Ocular distribution and pharmacokinetics of 125I-OPT302 and 125I-Aflibercept (EYLEA) following intravitreal administration to pigmented rabbits

Abstract Purpose OPT‐302 is a soluble receptor that specifically and potently blocks VEGF‐C and VEGF‐D activity which are involved in the progression of retinal and corneal diseases. OPT‐302 is currently under development for the treatment of wet AMD. The purpose of this study was to assess ocular distribution and pharmacokinetics of 125I‐OPT‐302 and 125I‐EYLEA following intravitreal (IVT)dosing in Dutch Belted rabbits. Methods 125I‐OPT‐302 and 125I‐EYLEA were prepared at ~10 mg/mL and 50 µCi/mg. Eight animals/group were dosed with 0.5 mg test article/eye. Serum and ocular tissues were collected at eight time points between 1 and 672 hours for radioanalysis. The formulations were homogeneous, stable, and active with their cognate ligands. Results Following IVT dosing the test articles were well tolerated. There was low systemic exposure of 125I‐OPT‐302 with AUC(0‐t) of 110000 ng eq*hours/mL. Systemic exposure to 125I‐EYLEA was ~4 fold greater at 420000 ng eq*hours/mL. Concentrations of 125I‐OPT‐302 and 125I‐EYLEA in the vitreous humor (VH) at C0 were 368000 and 337000 ng equivalents/g, respectively. Elimination t1/2 from VH were similar at 104 and 112 hours. For ocular tissues, the highest concentrations of radioactivity were found in retina, RPE and choroid at 1 and 12 hours postdose. Maximum concentrations were similar for each test article. Half‐lives were 104 & 102 hours in choroid and 109 & 137 hours in RPE for 125I‐OPT‐302 and 125I‐EYLEA,respectively. Conclusion 125I‐OPT‐302 and 125I‐EYLEA had prolonged exposure of posterior and anterior ocular tissues at similar concentrations for each compound, while systemic clearance of 125I‐OPT‐302 was faster than 125I‐Eylea..