June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Efficacy of a 6 month Sustained Hydrogel Delivery System for Tyrosine Kinase Inhibitors in a VEGF Induced Retinal Leakage Model
Author Affiliations & Notes
  • Rami F Elhayek
    R&D, Ocular Therapeutix, Bedford, Massachusetts, United States
  • Tim Jarrett
    R&D, Ocular Therapeutix, Bedford, Massachusetts, United States
  • Zach Lattrell
    R&D, Ocular Therapeutix, Bedford, Massachusetts, United States
  • Stephen Takach
    R&D, Ocular Therapeutix, Bedford, Massachusetts, United States
  • Peter K Jarrett
    R&D, Ocular Therapeutix, Bedford, Massachusetts, United States
  • Michael McGrath
    R&D, Ocular Therapeutix, Bedford, Massachusetts, United States
  • Jonathan H Talamo
    R&D, Ocular Therapeutix, Bedford, Massachusetts, United States
  • Amar Sawhney
    R&D, Ocular Therapeutix, Bedford, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Rami Elhayek, Ocular Therapeutix (E); Tim Jarrett, Ocular Therapeutix (E); Zach Lattrell, Ocular Therapeutix (E); Stephen Takach, Ocular Therapeutix (E); Peter Jarrett, Ocular Therapeutix (E); Michael McGrath, Ocular Therapeutix (E); Jonathan Talamo, Ocular Therapeutix (E); Amar Sawhney, Ocular Therapeutix (E)
  • Footnotes
    Support  Ocular Therapeutix supported this research.
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1968. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Rami F Elhayek, Tim Jarrett, Zach Lattrell, Stephen Takach, Peter K Jarrett, Michael McGrath, Jonathan H Talamo, Amar Sawhney; Efficacy of a 6 month Sustained Hydrogel Delivery System for Tyrosine Kinase Inhibitors in a VEGF Induced Retinal Leakage Model. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1968.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : We evaluated the efficacy over 6 months of sustained delivery of a tyrosine kinase inhibitor (TKI) with known anti-angiogenic properties from a preformed bioabsorbable hydrogel fiber depot delivered via intravitreal injection in Dutch belted rabbits.

Methods : Micronized TKI particles were formulated in a hydrogel matrix (OTX-TKI). Eighteen eyes of naïve Dutch belted rabbits (n=9) were bilaterally dosed with OTX-TKI at Day 0. Eyes were challenged with an injection of vascular endothelial growth factor (VEGF) at 2, 3 and 6 months and were evaluated for leakage by fluorescein angiography (FA). At each VEGF challenge time point, eyes treated with OTX-TKI were compared to blank control eyes (n=4). The scoring method for this disease model can be found in Figure 2. Retinal tissue was collected for pharmacokinetic (PK) analysis by liquid chromatography/mass spectrometry (LC/MS) immediately after FA evaluations.

Results : OTX-TKI significantly suppressed leakage at 2, 3 and 6 months when challenged with a VEGF suspension. The leakage scores in eyes treated with OTX-TKI show minimal to no vascular leakage through 6 months. Blank control eyes showed high tortuosity and leakage at all time points. Retinal tissue showed high drug concentrations (>3000X IC50) through all time points in the treated animals.

Conclusions : We have demonstrated for the first time the ability to deliver an efficacious dose of TKIs to the posterior segment of the eye using an intravitreal bioabsorbable hydrogel depot for up to 6 months. FA leakage scores showed minimal to no change from normal in all OTX-TKI treated eyes at all time points. PK sampling suggests that drug concentrations in retinal target tissues far exceed the IC50 for the study drug at all time points.The OTX-TKI delivery platform could provide patients with a 6 month therapy for the treatment of wet AMD as an alternative to the once every 4-6 week current industry standard of care.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

 

OTX-TKI vs Avastin in a VEGF-induced leakage model in Dutch Belted Rabbits

OTX-TKI vs Avastin in a VEGF-induced leakage model in Dutch Belted Rabbits

 

Scoring method for FA imaging

Scoring method for FA imaging

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×