Oscar Izervay (avancincaptad pegol) (PG168) Form

Age-related macular degeneration (AMD) is a common progressive eye condition and a leading cause of vision loss in those over 65 years old. The most common form is dry AMD, affecting about 90% of AMD patients, where abnormalities in the retinal pigment epithelium and accumulation of drusen deposits in the macula lead to geographic atrophy (GA). GA represents an advanced stage of dry AMD characterized by irreversible loss of retinal cells, leading to progressive vision difficulties like blurred areas or missing spots when reading. It impacts daily functioning and can ultimately cause severe central vision loss or blindness.

Despite the significant burden of GA, effective treatment options have been lacking until recently. On August 4, 2023, the FDA granted approval to Izervay (avacincaptad pegol) as the first C5 complement inhibitor for GA secondary to AMD. As an overactive complement system contributes to AMD pathology, inhibiting C5 may reduce this damaging effect.

1. The monthly intravitreal injections of Izervay were studied in two phase 3 trials, GATHER1 and GATHER2, which showed significantly reduced GA lesion growth rates compared to sham injections over 12 months. However, no differences in visual acuity were observed between the treatment and placebo groups.
2. While Izervay represents an important advance as the first approved pharmacotherapy for GA, concerns exist regarding its benefit-risk profile. Increased adverse events like endophthalmitis and conversion to wet AMD were seen with Izervay versus placebo. Additionally, the lack of efficacy on visual acuity, a key goal in managing AMD, raises uncertainty about its clinical value.
3. Further research is still needed to establish the long-term impact of Izervay on vision outcomes and safety.

Definitions

• "Age-related macular degeneration (AMD)" is a common progressive eye disease that results in damage to the macula and central vision loss. It has two main forms - dry and wet AMD.
• "Drusen" is yellow extracellular deposits that accumulate under the retinal pigment epithelium characterizing early AMD.
• "Dry AMD" is the most common form of AMD (~90% cases) characterized by drusen deposits and abnormalities in the retinal pigment epithelium in the macula.
• "Endophthalmitis" is a serious inflammation of the interior of the eye that can lead to vision loss.
• "Geographic atrophy (GA)" is an advanced form of dry AMD defined by irreversible atrophy and loss of retinal cells leading to progressive vision impairment. Also known as atrophic AMD.
• "Idiopathic Polypoidal Choroidal Vasculopathy (IPCV)" is a condition characterized by the presence of polypoidal, saccular dilations of blood vessels located beneath the RPE. It can lead to serous and hemorrhagic detachments of the RPE. While IPCV shares some similarities with nAMD, it's a distinct entity.
• "Intravitreal injection" refers to injection of a medication into the vitreous humor of the eye to directly deliver the drug to the retina.
• "Macula" is the small central area of the retina responsible for sharp, detailed central vision.
• "Neovascular Age-Related Macular Degeneration (nAMD)" is the wet form of AMD. It is characterized by the growth of abnormal blood vessels under the retina, which can leak fluid and blood. This leads to rapid and severe central vision loss if not treated.
• "Stargardt Disease" is an inherited form of juvenile macular degeneration. It typically begins in childhood or adolescence and is caused by mutations in specific genes. Over time, there's a progressive loss of central vision.

Medical Necessity Criteria for Initial Authorization

The Plan considers Izervay (avacincaptad pegol) medically necessary when ALL of the following criteria are met:

1. The medication is prescribed by or in consultation with an ophthalmologist; AND
2. The member is 18 years of age or older; AND
3. The member has a diagnosis of geographic atrophy secondary to age-related macular degeneration supported by clinical documentation; AND
4. The member does NOT have ANY of the following:
   • active ocular or periocular infections; or
   • active intraocular inflammation; AND
5. Izervay (avacincaptad pegol) is being prescribed at a dose and frequency that is within FDA approved labeling OR is supported by compendia or evidence-based published dosing guidelines for the requested indication.

Medical Necessity Criteria for Reauthorization

NOTE: Izervay is approved for administration by intravitreal injection to each affected eye once monthly (approximately every 28 "+/-" 7 days) for up to 12 months.

Reauthorization beyond 12 months will be reviewed on a case-by-case basis and may be granted based on BOTH of the following:

1. The medication is prescribed by or in consultation with an ophthalmologist; AND
2. Clinical documentation is provided showing ALL of the following:
   • continued disease stability or slowing in the growth rate of geographic atrophy lesions; AND
   • no evidence of unacceptable toxicity or adverse events, such as endophthalmitis, retinal detachment, or conversion to wet AMD; AND
   • clinical rationale and supporting evidence for extended Izervay treatment beyond the 12 months initially approved by the FDA.

Experimental or Investigational / Not Medically Necessary

Izervay (avacincaptad pegol) for any other indication or use is considered not medically necessary by the Plan, as it is deemed to be experimental, investigational, or unproven. Non-covered indications include, but are not limited to, the following:

• Neovascular Age-Related Macular Degeneration (nAMD)
• Stargardt Disease
• Idiopathic Polypoidal Choroidal Vasculopathy