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Yun Yu, Ward Peterson, Ming Yang, David McKenzie, Delia Cardona, David Culp, Brian C Gilger, Jeffrey Cleland; Sunitinib-Loaded Injectable Polymer Depot Formulation for Potential Once per Year Treatment of Neovascular Age-related Macular Degeneration (wet AMD). Invest. Ophthalmol. Vis. Sci. 2018;59(9):221. doi: https://doi.org/.
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To evaluate the ocular tolerability and pharmacokinetics (PK) of GB-103, a second-generation microparticle formulation of sunitinib malate. The first-generation formulation (GB-102) is in clinical development as a potential twice-per-year IVT treatment for wet AMD.
GB-103 was characterized in vitro (drug loading, particle size, and release kinetics), and in vivo (tolerability, pharmacokinetics, and drug release) following a single IVT injection in Dutch-belted rabbits. Sunitinib malate is the active ingredient of the FDA-approved, anti-cancer drug Sutent®.
The first-generation GB-102 formulation releases sunitinib for 2-3 months both in vitro and in rabbit vitreous. We previously reported that pharmacologically active levels of sunitinib are maintained for 4-5 months in retina and 6-7 months in RPE/choroid following a single IVT injection of GB-102 (1 mg sunitinib) in pigmented rabbits. The additional 1-2 months exposure in retina and 3-4 months exposure in RPE-choroid is due to reversible binding of sunitinib to ocular melanin, which serves as a secondary drug depot (Peterson W, et al. IOVS 2017; 58(8):1974). GB-103 releases sunitinib for ~8 months in vitro, 5-6 months longer than GB-102. Pharmacologically active drug levels in retina and RPE/choroid were observed throughout the initial five months of an ongoing rabbit study. In addition, no adverse ophthalmic findings have been observed to date in any of the 28 rabbit eyes dosed with GB-103 (0.5 - 1 mg sunitinib). As with GB-102, the drug release profile of GB-103 in vivo is similar to its in vitro release profile.
A single IVT injection of GB-103 is well-tolerated and able to maintain pharmacologically active levels of sunitinib in retina and RPE-choroid during the first 5 months of an ongoing study. Compared with GB-102, the GB-103 formulation extends the duration of drug release by an additional 5-6 months. GB-103 may enable once-per-year treatment for wet AMD.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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