Aviceda misses primary GA endpoint

Published May 17, 2026 by The Daily Scout

- Aviceda Therapeutics said on December 15, 2025, its Phase 2b SIGLEC trial of AVD-104 in geographic atrophy missed the primary endpoint. - The clearest figure was a reported roughly 31% reduction in lesion-growth rate at 12 months versus sham and natural-history benchmarks. - ClinicalTrials.gov lists SIGLEC, NCT05839041, as active and not recruiting, with study completion estimated in October 2026.

Why it matters

Aviceda Therapeutics said on December 15, 2025, that its Phase 2b SIGLEC study of AVD-104 in geographic atrophy secondary to age-related macular degeneration did not show a statistically significant difference on its primary endpoint against monthly avacincaptad pegol, sold as Izervay. The Cambridge, Massachusetts-based private biotech said the endpoint measured the rate of change in geographic atrophy area over 12 months. The company also reported secondary and contextual findings it described as favorable, including lower lesion-growth rates versus sham and natural-history benchmarks, modest visual-acuity gains and a low rate of conversion to neovascular age-related macular degeneration. ### If the trial missed its main comparison, what exactly did Aviceda say went right? Aviceda said the monthly AVD-104 arm showed an approximately 31% reduction in geographic atrophy lesion-growth rate at 12 months versus sham and natural-history rates. The company also said participants in that arm had a mean best-corrected visual acuity gain of 0.6 letters at month 12, while 28.9% gained at least 5 letters, 16.9% gained at least 10 letters and 4.8% gained at least 15 letters. (biospace.com) The same December 15 release said conversion to neovascular AMD occurred in 2% of participants in the monthly treatment arm, and no drug-related serious adverse events were observed in participants treated with AVD-104. Floaters were the most common treatment-emergent adverse event, according to the company. (biospace.com) ### What was the primary endpoint, and why does the avacincaptad comparison matter? ClinicalTrials.gov lists the SIGLEC study’s primary endpoint as the difference in the rate of growth of geographic atrophy area measured by fundus autofluorescence in the randomized portion of the trial. The registry says participants in Part 2 were randomized to high-dose AVD-104, low-dose AVD-104, or active comparator avacincaptad. (biospace.com) Astellas’ Izervay, the brand name for avacincaptad pegol intravitreal solution, is an FDA-approved treatment for geographic atrophy secondary to age-related macular degeneration. In February 2025, Astellas said the FDA approved an expanded U.S. label removing the prior limit on duration of dosing beyond 12 months. (clinicaltrials.gov) ### Why is Aviceda pointing to sham and natural-history data instead of the head-to-head result? Aviceda said the primary endpoint analysis showed no statistical difference between AVD-104 and monthly avacincaptad pegol, and it attributed the lesion-growth outcome in part to imbalances in key baseline lesion characteristics across treatment arms. That explanation came from the company’s own topline disclosure, not from an independent trial publication. (newsroom.astellas.com) Ophthalmology Times, citing the company’s data release, reported the same mix of findings: the primary comparison was not met, while the 12-month dataset showed a roughly 31% reduction in lesion growth and reported visual-acuity improvement. That leaves the evidence package centered on company-reported subgroup, contextual and cross-trial benchmark comparisons rather than a statistically successful active-comparator readout. (biospace.com) ### How does AVD-104 differ from the drugs already on the market? Aviceda said AVD-104 is intended to target SIGLEC receptors on retinal immune cells, and Chief Executive Officer Jeffrey Nau said the study represented “the first clinical validation” of glycoimmune checkpoint therapy in geographic atrophy. The company has positioned that mechanism as distinct from currently approved complement inhibitors. (ophthalmologytimes.com) The American Academy of Ophthalmology says two drugs were approved in 2023 for geographic atrophy: pegcetacoplan, sold as Syfovre, and avacincaptad pegol, sold as Izervay. A 2024 American Journal of Ophthalmology review said those approvals were based on slowing the anatomic expansion of geographic atrophy, while functional vision benefits were not demonstrated in the phase 3 programs cited in that review. (biospace.com) ### What happens next for the program? Aviceda said in a January 7, 2025 financing announcement that proceeds from its $207.5 million Series C round would support pivotal development of AVD-104, and that 12-month data from the fully enrolled Phase 2b/3 trial were anticipated in the second half of 2025. The company’s later December 15, 2025 update framed the SIGLEC dataset as support for advancing AVD-104. (aao.org) ClinicalTrials.gov now lists NCT05839041 as active and not recruiting, with primary completion estimated in April 2026 and study completion estimated in October 2026 across 56 locations. Those dates are the clearest public markers for the next formal update on the trial record. (clinicaltrials.gov) (avicedarx.com)

Key numbers

Aviceda Therapeutics said on December 15, 2025, its Phase 2b SIGLEC trial of AVD-104 in geographic atrophy missed the primary endpoint.
The clearest figure was a reported roughly 31% reduction in lesion-growth rate at 12 months versus sham and natural-history benchmarks.
ClinicalTrials.gov lists SIGLEC, NCT05839041, as active and not recruiting, with study completion estimated in October 2026.
The Cambridge, Massachusetts-based private biotech said the endpoint measured the rate of change in geographic atrophy area over 12 months.

What happens next

Aviceda said AVD-104 is intended to target SIGLEC receptors on retinal immune cells, and Chief Executive Officer Jeffrey Nau said the study represented “the first clinical validation” of glycoimmune checkpoint therapy in geographic atrophy.
(biospace.com) What happens next for the program?
Those dates are the clearest public markers for the next formal update on the trial record.

Sources

Quick answers

What happened in Aviceda misses primary GA endpoint?

Aviceda Therapeutics said on December 15, 2025, its Phase 2b SIGLEC trial of AVD-104 in geographic atrophy missed the primary endpoint. The clearest figure was a reported roughly 31% reduction in lesion-growth rate at 12 months versus sham and natural-history benchmarks. ClinicalTrials.gov lists SIGLEC, NCT05839041, as active and not recruiting, with study completion estimated in October 2026.

Why does Aviceda misses primary GA endpoint matter?

Aviceda Therapeutics said on December 15, 2025, that its Phase 2b SIGLEC study of AVD-104 in geographic atrophy secondary to age-related macular degeneration did not show a statistically significant difference on its primary endpoint against monthly avacincaptad pegol, sold as Izervay. The Cambridge, Massachusetts-based private biotech said the endpoint measured the rate of change in geographic atrophy area over 12 months. The company also reported secondary and contextual findings it described as favorable, including lower lesion-growth rates versus sham and natural-history benchmarks, modest visual-acuity gains and a low rate of conversion to neovascular age-related macular degeneration. If the trial missed its main comparison, what exactly did Aviceda say went right? Aviceda said the monthly AVD-104 arm showed an approximately 31% reduction in geographic atrophy lesion-growth rate at 12 months versus sham and natural-history rates. The company also said participants in that arm had a mean best-corrected visual acuity gain of 0.6 letters at month 12, while 28.9% gained at least 5 letters, 16.9% gained at least 10 letters and 4.8% gained at least 15 letters. (biospace.com) The same December 15 release said conversion to neovascular AMD occurred in 2% of participants in the monthly treatment arm, and no drug-related serious adverse events were observed in participants treated with AVD-104. Floaters were the most common treatment-emergent adverse event, according to the company. (biospace.com) What was the primary endpoint, and why does the avacincaptad comparison matter? ClinicalTrials.gov lists the SIGLEC study’s primary endpoint as the difference in the rate of growth of geographic atrophy area measured by fundus autofluorescence in the randomized portion of the trial. The registry says participants in Part 2 were randomized to high-dose AVD-104, low-dose AVD-104, or active comparator avacincaptad. (biospace.com) Astellas’ Izervay, the brand name for avacincaptad pegol intravitreal solution, is an FDA-approved treatment for geographic atrophy secondary to age-related macular degeneration. In February 2025, Astellas said the FDA approved an expanded U.S. label removing the prior limit on duration of dosing beyond 12 months. (clinicaltrials.gov) Why is Aviceda pointing to sham and natural-history data instead of the head-to-head result? Aviceda said the primary endpoint analysis showed no statistical difference between AVD-104 and monthly avacincaptad pegol, and it attributed the lesion-growth outcome in part to imbalances in key baseline lesion characteristics across treatment arms. That explanation came from the company’s own topline disclosure, not from an independent trial publication. (newsroom.astellas.com) Ophthalmology Times, citing the company’s data release, reported the same mix of findings: the primary comparison was not met, while the 12-month dataset showed a roughly 31% reduction in lesion growth and reported visual-acuity improvement. That leaves the evidence package centered on company-reported subgroup, contextual and cross-trial benchmark comparisons rather than a statistically successful active-comparator readout. (biospace.com) How does AVD-104 differ from the drugs already on the market? Aviceda said AVD-104 is intended to target SIGLEC receptors on retinal immune cells, and Chief Executive Officer Jeffrey Nau said the study represented “the first clinical validation” of glycoimmune checkpoint therapy in geographic atrophy. The company has positioned that mechanism as distinct from currently approved complement inhibitors. (ophthalmologytimes.com) The American Academy of Ophthalmology says two drugs were approved in 2023 for geographic atrophy: pegcetacoplan, sold as Syfovre, and avacincaptad pegol, sold as Izervay. A 2024 American Journal of Ophthalmology review said those approvals were based on slowing the anatomic expansion of geographic atrophy, while functional vision benefits were not demonstrated in the phase 3 programs cited in that review. (biospace.com) What happens next for the program? Aviceda said in a January 7, 2025 financing announcement that proceeds from its $207.5 million Series C round would support pivotal development of AVD-104, and that 12-month data from the fully enrolled Phase 2b/3 trial were anticipated in the second half of 2025. The company’s later December 15, 2025 update framed the SIGLEC dataset as support for advancing AVD-104. (aao.org) ClinicalTrials.gov now lists NCT05839041 as active and not recruiting, with primary completion estimated in April 2026 and study completion estimated in October 2026 across 56 locations. Those dates are the clearest public markers for the next formal update on the trial record. (clinicaltrials.gov) (avicedarx.com)