ARCHER: ANX007 Mitigates Visual Acuity Loss in Geographic Atrophy

Credit: ASRS

ANX007, a selective inhibitor of C1q, demonstrated consistent protection against visual acuity loss in geographic atrophy (GA) in the Phase 2 ARCHER trial, according to data presented at the 128th Annual American Academy of Ophthalmology (AAO) Meeting.¹

“ANX007 consistently protected against the loss of visual acuity in the Phase 2 ARCHER study,” wrote the investigative team, led by Rahul Khurana, MD, Northern California Retina Vitreous Associates. “Protection of photoreceptors, with the greatest impact in central subdomains that better correlate with visual function.”

ANX007 is an antigen-binding fragment (Fab) antibody, designed as a first-in-kind therapeutic to selectively inhibit C1q, the initiating molecule of the classical complement pathway and a key driver of neurodegeneration.² C1q inhibition has proven neuroprotective in dry age-related macular degeneration (AMD).

Retinal pigment epithelium (RPE) loss is apparent after the loss of photoreceptor cells, synapses, and function in eyes with GA. Fundus autofluorescence (FAF) can measure RPE loss and GA lesion growth but is unable to measure photoreceptor or synapse loss and can poorly correlate with visual function.

In Phase 2, multicenter, double-masked, sham-controlled ARCHER clinical trial, 270 participants with GA were randomized to intravitreal ANX007 5 mg per month (n = 89), 5 mg every other month (EOM) (n = 92), or sham monthly or EOM (n = 89) for 12 months, with a 6-month follow-up period.¹

The primary biomarker endpoint was the change in GA lesion area assessed by FAF at 12 months. Prespecified secondary functional endpoints included best-corrected visual acuity (BCVA) and low-luminance visual acuity (LLVA) and low-luminance visual deficits (LLVD). The end of the study was at Month 18.

Khurana and colleagues identified consistent and significant protection against vision loss with ANX007 treatment. At 12 months, significantly fewer eyes (5.6%) treated every month with ANX007 experienced BCVA ≥15-letter loss compared with sham (21.3%) (P = .002). Fewer EOM-treated eyes (9.8%) also experienced BCVA ≥15-letter loss compared with sham (P = .032).

In addition, ANX007 treatment protected against LLVA letter loss, with significantly fewer eyes (7.6%) treated every month with ANX007 experiencing LLVA ≥15-letter loss compared with sham (20.3%) (P = .022).

Notably, these findings showed BCVA ≥15-letter loss expedited after treatment cessation. These data showed a low frequency (<0.6% per month) of single BCVA ≥15-letter losses in ANX007 treatment cohorts during the 12 months. Although the benefit was maintained after treatment cessation, the rate of BCVA ≥15-letter loss increased parallel to sham (>1.6% per month), suggesting the on-treatment protective effect.

Across 12 months, ANX007 demonstrated significant photoreceptor protection, as measured by optical coherence tomography (OCT). Compared with sham, ANX007 achieved more robust protection in the central 2.0mm (48% decrease; P = .0218) and central 1.5 mm (59% decrease; P = .0319) versus the pan-macula (27%; P = .0457).

ANX007 exhibited a notable effect in eyes with less advanced disease at baseline LLVD <30, as no patient in this cohort treated with monthly ANX007 experienced persistence BCVA ≥15-letter loss at 12 months (P = .013). Based on ellipsoid zone (EZ) health at baseline (<80% loss), ANX007 also achieved enhanced protection in the central foveal in less advanced disease (61% decrease; P = .0575), compared with sham.

Safety data in ARCHER showed ANX007 remained generally well-tolerated through month 12, without elevation in choroidal neovascularization (CNV) rates between the treatment and sham arms, and no reported events of retinal vasculitis.

A global, regulatory-aligned Phase 3 program for ANX008 was initiated in July 2024, comprising the ARCHER II trial evaluating 630 patients randomized 2:1 to monthly ANX007 5 mg or sham. ARCHER II’s primary endpoint will consist of persistent BCVA ≥15-letter loss through 12 months, followed by secondary endpoints including safety, LLVA, and EZ.

References

1. _{Khurana RN, Jaffe G, Lad E, Csaky K, et al. Preservation of Vision by ANX007: Clinical Results and Anatomical Changes from the Phase 2 ARCHER Trial. Poster presented at American Academy of Ophthalmology (AAO) 2024 Meeting. Chicago, Illinois. October 18-21, 2024.}
2. _{Annexon to present new phase 2 archer data for ANX007 in dry AMD patients with less advanced GA at the American Academy of Ophthalmology 2024 meeting. Annexon Inc. October 15, 2024. Accessed October 16, 2024. https://ir.annexonbio.com/news-releases/news-release-details/annexon-present-new-phase-2-archer-data-anx007-dry-amd-patients.}