June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Oral delivery of a novel small molecule drug, OCX063, protects against vascular leakage and fibrosis in a rodent model of neovascular age-related macular degeneration.
Author Affiliations & Notes
  • Michelle Pauline Papadimitriou
    OccuRx Pty. Ltd., Melbourne, Victoria, Australia
    Department of Medicine, University of Melbourne, Fitzroy, Victoria, Australia
  • Zsolt Ablonczy
    Ora Inc., Andover, Massachusetts, United States
  • Andy Whitlock
    Ora Inc., Andover, Massachusetts, United States
  • Erica Fletcher
    Dept Anatomy/Neuroscience, University of Melbourne, Parkville, Victoria, Australia
  • Fay Lin Khong
    OccuRx Pty. Ltd., Melbourne, Victoria, Australia
    Department of Medicine, University of Melbourne, Fitzroy, Victoria, Australia
  • Darren Kelly
    OccuRx Pty. Ltd., Melbourne, Victoria, Australia
    Department of Medicine, University of Melbourne, Fitzroy, Victoria, Australia
  • Footnotes
    Commercial Relationships   Michelle Papadimitriou, OccuRx Pty. Ltd. (E); Zsolt Ablonczy, Ora (E); Andy Whitlock, Ora Inc. (E); Erica Fletcher, None; Fay Khong, OccuRx (E); Darren Kelly, OccuRx (P), OccuRx (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 3975. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Michelle Pauline Papadimitriou, Zsolt Ablonczy, Andy Whitlock, Erica Fletcher, Fay Lin Khong, Darren Kelly; Oral delivery of a novel small molecule drug, OCX063, protects against vascular leakage and fibrosis in a rodent model of neovascular age-related macular degeneration.. Invest. Ophthalmol. Vis. Sci. 2020;61(7):3975.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Anti-VEGF intravitreal injections improve the vision of patients with neovascular age-related macular degeneration (nAMD), but visual acuity starts to decline due to scar formation after 2 years of treatment. An adjunct therapy that inhibits fibrosis could prevent further vision loss in these patients. We hypothesize that an oral formulation of OCX063, a novel anti-fibrotic small molecule compound, will reduce fibrosis secondary to vascular leakage in a rat model of laser-induced choroidal neovascularisation.

Methods : Brown Norway rats (10/group) received vehicle from Day 0, 50 mg/kg OCX063 QD from Day 0 or 50 mg/kg pazopanib BID from Day -3. On Day 0, four 200 μm lesions were burned within two discs from the optic nerve head in each OD eye using a 532 nm laser (100 ms, 200 mW). Fundus imaging and optical coherence tomography (OCT) verified the lesions. Fluorescein angiography and OCT were performed on Day 7 and 14 to assess lesion size and volume, respectively. Eyes were enucleated on Day 14, sectioned and stained with Masson’s trichrome. The % of collagen deposition within the lesion area as well as a control area without lesion was quantified using Image J software. One-way or two-way ANOVAs were used for statistical analyses.

Results : OCX063 reduced lesion size on Day 7 (p<0.0001) and Day 14 (p<0.0001). OCX063 was more effective than pazopanib at reducing lesion size relative to vehicle (53% vs 28%, p<0.05) on Day 14, but not lesion volume (14% vs 58%, p < 0.0001). As expected, % of collagen deposition was higher in the lesion area compared to non-lesion control area for the vehicle group (33.3% vs 11.51%, p<0.0001). There was no such difference for the OCX063 and pazopanib groups, indicating complete attenuation of fibrosis with these treatments.

Conclusions : Oral delivery of the anti-fibrotic, OCX063, not only reduced fibrosis, but was also more effective at reducing vascular leakage in a rodent model of nAMD than the pan tyrosine kinase inhibitor, pazopanib, given at higher a dose. Thus, OCX063 may be used as an adjunct therapy in combination with anti-VEGF agents to not only improve long-term clinical outcomes in patients with nAMD, but also other retinal diseases, including diabetic retinopathy. As such, a Phase I clinical trial will begin in early 2020 to assess the safety and tolerability of oral OCX063.

This is a 2020 ARVO Annual Meeting abstract.

×
×

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.

×