Izervay Drug Information

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

• The following potentially serious adverse reactions are described elsewhere in the labeling:
• Ocular and periocular infections [see Contraindications (4.1) ]
• Active intraocular inflammation [see Contraindications (4.2) ]
• Endophthalmitis and retinal detachments [see Warnings and Precautions (5.1) ]
• Neovascular AMD [see Warnings and Precautions (5.2) ]
• Increase in intraocular pressure [see Warnings and Precautions (5.3) ] The most common adverse reactions (incidence ≥ 5%) were conjunctival hemorrhage, increased IOP, blurred vision, neovascular age-related macular degeneration, punctate keratitis, and eye pain ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Astellas Pharma US, Inc. at 1-800-727-7003 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 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. The safety of avacincaptad pegol was evaluated in 733 patients with AMD in two sham-controlled studies (GATHER1 and GATHER2). Of these patients, 292 were treated with intravitreal IZERVAY 2 mg (0.1 mL of 20 mg/mL solution) [see Clinical Studies (14) ] . Three hundred thirty-two (332) patients were assigned to sham. Adverse reactions reported in ≥2% of patients who received treatment with IZERVAY for up to 12 months pooled across the GATHER1 and GATHER2 studies are listed below in Table 1 . Table 1: Common Ocular Adverse Reactions (≥2%) and greater than Sham in Study Eye up to 12 months 1 Blurred vision includes visual impairment, vision blurred, visual acuity reduced, visual acuity reduced transiently. Adverse Drug Reactions IZERVAY N=292 Sham N=332 Conjunctival hemorrhage 13% 9% Increased IOP 9% 1% Blurred vision 1 8% 5% Choroidal neovascularization 7% 4% Eye pain 4% 3% Vitreous floaters 2% <1% Blepharitis 2% <1% Adverse reactions reported in ≥ 2% of patients who received treatment with IZERVAY for up to 24 months in the GATHER2 study are listed below in Table 2 . Table 2: Common Ocular Adverse Reactions (≥ 2%) and greater than Sham in Study Eye up to 24 months 1 Blurred vision includes visual impairment, vision blurred, visual acuity reduces, visual acuity reduced transiently and blindness transient. 2 Punctate keratitis includes punctate keratitis and keratitis. Adverse Drug Reactions IZERVAY (N=225) Sham (N=222) Conjunctival hemorrhage 17% 9% Blurred vision 1 14% 5% Increased IOP 13% 1% Choroidal neovascularization 12% 9% Punctate keratitis 2 10% 8% Eye pain 7% 4% Retinal hemorrhage 4% 3% Vitreous floaters 4% <1% Ocular hypertension 4% 0 Blepharitis 3% <1% Corneal abrasion 2% <1% Photopsia, optic ischemic neuropathy, vitreous hemorrhage, vitreal cells, vitritis, and endophthalmitis were each reported in ≤ 1% of patients treated with IZERVAY for up to 24 months across the GATHER1 and GATHER2 studies.

• Pregnancy Risk Summary There are no adequate and well-controlled studies of IZERVAY administration in pregnant women. The use of IZERVAY may be considered following an assessment of the risks and benefits. Administration of avacincaptad pegol to pregnant rats and rabbits throughout the period of organogenesis resulted in no evidence of adverse effects to the fetus or pregnant female at intravenous (IV) doses 5.5 times and 3.4 times the human exposure, respectively, based on Area Under the Curve (AUC), following a single 2 mg intravitreal (IVT) dose (see Data ) . In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15%-20%, respectively. Data Animal Data An embryo fetal developmental toxicity study was conducted with pregnant rats. Pregnant rats received daily IV injections of avacincaptad pegol from day 6 to day 17 of gestation at 0.1, 0.4, 1.2 mg/kg/day. No maternal or embryofetal adverse effects were observed at any dose evaluated. An increase in the incidence of a non-adverse skeletal variation, described as short thoracolumbar (ossification site without distal cartilage) supernumerary ribs, was observed at all doses evaluated. The clinical relevance of this finding is unknown. Plasma exposures at the high dose were 5.5 times the human AUC of 999 ng
• day/mL (23976 ng
• hr/mL) following a single 2 mg IVT dose. An embryo fetal developmental toxicity study was conducted with pregnant rabbits. Pregnant rabbits received daily IV injections of avacincaptad pegol from day 7 to day 19 of gestation at 0.12, 0.4, 1.2 mg/kg/day. No maternal or embryofetal adverse effects were observed at any dose evaluated. Plasma exposure in pregnant rabbits at the highest dose of 1.2 mg/kg/day was 3.4 times the human AUC of 999 ng
• day/mL (23976 ng
• hr/mL) following a single 2 mg IVT dose.

Pediatric Use Safety and effectiveness of IZERVAY in pediatric patients have not been established.

• Ocular or periocular infections ( 4.1 ).
• Active intraocular inflammation ( 4.2 ). 4.1 Ocular or Periocular Infections IZERVAY is contraindicated in patients with ocular or periocular infections. 4.2 Active Intraocular Inflammation IZERVAY is contraindicated in patients with active intraocular inflammation.