Aviceda’s AVD-104 misses Phase 2b primary endpoint vs Izervay but still headed to Phase 3
Aviceda’s lead GA drug *AVD-104 failed to meet the primary endpoint in its Phase 2b SIGLEC trial:*
it did not show a statistically significant difference in GA lesion growth versus Astellas’ Izervay (avacincaptad pegol) over 12 months.13
The company and independent reports attribute the miss primarily to imbalances in key baseline lesion characteristics between treatment arms, which likely confounded the head‑to‑head comparison with Izervay.13
Despite missing superiority vs Izervay, monthly AVD-104 dosing showed ~31–38% less GA lesion growth versus historical sham / natural history rates, which Aviceda labels as a clinically meaningful reduction in progression.13
AVD-104 also produced sustained visual acuity benefits, including average gains of about 0.6 letters at 12 months and protection from significant vision loss, outcomes that current complement-only GA drugs have struggled to show consistently.13
The safety profile in Phase 2b was favorable:
no drug‑related serious adverse events, no retinal vasculitis, and a low conversion to neovascular AMD (~2% in the monthly arm), addressing a known safety concern with existing GA therapies.13
Mechanistically, AVD-104 is a glycan‑coated nanoparticle targeting SIGLEC receptors (7, 9, 11) on macrophages and microglia, aiming to modulate innate immune–driven inflammation rather than block complement C3 or C5 like Syfovre and Izervay.123
Aviceda has raised $207.5 million in Series C financing to fund late‑stage development and plans to run two sham‑controlled Phase 3 trials starting in 2026, shifting away from a head‑to‑head superiority design vs Izervay.137
Because the Phase 3 trials will be sham‑controlled, they may have a better chance to show efficacy (lesion-slowing and vision benefit) versus natural history than to prove superiority over another active drug, reducing the risk that baseline imbalances obscure treatment effects.13
Regulatory precedent in GA (Syfovre and Izervay approvals) is based on slowing lesion growth versus sham, not necessarily on functional vision gains, so AVD-104’s lesion-slowing plus visual acuity signals could be regulator-acceptable if reproduced in Phase 3.123
Overall, the mid‑stage “failure” is *unlikely to block Phase 3 success:*
the drug showed biologic activity, safety, and functional signals; the key Phase 2b issue was trial design and baseline imbalance rather than lack of effect, but Phase 3 still carries standard risks of not replicating magnitude or consistency of benefit.13
Sources:
1. https://www.fiercebiotech.com/biotech/aviceda-geographic-atrophy-hopeful-fails-top-astellas-med-phase-2
2. https://www.clinicaltrialsarena.com/news/aviceda-reports-positive-topline-data-from-geographic-atrophy-trial/
3. https://www.biospace.com/press-releases/aviceda-therapeutics-announces-phase-2b-siglec-results-for-avd-104-in-geographic-atrophy
7. https://www.ophthalmologytimes.com/view/aviceda-therapeutics-completes-207-5-million-series-c-financing-in-support-of-avd-104-for-geographic-atrophy-treatment