CurrentUnitedHealthcarePolicy 2025D0118G

Ophthalmologic Complement Inhibitors

Defines medical necessity criteria for initial and continuation therapy with Izervay (pegcetacoplan) and Syfovre (avacincaptad pegol) for treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD), lists applicable HCPCS and ICD-10 codes, summarizes clinical evidence and FDA indications, and includes authorization durations and dosing adherence requirements.

Policy Summary

PayerUnitedHealthcare

PolicyOphthalmologic Complement Inhibitors

Policy CodePolicy 2025D0118G

Change TypeSupporting information updates

Effective DateDec 1, 2025

Next Review Date

Key ActionAuthorization is required and is limited to no more than 12 months for both initial and continuation therapy.

POLICY UPDATE CHANGES

Updated References section to reflect the most current information and archived previous policy version 2024D0118F.

2Drugs covered (avacincaptad pegol, pegcetacoplan)

12 moMaximum authorization duration

6Example ICD-10 codes listed

Coverage Summary

Defines medical necessity criteria for initial and continuation therapy with Izervay (pegcetacoplan) and Syfovre (avacincaptad pegol) for treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Coverage stance: covered_with_criteria. Authorization duration for both initial and continuation therapy is limited to no more than 12 months. Note: FDA indicates both agents are approved for treatment of GA secondary to AMD in adults.

Initial Therapy Criteria (Medically necessary)

Initial therapy (Medically necessary)

Izervay and Syfovre are medically necessary when ALL of the following are met:

Initial therapy (Medically necessary) - top level

Diagnosis of geographic atrophy (GA) secondary to age-related macular degeneration (AMD)
Diagnostic confirmation: Diagnosis has been confirmed by geographic atrophy secondary to age-related macular degeneration sensitive tests (e.g., optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging)
Exclude other causes: Macular atrophy is not secondary to any conditions other than AMD (e.g., Stargardt disease, cone rod dystrophy, toxic maculopathies)
Prescriber: Prescribed by or in consultation with an ophthalmologist experienced in treatment of retinal diseases
Dosing adherence: Dosing is in accordance with the United States Food and Drug Administration approved labeling
Authorization requires adherence to FDA labeling dosing schedule

Continuation Therapy Criteria (Medically necessary)

Continuation of therapy (Medically necessary)

Continuation is medically necessary when ALL of the following are met:

Continuation of therapy (Medically necessary) - top level

Physician attestation that patient would benefit from continued administration
Titration documentation: For long term treatment, documentation of titration to the minimum dosing frequency to achieve maximum benefit
Requires documentation of titration to minimum effective dosing frequency
Dosing adherence: Dosing is in accordance with the United States Food and Drug Administration approved labeling
Authorization requires adherence to FDA labeling dosing schedule

Exclusions and Limitations

Macular atrophy is covered only when it is secondary to AMD; the policy explicitly excludes macular atrophy secondary to other conditions (examples given: Stargardt disease, cone rod dystrophy, toxic maculopathies). The brief does not list other explicit 'not medically necessary' entries beyond requiring that macular atrophy be secondary to AMD.

Applicable Codes

Drug HCPCS/J-codes (applicable)HCPCS

J2781	Injection, pegcetacoplan, 1 mg
J2782	Injection, avacincaptad pegol, 0.1 mg

ICD-10 diagnosis codes (examples listed)ICD-10

H35.3113	Nonexudative age-related macular degeneration, right eye, advanced atrophic without subfoveal involvement
H35.3114	Nonexudative age-related macular degeneration, right eye, advanced atrophic with subfoveal involvement
H35.3123	Nonexudative age-related macular degeneration, left eye, advanced atrophic without subfoveal involvement
H35.3124	Nonexudative age-related macular degeneration, left eye, advanced atrophic with subfoveal involvement
H35.3133	Nonexudative age-related macular degeneration, bilateral, advanced atrophic without subfoveal involvement
H35.3134	Nonexudative age-related macular degeneration, bilateral, advanced atrophic with subfoveal involvement

Provider Actions & Requirements

Prior Authorization

Authorization required and limited duration

Authorization is required for treatment with these agents and is limited to a duration not to exceed 12 months for both initial and continuation therapy.

J2781
J2782

Documentation Required

Diagnostic confirmation documentation

Providers must document a diagnosis of geographic atrophy (GA) secondary to age-related macular degeneration (AMD) confirmed by GA-sensitive imaging and that the macular atrophy is not due to other conditions.

Optical coherence tomography (OCT)
Fundus autofluorescence (FAF)
Exclude non-AMD causes (e.g., Stargardt disease, cone-rod dystrophy, toxic maculopathies)

Documentation Required

Specialist involvement

Prescription must be made by or in consultation with an ophthalmologist experienced in the treatment of retinal diseases; for continuation of therapy the physician must attest that the patient would benefit from continued administration.

Documentation Required

Dosing adherence

Dosing must follow the United States Food and Drug Administration approved labeling. For long-term treatment, documentation must show titration to the minimum dosing frequency necessary to achieve maximum benefit.

Clinical Evidence Summary

OAKSOAKS met primary endpoint: GA lesion growth reduced 22% (monthly) and 16% (EOM) vs pooled sham at 12 months

DERBYDERBY alone did not meet primary endpoint; combined analysis (DERBY+OAKS) reduced GA growth 17% (monthly) and 14% (EOM) vs pooled sham at 12 months

Exudation pooledPooled new-onset exudation rates higher with pegcetacoplan: 6.0% (monthly), 4.1% (EOM) vs 2.4% (sham)

Both avacincaptad pegol (Syfovre) and pegcetacoplan (Izervay) are indicated for the treatment of geographic atrophy secondary to AMD. These agents target the complement pathway: pegcetacoplan inhibits C3 while avacincaptad pegol inhibits C5. Clinical trials demonstrated reduction in GA lesion growth but observed a safety signal of increased exudation/new neovascular (wet) AMD rates with treatment compared with sham (pooled neovascular rates higher in treated groups). Background context: complement overactivation, including C3, contributes to lesion growth in GA.

Background

Geographic atrophy (GA) is an advanced form of dry AMD causing progressive, irreversible loss of retinal cells and vision. Complement overactivation, including C3, contributes to lesion growth in GA. Avacincaptad pegol targets C5 and pegcetacoplan targets C3. Definitions: GA = geographic atrophy secondary to age-related macular degeneration; OCT = optical coherence tomography; FAF = fundus autofluorescence imaging.

Policy Summary

PayerUnitedHealthcare

PolicyOphthalmologic Complement Inhibitors

Policy CodePolicy 2025D0118G

Change TypeSupporting information updates

Effective DateDec 1, 2025

Next Review Date

Key ActionAuthorization is required and is limited to no more than 12 months for both initial and continuation therapy.

On This Page

OpenPayer

Ophthalmologic Complement Inhibitors

Coverage Summary

Initial Therapy Criteria (Medically necessary)

Continuation Therapy Criteria (Medically necessary)

Exclusions and Limitations

Applicable Codes

Provider Actions & Requirements

Clinical Evidence Summary

Background

Revision History