Interim Analysis of Low Dose ENV515 Travoprost XR with 11 Month Duration Followed by Dose Escalation and 28 Day Efficacy Evaluation of High Dose ENV515

Abstract

Purpose : ENV515 travoprost XR is an extended release formulation using nano- and microparticle engineering PRINT technology and a fully biodegradable polymer drug delivery system. Previously, ENV515 demonstrated 8 months of intraocular pressure (IOP) lowering effect after a single dose in nonclinical studies in dogs and sustained IOP lowering effect over 28 days after a single dose in glaucoma patients. To further evaluate ENV515, a 12-month dose escalation study was initiated with low and high doses of ENV515 using a single intracameral administration.

Methods : We enrolled 5 glaucoma patients in a 12-month Phase 2 study of low dose ENV515, and 10 glaucoma patients in a 12-month cohort of high dose ENV515. All enrolled patients were topical prostaglandin analogue (PGA) users at the time of enrollment. After washout, patients were administered a single low or high dose ENV515 in the study eye with timolol maleate 0.5% BID used as active comparator in the contralateral eye. We report 11-month interim analysis of low dose ENV515, and compare the 28-day response of the low vs. high dose of ENV515.

Results : In the low dose cohort, the mean IOP ± SD at the pre-washout visit on a PGA analogue was 19.7 ± 2.7 mmHg, with a post-washout baseline IOP of 26.1 ± 2.2 mmHg at 8 AM. ENV515 decreased the mean ± SD 8 AM IOP from baseline by 6.7 ± 3.7 mmHg (p < 0.005) or 25% over 11 months (mean of all 8 AM IOPs over 11 months). The mean 8 AM IOP after a single low dose of ENV515 was 19.5 mmHg over the 11-month period. There were no serious adverse events and the most common adverse event was early-onset transient hyperemia related to the dosing procedure. The high dose ENV515 demonstrated 1.1 mmHg better IOP lowering effect at 28 days when compared to the low dose ENV515.

Conclusions : Low dose ENV515 was well tolerated over 11 months, and demonstrated sustained IOP-lowering effect for 11 months following a single dose. High dose ENV515 demonstrated a potential to elicit a greater treatment effect compared to the low dose at 28 days and is currently being evaluated for sustained long-term IOP lowering effect.

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