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, 2023).

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

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

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, 2023a; 2023b).

: Requires Precertification:

Precertification of

is required of all Aetna participating providers and members in applicable plan designs. For precertification of pegcetacoplan (Syfovre),

(888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see

.

For Medicare Part B plans, call (866) 503-0857, or fax (844) 268-7263.

Exclusions

Aetna will not provide coverage for the treatment of geographic atrophy (GA) secondary to a condition other than AMD (such as Stargardt disease, cone rod dystrophy, toxic maculopathies).

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 and investigational.

Continuation of Therapy

Aetna considers continuation of pegcetacoplan (Syfovre) therapy medically necessary for treatment of an indication listed in Section II 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 normalization or reduction in total area of 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, 2023