Article Date: 1/1/2013

Clinical Trial Spotlight
CT SPOTLIGHT

Hope for Dry AMD?

MacuCLEAR bases its dry AMD therapy on a unique theory of the disease process.

Andrew E. Mathis, PhD, Medical Editor

A mid reports that patients with exudative AMD who responded to anti-VEGF treatment are developing geographic atrophy, retinal physicians are reconsidering their treatment paradigms, in particular because there are currently no FDA-approved treatments for GA, the ultimate outcome of dry AMD.

There are, however, several treatments in the pipeline. Among these treatments is MacuCLEAR’s MC-1101. Philip G. Ralston, Jr., MacuCLEAR’s CEO, spoke with Retinal Physician about the drug.

VASCULAR INSUFFICIENCY

“Our basic premise is that this condition starts with vascular insufficiency,” Ralston says. “This recognition is our greatest contribution to ocular drug development.” In particular, Ralston acknowledges the research of George C. Y. Chiou, PhD, regent professor and director of the Institute of Ocular Pharmacology at Texas A&M Health Science Center and MacuCLEAR’s chief scientific officer.

During his research into dry AMD, Dr. Chiou identified the “Chiou syndrome,” which describes the role of vascular insufficiency in ocular disease. Dr. Chiou saw there was no treatment for dry AMD and very little research under way, with most development focused on treating wet AMD. Dr. Chiou recognized vascular insufficiency and lack of choroidal blood flow, which contribute to metabolic waste buildup in Bruch’s membrane. This became the cornerstone of the research that led to MC-1101’s development.

In relieving this vascular insufficiency, Mr. Ralston says, MC-1101 offers a mechanism by which progression of dry AMD to neovascular AMD can be prevented, as well as progression of dry AMD to irreversible and vision-threatening GA.

MECHANISM AND DELIVERY

Perhaps unsurprisingly, MC-1101 is a vasodilator that increases blood vessel diameter in part due to nitric oxide production, resulting in increased blood flow to the retina. While many vasodilators can cause side effects in people with healthy cardiovascular systems, MC-1101 does not run that risk because it is topically delivered.

Topical delivery remains the holy grail of retina drug development. In addition, the small molecule on which MC-1101 is based was created and tested initially as an antihypertensive so MacuCLEAR already knew the drug was safe.

CHALLENGING THE MAINSTREAM

Asked whether MacuCLEAR was concerned about its focus on vascular insufficiency being relatively rare among retina researchers, Mr. Ralston was confident. “MacuCLEAR is not about following the mainstream,” he says. “We are purposely challenging conventional wisdom as the traditional thinking about the pathogenesis of AMD is not leading to viable treatments. Our approach of placing emphasis on vascular insufficiency makes logical sense considering that the basic role of blood is to supply nutrients to tissues and take waste away everywhere in the body.”

This confidence seems well founded, given MacuCLEAR’s success with MC-1101 in a phase 1b proof-of-concept trial. Not only was it demonstrated that MC-1101 could reach the back of the eye, but it was also proved that MC-1101 increased choroidal blood flow more than 550% one hour after administration.

Based on these results, MacuCLEAR has received fast-track status from the FDA and has launched a phase 3 study of MC-1101 1% TID in the treatment of dry AMD. The two-year randomized, double-blind parallel assignment trial will initially enroll 60 patients and will eventually increase to 500 patients before submitting its NDA.

For more information on this trial, please turn to page 68 of this issue or visit MacuCLEAR online at http://www.macuclear.com. RP



Retinal Physician, Volume: 10 , Issue: January 2013, page(s): 67