Avacincaptad pegol shows efficacy in preserving ellipsoid zone integrity
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SEATTLE — A post hoc analysis of the GATHER1 and GATHER2 trials showed the positive effect of avacincaptad pegol treatment in reducing progressive photoreceptor ellipsoid zone attenuation over time.
The ellipsoid zone (EZ) and the photoreceptors are a key marker that have been linked to visual function in multiple retinal diseases.
“In dry macular degeneration, ellipsoid zone integrity has been found to be a marker not only of functional loss but also risk of GA progression,” Justis P. Ehlers, MD, said at the American Society of Retina Specialists annual meeting.
Spectral-domain OCT scans were used in a machine learning-enhanced multilayer segmentation platform to provide multiple different thickness measurements related to the EZ. In addition, a novel deep-learning model was used to evaluate EZ-at-risk features, which was trained on areas of EZ loss and EZ attenuation while excluding areas of geographic atrophy (GA).
At baseline, EZ attenuation varied widely across participants and was almost always larger than the area of GA. Baseline EZ integrity and EZ-at-risk were well balanced between the avacincaptad pegol arm and the sham arm.
With avacincaptad pegol treatment, a 24% reduction in EZ partial attenuation was observed at 12 months in GATHER1, and a 62% reduction was seen in GATHER2. Pooled analysis showed a 55% reduction in partial EZ loss over time.
“When we look at total attenuation, similarly we see an 18% reduction in GATHER1, a 21% reduction in GATHER2 and, in the pooled analysis, a 20% significant reduction in EZ total attenuation,” Ehlers said.
He said that EZ attenuation is an exciting area of investigation that can provide new insight in terms of the overall impact of therapeutics.
“[It can also help us] targeting and understanding some of the earlier changes before we get to GA,” he said.
Further analysis will delve deeper into EZ integrity measures to predict which eyes are going to progress faster and may benefit most from therapy. The impact of EZ integrity on visual acuity outcomes and therapeutic response will also be investigated, Ehlers said.
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Ehlers JP, et al. Ellipsoid zone integrity preservation and characterization of ellipsoid zone integrity features in the GATHER 1 phase 2/3 study and the GATHER 2 phase 3 study. Presented at: American Society of Retina Specialists annual meeting; July 28-Aug. 1, 2023; Seattle.
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