July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Pharmacokinetics and Pharmacodynamics of a Novel Dexamethasone Intravitreal Implant
Author Affiliations & Notes
  • Baruch D Kuppermann
    Gavin Herbert Eye Inst. UCI Dept Ophthal, University of California Irvine, Irvine, California, United States
  • Ian Parrag
    Interface Biologics, Toronto, Ontario, Canada
  • Dimitra Louka
    Interface Biologics, Toronto, Ontario, Canada
  • Hans Fischer
    Interface Biologics, Toronto, Ontario, Canada
  • Gillian Mackey
    Interface Biologics, Toronto, Ontario, Canada
  • Ben B Muirhead
    Biomedical Engineering, McMaster University, Hamilton, Ontario, Canada
  • Emily Anne Hicks
    Biomedical Engineering, McMaster University, Hamilton, Ontario, Canada
  • Heather Sheardown
    Biomedical Engineering, McMaster University, Hamilton, Ontario, Canada
  • Wendy Naimark
    Interface Biologics, Toronto, Ontario, Canada
  • Footnotes
    Commercial Relationships   Baruch Kuppermann, Alcon (C), Alimera Sciences (C), Alimera Sciences (F), Allegro Ophthalmics (F), Allegro Ophthalmics LLC (C), Allergan (C), Allergan, Alcon (F), Apellis Pharmaceuticals (C), Apellis Pharmaceuticals (F), Cell Care Therapeutics (C), Dose Medical Corporation (C), Eyedaptic (C), Genentech (C), Genentech (F), Glaukos Corporation (C), Interface Biologics (C), Ionis Pharmaceuticals (F), jCyte (C), jCyte (F), Novartis (C), Ophthotech (C), Regeneron (F), Regeneron Pharmaceuticals (C), ReVana (C), Thromobogenics (F); Ian Parrag, Interface Biologics (E); Dimitra Louka, Interface Biologics (E); Hans Fischer, Interface Biologics (E); Gillian Mackey, Interface Biologics (E); Ben Muirhead, Interface Biologics (F); Emily Anne Hicks, Interface Biologics (F); Heather Sheardown, Eyepoint Pharmaceuticals (F), Interface Biologics (F); Wendy Naimark, Interface Biologics (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 1702. doi:
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      Baruch D Kuppermann, Ian Parrag, Dimitra Louka, Hans Fischer, Gillian Mackey, Ben B Muirhead, Emily Anne Hicks, Heather Sheardown, Wendy Naimark; Pharmacokinetics and Pharmacodynamics of a Novel Dexamethasone Intravitreal Implant. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1702.

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

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Abstract

Purpose : Local drug delivery via surface erosion enables highly controlled, sustained release of drug. We have developed a novel approach to drug delivery in the eye that employs an erosion-based mechanism of drug release from a fully degradable, nonpolymeric implant. The lead product in development is an intravitreal implant (IBE-814 IVT) that releases dexamethasone to treat posterior inflammatory conditions. We have evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) of the IBE-814 IVT implants in rabbits to demonstrate sustained dexamethasone release for ~6 months with implants delivered through a 30G needle.

Methods : PK of the IBE-814 IVT implants were tested in New Zealand white rabbits following intravitreal injection of the implants. Terminal time points of 1, 2, 8, 16, 26, and 40 weeks were used and drug was quantified in ocular tissues by LC/MS/MS. A rabbit VEGF-induced vascular leakage model was used to test the PD of IBE-814 IVT implants in inhibiting blood-retinal barrier breakdown. Dutch Belted rabbits underwent bilateral intravitreal injection on Day 0 and vascular leakage was induced by VEGF (1000 ng/eye) at 1, 10, and 26 weeks post-implantation. Inhibition of VEGF-induced vascular leakage was evaluated by fundus microscopy and fluorescein angiography. Commercially available dexamethasone implants were used as a control in both studies.

Results : The IBE-814 IVT implants released a low and consistent dose of dexamethasone (~6-15 ng/ml) in the vitreous humour of the rabbit eye out to at least 8 weeks, with later time points ongoing. In contrast, commercial dexamethasone implants had an initial burst release with no drug detected in the vitreous humor at week 8. The low, consistent dose of dexamethasone released from the IBE-814 IVT implants inhibited VEGF-induced vascular leakage at weeks 1 and 10 in the VEGF model as observed by fluorescein angiography. Commercial dexamethasone implants inhibited VEGF-induced vascular leakage at week 1 but not at week 10.

Conclusions : The IBE-814 IVT implant is a novel biodegradable surface-eroding implant delivered with a 30G needle that releases a low, consistent, and efficacious dose of dexamethasone out to at least 10 weeks in rabbits. Ongoing studies will assess drug release out to ~6 months.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

Drug in Vitreous Humour

Drug in Vitreous Humour

 

Results of VEGF-Stimulation at 10 weeks

Results of VEGF-Stimulation at 10 weeks

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