RESUMO
PRO-169 is an anti-VEGF monoclonal antibody developed by Laboratorios Sophia that shares its sequence with Bevacizumab (BVZ); though, PRO-169 is intended for intravitreal administration. In this study, analytical characterization showed that PRO-169 had glycosylation differences in comparison to BVZ reference product (RP); since it had more content of G1F, G2F, sialic acid and high mannose. Further investigation was performed to evaluate if differences between both products would affect the efficacy and safety profile of PRO-169. PRO-169 had no alteration in its in vitro biological activity; moreover, no cytotoxicity or immunogenicity concerns should be expected as demonstrated by different orthogonal methods at analytical, in vitro and in vivo assays. These results support moving to the clinical testing of PRO-169 since no major complications will be expected with its clinical use for the treatment of ophthalmic diseases.
Assuntos
Anticorpos Monoclonais Humanizados , Fator A de Crescimento do Endotélio Vascular , Bevacizumab/farmacologia , Glicosilação , Fator A de Crescimento do Endotélio Vascular/metabolismo , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais/uso terapêuticoRESUMO
PURPOSE: To evaluate the efficacy of a therapy on improving characteristics of laser-induced choroidal neovascularization (CNV) via single intravitreal injection of a humanized anti-human VEGF monoclonal antibody (PRO-169) versus bevacizumab in a rhesus monkey model. METHODS: To induce experimental CNV, small high-energy laser spots were used to treat several areas, around the macula in the retinas of monkeys at Day -21. Eighteen rhesus monkeys were used for CNV induction. The efficacy endpoints were fluorescein leakage by FFA and retinal thickness by OCT. FFA examinations were performed 19 days after induction. Appropriate animals were enrolled for treatment and randomly divided into 3 groups: bevacizumab (n=5, 7 eyes), PRO-169 (n=5, 7 eyes), and vehicle controls (n=4, 7 eyes). RESULTS: In 25 of 36 (69.4%) eyes, CNV lesions were identified. The average percent change of retinal thickness in the eyes of bevacizumab group was -159.3±62.2% and -154.0±45.1% (p<0.01 vs Vehicle) at Day 14 and Day 28, respectively; in the eyes of PRO-169 group it was -131.6±68.7% and -131.5±63.8% (p<0.01 vs Vehicle), respectively. The average percent change of leakage area in the eyes of bevacizumab group was -75.3±49.4% and -78.0±42.6% (p<0.01 vs Vehicle) at Day 14 and Day 28, respectively; in the eyes of PRO-169 group it was -82.0±19.3% and -81.4±21.0% (p<0.01 vs Vehicle), respectively. There were no abnormalities found in behavior, skin and hair, excretion and overall eye appearance before and after treatment in all groups. CONCLUSION: After photocoagulation, the eyes enrolled in this studio showed CNV related characteristics including increased retinal thickness, and fluorescein leakage at laser spots. PRO-169 (1.25 mg per eye) can reduce the retinal thickness and fluorescein leakage area after treatment for 14 and 28 days in this rhesus monkeys model, without toxic effect or adverse events. These findings suggested that PRO-169 can inhibit CNV.