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Konrad Kauper, Cahil McGovern, Paul Stabila, Sandy Sherman, Pam Heatherton, Brenda Dean, Crystal Cortellessa, Alice Lee, Weng Tao; Continuous Intraocular Drug Delivery over 5 ½ Years: Ciliary Neurotrophic Factor (CNTF)Production by Encapsulated Cell Technology Implants Treating Patients with Retinitis Pigmentosa and Geographic Atrophy. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3295.
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© ARVO (1962-2015); The Authors (2016-present)
Continuous intraocular delivery of biotherapeutics for treatment of chronic retinal diseases remains a major hurdle for drug development. We have previously reported the pharmacokinetics of CNTF delivered over 2 years by an intraocular encapsulated cell technology (ECT) implant in patients with retinitis pigmentosa (RP) and geographic atrophy (GA). This is a follow-up evaluation of patients implanted up to a 5.5 - year period.
All study patients received an ECT-CNTF implant, designated NT-501, in one eye. For the phase 1 RP (CNTF1) study, the protocol mandated explant of all patients at 6 months. For the phase 2 studies, including phase 2 GA (CNTF2), and phase 2 late and early stage RP (CNTF3, and CNTF4), explants were optional and occurred at 12, 18 and 24 months. Several additional patients from the CNTF4 study chose to be explanted at 30 (n=6), 44 (n=1), 54 (n=1) and 66 (n=1) months post implant. The rate of CNTF secretion from the explants and the corresponding vitreous CNTF levels, if available, were evaluated at each time point. Serum samples from these patients were evaluated for CNTF, anti-CNTF antibodies and antibodies to the encapsulated cells.
Cumulatively, the data demonstrates NT-501 implants produce CNTF continuously over a 5.5 year period. The range of explant CNTF production rate at each time point was statistically equivalent between the 0.5 year and 5.5 year implant period. The mean rates of CNTF production over this period varied between approximately 1 ng/day to 2 ng/day, a rate shown to be effective in protecting cone photoreceptors in RP patients (Talcott et el. IOVS, 2011). Encapsulated cells, subjectively evaluated following H&E staining of explant capsules, were viable and remained at a high population density, similar to the pre-implant condition. CNTF, anti-CNTF antibodies and antibodies to the encapsulated cells were not detected in the serum of patients.
This follow-up study demonstrates that the intraocular ECT implant continues to maintain a favorable pharmacokinetic profile for the treatment of chronic retinal degenerative diseases without systemic exposure for over a half decade.
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