David Lally discusses the ARCHER trial and the optimistic outcomes fueling future research

Note: Video captions are generated with the assistance of AI and may contain errors.

David Lally, MD, presented at the 2025 Retina Society meeting, discussing the ARCHER study (NCT04656561) of ANX007 for the treatment of age-related macular degeneration (AMD) and geographic atrophy (GA).

C1q, a key molecule in neuroinflammation that localizes to photoreceptor synapses and can lead to their removal by microglial cells. ANX007 is an antibody fragment designed to inhibit C1q and potentially protect photoreceptors. The ARCHER phase 2 clinical trial was a multi-centered, randomized study comparing monthly and every-other-month injections of the treatment against a sham treatment over 12 months, with an additional 6-month observational period.

The primary endpoint was measuring the rate of geographic atrophy lesion area growth. The study revealed significant findings in vision preservation. Patients treated with von approvement showed a 73% risk reduction in losing 15 or more letters of visual acuity in the monthly treatment arm, and a 50% reduction in the every-other-month arm. A loss of 15 letters represents a doubling of visual angle and can substantially impact daily activities like reading or driving.

During the 6-month off-treatment period, previously treated eyes demonstrated similar vision loss rates to the sham group, suggesting the drug's protective effect during active treatment. The drug showed reductions in both foveal and non-foveal lesion types. These results prompted the design of the Archer Two study, currently the only global pivotal phase three trial for geographic atrophy with vision protection as its primary endpoint. Unlike previous complement inhibitor therapies approved based on anatomical changes, this study aims to demonstrate functional vision preservation.

Lally emphasized that while recent complement inhibitor approvals were landmark achievements, the ultimate goal remains stopping, preventing, or reversing the disease. He characterized the current research stage as being in the "first inning" of understanding and treating geographic atrophy. The ongoing trials and research are providing valuable insights that may lead to next-generation therapies for protecting and potentially reversing vision loss in patients with geographic atrophy.