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

William R. Freeman MD 1;Francesco Bandello MD 2;Eric Souied MD;PhD 3;Robyn H. Guymer MBBS;PhD 4;Sunir J. Garg MD 5;Fred K. Chen MBBS;PhD 4 6;Ryan Rich MD 7;Frank G. Holz MD 8;Sunil S. Patel MD;PhD 9;Kimmie Kim PhD 10;Francisco J. López MD;PhD 11on behalf of the BEACON Study Group Author links open overlay panelFred Chen;Robyn Guymer;Jean-Francois Korobelnik;Eric Souied;Frank Holz;Focke Ziemssen;Francesco Bandello;Emilio Campos;Chiara GrignoloEandi;Edoardo Midena;Enrico Peiretti;Giovanni Staurenghi;Francesco Viola;Clare Bailey;Simona Degli Esposti;Timothy Jackson;Geeta Menon;Sergio Pagliarini;Fahd Quhill;Andrew Antoszyk;Logan Brooks;David Callanan;Karl Csaky;Albert Edwards;David Eichenbaum;William Freeman;Sunir Garg;Avtar Thomas Ghuman;Victor Gonzalez;Sunil Gupta;Richard Hamilton;Rahul Khurana;Derek Kunimoto;Baruch Kuppermann;Andreas Lauer;Seong Young Lee;Raj Maturi;Sunil Patel;Rahul Reddy;Ryan Rich;Mark Rivellese;Steven Rose;Zachary Segal;Robert Wong

2023-01-01

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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.