Syfovre Drug Information

is indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD). SYFOVRE is a complement inhibitor indicated for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. A total of 839 patients with GA in two Phase 3 studies (OAKS and DERBY) were treated with intravitreal SYFOVRE, 15 mg (0.1 mL of 150 mg/mL solution). Four hundred nineteen of these patients were treated in the affected eye monthly and 420 were treated in the affected eye every other month. Four hundred seventeen patients were assigned to sham.

The most common adverse reactions (≥5%) reported in patients receiving SYFOVRE were ocular discomfort, neovascular age-related macular degeneration, vitreous floaters, and conjunctival hemorrhage. Table 1: Adverse Reactions in Study Eye Reported in ≥2% of Patients Treated with SYFOVRE Through Month 24 in Studies OAKS and DERBY Adverse Reactions PM (N = 419) % PEOM (N = 420) % Sham Pooled (N = 417) % PM: SYFOVRE monthly; PEOM: SYFOVRE every other month Ocular discomfort The following reported terms were combined: Ocular discomfort included: eye pain, eye irritation, foreign body sensation in eyes, ocular discomfort, abnormal sensation in eye Neovascular age-related macular degeneration included: exudative age-related macular degeneration, choroidal neovascularization Punctate keratitis included: punctate keratitis, keratitis Intraocular inflammation included: vitritis, vitreal cells, iridocyclitis, uveitis, anterior chamber cells, iritis, anterior chamber flare 13 10 11 Neovascular age-related macular degeneration 12 7 3 Vitreous floaters 10 7 1 Conjunctival hemorrhage 8 8 4 Vitreous detachment 4 6 3 Retinal hemorrhage 4 5 3 Punctate keratitis 5 3 <1 Posterior capsule opacification 4 4 3 Intraocular inflammation 4 2 <1 Intraocular pressure increased 2 3 <1 Endophthalmitis, retinal detachment, hyphema and retinal tears were reported in less than 1% of patients. Optic ischemic neuropathy was reported in 1.7% of patients treated monthly, 0.2% of patients treated every other month and 0.0% of patients assigned to sham.

Deaths were reported in 6.7% of patients treated monthly, 3.6% of patients treated every other month and 3.8% of patients assigned to sham. The rates and causes of death were consistent with the elderly study population.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of SYFOVRE. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Eye disorders : retinal vasculitis with or without retinal vascular occlusion. Systemic reactions: anaphylaxis, rash, and urticaria.

Pregnancy Risk Summary There are no adequate and well-controlled studies of SYFOVRE administration in pregnant women to inform a drug-associated risk. The use of SYFOVRE may be considered following an assessment of the risks and benefits. Systemic exposure of SYFOVRE following ocular administration is low . Subcutaneous administration of pegcetacoplan to pregnant monkeys from the mid gestation period through birth resulted in increased incidences of abortions and stillbirths at systemic exposures 1040-fold higher than that observed in humans at the maximum recommended human ophthalmic dose (MRHOD) of SYFOVRE (based on the area under the curve (AUC) systemically measured levels). No adverse maternal or fetal effects were observed in monkeys at systemic exposures approximately 470-fold higher than that observed in humans at the MRHOD (see Data ). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Data Animal Data In embryofetal development studies, subcutaneous administration of pegcetacoplan to pregnant cynomolgus monkeys from the mid gestation period through birth produced increased incidences of abortions and stillbirths at doses of 28 mg/kg/day. Pegcetacoplan was not maternally toxic and did not produce adverse embryofetal effects in the monkey at subcutaneous doses of 7 mg/kg/day. (approximately 470-fold higher than the MRHOD). No developmental effects were observed in infants up to 6 months postpartum. Minimal systemic exposure to pegcetacoplan (less than 1%, not pharmacologically significant) was detected in fetuses from monkeys treated subcutaneously with 28 mg/kg/day from the period of organogenesis through the second trimester.

Pediatric Use The safety and effectiveness of SYFOVRE in pediatric patients have not been established.

Ocular or Periocular Infections

SYFOVRE is contraindicated in patients with ocular or periocular infections .

Active Intraocular Inflammation

SYFOVRE is contraindicated in patients with active intraocular inflammation.

Hypersensitivity

SYFOVRE is contraindicated in patients with hypersensitivity to pegcetacoplan or to any of the excipients in SYFOVRE. Systemic hypersensitivity reactions (e.g., anaphylaxis, rash, urticaria) have occurred in patients treated with SYFOVRE .