Dry eye syndrome, or keratoconjunctivitis sicca (KCS), is the most prevalent form of ocular discomfort and irritation. In the United States of America (USA), it has been estimated that as many as 3.2 million women and 1.7 million men over the age of 50 have dry eye syndrome. In addition, tens of millions more experience a mild form of dry eye or episodic problems with dry eye, usually associated with external stimuli. With the aging population in the USA and other developed countries, and with increasing computer use, dry eye is expected to become more prevalent.
While intermittent KCS can be related to external environmental factors, chronic KCS can be related to internal factors, such as hormonal imbalance, autoimmune disease, the use of many widely prescribed systemic medications, anatomical changes or trauma, and aging. The fundamental (and most likely the causative) problem behind chronic KCS is deficiency in either the volume or composition of the tear film. Problems related to the tear film produce an immune-based inflammation of the ocular surface. Symptoms of chronic KCS can range from a mildly irritating condition to loss of function and productivity, pain, light sensitivity, and the misery that accompanies significantly impaired vision and decreased quality of life.
Treatment of KCS consists initially (and primarily) of supplementing the tear film with lubricants generally known as “artificial tears.” Although artificial tears can improve KCS symptoms, there is no evidence that they can resolve the underlying condition(s) leading to the corneal and conjunctival inflammation, a hallmark of chronic KCS. Patients with the more severe forms of KCS may be unresponsive to treatment with artificial tear supplements.
Corticosteroids have unparalleled anti-inflammatory effects and a rapid onset of action. Corticosteroid ophthalmic solutions have been used for many years to treat acute inflammatory conditions in the anterior eye tissues. Treatment regimens are generally limited to 2 - 4 weeks. Corticosteroid ophthalmic solutions are an obvious candidate class of drugs for the treatment of KCS, but the well known side effect profiles associated with prolonged use of the most potent corticosteroids have limited their usage for chronic KCS. In topical ocular use, the steroid-related side effects that are of primary concern are an increase in intraocular pressure, cataract formation, and adrenal gland suppression from the low, but significant, systemic steroid concentrations associated with an ocular dosing regimen.
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 chronic KCS, 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 (in rabbits, 100s fold higher levels are achieved than with conventional drops).
EyeGate’s Clinical Study (Completed Phase 2 Study and On-going Phase 3 Study)
EyeGate recently completed a Phase 2 single-center, randomized (105 patients), double-masked, placebo-controlled patient study to evaluate the safety and efficacy of a corticosteroid solution (EGP-437) administered by the EyeGate® II Delivery System (at two dose levels) twice over a three-week period. (http://www.clinicaltrials.gov/ct2/show/NCT00765804)
For the dry eye clinical trial, EyeGate worked with Ora, Inc., a leading global clinical research and development organization located in Andover, MA. Over the past 30 years, Ora has been a pioneering force in the development of advanced research models across the field of ophthalmology. Ora’s Controlled Adverse Environment (CAE) clinical research system, which simulates the acute environmental challenges regularly faced by patients with dry eye syndrome, was used for this study.
In the top-level analysis, investigators observed that EGP-437 significantly (p < 0.05) improved signs and symptoms of dry eye syndrome during the three-week environmental component, which included three CAE exposures and two doses. EGP-437 also improved signs and symptoms when studied as a treatment and preventative in conjunction with the CAE.
EyeGate has completed a Phase 3 clinical study. In this randomized double-masked placebo-controlled nine week study, 198 patients were enrolled into three treatment groups: two EGP-437 arms and one placebo. On two of the study visits, patients were treated with the EyeGate® II Delivery System: one group received placebo solution and two groups received EGP-437, a corticosteroid solution tailored for iontophoresis. (http://www.clinicaltrials.gov/ct2/show/NCT01129856)