Abstract
Age-related macular degeneration (AMD) is a leading cause of irreversible blindness among older adults in the Western world. While therapies exist for patients with exudative AMD, there are currently no approved therapies for non-exudative AMD and its advanced form of geographic atrophy (GA). The discovery of genetic variants in complement protein loci with increased susceptibility to AMD has led to the investigation of the role of complement inhibition in AMD with a focus on GA. Here, we review completed and ongoing clinical trials evaluating the safety and efficacy of these studies. Overall, complement inhibition in GA has yielded mixed results. The inhibition of complement factor D has failed pivotal phase 3 trials. Studies of C3 and C5 inhibition meeting their primary endpoint are limited by high rates of discontinuation and withdrawal in the treatment arm and higher risks of conversion to exudative AMD. Studies evaluating other complement members (CFB, CFH, CFI and inhibitors of membrane attack complex—CD59) are ongoing and could offer other viable strategies.
Highlights
Is a leading cause of blindness among older adults [1]
We review clinical trials for complement inhibitor therapy in geographic atrophy (GA) over the past decade and carefully assess the analytic approaches used in these trials and their limitations
A phase 1b trial in 12 subjects with bilateral GA showed that patients tolerated pegcetacoplan at a dose of 15 mg/0.1 mL administered via intravitreal injection (NCT03777332)
Summary
Completed studies studies designed designed to to evaluate evaluate complement complement modulation modulation as as aa novel novel therapeutic therapeutic strategy strategy for for geographic geographic atrophy atrophy (GA);.
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