Abstract
Purpose :
MKIs have been shown to inhibit vascular leakage clinically in the treatment of wAMD, RVO and DME. The approved anti-VEGFs are effective; however, their short duration a creates burden on the practice and patient. Our goal is to develop a long-acting intravitreal biodegradable implant that would be effective in managing the disease for ~6-12 months. We investigated the tolerability and efficacy of MKI biodegradable intravitreal implant, to inhibit retinal vascular leakage in the DL-AAA Dutch-Belted rabbit model.
Methods :
Several biodegradable implant formulations were developed and tested in-vitro for drug release kinetics. The lead formulation was selected based on in-vitro release data to be tested in the rabbit model. DL-AAA rabbits were induced 8 weeks prior to study start. Seven DL-AAA female rabbits received 1 GLC-009 implant OD and 1 placebo implant OS, and 3 received 2 GLC-009 implants OU. Eyes were monitored using fluorescein angiography (FA), aide Angle (55°) IR imaging, and slit lamp ophthalmic exams including McDonald-Shadduck scoring at Days 1, 8 and monthly thereafter for 12 months. To assess tolerability, 3 naïve female Dutch Belted rabbits received 1 GLC-009 implant OD and sham injection OS, and 3 rabbits received 2 GLC-009 implants OD and 2 placebo implants OS. Plasma was collected to monitor systemic drug exposure.
Results :
Administration of 1 and 2 GLC-009 implants showed significant inhibition of retinal vascular leakage compared to placebo on FAs beginning at Day 8 and continuing for 12 months. Both 1 and 2 GLC-009 implants provided maximal inhibition of vascular leakage. Observations consistent with intravitreal injections were observed and fully resolved. Systemic exposure was minimal, with values near or below the lower limit of quantitation. Initial signs of implant biodegradation were observed beginning on Day 210.
Conclusions :
An MKI biodegradable intravitreal implant, was well tolerated in naïve DB rabbit eyes and significantly inhibited retinal vascular leakage in the DL-AAA rabbit model for 12 months. If confirmed clinically, such MKI long lasting implant could offer a long duration therapeutic alternative in the treatment of wAMD, RVO and DME.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.