Is continuation of Izervay (Avacincaptad Pegol) 2 mg intravitreal injection every 4 weeks medically necessary for a patient with non-exudative age-related macular degeneration of the right eye with advanced atrophic and subfoveal involvement?

Medical Necessity Assessment for Izervay Continuation

Continuation of Izervay (avacincaptad pegol) 2 mg intravitreal injection every 4 weeks is NOT medically necessary for this patient based on the available clinical documentation, as there is insufficient evidence of positive clinical response to therapy as required by the insurance criteria.

Critical Analysis of Insurance Continuation Criteria

The insurance policy requires demonstration of "positive clinical response to therapy (e.g., improvement or maintenance in best corrected visual acuity [BCVA] or visual field, or a reduction in the rate of vision decline or the risk of more severe vision loss)" for continuation approval. The clinical documentation presents conflicting evidence:

Visual Acuity Assessment

• Initial visit: Right eye (OD) 20/25, Left eye (OS) 20/20
• Follow-up visit: OD 20/20, OS 20/20
• The right eye (treated eye) showed improvement from 20/25 to 20/20, which represents maintenance or slight improvement in BCVA 1

Anatomical Response Concerns

• OCT findings show "Mod increased in Right eye" at the most recent visit, indicating progression of disease activity in the treated eye
• The left eye (untreated) remained stable, creating a concerning comparison
• This anatomical worsening contradicts the expected treatment response, as avacincaptad pegol is designed to reduce GA lesion growth 2

Evidence-Based Treatment Expectations

FDA-Approved Efficacy Profile

Izervay demonstrated statistically significant reductions in GA lesion growth in clinical trials:

• GATHER1 study: 0.10 mm/year reduction versus sham over 12 months 1
• GATHER2 study: 0.05 mm/year reduction versus sham, representing 14% slowing of GA growth 1, 2
• The drug's mechanism involves complement C5 inhibition to decrease membrane attack complex formation and slow photoreceptor loss 1

Dosing Compliance

• The prescribed regimen of 2 mg intravitreal every 4 weeks (approximately 28 ± 7 days) is FDA-approved and appropriate 1
• Treatment dates show monthly administration pattern, which aligns with labeled dosing 1

Critical Safety Consideration: Neovascular Conversion Risk

A significant concern exists regarding potential neovascular AMD development, which represents a serious adverse event:

Clinical Trial Data

• In GATHER2, macular neovascularization occurred in 7% of avacincaptad pegol-treated patients versus 4% in sham group at 12 months 2
• Exudative macular neovascularization specifically occurred in 5% versus 3% 2
• This represents a relative risk increase of approximately 1.75-fold 3

Real-World Evidence Shows Higher Conversion Rates

• Recent real-world data demonstrates conversion to neovascular AMD in 2.03% of eyes with a predicted annualized rate of approximately 6.17% 4
• Patients developing MNV during avacincaptad pegol treatment experience significantly worse outcomes: mean visual acuity loss of -0.22 logMAR and greater GA growth of 1.78 mm² at 12 months despite anti-VEGF therapy 5
• Patients with pre-existing neovascular AMD undergoing avacincaptad pegol have even worse outcomes with greater visual acuity decline (-0.2 logMAR) and GA growth (1.36 mm²) 6

Recommendation for Documentation and Monitoring

To support continuation, the following documentation is essential:

Required Clinical Evidence

• Quantitative OCT measurements comparing baseline GA lesion size to current measurements, demonstrating stable or reduced growth rate 7, 1
• Fundus autofluorescence imaging to objectively measure GA area progression, as this was the primary endpoint in pivotal trials 1, 2
• Serial visual acuity measurements documenting maintenance or improvement over multiple visits 7
• Detailed assessment for neovascular conversion including OCT evaluation for subretinal or intraretinal fluid, given the 6-7% annual risk 2, 4

Monitoring Protocol

• Monthly follow-up examinations with OCT imaging to detect early signs of neovascular conversion or disease progression 7
• Intraocular pressure monitoring at each visit, as 9% of patients develop IOP elevation 1
• Immediate evaluation if patient reports new metamorphopsia, scotoma, or vision changes suggesting neovascular conversion 7

Clinical Decision Framework

The insurance denial appears justified based on the documentation provided, specifically:

1. The notation "Mod increased in Right eye" suggests anatomical worsening rather than the required "positive clinical response" 1
2. Absence of quantitative GA lesion measurements prevents objective assessment of treatment efficacy 2
3. The improvement in visual acuity alone (20/25 to 20/20) may not be sufficient without corresponding anatomical stability 1

To overturn this decision, the provider must submit:

• Baseline and current fundus autofluorescence images with measured GA areas
• Demonstration that GA growth rate is reduced compared to expected natural history (typically 1.5-2.0 mm²/year untreated) 2
• Clarification of what "Mod increased" represents and whether this reflects measurement variability versus true progression

If anatomical progression is confirmed despite treatment, consideration should be given to:

• Discontinuing avacincaptad pegol due to lack of efficacy in this individual patient
• Evaluating for neovascular conversion requiring anti-VEGF therapy 5
• Discussing the 6-7% annual risk of developing vision-threatening neovascular AMD with continued treatment 2, 4