Novel sialic acid–coated nanoparticle AVD-104 modulates macrophages and complement dysfunction in nonexudative AMD in the SIGLEC phase 2/3 clinical trial part 1

Abstract

Purpose : Overactivation of both the cellular and noncellular components of the innate immune system drives chronic inflammation in dry age-related macular degeneration (AMD). The phase 2/3 SIGLEC trial investigated AVD-104, a novel sialic acid–coated nanoparticle with a dual mechanism of action, as a novel therapeutic for dry AMD.

Methods : The SIGLEC phase 2/3 trial evaluated the safety and efficacy of one intravitreal (IVT) injection of AVD-104 for geographic atrophy (GA) secondary to AMD. Part 1 was a dose-escalation safety study with 30 participants in 4 cohorts (0.1, 0.5, 1, and 3mg/eye). Participants ≥55 years had center-involving GA secondary to AMD, best-corrected visual acuity (BCVA) 20/80-20/800, and total lesion size ≥1.25mm². After one IVT injection of AVD-104, participants were followed for 3 months to assess dose-limiting toxicity (DLT) and safety, changes in BCVA, biomarkers, and GA lesion progression (by hypo-autofluorescence (AF) and hyper-AF at the leading edge). A part 1 case study is used to highlight encouraging study findings.

Results : All 4 part 1 cohorts have been injected and will complete the trial by January 2024. Cohorts 1 and 2 have completed the study with no observed DLT or serious ocular or systemic adverse events. Cohorts 3 & 4 are demonstrating similar safety profiles at 2 months. No patient has had ≥15 letters BCVA loss. Notably, the majority of study eyes have had BCVA gain or stabilization compared to baseline. A part 1 cohort 2 (0.5mg) case study demonstrated a reduction in the hyper-AF area at the leading edge of GA after 1 month of treatment (-0.37mm²) and BCVA gain compared to baseline was observed through 2 months (+5 letters). By the presentation, all study parameters will be fully characterized.

Conclusions : AVD-104, a novel sialic acid–coated nanoparticle, has shown excellent safety in part 1 of the SIGLEC phase 2/3 trial. Preliminary data demonstrate favorable changes in patient BCVA across all cohorts. The case study highlights the observed slowing in GA lesion progression and improvements in BCVA. Part 2 is a larger, randomized, double-masked study with 2 doses of AVD-104. All 4 part 1 cohorts will have finished the study at the time of presentation.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.