Ocular Safety and Toxicokinetics of Bevacizumab-bvzr (Zirabev), a Bevacizumab Biosimilar, Administered to Cynomolgus Monkeys by Intravitreal Injection.
J Ocul Pharmacol Ther
; 39(3): 215-224, 2023 04.
Article
em En
| MEDLINE
| ID: mdl-36880872
ABSTRACT
Purpose:
Bevacizumab-bvzr (Zirabev®), a recombinant humanized monoclonal antibody targeting vascular endothelial growth factor and a biosimilar to bevacizumab, is approved for intravenous administration for various indications worldwide. The objectives of this study were to evaluate the ocular toxicity, systemic tolerability, and toxicokinetics (TKs) of bevacizumab-bvzr following repeat intravitreal (IVT) injection to cynomolgus monkeys.Methods:
Male monkeys were administered saline, vehicle, or bevacizumab-bvzr at 1.25 mg/eye/dose once every 2 weeks (3 doses total) for 1 month by bilateral IVT injection, followed by a 4-week recovery phase to evaluate the reversibility of any findings. Local and systemic safety was assessed. Ocular safety assessments included in-life ophthalmic examinations, tonometry (intraocular pressure, IOP), electroretinograms (ERGs), and histopathology. In addition, concentrations of bevacizumab-bvzr were measured in serum and in ocular tissues (vitreous humor, retina, and choroid/retinal pigment epithelium) and ocular concentration-time profiles and serum TKs were evaluated.Results:
Bevacizumab-bvzr was tolerated locally and systemically, with an ocular safety profile comparable to the saline or vehicle control group. Bevacizumab-bvzr was observed in both serum and in the evaluated ocular tissues. There were no bevacizumab-bvzr-related microscopic changes or effects on IOP or ERGs. Bevacizumab-bvzr-related trace pigment or cells in vitreous humor (in 4 of 12 animals; commonly associated with IVT injection) and transient, nonadverse, mild ocular inflammation (in 1 of 12 animals) were noted upon ophthalmic examination and fully reversed during the recovery phase.Conclusions:
Bevacizumab-bvzr was well tolerated via biweekly IVT administration in healthy monkeys, with an ocular safety profile comparable to saline or its vehicle control.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Medicamentos Biossimilares
Limite:
Animals
Idioma:
En
Revista:
J Ocul Pharmacol Ther
Assunto da revista:
FARMACOLOGIA
/
OFTALMOLOGIA
/
TERAPEUTICA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos