GB-102 for Wet AMD: A Novel Injectable Formulation that Safely Delivers Active Levels of Sunitinib to the Retina and RPE/Choroid for Over Four Months

Abstract

Purpose : To evaluate the ocular tolerability, safety, and pharmacokinetics (PK) of an intravitreal injection of novel depot formulation of sunitinib malate, a potent dual VEGFR/PDGFR inhibitor.

Methods : A formulation of sunitinib malate-containing, biodegradable microparticles (GB-102) was developed to deliver pharmacologically active levels of sunitinib for at least 4 months to the retina and RPE/choroid following a single intravitreal injection. Sunitinib malate is an FDA-approved, anti-cancer drug. Drug-containing and placebo GB-102 microparticles were fully characterized in vitro. Two doses of GB-102 (0.2 and 1.0 mg sunitinib malate) and placebo microparticles were injected into the vitreous of pigmented New Zealand rabbits using a 27G needle. Ocular slit-lamp and fundus examinations were performed 5 days after dosing and monthly thereafter for four months. Ocular histopathology and ocular/plasma levels of sunitinib were assessed at 1, 2 and 4 months after dosing.

Results : GB-102 microparticles coalesced in the inferior vitreous into an immobile, implant-like depot that remained outside of the visual axis. There were no clinically significant findings by ocular exam and no toxicologically significant findings by histopathology in any of the eyes treated with sunitinib malate-containing or placebo microparticles. Sunitinib levels in eyes dosed with the low-dose group were >20 ng/mL (retina) and >2000 ng/mL (RPE/choroid) at 1, 2 and 4 months. These retina and RPE/choroid levels are 10- and 1000-fold higher than the well-established target plasma level of free sunitinib (~2 ng/mL) needed for anti-cancer efficacy. In contrast, plasma levels of free sunitinib following an IVT injection of GB-102 were <0.02 ng/mL at all time points.

Conclusions : Intravitreal injection of GB-102 is well-tolerated and non-toxic in pigmented rabbit eyes over the first four months of the ongoing study. Microparticles containing 0.2 mg sunitinib malate deliver pharmacologically active levels of sunitinib to retina and RPE/choroid for at least four months. This novel formulation may enable treatment only two to three times per year for neovascular age-related macular degeneration.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.