Studying Progression in Early Geographic Atrophy

Dermot McGrath reports from the EURETINA 2021 Virtual Congress. The complement C5 inhibitor avacincaptad pegol (Zimura, Iveric Bio) could have a therapeutic benefit in the early stages of geographic atrophy, suggests a recent analysis of phase 3 clinical trial data. “As this is a post-hoc analysis the results should be considered as hypothesis-generating only, but they do suggest that further exploration of Zimura in dry AMD is definitely warranted,” noted SriniVas R Sadda MD, PhD. The post-hoc analyses focused on the progression of drusen and nascent GA using terminology derived from the Classification of Atrophy Meetings (CAM-Group), an assembly of experts in imaging and AMD that established consensus terminology for the description of early atrophic features. One of the key outcomes of the CAM-Group meetings was the introduction of a Spectral Domain-OCT based nomenclature for early atrophy including the terms cRORA (Complete RPE and Outer Retinal Atrophy) and iRORA (Incomplete RPE and Outer Retinal Atrophy). “I think we would all agree that if effective treatments for AMD could be developed it may actually be ideal to intervene earlier prior to the development of irreversible loss of photoreceptors and vision. This requires the development of earlier endpoints to describe the progression of early AMD to atrophy,” Dr Sadda said. Zimura achieved its primary endpoint in the GATHER1 trial, showing a reduction of GA relative to sham of 28% with 2 mg dosage up to 18 months and 30% less with 4 mg up to 18 months. The post-hoc analysis showed that Zimura 2 mg was associated with greater numerical reduction compared to sham in the progression of iRORA to cRORA. “This was evident as early as six months and with an increasing separation between Zimura and sham over time,” Dr Sadda noted. Zimura 2 mg was associated with a greater numerical reduction compared to sham in progression of drusen to iRORA or cRORA with no additional patients developing iRORA or cRORA lesions following month 12 in the Zimura 2 mg arm in contrast to the sham arm, he added. SriniVas R. Sadda MD, is the Director, Artificial Intelligence & Imaging Research, Doheny Eye Institute at the University of California–Los Angeles (UCLA), USA. ssadda@doheny.org