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Michael Rivera, Alline Lelis, Bruce Bouchard, Melissa Stiles, Vincent Ling, Konrad Kauper, Weng Tao; Pharmacokinetics of a VEGF Antagonist Delivered by an Intraocular Encapsulated Cell Technology Implant. Invest. Ophthalmol. Vis. Sci. 2012;53(14):474.
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Agents that neutralize VEGF isoforms have been shown to be effective for treating the wet form of Age-Related Macular Degeneration (AMD), a leading cause of blindness. Neurotech’s encapsulated cell technology (ECT) platform utilizes genetically engineered cells to secrete therapeutic proteins from an implantable hollow fiber capsule. The purpose of the current study was to investigate the pharmacokinetics (PK) of a VEGF antagonist delivered by an intraocular ECT implant in rabbits over a 3 months implantation period. Additionally, an arm evaluating the PK of Bevacizumab injection was included for comparison.
ECT implants were manufactured using polymer membrane encapsulated cells genetically engineered to continuously secrete a VEGF antagonist molecule, designated NT-503. Standard-of-care injections of 1.25 mg Bevacizumab were given at Day 0 and Day 42. Plasma and vitreous were harvested from 4 eyes/two animals per time point following implantation or injection. Implant secretion rates, vitreous and serum concentrations of the VEGF antagonist were quantified by ELISA. Samples were collected at days 1, 3, 7, 14, 28, 40, 56 and 84 for both ECT implanted and injected eyes.
The NT-503 implants have demonstrated stable expression of the VEGF antagonist molecule through the time period evaluated. Data suggests that the levels of VEGF antagonist are delivered at up to 5 µg/day, maintaining a vitreous steady state concentration of approximately 25 µg/eye. Bevacizumab injections have been shown to maintain vitreous steady state concentrations of > 5 µg/mL for up to 30 days.
Pharmacokinetics data demonstrates that ECT delivery of a VEGF antagonist can maintain microgram per eye concentrations over an extended period and the steady state level established by the ECT implant exceeds the maintenance dose established by Bevacizumab monthly intraocular injections.
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