ANX007 May Protect Visual Function, Structure in Geographic Atrophy

ANX007 treatment protected against total ellipsoid zone (EZ) loss, with greater impact in subfields closer to the foveal center, according to an analysis of data from the Phase 2 ARCHER study in geographic atrophy (GA).

These late-breaking data, presented at the American Society of Retina Specialists (ASRS) 42nd Annual Meeting, showed significant EZ disruption in the central 1.5 mm at baseline appeared predictive of eventual 15-letter best-corrected visual acuity (BCVA) loss. Loss of retinal pigment epithelium (RPE) 1.5 mm subfield was additionally slowed with ANX007 treatment.

“These results suggest that the selective anatomical impact of ANX007 within the central fovea subfields may be associated with its unique protective effect on visual acuity,” wrote presenting investigator Glenn Jaffe, MD, department of ophthalmology, Duke University Medical Center.

ANX007 is an antigen-binding fragment (Fab) antibody designed as a first-in-kind therapeutic to selectively inhibit C1q. ARCHER is a Phase 2, multicenter, randomized, parallel-group, double-masked, 4-arm, sham-controlled study of the efficacy, safety, and tolerability of intravitreal ANX007 administration for GA.

Results from ARCHER showed that ANX007 treatment was linked to significant, dose-dependent protection against VA loss. However, the C1q inhibitor did not exhibit a notable slowing of RPE loss across the 6 x 6 mm field of the macula.

Photoreceptors in the central macular are essential to visual acuity, as well as the mechanism of action of ANX007. This analysis was performed to assess the proactive effect of ANX007 on EZ integrity across both the 6 x 6 mm field of the macula and EZ and RPE integrity within the central foveal subfields.

Overall, 270 GA participants were randomized to intravitreal ANX007 5 mg monthly, every other month, or matched sham for 12 months. Prospectively defined endpoints included the assessment of EZ and RPE loss and GA lesion growth across the entire macular region.

Heidelberg Spectralis 97-line high-resolution volume scans were collected in a majority of eyes in the study. Five-fold cross-validation trained and tested the EZ algorithm on all available data to avoid selection bias and allow independent training and testing sets.

Overall, total EZ loss (0 µm) and RPE loss were evaluated in the 6 x 6 mm macular field and the central 1.0 mm, 1.5 mm, and 2.0 mm foveal diameter subfields. RPE loss was confirmed from fundus autofluorescence (FAF) images registered to optical coherence tomography (OCT) images in the foveal diameter subfields.

Upon analysis, more than 75% of study eyes had total (>98%) EZ loss at baseline in the 1.5 mm diameter subfield. Most eyes experienced preserved functional baseline VA, with BCVA measures ranging a wide spectrum, with an average of 55 letters.

Among eyes with ≥15-letter BCVA loss over the next 12 months, 83% had total EZ loss at baseline in the central 1.5 mm subfield. At 12 months, treatment with ANX007 significantly reduced total EZ loss in the central 1.5 mm subfield by 54% compared with sham (P = .017) and over the entire macula by 29% (P = .017).

Meanwhile, RPE loss in the central 1.5 mm subfield was lowered by 18% in ANX007-treated eyes, compared with sham, at Month 12.

“The central subfield anatomical measures of both EZ and RPE may better relate to visual acuity than measures across the entire macula,” Jaffe wrote.

Reference

_{Jaffe G. Protective Effects of ANX007 on Central Macular Ellipsoid Zone (EZ) and Retinal Pigment Epithelium (RPE) and Association with Visual Acuity in the Phase 2 ARCHER GA Study. Paper presented at the American Society of Retina Specialists (ASRS) 42nd Annual Meeting. Stockholm, Sweden. July 17-20, 2024.}

_{Annexon to present additional phase 2 data showing preservation of visual function and structure by anx007 in geographic atrophy at the 42nd ASRS annual scientific meeting. Annexon Inc. July 16, 2024. Accessed July 18, 2024. https://ir.annexonbio.com/news-releases/news-release-details/annexon-present-additional-phase-2-data-showing-preservation.}