Post hoc analysis of patients in avacincaptad pegol clinical trial shows growth of GA lesions slowed

In a presentation at the Bascom Palmer Eye Institute’s 19th annual Angiogenesis, Exudation, and Degeneration 2022 Virtual Edition, Glenn J. Jaffe, MD, noted that the analysis showed, for the first time, a decreased growth rate in the central foveal area by a therapeutic intervention when compared with sham treatment.

The results of a post hoc analysis of a subgroup of patients in the phase III clinical trial of avacincaptad pegol (ACP) (Zimura, Iveric Bio) showed that the 2-mg dose of the drug slowed growth of geographic atrophy (GA) lesions secondary to age-related macular degeneration (AMD) in the central area that included the fovea, and in each quadrant surrounding the central area.

During a presentation at the Bascom Palmer Eye Institute’s 19th annual Angiogenesis, Exudation, and Degeneration 2022 Virtual Edition, Glenn J. Jaffe, MD, director of the Duke Reading Center, chief of the Retina Division at the Duke Eye Center, and the Robert Machemer Professor of Ophthalmology, told attendees the largest decrease in the growth rate was seen in the quadrants surrounding the central area, which were also the regions with the greatest historic natural growth rate.

However, Jaffe also noted that the analysis also showed, for the first time, a decreased growth rate in the central foveal area by a therapeutic intervention when compared with sham. Longer-term studies are needed to confirm the impact of these findings on the patient’s visual function.

GATHER1 study

GATHER1 is a prospective, randomly assigned, double-masked phase III trial that compared ACP with sham treatment in patients with GA associated with AMD.

At the 18-month time point, patients randomly assigned to active treatment had a 28.11% reduction of the GA area of compared with the sham-treated eyes, Jaffe said.

Moreover, the results at 18 months were a continuation of the treatment effect seen at 12 months, a 27.38% difference between active treatment and sham, favoring the former (p = 0.0072).

According to Jaffe, due to the natural history of GA and the results of recent GA studies, the GATHER1 investigators theorized that larger decreases in the growth of faster growing GA lesions in the outer quadrants versus slower growing lesions in the central fovea would be seen with ACP compared with sham treatment.

Post hoc analysis

In the post hoc analysis, they tested this theory in 47 eyes treated with the 2-mg dose of ACP compared with 79 sham eyes. All of these eyes had undergone Heidelberg fundus autofluorescence (FAF) and Spectralis optical coherence tomography (OCT) imaging at various times. 

The investigators did this by comparing the images from the 2 populations. The GA regions were segmented using the Spectralis RegionFinder software and these segmented GA areas were exported and saved. The foveal centerpoint was identified on OCT images and the co-registered infrared images. The centerpoint on the infrared image then was registered to the FAF image.

The center point and a grid that included the central region and surrounding quadrants was then overlaid on the GA regions. This approach facilitated measurement of the GA area growth in the different regions over time.

Jaffe demonstrated the decrease in lesion growth in the central area, and the quadrants surrounding the central area.

“Similar to the overall results of GATHER1, lesion growth was slowed compared to sham treatment in all 4 extrafoveal quadrants, inferior, nasal, superior, and temporal,” he said. “This was seen early and steadily increased over time.”

Jaffe explained that the reduction in growth of the surrounding regions translated into slowed growth in the central foveal area.

“The reduction seen in the central area was slower than in other regions, which is what was expected and consistent with the natural history of GA growth,” he pointed out.

The percentages of decreased growth were as follows: 29.3% superiorly, 25.9% nasally, 27.7% inferiorly, 47.0% temporally, and 12.9% centrally. The central result is in line with the natural history of slower moving disease in the fovea.

“The results of this analysis are very encouraging. For the first time ever, we are able to show a slowing of disease in the area of the retina that is critical for maintaining good visual function,” Jaffe concluded. “While longer-term studies are needed to fully understand the impact of slowing growth in each region, these results give us hope that long-term treatment with ACP could help maintain visual function in patients with GA.”

This article is adapted from Jaffe’s Feb. 11 presentation at the Angiogenesis, Exudation, and Degeneration 2022 virtual conference. Iveric Bio provided funding for this research. Duke was the reading center for the GATHER1 study.