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Zafar Gill, Jeffrey L Olson, Josh Morgenstern, Anthony Jones, Anne Strong, Steven Droho, Shaun Bevers, Niklaus Mueller, Nihaal Mehta, Michael Huvard, Peter K Kaiser, Ramanath Bhandari; RO-634 half-life as compared to published data on Aflibercept, Faricimab, Ranibizumab, and Bevacizumab.. Invest. Ophthalmol. Vis. Sci. 2022;63(7):308 – F0111.
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© ARVO (1962-2015); The Authors (2016-present)
RO-634 is a novel intravitreal bispecific protein (surrobody) with dual inhibition of both Vascular Endothelial Growth Factor-A (VEGF-A) and Angiopoietin-2 (ANG-2). We aim to investigate the half-life of this protein as compared to published data on Aflibercept, Faricimab, Ranibizumab, and Bevacizumab. These findings may have important clinical implications for treatment of retinal disease including diabetic macular edema (DME), proliferative diabetic retinopathy (PDR), and exudative age-related macular degeneration (AMD).
All experiments were performed in accordance with the ARVO statement for Use of Animals in Ophthalmic and Vision Research. The half -life of RO-634 was determined by measuring vitreous VEGF levels in 6 New Zealand White Cross rabbits with an ocular fluorophotometer (Ocumetrics, Mountain View, CA). These measurements were taken before an injection of fluorescein labeled VEGF (concentration 0.3 ug/mL) and post-injection at hours 1, 12, 24, 48, 72, 96, and 120. Determination of the vitreous fluorescence was made by averaging the values around the vitreous plateau as described by Gray et al.
In vivo intraocular half-life measurements of RO-634 in New Zealand White Cross rabbits were longer than previously published data on aflibercept (3.92 days), ranibizumab (2.88 days), and similar to bevacizumab (6.51 days). Measurements taken from peak averages, demonstrated RO-634 half-life was an average of 6.75 days ± 2.13 days.
Our study demonstrates that RO-634 has a similar half-life when compared to bevacizumab and a longer half-life when compared to aflibercept and ranibizumab. Given RO-634’s excellent half-life and novel dual-inhibitory mechanism of action, we propose that this protein is a possible therapeutic candidate for exudative AMD, DME, and PDR. We are hopeful that future studies will continue to shed light on RO-634s safety and efficacy in both animal and human models.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.
Measurement of vitreous VEGF levels with an ocular fluorophotometer were used to calculate intraocular half-life measurements of the surrobody. Results for surrobody half-life averaged 6.75 ± 2.13 days, compared to previously published data on aflibercept (3.92 days), ranibizumab (2.88 days), and bevacizumab (6.51 days).
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