonates

3. Treatment with bevacizumab or a bevacizumab biosimilar has been ineffective, not tolerated, or contraindicated;

4. The prescriber is a specialist or has consulted with a specialist in an area of the individual's diagnosis (i.e., ophthalmologist);

5. The individual does not have any FDA-labeled contraindication(s) to therapy with the requested agent; AND

6. The prescribed dosage is within the program quantity limits based on FDA approved labeled dosage.

Services related to delivery and/or administration of a medication which have not been approved through the BCBSMS PA review process will be considered not medically necessary.

Alymsys (bevacizumab-maly), Beovu (brolucizumab), Cimerli (ranibizumab-eqrn), Eylea HD (aflibercept), Izervay (avacincaptad pegol), Susvimo (ranibizumab), Vabysmo (faricimab-svoa), and Vegzelma (bevacizumab-adcd) are considered not medically necessary as there are other alternatives covered by the Plan for the treatment of neovascular (Wet) age-related macular degeneration (nAMD), macular edema, diabetic retinopathy and/or myopic choroidal neovascularization.

Intravitreal use of bevacizumab is considered investigational for the treatment of individuals with sickle cell retinopathy.

Intravitreal use of vascular endothelial growth factor inhibitors other than bevacizumab is considered investigational for the treatment of individuals with sickle cell retinopathy.

Anti-vascular endothelial growth factor therapies (anti-VEGF) are considered investigational for all other indications.

POLICY EXCEPTIONS

State Health Plan (State and School Employees) Participants

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

A. consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

B. appropriate with regard to standards of good medical practice; and

C. not solely for the convenience of the Member, his or her Provider; and

D. the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

BCBSMS may request medical records for determination of medical necessity. When medical records are requested, letters of support and/or explanation are often useful, but are not sufficient documentation unless all specific information needed to make a medical necessity determination is included.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.

Medication Failure

Medication failure is defined as disease progression despite maximally tolerated dose (≥3 months use) as appropriate for disease state being treated. Dosages below the recommended dose for the specific condition being treated and/or experience of common side effects of medication will not be considered medication failure for the purpose of this review.

POLICY HISTORY

07/28/2020: New policy added. Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee.

07/13/2021: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Policy updated to remove Macugen (pegaptanib sodium). Policy description updated regarding anti-VEGF molecules. Revised medically necessary policy statement to include criteria for Eylea (aflibercept) and Lucentis (ranibizumab). Added statement that services related to delivery and/or administration of a medication which have not been approved through the BCBSMS PA review process will be considered not medically necessary. Policy statement for Beovu updated to state that Beovu (brolucizumab) is considered not medically necessary on any BCBSMS formulary as there are other alternatives covered by the Plan for the treatment of Neovascular (Wet) Age-related Macular Degeneration (AMD). Policy Exceptions updated regarding State Health Plan members. Policy Guidelines updated to change "Nervous/Mental Conditions" to "Mental Health Disorders" and "Medically Necessary" to "medical necessity." Added information regarding BCBSMS request for medical records. Revised information regarding medication failure. Sources updated. Code Reference section updated to remove HCPCS code J2503.

09/17/2021: Code Reference section updated to delete J3490. Added HCPCS codes C9257, J9035, Q5107, and Q5118 to the Medically Necessary Codes table. Added HCPCS J0179 to the Not Medically Necessary Codes table.

11/03/2022: Policy updated to add Vabysmo (faricimab-svoa). Policy statement revised to state that Beovu (brolucizumab) and Vabysmo (faricimab-svoa) are considered not medically necessary as there are other alternatives covered by the Plan for the treatment of neovascular (Wet) age-related macular degeneration (nAMD) and/or diabetic macular edema (DME). Code Reference section updated to add HCPCS code J2777.

11/28/2022: Policy Guidelines updated to make the following correction regarding medication failure: "≥1 months use" changed to "≥3 months use."

02/01/2023: Policy Exceptions updated to add the following: State Health Plan (State and School Employees): The prescription drug(s) in this medical policy may be covered under a prescription drug benefit plan administered by the State Health Plan’s Pharmacy Benefit Manager. Please perform a formulary drug search at https://www.dfa.ms.gov/cvs-caremark and submit any required Prior Authorization Requests for coverage determination to the Plan’s Pharmacy Benefit Manager. Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary. Services related to delivery and/or administration of a self-administered drug are not covered.

07/01/2023: Policy Exceptions updated regarding State Health Plan (State and School Employees) Participants.

10/01/2023: Policy updated to add Alymsys (bevacizumab-maly), Byooviz (ranibizumab-nuna), Cimerli (ranibizumab-eqrn), Eylea HD (aflibercept), Susvimo (ranibizumab), and Vegzelma (bevacizumab-bvzr). Policy description updated regarding related medical policies. Policy section updated to state that prior authorization is required for Byooviz (ranibizumab-nuna). Medically necessary policy statement updated regarding Byooviz (ranibizumab-nuna), Eylea (aflibercept), and Lucentis (ranibizumab). Revised policy statement to state that Beovu (brolucizumab), Cimerli (ranibizumab-eqrn), Eylea HD (aflibercept), Susvimo (ranibizumab), and Vabysmo (faricimab-svoa) are considered not medically necessary as there are other alternatives covered by the Plan for the treatment of neovascular (Wet) age-related macular degeneration (nAMD), macular edema, diabetic retinopathy and/or myopic choroidal neovascularization. Sources updated. Code Reference section updated to add HCPCS code Q5124 to the Medically Necessary Codes table and HCPCS code Q5128 to the Not Medically Necessary Codes table.

03/11/2024: Policy section updated to state that intravitreal use of bevacizumab and intravitreal use of vascular endothelial growth factor inhibitors other than bevacizumab is considered investigational for the treatment of individuals with sickle cell retinopathy. Sources updated. Code Reference section updated to add ICD-10 diagnosis codes H32, H34.8110 – H34.8192, H34.8310 – H34.8392, H35.101 – H35.169, and H44.2A1 – H44.2A9. Added HCPCS code Q5126 to the Not Medically Necessary Codes table.

04/01/2024: Policy updated to add Izervay (avacincaptad pegol) as not medically necessary as there are other alternatives covered by the Plan for the treatment of neovascular (Wet) age-related macular degeneration (nAMD), macular edema, diabetic retinopathy and/or myopic choroidal neovascularization. Sources updated. Code Reference section updated to add HCPCS code C9162.

05/15/2024: Code Reference section updated to replace deleted HCPCS code C9162 with new HCPCS code J2782.

10/01/2024: Policy reviewed and approved by the Pharmacy & Therapeutics (P&T) Committee. Policy language updated to change "member" to "individual." Medically necessary criteria for Eylea (aflibercept) updated to add retinopathy of prematurity in preterm neonates as an indication. Sources updated.

03/27/2025: Policy updated to make the following correction for Vegzelma: "bevacizumab-bvzr" changed to "bevacizumab-adcd."

09/09/2025: Policy reviewed and approved by the Pharmacy & Therapeutics (P&T) Committee. Policy statement revised to state that the use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements. Medically necessary criteria updated with minor changes. Sources updated. Code Reference section updated to remove deleted HCPCS code C9162.

10/01/2025: Code Reference section updated to add HCPCS codes J0177, J2779, and Q5129 to the Not Medically Necessary Codes table.

SOURCE(S)

1. Age-related macular degeneration. In: UpToDate, Connor RF (Ed), Wolters Kluwer. Accessed on June 25, 2025. Available at https://www.uptodate.com/contents/age-related-macular-degeneration.

2. Alymsys prescribing information. Amneal Pharmaceuticals LLC. April 2022. Last accessed June 2025.

3. Avastin prescribing information. Genentech, Inc. January 2025. Last accessed June 2025.

4. Beovu prescribing information. Novartis Pharmaceuticals Corporation. February 2025. Last accessed June 2025.

5. Blue Cross Blue Shield Association policy # 9.03.24

6. Blue Cross Blue Shield Association policy # 9.03.27

7. Blue Cross Blue Shield Association policy # 9.03.31

8. Byooviz prescribing information. Biogen Inc. January 2025. Last accessed June 2025.

9. Cimerli prescribing information. Coherus BioSciences Inc. May 2025. Last accessed June 2025.

10. Eylea prescribing information. Regeneron Pharmaceuticals, Inc. October 2024. Last accessed June 2025.

11. Eylea HD prescribing information. Regeneron Pharmaceuticals, Inc. October 2024. Last accessed June 2025.

12. Fierson WM, American Academy of Pediatrics Section on Ophthalmology, American Academy of Ophthalmology, et al. Screening examination of premature infants for retinopathy of prematurity. Pediatrics. 2018 Dec. 142.

13. Izervay prescribing information. Astellas Pharma US, Inc. March 2025. Last accessed June 2025.

14. Lucentis prescribing information. Genentech, Inc. November 2024. Last accessed June 2025.

15. Mvasi prescribing information. Amgen Inc. October 2024. Last accessed June 2025.

16. Susvimo prescribing information. Genentech, Inc. May 2025. Last accessed June 2025.

17. Vabysmo prescribing information. Genentech, Inc. December 2024. Last accessed June 2025.

18. Vegzelma prescribing information. Celltrion USA, Inc. May 2025. Last accessed June 2025.

19. Zirabev prescribing information. Pfizer Laboratories Div Pfizer Inc. January 2025. Last accessed June 2025.

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.

Medically Necessary Codes

Not Medically Necessary Codes

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