Comparing The Efficacy Of An Anti-Human VEGF-A Neutralizing Antibody Versus Bevacizumab On A Laser-Induced Choroidal Neovascularization (CNV) Rhesus Monkey Model

Abstract

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.

Keywords:

• age-related macular degeneration
• monoclonal antibodies
• fundus fluorescein angiography
• optical coherence tomography

Acknowledgments

We thank Sichuan Primed Shines for providing the experimental monkeys and conducting the monkey study and for their help during the experiment. This study was sponsored by Laboratorios Sophia, SA de CV (Zapopan, Jalisco, Mexico).

Abbreviations

AMD, age-related macular degeneration; CNV, choroidal neovascularization; FFA, fluorescein fundus angiography; FP, fundus photography; NHP, non-human primate; OCT, optical coherence tomography; VEGF, vascular endothelial growth factor.

Author Contributions

All authors contributed to data analysis, drafting or revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

Olvera-Montaño O, Baiza-Duran L and Muñoz-Villegas P are employees of Laboratorios Sophia, SA de CV. Quintana-Hau JD and Quiñonez-Alvarado MG are employees of Centro de Investigación Sophia (CIS). The authors report no other conflicts of interest in this work.