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

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.