| Coverage Policy Manual | |
| Policy #: | 2024021 |
| Category: | Pharmacy |
| Initiated: | July 2024 |
| Last Review: | July 2025 |
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| Bevacizumab (e.g., Avastin) and Biosimilars for Ophthalmic Use | |
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| Description: |
Bevacizumab (Avastin and biosimilars) is a recombinant humanized monoclonal IgG1 antibody that binds to and inhibits vascular endothelial growth factor (VEGF), reducing the growth of new blood vessels. VEGF is a biochemical signal protein that promotes angiogenesis throughout the body and in the eye.
Bevacizumab used in ophthalmology is off-label and it is commonly utilized to treat diabetic macular edema, proliferative diabetic retinopathy, macular degeneration, and choroidal neovascularization. Interest in bevacizumab for ocular use began due to the molecular similarity it shares with ranibizumab (e.g., Lucentis), which is FDA approved for AMD (Age related Macular Degeneration) (Age related Macular Degeneration), DME, and macular edema due to retinal vein occlusions. Both practitioners and patients should weigh the risks and benefits of using medication in an off-label manner and patients should always be informed of their treatment options. Bevacizumab is one of many such drugs with a long history of safety and efficacy, albeit without FDA approval for ocular use. Based on its affordability, the world health organization has put bevacizumab and not ranibizumab in WHO (World Health Organization) model list of essential drugs.
Regulatory Status
Bevacizumab (e.g., Avastin) was approved by the U.S. Food and Drug Administration (FDA) on 26 February 2004, for the treatment of metastatic colon cancer. Bevacizumab is used off-label for ophthalmic indications.
Coding
See CPT/HCPCS Code section below.
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Policy/ Coverage: |
This policy addresses ophthalmologic use only. For oncologic indications, please refer to policy 2017006 and for non-oncologic and non-ophthalmologic indications please refer to policy 2023014.
Effective July 23, 2025
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Intravitreal administration of bevacizumab (e.g., Avastin and biosimilars)
meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when
ALL of the following criteria are met:
For off-label indications, authorizations will not exceed
2.5 milligrams per treatment per eye OR
maximum recommended doses as outlined in dosage and administration section
unless medical literature supports a higher dose.
Off-Label Indications:
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
CONTINUED APPROVAL for up to 12 months:
The use of bevacizumab for treatment of sickle cell retinopathy does not meet primary coverage criteria and is not covered. For all other ophthalmic conditions other than those specified above, the use of bevacizumab is not covered.
Dosage and Administration
For off-label indications, authorizations will not exceed 2.5 milligrams per treatment per eye OR maximum recommended doses as outlined below unless medical literature supports a higher dose.
In ophthalmology bevacizumab is typically given by transconjunctival intravitreal injections into the posterior segment of an eye, although it has been used in the form of topical drops or sub-conjunctival injection. Intravitreal injections for retinal pathologies are typically administered at 4–6-week intervals, although this varies widely based on disease and response. The typical dose is 1.25mg in 0.05ml in adults. While other doses (2.5mg) have been evaluated in large trials, no significant benefit has been shown over the 1.25mg standard dose, although some sources advocate larger doses in certain situations (Wykoff et al, 2013).
The recommended dose of bevacizumab (e.g., Avastin and biosimilars) for diabetic macular degeneration is 1.25 to 1.5 milligram per eye based on central subfield thickness and visual acuity evaluations.
The recommended dose of bevacizumab (e.g., Avastin and biosimilars) for proliferative diabetic retinopathy is 1.25 milligram per eye alone or as an adjunctive treatment to photocoagulation.
The recommended dose of bevacizumab (e.g., Avastin and biosimilars) for macular degeneration is 1.25 mg (0.05 mL) once a month per eye. Treatment continues on a monthly basis until macular edema, subretinal fluid, and/or pigment epithelial detachment is resolved.
Bevacizumab (e.g., Avastin and biosimilars) is available as a 100 mg/4 mL vial of solution for injection
Bevacizumab (e.g., Avastin and biosimilars) should be administered as an intravitreal injection
by a healthcare professional.
Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Bevacizumab (e.g., Avastin and biosimilars), for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, bevacizumab (e.g., Avastin and biosimilars), for any indication or circumstance not described above, is considered
investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
Effective July 24, 2024 to July 22, 2025
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
Intravitreal administration of bevacizumab (e.g., Avastin and biosimilars)
meets member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes when
ALL of the following criteria are met:
For FDA labeled indications, all products must be dosed in accordance with the FDA label unless otherwise specified.
For off-label indications, authorizations will not exceed
2.5 milligrams per treatment per eye OR
maximum recommended doses as outlined in dosage and administration section
unless medical literature supports a higher dose.
INITIAL APPROVAL STANDARD REVIEW for up to 12 months:
CONTINUED APPROVAL for up to 12 months:
The use of bevacizumab for treatment of sickle cell retinopathy does not meet primary coverage criteria and is not covered. For all other ophthalmic conditions other than those specified above, the use of bevacizumab is not covered.
Dosage and Administration
Dosing per FDA Guidelines where applicable. For off-label indications, authorizations will not exceed 2.5 milligrams per treatment per eye OR maximum recommended doses as outlined below unless medical literature supports a higher dose.
In ophthalmology bevacizumab is typically given by transconjunctival intravitreal injections into the posterior segment of an eye, although it has been used in the form of topical drops or sub-conjunctival injection. Intravitreal injections for retinal pathologies are typically administered at 4–6-week intervals, although this varies widely based on disease and response. The typical dose is 1.25mg in 0.05ml in adults. While other doses (2.5mg) have been evaluated in large trials, no significant benefit has been shown over the 1.25mg standard dose, although some sources advocate larger doses in certain situations (Wykoff et al, 2013).
The recommended dose of bevacizumab (e.g., Avastin and biosimilars) for diabetic macular degeneration is 1.25 to 1.5 milligram per eye based on central subfield thickness and visual acuity evaluations.
The recommended dose of bevacizumab (e.g., Avastin and biosimilars) for proliferative diabetic retinopathy is 1.25 milligram per eye alone or as an adjunctive treatment to photocoagulation.
The recommended dose of bevacizumab (e.g., Avastin and biosimilars) for macular degeneration is 1.25 mg (0.05 mL) once a month per eye. Treatment continues on a monthly basis until macular edema, subretinal fluid, and/or pigment epithelial detachment is resolved.
Bevacizumab (e.g., Avastin and biosimilars) is available as a 100 mg/4 mL vial of solution for injection
Bevacizumab (e.g., Avastin and biosimilars) should be administered as an intravitreal injection
by a healthcare professional.
Please refer to separate policy on Site of Care or Site of Service Review (policy #2018030) for pharmacologic/biologic medications.
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Bevacizumab (e.g., Avastin and biosimilars), for any indication or circumstance not described above, does not meet member benefit certificate primary coverage criteria that there be scientific evidence of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, bevacizumab (e.g., Avastin and biosimilars), for any indication or circumstance not described above, is considered
investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
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| Rationale: |
Bevacizumab is considered efficacious for treatment of choroidal neovascularization and macular edema by the ophthalmologic community. As this drug has not been FDA approved for ophthalmic indications, classic clinical trials do not uniformly exist, however convincing data has been published for the most commonly treated pathologies.
Age-related Macular Degeneration (neovascular with CNV): The sham injection/untreated arm of the Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular Age-Related Macular Degeneration (MARINA) trial showed vision loss of 14.9 letters from baseline over 24 months, which is often quoted as the natural history of neovascular AMD (Rosenfeld et al, 2006). The Comparison of Age-related Macular Degeneration Treatments Trials (CATT) did not have an untreated arm, it was perhaps the most well-structured clinical trial involving bevacizumab and showed a 7.8 letter gain from baseline with monthly administration (Martin et al, 2012). The Inhibit VEGF in the Age-Related Choroidal Neovascularization (IVAN) trial has echoed this positive result (Chakravarty et al, 2013).
Diabetic Macular Edema (DME): The Pan-American Collaborative Retina Study Group (PACORES) trial compared monthly intravitreal bevacizumab with macular focal-grid laser photocoagulation (standard of care at that time) and showed an average of 11.86 letters gained with bevacizumab and 3.66 letters gained with focal grid laser over 24-months (Arevalo et al, 2013).
The incidence of serious systemic adverse effects is rare with both intravitreal bevacizumab and ranibizumab (Johnson et al, 2013). The large head-to-head clinical trials show no statistical difference in serious arteriothrombotic events or all-cause death between bevacizumab and ranibizumab (CATT, 2011; Chakravarty et al, 2013).
2025 Update
Annual policy review completed with a literature search using the MEDLINE database through July 2025. No new literature was identified that would prompt a change in the coverage statement.
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| References: |
Arevalo JF, Lasave AF, Wu L, Diaz-Llopis M, Gallego-Pinazo R, Alezzandrini AA et al.(2013) Intravitreal bevacizumab plus grid laser photocoagulation or intravitreal bevacizumab or grid laser photocoagulation for diffuse diabetic macular edema: results of the Pan-american Collaborative Retina Study Group at 24 months. Retina. 2013;33(2):403-13. Avastin(2022) package insert San Francisco, CA: Genentech; 2022. CATT Research Group, Martin DF, Maguire MG, Ying GS, Grunwald JE, Fine SL et al.(2011) Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med. 2011;364(20):1897-908. Chakravarthy U, Harding SP, Rogers CA, Downes SM, Lotery AJ, Culliford LA et al.(2013) Alternative treatments to inhibit VEGF in age-related choroidal neovascularisation: 2-year findings of the IVAN randomised controlled trial. Lancet. 2013;382(9900):1258-67. Huang L, Pang D, Yang H, Li W, Wang S, Cui S, Liao N, Wang Y, Wang C, Chang YC, Wang HC, Kang SY, Seo JH, Shen K, Laohawiriyakamol S, Jiang Z, Wang H, Lamour F, Song G, Curran M, Duan C, Lysbet de Haas S, Restuccia E, Shao Z.(2024) Neoadjuvant-adjuvant pertuzumab in HER2-positive early breast cancer: final analysis of the randomized phase III PEONY trial. Nat Commun. 2024 Mar 9;15(1):2153. doi: 10.1038/s41467-024-45591-7. PMID: 38461323; PMCID: PMC10925021. Johnson D, Sharma S.(2013) Ocular and systemic safety of bevacizumab and ranibizumab in patients with neovascular age-related macular degeneration. Curr Opin Ophthalmol. 2013;24(3):205-12. Martin D, Maguire M, Fine S, Ying G, Jaffe G, Grunwald J et al.(2012) Comparison of Age-related Macular Degeneration Treatments Trials (CATT) Research Group, 3rd. Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results. Ophthalmology Jul. 2012;119(7):1388-98. Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY et al.(2006) Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355(14):1419-31. Wykoff CC, Brown DM, Chen E, Major JC, Croft DE, Mariani A et al.(2013) SAVE (Super-dose anti-VEGF) trial: 2.0 mg ranibizumab for recalcitrant neovascular age-related macular degeneration: 1-year results. Ophthalmic surgery, lasers & imaging retina. 2013;44(2):121-6. |
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| Group specific policy will supersede this policy when applicable. This policy does not apply to the Wal-Mart Associates Group Health Plan participants. | |
| CPT Codes Copyright © 2025 American Medical Association. | |