Randomized Phase IIb Study of Brimonidine Drug Delivery System Generation 2 for Geographic Atrophy in Age-Related Macular Degeneration

Abstract

Purpose: To evaluate the safety and efficacy of repeat injections of Brimonidine Drug Delivery System (Brimo DDS) Generation 2 (Gen 2) containing 400-μg brimonidine in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

Design: A phase IIb, randomized, multicenter, double-masked, sham-controlled, 30-month study (BEACON).

Participants: Patients diagnosed with GA secondary to AMD and multifocal lesions with total area of > 1.25 mm² and ≤ 18 mm² in the study eye.

Methods: Enrolled patients were randomized to treatment with intravitreal injections of 400-μg Brimo DDS (n = 154) or sham procedure (n = 156) in the study eye every 3 months from day 1 to month 21.

Main outcome measures: The primary efficacy endpoint was GA lesion area change from baseline in the study eye, assessed with fundus autofluorescence imaging, at month 24.

Results: The study was terminated early, at the time of the planned interim analysis, because of a slow GA progression rate (∼ 1.6 mm²/year) in the enrolled population. Least squares mean (standard error) GA area change from baseline at month 24 (primary endpoint) was 3.24 (0.13) mm² with Brimo DDS (n = 84) versus 3.48 (0.13) mm² with sham (n = 91), a reduction of 0.25 mm² (7%) with Brimo DDS compared with sham (P = 0.150). At month 30, GA area change from baseline was 4.09 (0.15) mm² with Brimo DDS (n = 49) versus 4.52 (0.15) mm² with sham (n = 46), a reduction of 0.43 mm² (10%) with Brimo DDS compared with sham (P = 0.033). Exploratory analysis showed numerically smaller loss over time in retinal sensitivity assessed with scotopic microperimetry with Brimo DDS than with sham (P = 0.053 at month 24). Treatment-related adverse events were usually related to the injection procedure. No implant accumulation was observed.

Conclusions: Multiple intravitreal administrations of Brimo DDS (Gen 2) were well tolerated. The primary efficacy endpoint at 24 months was not met, but there was a numeric trend for reduction in GA progression at 24 months compared with sham treatment. The study was terminated early because of the lower-than-expected GA progression rate in the sham/control group.

Financial disclosure(s): Proprietary or commercial disclosures may be found after the references.

Keywords: Age-related macular degeneration; Brimonidine; Geographic atrophy; Implant; Nonexudative.