Aviceda's AVD-104 Shows 31% Reduction in Geographic Atrophy Lesion Growth in Phase 2b Trial
核心洞察
Aviceda Therapeutics (搜索) reported positive phase 2b SIGLEC trial results for AVD-104 in geographic atrophy (搜索) secondary to age-related macular degeneration (搜索), showing approximately 31% reduction in lesion growth versus natural history rates.
The monthly AVD-104 treatment arm demonstrated sustained visual acuity improvement of +0.6 letters at 12 months, with 28.9% of participants achieving gains of ≥5 letters.
AVD-104 showed a favorable safety profile with only 2% conversion to neovascular AMD (搜索) and no drug-related serious adverse events in the 300-patient study.
Aviceda Therapeutics (搜索) has announced positive topline results from its phase 2b SIGLEC study evaluating AVD-104 in patients with geographic atrophy (搜索) (GA) secondary to age-related macular degeneration (搜索) (AMD). The trial demonstrated clinically meaningful reductions in GA lesion growth rates, sustained visual acuity gains, and a favorable safety profile.
Study Design and Patient Population
The SIGLEC trial (NCT05839041) was a randomized, multi-center, double-masked, active comparator-controlled clinical trial that enrolled 300 patients with an average age of 79 years. Participants had an average baseline visual acuity of 58.5 letters and were randomized to receive either an intravitreal dose of 2 mg AVD-104 every other month (n=100), 1 mg AVD-104 monthly (n=100), or 2 mg avacincaptad pegol (n=100) for a 24-month treatment period.
The primary outcome measured the rate of change from baseline in GA area by fundus autofluorescence at month 12. While the primary endpoint analysis showed no statistical difference in the rate of change in GA area between AVD-104 versus monthly avacincaptad pegol, the company noted that imbalances in key baseline lesion characteristics across treatment arms contributed to the lesion-growth outcomes.
Efficacy Results
The monthly AVD-104 treatment arm demonstrated approximately 31% reduction in GA lesion growth rate versus growth rates from sham and natural history rates at 12 months. Notably, participants experienced a sustained improvement in mean best-corrected visual acuity (BCVA) over the entire study period, with a +0.6 letter gain at month 12, which according to the company has not been observed in other GA clinical trials to date.
Categorical BCVA improvements showed that 28.9%, 16.9%, and 4.8% of participants achieved gains of ≥5, ≥10, and ≥15 letters, respectively. The treatment also demonstrated a low conversion rate to choroidal neovascularization (CNV), with only 2% of participants in the monthly treatment arm developing neovascular AMD (搜索).
Mechanism of Action
AVD-104 is a polysialic acid-coated nanoparticle where the polysialic acid ligands on the surface interact with sialic acid-binding immunoglobulin-like lectins (SIGLEC) receptors -7, -9, and -11 found on macrophages (搜索), microglia (搜索), and monocytes in the retina. The binding of AVD-104 to these SIGLEC receptors (搜索) inhibits pro-inflammatory cytokine release and phagocytosis while reducing monocyte differentiation into M1 macrophages.
Safety Profile
AVD-104 demonstrated a favorable safety and tolerability profile throughout the study. No drug-related serious adverse events were observed in participants treated with AVD-104, including no cases of retinal vasculitis. The most common treatment-emergent adverse event was floaters.
Clinical Significance and Future Plans
"The SIGLEC study represents the first clinical validation of glycoimmune checkpoint therapy to modulate macrophages (搜索) and microglia (搜索) to treat geographic atrophy (搜索)," said Jeffrey Nau, PhD, MMS, CEO of Aviceda Therapeutics (搜索). "These results reinforce our belief that AVD-104 can provide meaningful functional vision benefit while reducing lesion progression, and has the potential to become a differentiated therapy addressing a significant unmet medical need for patients living with GA."
David Callanan, MD, CMO of Aviceda Therapeutics (搜索), emphasized the differentiation potential: "We believe AVD-104 is poised to address critical gaps in current GA therapies that limit adoption, such as the lack of functional vision benefit and the safety limitations of neovascular AMD (搜索) conversion."
The company plans to advance AVD-104 into two randomized, sham-controlled phase 3 confirmatory studies. The final design of the clinical trial is currently underway, with the trial expected to begin in 2026.