There are no adequate and well-controlled studies of avacincaptad pegol administration in pregnant women. The use of avacincaptad pegol 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.
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.
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 avacincaptad pegol, and any potential adverse effects on the breastfed infant from avacincaptad pegol.
No studies have been conducted on the carcinogenic potential of avacincaptad pegol.
Avacincaptad pegol was negative in in vitro (bacterial reverse mutation assay, chromosomal aberration in mammalian cells) and in vivo (mouse bone marrow micronucleus) assays.
Studies to evaluate the effect of avacincaptad pegol on male or female fertility in animals have not been performed.
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 avacincaptad pegol 2 mg (0.1 mL of 20 mg/mL solution). Three hundred thirty-two (332) patients were assigned to sham.
Adverse reactions reported in ≥2% of patients who received treatment with avacincaptad pegol pooled across GATHER1 and GATHER2, are listed below in the following table.
Common Ocular Adverse Reactions (≥2%) and greater than Sham in Study Eye:
| Adverse Drug Reactions | Avacincaptad pegol N=292 | Sham N=332 |
|---|---|---|
| Conjunctival hemorrhage | 13% | 9% |
| Increased IOP | 9% | 1% |
| Blurred vision* | 8% | 5% |
| Choroidal neovascularization | 7% | 4% |
| Eye pain | 4% | 3% |
| Vitreous floaters | 2% | <1% |
| Blepharitis | 2% | <1% |
* Blurred vision includes visual impairment, vision blurred, visual acuity reduced, visual acuity reduced transiently.
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