June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Continuous Intraocular Drug Delivery Lasting Over a Decade: Ciliary Neurotrophic Factor (CNTF) Secreted from Neurotech's NT-501 Implanted in Subjects with Retinal Degenerative Disorders
Author Affiliations & Notes
  • Konrad Kauper
    Neurotech Pharmaceuticals, Cumberland, Rhode Island, United States
  • Lisa Orecchio
    Neurotech Pharmaceuticals, Cumberland, Rhode Island, United States
  • Arne Nystuen
    Neurotech Pharmaceuticals, Cumberland, Rhode Island, United States
  • Kayla Medeiros
    Neurotech Pharmaceuticals, Cumberland, Rhode Island, United States
  • Alice Lee
    Neurotech Pharmaceuticals, Cumberland, Rhode Island, United States
  • Vanessa Cavallaro
    Neurotech Pharmaceuticals, Cumberland, Rhode Island, United States
  • Jacque L Duncan
    Ophthalmology, Univ of California - SF, San Francisco, California, United States
  • Thomas Aaberg
    Neurotech Pharmaceuticals, Cumberland, Rhode Island, United States
  • Footnotes
    Commercial Relationships   Konrad Kauper Neurotech Pharmaceuticals, Code E (Employment); Lisa Orecchio Neurotech Pharmaceuticals, Code E (Employment); Arne Nystuen Neurotech Pharmaceuticals, Code E (Employment); Kayla Medeiros Neurotech Pharmaceuticals, Code E (Employment); Alice Lee Neurotech Pharmaceuticals, Code E (Employment); Vanessa Cavallaro Neurotech Pharmaceuticals, Code E (Employment); Jacque Duncan ConeSight, DTx Therapeutics, Editas, Eloxx, Eyevensys, Gyroscope, Helios, Nacuity, ProQR, PYC Therapeutics, Replay Therapeutics, Spark, SparingVision, Vedere Bio, Code C (Consultant/Contractor), Acucela, AGTC, Allergan/Abbvie, Biogen/NightstaRx, ProQR, PYC Therapeutics, Code F (Financial Support); Thomas Aaberg Neurotech Pharmaceuticals, Code E (Employment)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 3680. doi:
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      Konrad Kauper, Lisa Orecchio, Arne Nystuen, Kayla Medeiros, Alice Lee, Vanessa Cavallaro, Jacque L Duncan, Thomas Aaberg; Continuous Intraocular Drug Delivery Lasting Over a Decade: Ciliary Neurotrophic Factor (CNTF) Secreted from Neurotech's NT-501 Implanted in Subjects with Retinal Degenerative Disorders. Invest. Ophthalmol. Vis. Sci. 2023;64(8):3680.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Neurotech's encapsulated cell technology implant (NT-501) was developed to deliver intraocular CNTF to slow progression of photoreceptor degeneration in diseases such as Macular Telangiectasia Type 2 (Mactel). This retrospective study reports on the CNTF delivery rate, potency, and cell histomorphology of NT-501, following implant durations of 0.5 to 14.5-years.

Methods : Samples for this analysis were collected from subjects implanted with NT-501 and removed following completion of the subject's respective study. NT-501 explants from subjects with retinitis pigmentosa (clinical trials: NCT00063765; NCT00447993; NCT00447980; NCT00447993; NCT01530659) and atrophic macular degeneration (NCT00447954) were analyzed following implant durations of 0.5 to 14.5-years. The secretion rate of CNTF by NT-501 and accumulated vitreous CNTF levels were analyzed by ELISA; potency of CNTF was determined using a cell proliferation bioassay. Histomorphology of the NT-501 encapsulated cells engineered to secrete CNTF were evaluated following explant. Serum samples collected from subjects in four of the six listed studies, and in two Mactel studies (NCT01327911, NCT04729972), were evaluated to determine circulating levels of CNTF, anti-CNTF antibodies and antibodies to the encapsulated cells.

Results : Cumulatively, the data from 64 subjects demonstrate NT-501 implants produce steady levels of bioactive CNTF over a duration of 14.5 years. The mean secretion rate of CNTF produced by NT-501 at the time of explantation was 1.7 +/- 0.7 ng/day, a rate shown to be effective in slowing photoreceptor loss in animal models of RP (Tao; IOVS, 2002) and in Mactel subjects implanted with NT-501 (Chew; Ophthalmology, 2019). Potency of secreted CNTF from NT-501 explants remained equally bioactive compared to the CNTF control. Collected vitreous levels of CNTF averaged 44 ± 18 pg/mL. H&E histological evaluation revealed cells were similar in distribution and morphology comparing pre-implant NT-501 cells to those explanted over 14.5-years. Finally, CNTF, anti-CNTF antibodies and antibodies to NT-501 cells were not detected in any subject’s serum.

Conclusions : This retrospective analysis suggests that a single, intraocular administration of NT-501 provides sustained, bioactive CNTF to the vitreous for implant durations exceeding a decade.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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