In vivo characterization of RC28-E, a fusion protein targeting VEGF and bFGF: Pharmacokinetics and ocular distribution in primates

Administration of RC28-E, a VEGF/bFGF dual decoy receptor (IgG1 Fc-fusion protein), have shown relative therapeutic value in ocular in vivo models, including laser-induced choroidal neovascularization (CNV) in monkeys and streptozotocin (STZ)-induced diabetic retinopathy (DR) in rats. In the present study, we have elucidated the pharmacokinetics profiles of RC28-E at the systemic, vitreous and aqueous humor after administration in a primate model (Macaca fascicularis). Moreover, here we tease out the ocular tissue distribution of RC28-E after intravitreal administration, and we also determine the systemic bioavailability after both intravitreal and intravenous administration. Our results show that RC28-E is rapidly and well-distributed into ocular tissues after intravitreal administration. Drug exposure in choroid and retina was approximately one-quarter and one-twelfth of that in vitreous humor, while its half-life in vitreous and aqueous humor were well-sustained (3.3 and 3.0 days). Remarkably, RC28-E could cross the blood-ocular barrier, and the systemic bioavailability of RC28-E was ~25%. No drug accumulation after multiple administration was noticed, but low titers of antibody produce against RC28-E were detected. Overall, RC28-E exhibited high clinical value due to adequate pharmacokinetic profiling, safety and efficacy.

Dual blockage; Intravitreal injection; Ocular distribution; Pharmacokinetics; VEGF; bFGF.