IZERVAY Intravitreal solution Ref.[107401] Active ingredients: Avacincaptad pegol

5.1 Endophthalmitis and Retinal Detachments

Intravitreal injections may be associated with endophthalmitis and retinal detachments [see Adverse Reactions (6.1)]. Proper aseptic injection techniques must always be used when administering IZERVAY in order to minimize the risk of endophthalmitis [see Dosage and Administration (2.4)]. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay, to permit prompt and appropriate management [see Patient Counseling Information (17)].

5.2 Neovascular AMD

In clinical trials, use of IZERVAY was associated with increased rates of neovascular (wet) AMD or choroidal neovascularization (7% when administered monthly and 4% in the sham group) by Month 12. Patients receiving IZERVAY should be monitored for signs of neovascular AMD.

5.3 Increase in Intraocular Pressure

Transient increases in intraocular pressure (IOP) have been observed after an intravitreal injection, including with IZERVAY [see Adverse Reactions (6.1)]. Perfusion of the optic nerve head should be monitored following the injection and managed as needed [see Dosage and Administration (2.4)].

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)

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 pooled across GATHER1 and GATHER2, are listed below in Table 1.

Table 1. Common Ocular Adverse Reactions (≥2%) and greater than Sham in Study Eye:

^* Blurred vision includes visual impairment, vision blurred, visual acuity reduced, visual acuity reduced transiently.

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 5.1 times and 3.2 times the human exposure (based on AUC) at the maximum recommended human dose (MRHD) of 2 mg once monthly, respectively (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 intravenous (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 5.1 times the MRHD, based on Area Under the Curve (AUC).

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 3.2 times the human exposure at the MRHD, based on AUC.

Risk Summary

There is no information regarding the presence of avacincaptad pegol in human milk, the effects of the drug on the breastfed infant, or the effects of avacincaptad pegol on milk production. Many drugs are transferred in human milk with the potential for absorption and adverse reactions in the breastfed child.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for IZERVAY, and any potential adverse effects on the breastfed infant from IZERVAY.

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

Of the total number of patients who received IZERVAY in the two clinical trials, 90% (263/292) were ≥65 years and 61% (178/292) were ≥75 years of age. No significant differences in efficacy or safety of avacincaptad pegol were seen with increasing age in these studies. No dose adjustment is required in patients 65 years and above.