July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Effectiveness of Sustained Release TKI Hydrogel Combined with Bevacizumab in a VEGF Induced Retinal Leakage Model Through 12 Months
Author Affiliations & Notes
  • Rami F Elhayek
    R&D, Ocular Therapeutix, Bedford, Massachusetts, United States
  • Tim Jarrett
    R&D, Ocular Therapeutix, Bedford, Massachusetts, United States
  • Zachary Lattrell
    R&D, Ocular Therapeutix, Bedford, Massachusetts, United States
  • Erica Kahn
    R&D, Ocular Therapeutix, Bedford, Massachusetts, United States
  • Stephen Takach
    R&D, Ocular Therapeutix, Bedford, Massachusetts, United States
  • Jamie Lynne Metzinger
    R&D, Ocular Therapeutix, Bedford, Massachusetts, United States
  • Michael H Goldstein
    R&D, Ocular Therapeutix, Bedford, Massachusetts, United States
  • Peter K Jarrett
    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); Zachary Lattrell, Ocular Therapeutix (E); Erica Kahn, Ocular Therapeutix (E); Stephen Takach, Ocular Therapeutix (E); Jamie Lynne Metzinger, Ocular Therapeutix (E); Michael Goldstein, Ocular Therapeutix (E); Peter Jarrett, Ocular Therapeutix (E); Amar Sawhney, Ocular Therapeutix (E)
  • Footnotes
    Support  This research was supported in full by Ocular Therapeutix.
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 245. doi:
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      Rami F Elhayek, Tim Jarrett, Zachary Lattrell, Erica Kahn, Stephen Takach, Jamie Lynne Metzinger, Michael H Goldstein, Peter K Jarrett, Amar Sawhney; Effectiveness of Sustained Release TKI Hydrogel Combined with Bevacizumab in a VEGF Induced Retinal Leakage Model Through 12 Months. Invest. Ophthalmol. Vis. Sci. 2018;59(9):245.

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

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Abstract

Purpose : The study evaluated the pharmacodynamic effect of a single dose of OTX-TKI as a combination therapy with bevacizumab, compared to bevacizumab monotherapy, delivered via intravitreal injection in Dutch belted rabbits for 12 months.

Methods : Micronized tyrosine kinase inhibitor (TKI) particles were formulated in a hydrogel matrix, OTX-TKI. Animals were randomized to receive an injection of OTX-TKI plus 1.25 mg of bevacizumab (n=15, 30 eyes) or 1.25 mg of bevacizumab alone (n=9, 18 eyes) at Day 0. Eyes were challenged with an injection of vascular endothelial growth factor (VEGF) at predetermined timepoints over 12 months and were evaluated for leakage by fluorescein angiography (FA) and dilated fundus examination. At each VEGF challenge timepoint, treated eyes were compared to untreated control eyes (n=4). Tolerability was assessed via MacDonald Shadduck scores and clinical observations.

Results : OTX-TKI with bevacizumab significantly suppressed leakage at 2 weeks, and sustained efficacy through 12 months when challenged with a VEGF suspension. Bevacizumab monotherapy suppressed leakage at 2 and 4 weeks; leakage returned as expected at the next VEGF challenge timepoint. Untreated control eyes showed high tortuosity and leakage at all time points. Retinal tissue showed high TKI concentration (>2150X IC50) through all time points in the treated animals. MacDonald Shadduck scores showed the treatment was well-tolerated. Other clinical observations raised no safety concerns.

Conclusions : We have demonstrated that a combination of OTX-TKI plus bevacizumab is able to suppress leakage at 2 weeks, with sustained effects seen through 12 months. Bevacizumab monotherapy was efficacious through 4 weeks with leakage returning by week 12, which is consistent with current standard of care. One treatment of OTX-TKI with bevacizumab appears to be superior to bevacizumab monotherapy with regard to duration of therapy for the treatment of wet AMD.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

 

Pharmacodynamic Effect of OTX-TKI plus bevacizumab, versus bevacizumab monotherapy through 12 months

Pharmacodynamic Effect of OTX-TKI plus bevacizumab, versus bevacizumab monotherapy through 12 months

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