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William R Freeman, Francesco Bandello, Eric H Souied, Robyn H Guymer, Sunir Garg, Fred Kuanfu Chen, Ryan M Rich, Frank G Holz, Yan Li, Kevin Kerr, Francisco J. Lopez; Phase 2b Study of Brimonidine DDS: Potential Novel Treatment for Geographic Atrophy. Invest. Ophthalmol. Vis. Sci. 2019;60(9):971. doi: https://doi.org/.
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Geographic atrophy (GA) secondary to age-related macular degeneration has no treatment. Therapies targeting the alternative complement pathway and visual cycle modulation have failed to meet primary endpoints in recent trials. Brimonidine has both cyto- and neuroprotective mechanisms which offer a novel approach to treatment. In this Phase 2b study (BEACON), a sustained-release intravitreal formulation of brimonidine (Brimo DDS) was compared with sham treatment to assess safety and efficacy in the reduction of GA expansion rate.
Approximately three-hundred patients with baseline GA areas 1.25-18mm2 were planned to be recruited and randomized 1:1 to Brimo DDS 400µg or Sham, administered at baseline and every 3 months through Month 21. Safety and efficacy assessments, including GA area by fundus autofluorescence (FAF), were conducted through Month 30. FAF data were analyzed by mixed model repeated measures. A sensitivity analysis was conducted with data transformed to effective radius units (square root of GA lesion area divided by π).
Three hundred and ten patients were enrolled and 53.2% (Brimo DDS) and 54.5% (Sham) of patients completed the Month 24 primary endpoint. Brimo DDS significantly decreased GA growth by 10% (-0.36mm2, p=0.047) at Month 24 and by 12% at Month 30 (-0.52mm2, p=0.017). The effect size increased by 71% in the population with lesion sizes > 4.5 mm2. These results were robust in a sensitivity analysis using effective radius units as the endpoint. Consistent trends in the entire population with reductions of 9% (-0.034mm, p=0.070) were observed at Month 24 and 9% (-0.042mm, p=0.066) at Months 30. Brimo DDS was well-tolerated and there were no unexpected adverse events. Treatment-related events were consistent with those seen with intravitreal injections or visual disturbance from presence of the implant.
Brimo DDS significantly reduced GA progression at Months 24 and 30. Results were robust to a sensitivity analysis in effective radius units. The study intervention was well-tolerated with no unexpected adverse events.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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