LAUSR

PURPOSE The complement pathway may play a key role in the pathogenesis of age-related macular degeneration (AMD). The safety and efficacy of avacincaptad pegol (Zimura®), a C5 inhibitor, was assessed in participants with geographic atrophy (GA) secondary to AMD (GATHER1 Study). DESIGN International, prospective, randomized, double-masked, sham-controlled, pivotal phase 2/3 clinical trial. PARTICIPANTS 286 participants with GA secondary to AMD. MAIN OUTCOME MEASURES The primary efficacy endpoint was the mean rate of change in GA over 12 months measured by fundus autofluorescence (FAF) at three time points: baseline, month 6, and month 12. RESULTS The reduction in the mean rate of GA growth (square root transformation) over 12 months was 27.4% (p-value = 0.0072) for the avacincaptad pegol 2 mg cohort and 27.8% (p-value = 0.005) for the avacincaptad pegol 4 mg cohort as compared to their corresponding sham cohorts. The results for both dose groups were statistically significant. Avacincaptad pegol was generally well tolerated after monthly administration over 12 months. There were no avacincaptad pegol related adverse events or inflammation. Further, there were no ocular serious adverse events and no cases of endophthalmitis. The most frequent ocular adverse events were related to the injection procedure. CONCLUSIONS Intravitreal administration of avacincaptad pegol 2 mg and 4 mg led to a significant reduction of GA growth in eyes with AMD over a 12 month period. As C5 inhibition theoretically preserves C3 activity it may offer additional safety advantages. A second confirmatory pivotal clinical trial is underway to confirm the efficacy and safety of avacincaptad pegol in slowing the GA growth (GATHER2 Study).