title: Two-year intraocular delivery of ciliary neurotrophic factor by encapsulated cell technology implants in patients with chronic retinal degenerative diseases.
abstract: OBJECTIVE
  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.).
authors.affiliation: Neurotech Pharmaceuticals, Inc, Lincoln, Rhode Island, USA. k.kauper@neurotechusa.com
authors.forename: Konrad
authors.initials: K
authors.lastname: Kauper
authors.forename: Cahil
authors.initials: C
authors.lastname: McGovern
authors.forename: Sandy
authors.initials: S
authors.lastname: Sherman
authors.forename: Pam
authors.initials: P
authors.lastname: Heatherton
authors.forename: Rob
authors.initials: R
authors.lastname: Rapoza
authors.forename: Paul
authors.initials: P
authors.lastname: Stabila
authors.forename: Brenda
authors.initials: B
authors.lastname: Dean
authors.forename: Alice
authors.initials: A
authors.lastname: Lee
authors.forename: Suzanna
authors.initials: S
authors.lastname: Borges
authors.forename: Bruce
authors.initials: B
authors.lastname: Bouchard
authors.forename: Weng
authors.initials: W
authors.lastname: Tao
mesh_terms: D002908:Chronic Disease; D020934:Ciliary Neurotrophic Factor / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004343:Drug Implants; D005260:Female; D005500:Follow-Up Studies; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012162:Retinal Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D020934:Ciliary Neurotrophic Factor; D004343:Drug Implants