Lesions aside, functional vision keeps AVD-104 in the GA therapy race.
In geographic atrophy (GA) drug development, a missed primary endpoint is not always a full stop. Aviceda Therapeutics (Massachusetts, USA) is betting on that premise as it advances AVD-104 into Phase III.
In the Phase IIb SIGLEC trial (NCT05839041), AVD-104 did not demonstrate a statistical difference versus avacincaptad pegol (Izervay; Astellas Pharma, Tokyo, Japan), a current standard-of-care therapy, in patients with GA secondary to age-related macular degeneration (AMD). The study’s primary endpoint focused on anatomical outcomes, specifically GA lesion growth.
Aviceda attributed the primary endpoint outcome to imbalances in key baseline lesion characteristics across treatment arms. Despite this, the company reported encouraging signals in secondary endpoints, including a clinically meaningful 31% reduction in GA lesion-growth rates in AVD-104–treated patients compared with sham and natural history data.
READ MORE: All Eyes on Geographic Atrophy at APVRS 2025: Diagnostic Challenges and Scientific Advances
Notably, the company highlighted functional outcomes, with sustained improvements in best-corrected visual acuity (BCVA) observed during the study. BCVA gains of at least 5, 10 and 15 letters were reported in 28.9%, 16.9% and 4.8% of patients, respectively. From a safety perspective, 2% of patients developed neovascular AMD, which Aviceda described as a favorable safety profile.
“We are encouraged by the magnitude of visual acuity gains, including protection from significant vision loss, reduction in lesion growth relative to historical sham and expected natural history, and the compelling safety profile observed with monthly AVD-104,” said Aviceda’s Chief Medical Officer, Dr. David Callanan, in a news release. “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 conversion.”
On the strength of these findings, Aviceda plans to advance AVD-104 into two randomized, sham-controlled Phase III confirmatory trials, with study initiation expected in 2026. Further data from the SIGLEC trial are also slated for presentation at medical congresses in 2026.
READ MORE: Photovoltaic Retina Implant Offers “New Light” for Vision in GA Patients
Beyond GA, AVD-104 is being evaluated in uveitis and retinal degeneration. A Phase II trial in diabetic macular edema (DME) was terminated due to insufficient drug supply and funding constraints, according to the ClinicalTrials.gov listing.
Shifts in GA standard of care
Avacincaptad pegol received US Food and Drug Administration (FDA) approval in August 2023, followed by pegcetacoplan (Syfovre; Apellis Pharmaceuticals, Massachusetts, USA) in February 2023. Together, these approvals marked a transition in GA management from supportive care, monitoring and AREDS2 supplementation to disease-modifying therapies.
READ MORE: SYFOVRE 5-Year GALE Analysis Shows ~1.5-Year Delay in GA Progression in Nonsubfoveal Disease
Other companies active in the GA space include Boehringer Ingelheim (Ingelheim am Rhein, Germany), which has initiated a Phase II trial of its oral candidate BI 1584862, and Alkeus Pharmaceuticals (Massachusetts, USA), which is evaluating gildeuretinol in a Phase III GA study.
According to GlobalData analysis, the global AMD market is projected to reach $27.5 billion in sales by 2031, with the U.S. expected to account for 72.1% of the total.*
Editor’s Note: This content is intended exclusively for healthcare professionals. It is not intended for the general public. Products or therapies discussed may not be registered or approved in all jurisdictions, including Singapore.
*Age-Related Macular Degeneration in Major Markets, Disease Management, Epidemiology, Pipeline Assessment, Unmet Needs and Drug Forecast to 2031. GlobalData. December 22, 2023. Available at: https://www.globaldata.com/store/report/age-related-macular-degeneration-major-market-analysis. Accessed on December 17, 2025.