David Xu, MD
Wills Eye Hospital, Philadelphia, PA
The highly anticipated two-year results of the GATHER2 trial of avacincaptad pegol for geographic atrophy was presented by Dr. Arshad Khanani at this year’s AAO Retina Subspecialty Day in San Francisco. Avacincaptad pegol (ACP) is a small synthetic pegylated RNA aptamer that inhibits complement C5 which plays a key role in the complement cascade leading to cell death and geographic atrophy.
GATHER2 is a phase 3, two-year multicenter, randomized clinical trial studying ACP in patients with non-center-involving geographic atrophy secondary to age-related macular degeneration. In the first year of the study, patients were randomized to monthly ACP injection versus sham. In the second year, patients who were receiving ACP were re-randomized to continue receiving monthly ACP or every other month study drug, while patients who received sham continue to receive sham.
The clinical trial successfully met its primary endpoint at two years. Patients who received ACP had a statistically significant reduction in the size of GA growth by 14% in the every month group (p=0.0165) and 19% in the every other month group (p=0.0015) as compared to sham. When the curves of GA area were plotted over time, the reduction in GA growth could be detected as early as 6 months with continued linear divergence of GA growth over 2 years. Treatment effect, as measured by the difference in mean rate of GA growth, more than doubled over the first 12 months as compared to the full 24-month study window in both monthly and every other month dosing.
The prespecified secondary endpoint of ≥15-letter vision loss compared to baseline was not met at two years. The best-corrected visual acuity loss between the ACP and sham groups was similar at the end of the study.
Ocular adverse events of ≥2% in the study eye include increased intraocular pressure and choroidal neovascularization. There were no new safety signals for serious ocular adverse effects. There was 1 case of culture-positive endophthalmitis and 1 case of dislocated intraocular lens not felt to be related to treatment. There was also 1 case of non-serious intraocular inflammation reported as trace vitreous cells, and no cases of ischemic optic neuropathy or retinal vasculitis among the 225 patients treated with ACP.