Beovu (brolucizumab) Clinical Policy Form

AHP- Beovu (brolucizumab) PART B DRUG MEDICAL/PHARMACY Effective Date May 15, 2025 Policy # BEOVU (brolucizumab) Beovu (brolucizumab) Review Date Applicable to: 02/25/2025 Medicare Advantage Commercial Elevance Health HMO Blue Shield Trio Approver’s Name & Title QI & UM Drug Subcommittee Aspire Health Plan applies medical drug clinical criteria as a reference for medical policy information only. Federal and state laws or requirements, contract language, and Plan benefit may take precedence over the application of these clinical criteria. Please consult the applicable certificate or contract for benefit details. This policy is subject to revision at the discretion of the Plan and is therefore subject to change. Refer to the disclaimer section below for more information. POLICY This policy outlines the coverage of intravitreal Beovu (brolucizumab) for ophthalmic use. APPLICABLE HCPCS J0179: Injection, brolucizumab-dbll, 1 mg Available as: • 6 mg/0.05 mL single-dose vial kit • 6 mg/0.05 mL single-dose prefilled syringe CLINICAL CRITERIA A. INITIAL CRITERIA Beovu (brolucizumab-dbll) may be authorized when ALL of the following are present: 1. Member has a confirmed diagnosis of ONE of the following: a. Neovascular (wet, or exudative) age-related macular degeneration (AMD); OR b. Diabetic Macular Edema (DME). AND

2. Absence of Contraindications a. No active intraocular inflammation; and b. No concurrent ocular or periocular infection.

AHP- Beovu (brolucizumab) AND 3. Best corrected visual acuity (BCVA) has been assessed prior to treatment initiation and will be monitored periodically during therapy; AND 4. Beovu (brolucizumab-dbll) is prescribed as monotherapy. The member is not concurrently receiving other ophthalmic vascular endothelial growth factor (VEGF) inhibitors (i.e., aflibercept, ranibizumab, pegaptanib, bevacizumab). B. REAUTHORIZATION / CONTINUATION OF THERAPY CRITERIA Beovu (brolucizumab-dbll) may be authorized for continuation of therapy when ALL of the following criteria are met: 1. Member continues to meet the initial therapy criteria (as stated above); AND 2. Absence of adverse events related to Beovu (brolucizumab-dbll) (e.g., intraocular inflammation, retinal vasculitis, retinal vascular occlusion, endophthalmitis, retinal detachment, or increased intraocular pressure); AND

3. Positive response to therapy documented by ONE or more of the following: a. Improvement or stabilization in best corrected visual acuity (BCVA) or visual field; or b. Reduction in central retinal thickness (as measured by OCT) c. Other objective measures of disease activity as determined by the treating physician. AND
4. Documentation of the following: a. Administration records with dates and eye(s) administered and dose. b. Adherence to the treatment plan. STEP THERAPY Step Therapy Does NOT Apply if: • The member is currently being treated with the requested medication. • The member has received the requested drug within the last 365 days. Step Therapy Applies if: • The member is new to therapy (i.e., has not received the requested drug in the last 365 days). A. PREFERRED PRODUCT(S): AVASTIN (no step therapy required) B. NONPREFERRED PRODUCT: Beovu (brolucizumab-dbll) Beovu (brolucizumab-dbll) may be authorized when all of the clinical criteria (in the Initial Therapy section above are met) AND the member meets the following criteria: 1. Inadequate response to a trial of the preferred agent, bevacizumab (Avastin); or 2. History of contraindication or adverse event(s) to Avastin (bevacizumab); or 3. Member has been on the requested agent within the past 365 days.

AHP- Beovu (brolucizumab) DOSAGE AND AUTHORIZATION TIMEFRAMES 1. Recommended Dosage Indication Initial / Maintenance Dosing Neovascular AMD Initial dosage: 6 mg by intravitreal injection once per month (approximately every 25 to 31 days) for 3 months. Maintenance dosage: 6 mg by intravitreal injection once every 8 to 12 weeks. Diabetic Macular Edema Initial dosage: 6 mg by intravitreal injection every 6 weeks (approximately every 39 to 45 days) for 5 doses. Maintenance dosage: 6 mg by intravitreal injection once every 8 to 12 weeks 2. Quantity Limit a. Neovascular AMD:  Dosage: 6 mg single-dose vial or pre-filled syringe for injection  Frequency: ― Initial phase: 1 vial/syringe per eye every 25 days for three doses ― Maintenance phase: 1 vial/syringe every 8 weeks. b. Diabetic Macular Edema: • Dosage: 6 mg single-dose vial or pre-filled syringe for injection • Frequency: ― Initial phase: 1 vial/syringe per eye every 6 weeks for five doses ― Maintenance phase: 1 vial/syringe per eye every 8 weeks. 3. Authorization Period a. May be authorized for 12 months and reauthorized if the member meets continuation of therapy criteria. b. Excessive Frequency: Services performed more frequently than FDA-approved labeling or generally accepted by guidelines may be considered excessive unless justified with documented rationale. Dosage and frequency must align with FDA labeling or CMS-recognized compendia for off-label use. Services exceeding the standard of care may be subjected to review. 4. Limitations a. Single anti-VEGF medication per eye per session: It is not reasonable and necessary to inject more than one anti-VEGF medication (e.g., aflibercept, pegaptanib, brolucizumab, bevacizumab, ranibizumab, faricimab-svoa, etc.) in the same eye during the same treatment session. • It is not typical to inject one anti-VEGF medication into one eye and another in the other eye. If different medications are injected into each eye during the same date of service, the rationale for this therapy must be documented in the medical record and the billing modifier [right (RT) and left (LT) modifiers] must be appended to the correct drug.

AHP- Beovu (brolucizumab) b. Frequency of intravitreal injections: Intravitreal injection for the treatment of macular edema more frequently than every 4 weeks regardless of which drug is used for any given injection i.e. alternating drugs every 2 weeks will not be covered. c. Concurrent use of more than one VEGF inhibitor in the same eye: The safety and effectiveness of using more than one VEGF inhibitor in the same eye have not been established. Combination use of VEGF inhibitors for ocular indications is not considered the standard of care based on clinical evidence and guidelines. DRUG INFORMATION PHARMACOLOGIC CATEGORY: Ophthalmic Agent; Vascular Endothelial Growth Factor (VEGF) Inhibitor
ROUTE OF ADMINISTRATION: Intravitreal Injection FDA-APPROVED INDICATIONS 1. Neovascular (wet) AMD • Initial dosage: 6 mg by intravitreal injection once monthly (approximately every 25 to 31 days) for the first 3 months. • Maintenance dosage: 6 mg by intravitreal injection once every 8 to 12 weeks thereafter. 2. Diabetic Macular Edema (DME) • Initial dosage: 6 mg by intravitreal injection once every 6 weeks (approximately every 39 to 45 days) for up to 5 doses. • Maintenance dosage: 6 mg by intravitreal injection once every 8 to 12 weeks thereafter. COMPENDIAL APPROVED (OFF-LABEL) USES: None CONTRAINDICATIONS:
• Hypersensitivity (e.g., rash, pruritus, urticaria, erythema, severe intraocular inflammation) to brolucizumab or any component of the formulation • Ocular or periocular infections • Active intraocular inflammation. OTHER CONSIDERATIONS: Monitoring Parameters • Intraocular pressure (via tonometry) and optic nerve head perfusion immediately following administration • Symptoms of endophthalmitis and retinal detachment • Symptoms of retinal vasculitis and retinal vascular occlusion (especially in patients with intraocular inflammation) • Changes in vision

AHP- Beovu (brolucizumab) CLINICAL SUMMARY / APPENDIX Beovu (brolucizumab-dbll) is indicated for the treatment of neovascular (wet) age-related macular degeneration (AMD). It is a monoclonal single-chain antibody fragment that may offer comparable efficacy to existing anti-VEGF therapies, with the potential benefit of fewer injections due to its individualized treatment regimen. Its smaller molecular size may enhance tissue penetration and systemic exposure. Beovu should be used with caution due to the risk of intraocular inflammation and retinal vascular events. Treatment should be tailored to the patient’s clinical response and tolerability, with regular monitoring for adverse effects. American Academy of Ophthalmology (AAO) Guidelines The AAO recognizes brolucizumab-dbll (Beovu) as an anti-VEGF therapy for the treatment of neovascular (wet) AMD. Key points from the guidelines include the approval of Beovu for the treatment of wet AMD to reduce retinal fluid and improve visual outcomes. The recommended dosing (6 mg administered intravitreally every 12 weeks after initial monthly doses for the first three months) was also noted to allows for a less frequent dosing schedule compared to some other anti-VEGF therapies. Beovu has demonstrated non-inferiority to aflibercept (Eylea) in clinical trials, with similar improvements in visual acuity and reductions in retinal thickness and while effective, Beovu has been associated with a risk of intraocular inflammation, including rare cases of retinal vasculitis and retinal vascular occlusion. Patients should be monitored closely for these adverse events. The AAO emphasizes the importance of individualized treatment plans based on patient response and tolerance to therapy. REFERENCES Government Agency Centers for Medicare and Medicaid Services (CMS). Medicare coverage database (no National Coverage Determination identified; no applicable LCD identified). Available from CMS. Prescribing Information Beovu (brolucizumab) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; May 2022. Peer-reviewed Literature, Guidelines, and Consensus 1. Brolucizumab (Beovu) for age-related macular degeneration. Medical Letter on Drugs and Therapeutics 2020;62(1591):23-24. 2. Brown DM, et al. KESTREL and KITE: 52-week results from two phase III pivotal trials of brolucizumab for diabetic macular edema. American Journal of Ophthalmology 2022;238:157-172. DOI: 10.1016/j.ajo.2022.01.004. 3. American Academy of Ophthalmology. (2023). Age-Related Macular Degeneration PPP– Updated Guidelines. Retrieved from [AAO website]. 4. Dugel PU, et al. HAWK and HARRIER: phase 3, multicenter, randomized, double-masked trials of rolucizumab for neovascular age-related macular degeneration. Ophthalmology 2020;127(1):72-

84. DOI: 10.1016/j.ophtha.2019.04.017. 5. Milliman Care Guidelines (MCG). Ambulatory Care 27th Edition. ACG: A-1026 (AC). 2023. IMPORTANT REMINDER This Medicare Part B Step Therapy Medical Necessity Guideline is for informational purposes only and does not constitute or replace professional medical advice. Physicians, hospitals, and other providers are responsible for administering and using drugs/biologicals in the most effective and clinically appropriate manner and are solely responsible for all medical care decisions. This guideline is not a substitute for clinical judgment or individualized patient care.

AHP- Beovu (brolucizumab) Coverage determinations are based on the member's Evidence of Coverage (EOC), which contains specific coverage provisions, limitations, and exclusions. In the event of a conflict between this guideline and the member's EOC, the EOC will govern. Aspire Health Plan (AHP) adheres to applicable Medicare guidelines, including National Coverage Determinations (NCDs), Local Coverage Determinations (LCDs), Local Coverage Articles (LCAs), and other relevant Medicare manuals published by the Centers for Medicare & Medicaid Services (CMS). Compliance with these guidelines is required where applicable. For the most current Medicare policies and coverage information, please refer to the CMS website at cms.gov and search the Medicare Coverage Database. All LCDs are the same for each state within a Jurisdiction. The Medicare Administrative Contractor (MAC) for California (Jurisdiction E) is Noridian. Active LCDs for JE Part B can be found on the Noridian Medicare website (noridianmedicare.com). In the event of a discrepancy between this guideline and a Medicare NCD or LCD, the NCD/LCD will govern. This guideline is used by AHP to determine coverage in the absence of applicable CMS Medicare guidelines. The Medicare source materials used to develop this guideline are referenced below. This document does not replace the official Medicare source materials, which provide detailed information on Medicare coverage requirements. In the event of a conflict between this document and Medicare source materials, the Medicare source materials will prevail. The inclusion of a code in this guideline does not guarantee coverage or reimbursement. Benefit coverage is determined by the member's specific plan document, applicable state and federal laws, and CMS guidelines. Other policies and standards may also apply. Providers are expected to maintain documentation to support coverage decisions and make it available upon request. POLICY HISTORY Version Committee Date Summary of Changes 1 9/27/2023 New Policy 2 02/25/2025 Annual Review. The policy has been revised and reformatted to enhance clarity with no alteration to the intent or clinical criteria. References reviewed and policy updated where applicable. Effective date: 05/15/2025