Brimonidine Drug Delivery System (Brimo DDS) in an intravitreally administered, sustained-release implant (Allergan) shows promise as a treatment for geographic atrophy (GA), secondary to age-related macular degeneration in a phase IIa clinical trial.
Based on the encouraging results, a larger phase II study is underway, using an investigational product that will provide more exposure of retinal tissues to the therapeutic agent, said William R. Freeman, MD.
“There is a significant unmet medical need for treatments that can halt or slow the inexorable progression of GA,” said Dr. Freeman, distinguished professor of ophthalmology, and director, Jacobs Retina Center, Shiley Eye Center, University of California San Diego, La Jolla. “Several modalities addressing various pathogenic mechanisms have either failed or have shown minimal efficacy in multiple studies evaluating various mechanisms of action.”
Although this phase IIa study was not powered to show statistically significant differences with regards to efficacy, the analyses showed a statistically significant treatment benefit at month 3 in brimonidine-treated eyes with a trend that is maintained through month 24, 18 months after the last injection.
“I am also happy to report that a second phase II study investigating a second generation Brimo DDS intravitreal implant is completely enrolled and underway,” Dr. Freeman said.
Brimonidine is being investigated as a cyto/neuroprotective agent with the goal of reducing the risk of GA progression by making the retinal pigment epithelial (RPE) cells and photoreceptors more resistant to injury.
“It is well known, from results of preclinical studies in tissue cultures of RPE and Müller cells, and in various animal models of retinal disease, that brimonidine has cyto/neuroprotective activity,” said Dr. Freeman.
The completed phase IIa study had a randomized, double-masked, sham-controlled design. It randomized 113 patients into 3 groups (2:2:1) to receive low-dose or high-dose Brimo DDS (brimonidine = 132 mcg and 264 mcg, respectively; formulated as 200 mcg or 400 mcg of brimonidine tartrate, respectively) or sham treatment in the study eye.
The device, built with a biodegradable polymer drug delivery system similar to the dexamethasone implant (Ozurdex, Allergan), was injected into the vitreous with a 22-gauge needle attached to a proprietary applicator system. It is designed to release brimonidine over 6 months, and patients received a second injection at month 6.
Baseline characteristics of the enrolled patients were typical of those expected in a GA population. Mean visual acuity was about 20/80, Dr. Freeman said.