Preclinical Evaluation of ENV515 (travoprost) Intracameral Implant - Clinical Candidate for Treatment of Glaucoma Targeting Six-Month Duration of Action

Abstract

 

Purpose

 

Prostaglandin analogues (PGA) are the most prescribed class of therapies for glaucoma in the US but possess several shortcomings: low adherence, hyperemia, and fluctuation in ocular drug levels and intraocular pressure (IOP). The purpose of this work was to evaluate the efficacy, duration of action, and safety/tolerability of the ENV515 (travoprost) Intracameral Implant experimental therapy prior to further preclinical and clinical development. ENV515 is a biodegradable polymer drug delivery system using an extended release formulation of the PGA travoprost. ENV515 is being developed with the aim to address the shortcomings of the topical PGA therapies.

 

Methods

 

We used PRINT® technology to fabricate ENV515 to fit the anatomy of the human iridocorneal angle and allow administration via acceptably-sized needle. We used hypertensive and normotensive Beagle dogs using a modified McDonald-Shadduck scale to evaluate safety and tolerability over a period of 24 weeks in vivo. The in vivo location of the implant was imaged via anterior chamber OCT and Gonioscopy exams. IOP was evaluated in non-sedated animals.

 

Results

 

In vitro, the extended release of travoprost from ENV515 occurred over a period of 180 days. The implant administrations were conducted in Beagle dogs by intracameral injections via a custom injector and resulted in 100% success rate for implant delivery. Gonioscopy and anterior chamber OCT imaging showed stability without movement in the iridocorneal angle in hypertensive Beagle dogs (Figures 1 and 2). The baseline IOP in hypertensive Beagle dog study was 23.4±1.0 mmHg (mean±SEM, n=6 eyes). The mean decrease in intraocular pressure was 7.2±0.5 mmHg or 30±2% change from baseline IOP over 24 week treatment period (p<0.001). Only minor and transient ocular irritation occurred due to the insertion procedure. Notably, there was lower incidence of hyperemia compared to topical TRAVATAN Z. Similar outcomes were observed in a replicatory study in normotensive Beagle dogs.

 

Conclusions

 

ENV515 demonstrated robust, sustained IOP-lowering effect for 24 weeks following single implantation via intracameral injection with acceptable safety and tolerability in hypertensive and normotensive Beagle dogs. ENV515 preclinical safety and tolerability profile supports advancing ENV515 into clinical studies in glaucoma patients.

 

 

Keywords: 568 intraocular pressure • 608 nanomedicine • 420 anterior chamber