Posters

Advancing ENV515 travoprost extended release (XR) for glaucoma into clinical development: non-clinical evaluation of ENV515 in support of first time in human phase 2a clinical study

Poster Details

First Author: T.Navratil USA

Co Author(s):    A. Garcia   R. Verhoeven   B. Gilger   I. Ahmed   J. Pepose   B. Yerxa     

Abstract Details

Purpose:

ENV515 Travoprost XR is an experimental therapy currently in clinical development for glaucoma and ocular hypertension (US Clinical Trials.gov identifier NCT02371746). ENV515 is a fully biodegradable, rod-shaped intracameral formulation based on a biodegradable polymer drug delivery system and travoprost. To advance ENV515 into first-time in human studies, we evaluated key pharmacodynamic, pharmacokinetic, and safety/tolerability attributes of ENV515 in non-GLP and GLP toxicology studies. ENV515 is being developed with the aim to address the shortcomings of the topical glaucoma therapies.

Setting:

1. Envisia Therapeutics, Research Triangle Park, NC, United States 2. North Carolina State University, Raleigh, NC, United States

Methods:

Beagle dogs were used to evaluate 1) efficacy and the full duration of action of ENV515 for a period of up to 14 months in non-GLP pharmacology studies; 2) safety and tolerability in GLP toxicology studies for 28-days and for 6 months; and 3) 28 day and 6-month PK in aqueous humor and other ocular tissues. ENV515 was administered via intracameral injection. ENV515 used in the GLP studies was manufactured in an aseptic manufacturing process developed utilizing PRINT microparticle engineering technology.

Results:

After a single dose of ENV515, the IOP-lowering treatment effect was maintained over 8 months with 35±3% or 6.4 ± 0.6 mmHg average decrease in IOP from a baseline of 18.6 ± 0.2 mmHg (mean ± SEM, p < 0.001, n=6 eyes). The Beagle dog aqueous humor concentration of travoprost, based on ENV515 dose showing robust and sustained IOP-lowering effect, was significantly lower than historical aqueous humor concentration of travoprost in human subjects dosed with topical TRAVATAN Z. The completed 28-day GLP toxicology study identified the highest dose of 6 ENV515 biodegradable inserts/eye as the no adverse effect level.

Conclusions:

ENV515 Travoprost XR demonstrated robust and sustained IOP-lowering effect for 8 months following a single dose via intracameral injection, with excellent safety and tolerability in GLP toxicology studies in Beagle dogs. The ENV515 Travoprost XR tested in GLP toxicology studies was manufactured in an aseptic manufacturing process developed to support an ongoing Phase 2a clinical study of ENV515 in glaucoma patients. ENV515 is being developed as a treatment for ocular hypertension and glaucoma with the goal of addressing the low compliance with topical therapies for glaucoma and consequently, slowing down the progression of visual field loss in glaucoma patients.

Financial Disclosure:

One or more of the authors gains financially from product or procedure presented, One or more of the authors receives consulting fees, retainer, or contract payments from a company producing, developing or supplying the product or procedure presented