Two-year intraocular delivery of ciliary neurotrophic factor by encapsulated cell technology implants in patients with chronic retinal degenerative diseases.

PURPOSE To evaluate the pharmacokinetics of ciliary neurotrophic factor (CNTF) delivered over a period of up to 2 years by an intraocular encapsulated cell technology (ECT) implant in patients with retinitis pigmentosa (RP) and geographic atrophy (GA). METHODS Patients from phase 1 RP (CNTF1); phase 2 GA (CNTF2); and phase 2 late and early stage RP (CNTF3, and CNTF4) studies received an ECT-CNTF implant, designated as "NT-501," in one eye. Per protocol, all implants (n = 10) were removed at 6 months from the CNTF1 study patients. Explant for the phase 2 studies was optional, but several patients were explanted at 12, 18, and 24 months post implant. A small amount of vitreous sample was collected at the time of explant. The rate of CNTF secretion from the explants and the corresponding vitreous CNTF levels were evaluated for each time point. Serum samples from these patients were evaluated for CNTF, anti-CNTF antibodies, and antibodies to the encapsulated cells. RESULTS NT-501 implants produced CNTF consistently over a 2-year period. The calculated half-life of CNTF in the vitreous continuously delivered by ECT implants was 51 months, with CNTF levels statistically equivalent between the 6- and 24-month implant period. CNTF, anti-CNTF antibodies, and antibodies to the encapsulated cells were not detected in the serum of patients. CONCLUSIONS This retrospective study demonstrated that the intraocular ECT implant has a favorable pharmacokinetic profile for the treatment of chronic retinal degenerative diseases without systemic exposure. (ClinicalTrials.gov numbers, NCT00063765, NCT00447954, NCT00447980, NCT00447993.).