Pegcetacoplan Intravitreal Injection (Syfovre)

Number: 1029

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses pegcetacoplan (Syfovre) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification: 

Precertification of pegcetacoplan (Syfovre) is required of all Aetna participating providers and members in applicable plan designs. For precertification of pegcetacoplan (Syfovre), call (866) 752-7021 or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification.  

1. Exclusions 

   Aetna considers members not eligible for Syfovre for the treatment of geographic atrophy (GA) secondary to a condition other than age-related macular degeneration (AMD) (such as Stargardt disease, cone rod dystrophy, toxic maculopathies).

2. Prescriber Specialties

   This medication must be prescribed by or in consultation with an ophthalmologist.

3. Criteria for Initial Approval

   Geographic Atrophy (GA) Secondary to Age-related Macular Degeneration (AMD)

   Aetna considers pegcetacoplan (Syfovre) medically necessary for treatment of geographic atrophy when the member has a diagnosis of geographic atrophy secondary to age-related macular degeneration.

   Aetna considers all other indications as experimental, investigational, or unproven.

4. Continuation of Therapy

   Aetna considers continuation of pegcetacoplan (Syfovre) therapy medically necessary for treatment of an indication listed in the Criteria for Initial Approval section for members who have demonstrated a positive clinical response to therapy (e.g., a reduction or stabilization in the rate of vision decline or the risk of more severe vision loss, stabilization or reduction in total area of geographic atrophy (GA) lesions).

Dosage and Administration

Pegcetacoplan is supplied as Syfovre 150 mg/mL in a single-dose vial for intravitreal injection.

The recommended dose for Syfovre is 15 mg (0.1 mL of 150 mg/mL solution) administered by intravitreal injection to each affected eye once every 25 to 60 days.

Refer to the full prescribing information for Syfovre for preparation and administration instructions.

Source: Apellis Pharmaceuticals, 2025

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
67028	Intravitreal injection of a pharmacologic agent (separate procedure)
HCPCS codes covered if selection criteria are met:
J2781	Injection, pegcetacoplan, intravitreal, 1 mg
ICD-10 codes covered if selection criteria are met:
H35.30	Unspecified macular degeneration [Geographic atrophy]
H35.3110 - H35.3194	Nonexudative age-related macular degeneration [Geographic atrophy]
H35.3210 – H35.3293	Exudative age-related macular degeneration [Geographic atrophy]

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Background

U.S. Food and Drug Administration (FDA)-Approved Indications 

• Syfovre is indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

Pegcetacoplan is available as Syfovre (Apellis Pharmaceuticals, Inc.) which is a complement inhibitor. It binds to complement protein C2 and its activation fragment C3b with high affinity thereby regulating the cleavage of C3 and the generation of downstream effectors of complement activation (Apellis Pharmaceuticals, 2025).

According to the prescribing information, Syfovre carries the following contraindications:

• Ocular or periocular infections
• Active intraocular inflammation

Per the prescribing information, Syfovre carries the following warnings and precautions:

• Endophthalmitis and retinal detachments
• Neovascular AMD
• Intraocular inflammation
• Increased intraocular pressure 

Per the prescribing information for Syfovre, the most common adverse reactions (incidence ≥5%) are ocular discomfort, neovascular age-related macular degeneration, vitreous floaters, and conjunctival hemorrhage.

Age-related macular degeneration (AMD) is a progressive degradation of the macula which is responsible for visual acuity, thereby, resulting in central vision loss. AMD is a leading cause of severe, irreversible vision impairment as well as blindness in people over 65 years of age. Although an estimated 80% of AMD patients have non-neovascular or non-exudative (dry) or atrophic AMD, the neovascular or exudative (wet) form is responsible for the majority of the severe central visual acuity (VA) loss associated with AMD (Flaxel, et al., 2020). Geographic atrophy (GA) is an advanced form of dry AMD which involves a chronic progressive degeneration of the macula, as part of late-stage AMD. GA is characterized by localized sharply defined atrophy of the outer retinal tissue, retinal pigment epithelium and choriocapillaris. It usually begins in the perifoveal region and expands to involve the fovea with time, leading to central scotomas and permanent loss of visual acuity. It is bilateral in most cases and the prevalence of GA is estimated to affect 8 million people worldwide, approximately 20% of all individuals with AMD (Shah, et al., 2023). Although GA is more common in dry AMD, 25% of patients with wet AMD also have GA.

On February 17, 2023, the U.S. Food and Drug Administration (FDA) approved Syfovre (pegcetacoplan injection) for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Syfovre is the first and only FDA-approved treatment for GA. The FDA approval was based on positive results from the two multi-center, randomized, double-masked, sham-controlled phase 3 OAKS and DERBY studies. Both studies evaluated the safety and efficacy of monthly and every-other-month Syfovre in a total of 1258 patients [OAKS (n=637) and DERBY (n=621)] with GA (atrophic nonexudative age-related macular degeneration), with or without subfoveal involvement, secondary to AMD for a duration of 24 months with treatment for the entire study length. Patients were randomized (Syfovre 839 patients, sham 419 patients) in a 2:2:1:1 ratio to 1 of 4 dosing regimens administered as: 1) Syfovre 15 mg/0.1 mL monthly; 2) Syfovre 15 mg/0.1 mL every other month; 3) sham administered monthly; and 4) sham administered every other month. Both studies showed that Syfovre reduced the GA lesion growth compared to sham and demonstrated increasing treatment effects over time, with the greatest benefit (up to 36% reduction in lesion growth with monthly treatment in DERBY) occurring between months 18-24 (Apellis Pharmaceuticals, 2023; 2025).

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References