Safety of Intravitreal Injection of Stivant, a Biosimilar to Bevacizumab, in Rabbit Eyes

Abstract

Purpose: To evaluate the safety of intravitreal injection of Stivant, a biosimilar to bevacizumab, in rabbits using electrophysiological and histological analysis.
 Methods: Both eyes of 41 New Zealand albino rabbits were injected with 0.1 mL (2.5 mg) of Stivant. The rabbits were scheduled to be sacrificed 1, 2, 7, 14, and 28 days after injection for histopathological evaluations. Clinical examinations and electroretinography (ERG) were performed at baseline and just before sacrificing the rabbits. Fourteen separate rabbits received a reference drug (Avastin) and were considered as the control group. Furthermore, three other rabbits received the same volume of saline (saline control group). Rabbits of both control groups were sacrificed four weeks after injection. ERG was performed 1, 2, 7, 14, and 28 days after injections.
 Results: No significant difference was observed in a- and b-wave amplitudes and latency after intravitreal Stivant injection between baseline and different time points. Moreover, there was no statistically significant difference in wave amplitudes and latency between the Stivant and control groups. The histology of rabbit eyes of the Stivant and control groups after intravitreal injections was not distinguishable.
 Conclusion: The biosimilar Stivant, up to a dose of 2.5 mg, did not appear to be toxic to the retina in albino rabbits. These results suggest that this drug could be a safe and inexpensive alternative to intravitreal bevacizumab. The efficacy of these injections was not investigated in this study and needs to be evaluated in future studies.

Intraocular Injection of Stivant® (A Biosimilar to Bevacizumab): A Case Series

“…Intravitreal injection of 2.5 mg Stivant® did not show any adverse effect on retinal function evaluated by electroretinography (ERG). Additionally, histologic examination of the enucleated globes did not reveal any visible histopathologic changes at the cellular level [8] .…”

“…This biosimilar did not show histopathologic changes at the cellular level after being injected into the eyes of albino rabbits evaluated by clinical examinations, ERG, and histopathological assessment. [8] Biosimilars which are produced by modified cellular processes are identical to their reference biologic agents in terms of structure and active substance, although some minor variations are inevitable. Therefore, biosimilars are the end products similar to the original molecule with minor non-significant differences.…”

“…The World Health Organization (WHO) defines biosimilar drugs as a biotherapeutic product that is similar in terms of quality, safety, and efficacy to an already licensed reference biotherapeutic product. Biosimilars have the potential to reduce the healthcare costs relative to reference biologics, thereby increasing the treatment access [8][9][10]. Stivant® (CinnaGen Co., Iran) has been developed as a biosimilar to Avastin®.…”

Three-dimensional spheroids of choroid-retinal vascular endothelial cells as an in-vitro model for diabetic retinopathy: Proof-of-concept investigation

“…Bevacizumab is administered at a clinically relevant dose of 1.25 ​mg in cases of advanced DR ( Gudla et al., 2018 ). However, effects of doses up to 2.5 ​mg have been assessed in animal models and human subjects ( Arevalo et al., 2011 ; Lashay et al., 2020 ; Park et al., 2016 ). Thus, the present study investigated the effect of Bevacizumab below, at and above the clinically relevant doses, on 3D and 2D cultures of RF/6A cells.…”

The Development Pathway for Biosimilar Biotherapeutics

“…[7] Studies such as the one reported by Lashay and coworkers in this issue of the Journal of Ophthalmic and Vision Research constitute an essential step toward adopting use of Stivant, a biosimilar to bevacizumab, for non-approved ophthalmic indications. [8] This work has been executed expertly and provides reassurance that Stivant may well be an appropriate substitute for intravitreal bevacizumab, which is more expensive. The authors qualify their results with great care, but it may be worth emphasizing a few points.…”