Fundus Hyperautofluorescence and Autofluorescence Changes in Patients Following a Single Dose of AVD-104 for the Treatment of Geographic Atrophy Secondary to Age-Related Macular Degeneration in the SIGLEC Phase 2a Study

Document Type

Conference Proceeding

Publication Date

6-2025

Publication Title

Investigative Ophthalmology and Visual Science

Abstract

Purpose : AVD-104 (Aviceda Therapeutics, Cambridge, MA, United States) is a novel sialic acid–coated nanoparticle that directly modulates self-recognition receptors on overactivated retinal macrophages and microglia (called Siglecs) to dampen inflammation and repolarize these immune cells to a healing state, and regulates overproduction of complement by directly binding to complement factor H. AVD-104 may be a novel treatment for geographic atrophy (GA) secondary to age-related macular degeneration (AMD). The safety and efficacy of AVD-104 as a treatment for GA was assessed in the Phase 2a SIGLEC study.

Methods : The SIGLEC Phase 2a study was a multicenter, US-based, open-label, dose-escalation safety and tolerability study that enrolled patients (N = 30) with bilateral foveal GA into 1 of 4 dose-ascending cohorts (0.1 mg, 0.5 mg, 1.0 mg, 3.0 mg); patients who received 1.0-mg or 3.0-mg doses were considered part of clinical-dose cohorts. Patients were followed for 3 months after a single intravitreal injection of AVD-104. Hyper-autofluorescence (hyper-AF) changes in the peri-lesional area (termed the junctional zone) and changes in lesion growth rate as assessed on fundus autofluorescence (FAF) were assessed monthly. Safety, tolerability, and BCVA changes from baseline were also assessed.

Results : Study eyes in all cohorts combined (N=27) had a decrease in hyper-AF area of -0.08mm2 at Month 3 (demonstrating lesion improvement) compared to an increase of +0.01mm2 in fellow eyes at Month 3. At Month 3, a GA growth rate reduction of 48% as measured on FAF was observed among eyes in the clinical-dose cohorts (3 & 4) compared with fellow eyes. Study eyes in the clinical-dose cohorts gained 5.2 letters from baseline versus 1.7 letters gained among fellow eyes (difference 3.5 letters) at Month 3. Safety was positive, with no dose-limiting toxicity, ocular SAEs, or drug-related systemic SAEs observed.

Conclusions : Among patients with GA secondary to AMD at 3 months in the Phase 2a SIGLEC study, those who received a single dose of AVD-104 experienced improvement of hyper-AF and reduction of GA lesion growth rates as seen on FAF. The ongoing Phase 2b/3 SIGLEC study assessing AVD-104 in a head-to-head fashion against avacincaptad pegol in 300 patients with GA secondary to AMD is fully enrolled.

Volume

66

Issue

8

First Page

4590

Comments

Association for Research in Vision and Ophthalmology ARVO Annual Meeting, May 4-8, 2025, Salt Lake City, UT

Last Page

4590

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