Syfovre vs Izervay access guide: geographic atrophy complement inhibitor coverage, imaging requirements, retina benefit routing, step therapy, and renewal evidence

Geographic atrophy (GA), the advanced form of dry age-related macular degeneration (AMD), affects approximately one million Americans and is a leading cause of irreversible central vision loss in people over 65. Until 2023, no FDA-approved treatment existed. Two complement inhibitors now compete for this population: Syfovre (pegcetacoplan, Apellis), a C3 inhibitor approved in February 2023, and Izervay (avacincaptad pegol, Astellas/IVERIC bio), a C5 inhibitor approved in August 2023.

Both drugs are administered by intravitreal injection in a retina practice, billed through the medical benefit as buy-and-bill, and require prior authorization from nearly all commercial and Medicare Advantage plans. Despite being the only two products in the GA therapeutic class, payers have begun imposing step therapy between them — most notably Aetna, which requires a Syfovre trial before covering Izervay, a policy the American Academy of Ophthalmology (AAO) formally challenged in 2025 as lacking clinical evidence.

This guide covers the access, coding, documentation, step therapy, reauthorization, and support program workflows for both products side by side.

Short answer

Mechanism and evidence comparison

Syfovre targets complement protein C3 upstream, regulating cleavage of C3 and the generation of all downstream complement effector pathways (alternative, classical, and lectin). Izervay targets complement protein C5 downstream, preventing formation of C5a and C5b-9 (membrane attack complex), regardless of which upstream activation pathway triggered it.

Syfovre evidence

The Phase 3 OAKS (n=637) and DERBY (n=621) trials demonstrated statistically significant slowing of GA lesion growth versus sham at 24 months, with treatment effects increasing over time. Monthly dosing reduced GA growth by 22% in OAKS and 18% in DERBY; every-other-month dosing reduced growth by 18% and 17%, respectively. By months 18–24, reductions reached up to 36% in DERBY. The open-label extension GALE provided 36-month data showing continued increasing efficacy, with up to 32% mean reduction in GA area change versus projected sham and an 18% reduction in new scotomatous points (P=0.0156) in a prespecified microperimetry analysis — the first GA treatment to show benefit in a prespecified functional analysis. Patient retention through the first 12 months of GALE was 92%.

Izervay evidence

The GATHER1 (Phase 2/3) and GATHER2 (Phase 3) trials demonstrated GA lesion growth reductions ranging from 14% to 30% depending on study and time point. The open-label extension of GATHER2, presented at AAO 2025, showed monthly Izervay continued to reduce GA lesion growth for up to 3.5 years, with earlier intervention resulting in greater protection of retinal tissue area. No cases of retinal vasculitis or occlusive vasculitis were reported in the extension. Izervay is marketed as the most prescribed choice for patients new to GA treatment, based on Symphony data from March 2024 through December 2025.

In February 2025, the FDA approved an expanded label removing the original 12-month duration limitation, following Astellas' resubmission of its supplemental NDA. The sNDA was filed after a November 2024 Complete Response Letter and a December 2024 FDA meeting to clarify agency feedback.

Prior authorization criteria

Both products follow similar PA frameworks across major payers, with requirements drawn from FDA labeling and clinical trial enrollment criteria.

Common initial authorization requirements

Most plans — including Express Scripts, Prime Therapeutics, CVS Caremark, and major Medicare Advantage carriers — require all of the following:

1. Age: Patient is 18 years or older.
2. Diagnosis: GA of the macula secondary to AMD, confirmed by fundus autofluorescence (FAF), optical coherence tomography (OCT), or fluorescein angiography. The GA must not be secondary to other conditions (e.g., Stargardt disease, cone-rod dystrophy, toxic maculopathies).
3. GA lesion criteria (varies by plan): Some payers specify a minimum lesion area (e.g., ≥2.5 mm² and ≤17.5 mm² using FAF); if multifocal, at least one focal lesion ≥1.25 mm². Others require presence of hyperautofluorescence in the junctional zone.
4. Baseline assessment: Best corrected visual acuity (BCVA), FAF imaging, and OCT at baseline.
5. Specialist requirement: Prescribed by or in consultation with an ophthalmologist experienced in retinal diseases.
6. Exclusion criteria: No ocular or periocular infections, no active intraocular inflammation, no concurrent use of other intravitreal complement inhibitors, and no category 5 or higher visual impairment or blindness.
7. Authorization length: Typically 12 months initially.

Reauthorization criteria

Most plans renew for an additional 12 months if:

• The patient continues to meet initial criteria.
• Clinical response is demonstrated — typically stabilization or reduction in GA lesion growth rate on FAF or OCT, or maintenance of BCVA.
• Absence of unacceptable toxicity, including endophthalmitis, retinal detachment, retinal vasculitis and/or retinal vascular occlusion, neovascular (wet) AMD conversion, or intraocular inflammation that cannot be adequately managed.

Step therapy: Aetna's Syfovre-first policy and the AAO challenge

In 2025, Aetna updated its Medicare Part B Preferred Drug List for GA treatments, removing Izervay from its preferred list and imposing step therapy requiring patients to try and fail Syfovre before receiving Izervay. Aetna confirmed to the AAO that the policy was cost-driven: Syfovre injections can be spaced 25–60 days apart, making it potentially less expensive per patient than Izervay, which requires monthly dosing.

The AAO formally protested the policy in a letter to CMS, arguing that:

• There is no peer-reviewed literature or clinical evidence concluding that clinical outcomes for Syfovre are equivalent or superior to Izervay.
• The two drugs target different complement proteins (C3 vs C5), and head-to-head data do not exist.
• Step therapy forces cost-based switching over physician clinical judgment.
• The policy is particularly concerning for GA, a chronic, progressive disease where delayed appropriate treatment risks irreversible vision loss.

As of early 2026, the Aetna step edit remains in place for its Medicare Advantage plans. Other major carriers — including UnitedHealthcare, Express Scripts, and Prime Therapeutics — generally cover both products without cross-step requirements, though individual plan formularies may vary.

HCPCS coding and buy-and-bill billing

Both products are billed through the medical benefit under Medicare Part B and commercial medical benefit. They are not pharmacy-benefit drugs.

Syfovre coding

• HCPCS: J2781 — Injection, pegcetacoplan, intravitreal, 1 mg
• Units per dose: 15 units (15 mg dose)
• NDC: 73606-0020-xx (15 mg/0.1 mL single-dose vial)
• CPT: 67028 (intravitreal injection)
• ICD-10: H35.3113–H35.3194 (nonexudative AMD with GA descriptors)
• Modifiers: LT/RT for laterality; JZ or JW for drug wastage

Izervay coding

• HCPCS: J2782 — Injection, avacincaptad pegol, 0.1 mg
• Units per dose: 20 units (2 mg dose, since 1 unit = 0.1 mg)
• NDC: 82829-0002-xx (2 mg/0.1 mL single-dose vial)
• CPT: 67028 (intravitreal injection)
• ICD-10: H35.3113–H35.3194 (same GA-related codes)
• Modifiers: LT/RT for laterality; JZ or JW for drug wastage

Billing workflow

1. Purchase the drug from the specialty distributor (buy-and-bill model).
2. Submit the claim with the appropriate J-code, units, NDC, CPT 67028, ICD-10, and modifiers.
3. Include documentation of the dose, laterality, and drug wastage.
4. For Medicare Part B: CMS pays 106% of ASP (average sales price) for the drug, plus the administration fee. The patient is responsible for 20% coinsurance after the Part B deductible.
5. For Medicare Advantage: similar cost-sharing applies, but the plan's PA and site-of-care requirements must be satisfied first.

Medicare coverage

Medicare Part B covers both Syfovre and Izervay when medically necessary for GA secondary to AMD. After meeting the annual Part B deductible, Medicare typically pays 80% of the approved amount for the drug and injection visit. The patient is responsible for the remaining 20% unless supplemented by Medigap or other coverage. Apellis reports 100% Syfovre payer coverage for Traditional Medicare, based on data as of April 2026. Medicare Advantage plans also cover both products as Part B medical benefits but almost always require prior authorization and may impose step therapy or preferred-product designations.

Manufacturer support programs

ApellisAssist (Syfovre)

• Benefits investigation and prior authorization support.
• Claims advisory and appeals assistance.
• Patient affordability programs for eligible commercially insured patients.
• Access Support Navigator online tool for checking payer coverage and PA requirements.
• Contact: 1-888-APELLIS (1-888-273-5547).

IZERVAY My Way (Izervay)

• Benefits investigation and patient enrollment.
• Online enrollment portal for document upload and status tracking.
• Sample letters of medical necessity, appeal, coverage delays, and reauthorization.
• Commercial copay support for eligible patients.
• Billing and coding guide with claim form examples.
• Contact: Support@IZERVAYMyWay.com or 1-833-C5MYWAY (1-833-256-9929).

Izervay reports that 98% of patients covered by any Medicare plan can start Izervay as their first branded GA treatment, based on Managed Markets Insight & Technology data as of March 2026.

Key access considerations for retina practices

1. Imaging documentation is critical. Plans require FAF and/or OCT demonstrating GA lesion size and characteristics. Submit baseline imaging with the initial PA and follow-up imaging at reauthorization.

2. Monitor for neovascular AMD conversion. Both drugs carry a risk of conversion to wet AMD, which is an exclusion criterion for continued treatment. Document regular OCT surveillance.

3. Prepare for step therapy in Aetna Medicare Advantage. If prescribing Izervay for an Aetna MA patient, be ready to document medical necessity for Izervay over Syfovre or initiate with Syfovre if the plan requires it. Appeal pathways exist but may delay treatment.

4. Dosing flexibility differs. Syfovre can be dosed every 25–60 days, allowing extension for stable patients. Izervay is dosed every 28 ± 7 days and is now approved without a duration cap. This difference affects both treatment burden and payer cost assumptions.

5. Reauthorization requires response evidence. Most plans require documentation of clinical response (stabilization, reduced growth rate, or maintained BCVA) for renewal. Plan for imaging at least 6 months into treatment to capture response data.

6. Buy-and-bill economics. Both products require the practice to purchase drug inventory. Syfovre's higher per-vial WAC ($26,000) versus Izervay ($15,500) affects cash flow, but Syfovre's flexible dosing interval may mean fewer total injections per year.

Sources

• FDA approval letter: Izervay (avacincaptad pegol intravitreal solution). NDA 217225. August 4, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/217225Orig1s000Approv.pdf
• FDA summary review: Izervay (avacincaptad pegol). NDA 217225. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/217225Orig1s000SumR.pdf
• FDA approves expanded label for IZERVAY. Astellas Pharma press release. February 12, 2025. https://newsroom.astellas.com/2025-02-13-U-S-FDA-Approves-Expanded-Label-for-Astellas-IZERVAY-TM-avacincaptad-pegol-intravitreal-solution-for-Geographic-Atrophy
• Wykoff CC, Holz FG, Chiang A, et al. Pegcetacoplan treatment for geographic atrophy in age-related macular degeneration over 36 months. Am J Ophthalmol. 2025;276:350-364. https://www.sciencedirect.com/science/article/pii/S000293942500193X
• Khanani AM, Josephs KA, Dugel PU, et al. Efficacy and safety of avacincaptad pegol in patients with geographic atrophy (GATHER2). Lancet. 2023;402(10411):1449-1458.
• American Academy of Ophthalmology. Syfovre and Izervay for geographic atrophy. https://www.aao.org/eye-health/tips-prevention/syfovre-izervay-geographic-atrophy-amd-macular-deg
• Aetna. Pegcetacoplan intravitreal injection (Syfovre) clinical policy. https://www.aetna.com/cpb/medical/data/1000_1099/1029.html
• CMS HCPCS code J2781 and J2782. https://www.cms.gov/Medicare/Coding/HCPCSReleaseCodeSets
• Express Scripts. Ophthalmology — Syfovre UM medical policy. March 2025. https://www.commonwealthcarealliance.org/ma/wp-content/uploads/2026/03/Ophthalmology-%E2%80%93-Syfovre.pdf
• Prime Therapeutics. Syfovre clinical coverage criteria. September 2025. https://www.ohsu.edu/sites/default/files/2025-11/ohsu-hs-mps-syvofre-09-25.pdf
• Syfovre Access Support Navigator. https://accesssupportnavigator.syfovreecp.com/payer-coverage
• IZERVAY My Way support program. https://www.izervayecp.com/access-support