June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Extended PGA Delivery Results in Significant Drug Sparing Compared to Topical PGAs and Achieves Sustained IOP Lowering for 11 Months without Any Loss of Efficacy
Author Affiliations & Notes
  • Tomas Navratil
    Envisia Therapeutics, Research Triangle Park, North Carolina, United States
  • Jinny Conley
    Envisia Therapeutics, Research Triangle Park, North Carolina, United States
  • Rozemarijn S Verhoeven
    Envisia Therapeutics, Research Triangle Park, North Carolina, United States
  • Kristin Blackwell
    Envisia Therapeutics, Research Triangle Park, North Carolina, United States
  • Akshay Nadkarni
    Envisia Therapeutics, Research Triangle Park, North Carolina, United States
  • Leo Trevino
    Envisia Therapeutics, Research Triangle Park, North Carolina, United States
  • Benjamin R Yerxa
    Envisia Therapeutics, Research Triangle Park, North Carolina, United States
  • Michael Depenbusch
    Arizona Eye Center, Chandler, Arizona, United States
  • Tracey Knox
    Keystone Research Ltd., Austin, Texas, United States
  • Iqbal Ahmad
    University of Toronto, Toronto, Ontario, Canada
  • Thomas R Walters
    Keystone Research Ltd., Austin, Texas, United States
  • Steven L Mansberger
    Devers Eye Institute, Portland, Oregon, United States
  • Footnotes
    Commercial Relationships   Tomas Navratil, Envisia Therapeutics (E); Jinny Conley, Envisia Therapeutics (E); Rozemarijn Verhoeven, Envisia Therapeutics (E); Kristin Blackwell, Envisia Therapeutics (E); Akshay Nadkarni, Envisia Therapeutics (E); Leo Trevino, Envisia Therapeutics (E); Benjamin Yerxa, Envisia Therapeutics (E); Michael Depenbusch, None; Tracey Knox, None; Iqbal Ahmad, Envisia Therapeutics (C); Thomas Walters, Envisia Therapeutics (C); Steven Mansberger, Envisia Therapeutics (C)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2108. doi:
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      Tomas Navratil, Jinny Conley, Rozemarijn S Verhoeven, Kristin Blackwell, Akshay Nadkarni, Leo Trevino, Benjamin R Yerxa, Michael Depenbusch, Tracey Knox, Iqbal Ahmad, Thomas R Walters, Steven L Mansberger; Extended PGA Delivery Results in Significant Drug Sparing Compared to Topical PGAs and Achieves Sustained IOP Lowering for 11 Months without Any Loss of Efficacy. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2108.

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

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Abstract

Purpose : Topical PGAs are the most utilized glaucoma therapeutics in the US but their administration results in very high transient intraocular drug concentrations that are far above the EC50 value for FP receptor activation. PGA super-therapeutic levels may lead to hyperemia and tachyphylaxis as shown with twice a day bimatoprost administration. Intracameral ENV515 travoprost XR was used to answer whether the long-term, sustained release of PGAs can achieve both significant dose sparing and long term IOP lowering without tachyphylaxis.

Methods : Intracameral ENV515 travoprost XR was formulated with > 6 month duration target. To evaluate IOP lowering effect and to measure intraocular levels of travoprost, 17 glaucoma patients scheduled for cataract surgery were enrolled, and low and high doses of ENV515 travoprost XR were administered 28 days before the surgery. During cataract removal, the aqueous humor and ENV515 implant were collected. Duration of action was evaluated in a separate 12-month study where 5 glaucoma patients received a single unilateral dose of ENV515 with timolol used as active comparator in the contralateral eye.

Results : In the 28-day study, low and high doses of ENV515 lowered IOP in a dose related manner, with timolol and TRAVATAN®-like efficacy. This IOP lowering effect was achieved at lower aqueous humor levels of travoprost vs the drug levels observed after topical dosing: high dose ENV515 mean ± SD of 95 ± 41 pg/ml travoprost (n=10) vs ~1,800 pg/ml measured in aqueous humor after topical TRAVATAN Z. In a separate 12-month study, low dose ENV515 demonstrated an IOP-lowering effect for 11 months after a single dose without any loss of efficacy over this period, matching the pre-study PGA and in-study timolol IOP-lowering effects. ENV515 decreased the mean +/- SD 8 AM IOP by 6.7 ± 3.7 mmHg (p < 0.005) or 25% over 11 months (mean of all 8 AM IOPs over 11 months).

Conclusions : In a short term study, ENV515 intracameral travoprost XR demonstrated IOP lowering effect similar to TRAVATAN Z at much lower intraocular travoprost levels. In a long term evaluation, ENV515 lowered IOP consistently for 11 months after a single dose without any tachyphylaxis, matching in-study timolol and pre-study topical PGAs with a dose that was significantly lower compared to topical TRAVATAN Z needed over the same period.

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

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