Brimonidine Drug Delivery System (DDS) Generation 1 in patients with geographic atrophy: Post-hoc analysis of a phase 2 study

Abstract

Purpose : Geographic atrophy (GA) is a blinding disease with a complex pathogenesis. Protection of retinal pigment epithelium (RPE) and photoreceptors may slow progression of retinal degeneration and preserve visual function. Brimonidine, an alpha2-adrenergic agonist, has demonstrated cytoprotective activity in animal models in vivo, and in human RPE and Muller cells in vitro. The Low-Pressure Glaucoma Treatment Study provided evidence of neuroprotective effects of the drug in humans. The effectiveness and safety of Brimonidine Drug Delivery System (Brimo DDS), an intravitreal implant with brimonidine in a slow-release matrix, is being evaluated in the treatment of GA.

Methods : A phase 2, multicenter double-masked study (NCT00658619) evaluated patients with bilateral GA secondary to AMD. Best-corrected visual acuity in the treated eye was between 70 and 35 ETDRS letters. Patients were randomized (2:2:1) to Brimo DDS 132 or 264 µg, or sham in the treated eye at Baseline and Month 6. The primary endpoint (change in GA area from baseline) was evaluated at Month 12. Patients were followed to Month 24.

Results : One hundred thirteen patients received Brimo DDS 132 or 264 µg, or sham treatment (N=49, 41, and 23, respectively). Mean change in GA area from Baseline was consistently lower in both Brimo DDS-treated groups versus the sham group and was significantly (P = 0.032) smaller with Brimo DDS 132 and 264 µg versus sham at Month 3. A sensitivity analysis, using observed data and a mixed model repeated measure analysis with covariate of baseline GA lesion area, confirmed that Brimo DDS reduced the rate of progression at year 1. At 2 years, lesion growth was reduced in the Brimo DDS 264 µg group (P = 0.059). Treatment-related ocular adverse events (AEs) were reported in 17/48 (35%), 11/40 (28%), and 2/23 (9%) of patients in the 132 and 264 µg and sham arms, respectively. The majority of treatment-related AEs were attributed to the injection procedure. Incidence of serious AEs was similar across groups.

Conclusions : Brimo DDS was safe and well-tolerated. The change in GA lesion growth was significantly lower in Brimo DDS-treated groups compared with sham at Month 3. Post-hoc analysis confirmed the observation that Brimo DDS reduced lesion growth, nearing statistical significance at year 2 (P = 0.059) with the higher dose. A Phase 2b study is ongoing.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.