June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
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
Author Affiliations & Notes
  • Konrad Kauper
    Core Technology Development, Neurotech USA, Cumberland, RI
  • Cahil McGovern
    Core Technology Development, Neurotech USA, Cumberland, RI
  • Paul Stabila
    Core Technology Development, Neurotech USA, Cumberland, RI
  • Sandy Sherman
    Core Technology Development, Neurotech USA, Cumberland, RI
  • Pam Heatherton
    Core Technology Development, Neurotech USA, Cumberland, RI
  • Brenda Dean
    Core Technology Development, Neurotech USA, Cumberland, RI
  • Crystal Cortellessa
    Core Technology Development, Neurotech USA, Cumberland, RI
  • Alice Lee
    Core Technology Development, Neurotech USA, Cumberland, RI
  • Weng Tao
    Core Technology Development, Neurotech USA, Cumberland, RI
  • Footnotes
    Commercial Relationships Konrad Kauper, Neurotech Pharmaceuticals (E); Cahil McGovern, Neurotech (E); Paul Stabila, Neurotech Pharmaceuticals (E); Sandy Sherman, Neurotech USA Inc (E); Pam Heatherton, None; Brenda Dean, Neurotech USA, Inc (E); Crystal Cortellessa, U.S.S.N. 61/653,191 (P), Neurotech USA Inc. (E); Alice Lee, Neurotech USA, Inc. (E); Weng Tao, Neurotech (E)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 3295. doi:
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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)

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Abstract
 
Purpose
 

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.

 
Methods
 

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.

 
Results
 

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.

 
Conclusions
 

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.

 
Keywords: 412 age-related macular degeneration • 609 neovascularization • 701 retinal pigment epithelium  
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