Duration of Effect of a Single Intravitreal Injection of a Sustained-Release Formulation of Abicipar Pegol Compared to a Bolus Dose of Aflibercept in a Rabbit Model of Persistent Retinal Vascular Leak

Abstract

Purpose : The high treatment burden of frequent intravitreal (IVT) anti-VEGF injections for treatment of nAMD and DME presents an opportunity for sustained release (SR) technologies to increase the interval between injections. To address this unmet need, duration of effect of a single IVT injection of an SR formulation of bioerodible polymer microsphere particles loaded with the DARPin anti-VEGF abicipar pegol (abicipar SR) compared to a bolus dose of aflibercept was evaluated in a rabbit model of persistent retinal vascular leak (PRVL).

Methods : New Zealand Red rabbits previously injected IVT with DL-2-aminoadipic acid (0.8 mg; OD) to induce PRVL were injected IVT with 50 µL of either abicipar SR (500 µg drug load; n=8) or aflibercept (700 µg bolus; n=7). Duration of effect was determined by quantitation of retinal leak area compared to pre-treatment leak area using fluorescein angiography bi-weekly for 32 weeks after injection. Retinas were then collected, fixed, and immunofluorescent co-labeling of retinal vasculature with IB4 and CD31 antibody was performed. Confocal images of retinal whole mounts were acquired and the degree of vascular regression in the area of baseline retinal leak was determined by calculating the ratio of CD31/IB4 signal overlap, which inversely correlates with the extent of vascular regression.

Results : A single IVT injection of abicipar SR completely inhibited retinal leak in all eyes for 22 weeks versus 10 weeks with aflibercept treatment. Complete leak suppression persisted in 71, 43, and 17% of abicipar SR-treated eyes at Weeks 24, 26, and 28, respectively. Robust suppression (>90% reduction of baseline leak area) was shown 26 weeks after abicipar SR treatment, which was significantly longer (P<0.05) than 12 weeks with aflibercept treatment. IHC analysis of retinal vasculature revealed that abicipar SR and aflibercept induced regression of neovessels within the baseline leak area to a similar extent. Intra-ocular inflammation was not observed in either treatment group.

Conclusions : These data demonstrate that a single IVT injection of abicipar SR was well tolerated in NZW rabbits and suppressed retinal leak for 6 months. Compared to aflibercept, abicipar SR was at least twice as durable with a minimum of 14 additional weeks of activity.

This is a 2021 ARVO Annual Meeting abstract.