Anterior Segment Uveitis is an eye disorder associated with intraocular inflammation of the anterior portion of the uvea, particularly the iris and/or ciliary body. Topical corticosteroids are the mainstay treatment. Early, aggressive intervention delivers the best therapeutic responses. Typically, high frequency steroid drops are utilized in order to achieve and maintain adequate therapeutic steroid levels in the anterior segment. While these drugs are generally helpful in treating the disease, their effectiveness is limited due to insufficient absorption and rapid clearance. As a result, patients who are prescribed topically administered corticosteroids must instill the drops several times per day, sometimes hourly, until the uveitis resolves.
Also, patients who receive systemic medications can experience side effects, which may be serious enough to require hospitalization. Given the lack of optimal treatments and the risks associated with systemic treatment, superior methods for rapid and more effective steroid delivery into the eye are of clinical interest.
EyeGate’s Iontophoresis Technology
The iontophoresis of therapeutic agents into the eye is of interest as a means of non-invasively achieving higher drug levels inside the eye by promoting the movement of charged substances (drug molecules) across biological membranes by applying a low electrical current forming an electrical field. The electric field causes electrorepulsion between the newly formed ions and the drug molecules, which propels the drug product into ocular tissue.
In order to achieve adequate therapeutic steroid levels in the anterior segment in patients with uveitis, EyeGate has developed an ocular iontophoresis device and a drug product customized for safe and effective delivery of dexamethasone phosphate utilizing cathodic iontophoresis with an inert electrode. When EGP-437 (dexamethasone phosphate formulated for iontophoresis) is dosed with the EyeGate® II Delivery System, substantial levels of dexamethasone are distributed into the eye (100s fold higher levels are achieved than with conventional drops).
EyeGate’s Clinical Study
EyeGate completed a Phase 1/2 clinical safety and efficacy study to evaluate the safety, tolerability, and efficacy of iontophoresis delivery via the EyeGate® II Delivery System of a potent dexamethasone derivative (EGP-437) at four iontophoresis dose levels in patients with non-infectious anterior segment uveitis.
To be enrolled into this randomized double-masked study, subjects needed to have non-infectious anterior segment uveitis with a cell score of > 1.5 (on a 0 – 5 scale, 5 = worst and 0 = best). Enrolled subjects received a single dose of EGP-437 delivered at one of four dose levels using the EyeGate® II Delivery System, and were followed for 28 days. (http://www.clinicaltrials.gov/ct2/show/NCT00694135)
Following the single EGP-437 treatment, about half of the subjects achieved an anterior cell score of zero within two weeks. By day 28, the majority of patients achieved cell scores of zero and required no further treatment. No significant changes in intraocular pressure or signs of cataract formation were detected. Data from the study were presented at the Association for Research in Vision and Ophthalmology annual meeting in Fort Lauderdale in May 2010.
For uveitis patients, there is an unmet medical need, and doctors need more predictable, effective treatments for severe uveitis. The EGP-437 clinical data show promising signs of efficacy and may address compliance issues, by providing the doctor with direct control of the dosing. These results suggest that EGP-437 treatment via the EyeGate® II Delivery System may lead to a more predictable clinical response in treating severe uveitis.
For enrollment information, please contact Carol Assang, Clinical Project Manager, 781-788-8869.