Safety of Intravitreal Injection of Biosimilar of Aflibercept in Rabbit Eyes

Abstract

<jats:p><jats:italic>Purpose</jats:italic>. To assess the safety of biosimilar intravitreal aflibercept (CinnaGen Co., Iran) compared to the reference product (Eylea®; Bayer Schweiz AG, Zurich, Switzerland) in rabbit eyes through functional and histologic studies. <jats:italic>Methods</jats:italic>. Forty New Zealand albino rabbits were recruited to the study and were divided into four groups to be sacrificed at 48 hours, one, two, and four weeks after injections. In each group, five rabbits received 0.05 mL (2 mg) biosimilar aflibercept in the right eye and 0.05 mL saline in the left eye as the control, and in a similar manner, the remaining five rabbits received the reference drug in the right eye and saline in the left eye. All the rabbits underwent comprehensive ophthalmic examination and electroretinography (ERG) tests at baseline and also just before enucleation at the specific predefined time points. The enucleated eyes were prepared for retinal toxicity histological examination. <jats:italic>Results</jats:italic>. No retinal toxicity was observed based on histologic and ERG findings in all groups. Choroidal congestion was revealed after 1 week in an eye that was injected with biosimilar aflibercept, although the similar finding was detected in the contralateral eye which received saline. Also, one subject which received the reference drug showed chronic vitritis and lymphoplasmocytic reaction of the optic disc at week 4. The remaining subjects showed no histologic changes. <jats:italic>Conclusion</jats:italic>. The 2 mg intravitreal injection of biosimilar aflibercept (CinnaGen Co., Iran) was found to be nontoxic in rabbit eyes in the short-term period. Further studies are required to warrant the efficacy and safety profile of the drug in human subjects.</jats:p>

Electrophysiological evaluation and 18-month follow-up of two regimens with aflibercept for neovascular age-related macular degeneration

“…At the end of exposure and wash-out time, however, no reduction compared to baseline measurements could be detected. Short-term animal studies have not found retinal toxicity with ERG in the retina of rabbits with aflibercept at 4-week or ziv-aflibercept at 2-week follow-up [36,37]. Six-month and 1-year follow-up of 15 eyes of nAMD patients treated with ziv-aflibercept have not shown signs of toxicity on ffERG [29,30].…”

In vitro and in ovo experimental study of two anti-VEGF agents used in ophthalmology

“…Preliminary in vitro studies have shown that the concentration of 1000 μg/mL of Aflibercept does not show cytotoxic effects in the cell lines of primary cultures of human trabecular meshwork cells, human scleral fibroblasts, and a retinal pigment epithelial cell line [ 24 ]. In vivo studies in rabbit eyes have suggested that short-term administration of Aflibercept does not cause eye irritation [ 25 ]. On the other hand, a 6-month clinical trial found that intravitreal administration of Aflibercept may cause corneal endothelial alterations, but these potential side effects have not been studied in detail [ 26 ].…”

Network analysis and the impact of Aflibercept on specific mediators of angiogenesis in HUVEC cells

“…The aforesaid concentration is consistent to the peak of serum concentration of Aflibercept (Cmax) in vivo and after the first intravitreal injection would mimics its systemic effect reasonably. Cmax is obtained by investigating recent anti–VEGF‐associated studies that evaluated the expression level of specific genes on vascular endothelial cells 47‐52 . RNA extraction was performed from HUVEC cells that had been treated 6 hours or 24 hours by Aflibercept (Bayer, Germany) or phosphate‐buffered saline (PBS, as a control).…”