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.

• Authors: William R Freeman, Francesco Bandello, Eric Souied, Robyn H Guymer, Sunir J Garg, Fred K Chen, Ryan Rich, Frank G Holz, Sunil S Patel, Kimmie Kim, Francisco J López, BEACON Study Group
• Journal: Ophthalmology. Retina (Ophthalmol Retina) Vol. 7 Issue 7 Pg. 573-585 (Jul 2023) ISSN: 2468-6530 [Electronic] United States
• PMID: 36906177 (Publication Type: Randomized Controlled Trial, Multicenter Study, Clinical Trial, Phase II, Journal Article)
• Copyright: Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Topics

• Humans
• Geographic Atrophy (diagnosis, drug therapy, etiology)
• Macular Degeneration (complications, diagnosis, drug therapy)
• Retina
• Drug Delivery Systems (adverse effects)
• Intravitreal Injections