Phase 2b Study of Brimonidine DDS: Potential Novel Treatment for Geographic Atrophy

Abstract

Purpose : 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.

Methods : 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).

Results : 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.

Conclusions : 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.