Annexon completes enrollment in phase 3 ARCHER II trial of vonaprument for geographic atrophy

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Annexon has completed enrollment in its phase 3 ARCHER II trial of vonaprument (formerly ANX007) for dry age-related macular degeneration (AMD) with geographic atrophy (GA).

ARCHER II is a global, randomized, double-masked, sham-controlled pivotal trial designed to assess visual acuity and structural measures to satisfy the global registration path in the US and Europe, according to the company. The trial has enrolled over 630 patients with advanced AMD/GA. Patients will be randomly assigned 2:1 to receive either a monthly dose of vonaprument or sham procedure.

The primary end point is the prevention of 15-letter loss or greater of best corrected visual acuity (BCVA), which represents 3 lines on the standard Early Treatment of Diabetic Retinopathy Study (ETDRS) eye chart. Secondary end points include safety, low-luminance VA (LLVA), and photoreceptor integrity. Primary analysis will occur 12 months after the initial dosing.

Vonaprument is an antigen-binding fragment (Fab) antibody designed as a first-in-kind therapeutic to selectively inhibit C1q, the initiating molecule of the classical complement pathway and a key driver of neurodegeneration. The company noted that in advanced dry AMD, or GA, C1q binds to photoreceptor synapses, causing aberrant activation of the classical pathway with synapse loss, inflammation, and neuronal damage that results in vision loss.

Vonaprument has been granted a fast track designation from the FDA and is the first therapeutic candidate for the treatment of GA to receive a priority medicine (PRIME) designation in the EU, according to the company.

David Eichenbaum, MD, director of research at Retina Vitreous Associates of Florida, commented on the trial in a press release from the company, saying, “The global reach of ARCHER II has increased awareness of vonaprument’s innovative mechanism and compelling phase 2 results. With no approved therapies in Europe and limited options in the US, there is an urgent need for a treatment for GA that protects vision, the most clinically meaningful outcome for patients.”

The company plans to release topline data from the phase 3 ARCHER II trial in the second half of 2026.

Phase 2 ARCHER trial

The phase 2 ARCHER trial was a randomized, multicenter, double-masked, sham-controlled trial comparing the safety and efficacy of vonaprument in patients with GA secondary to AMD. The study enrolled 270 patients, stratified by GA lesion size, location, and choroidal neovascularization in the fellow eye at the time of enrollment. Patients were nearly equally split between foveal (49.4% to 57.3%) and nonfoveal groups, had an average age of 80 years, and were balanced between female and male. Ninety-six percent of patients enrolled were from the United States.

Patients were randomly assigned to receive an intravitreal dose of 5 mg vonaprument monthly (n=89), 5 mg vonaprument every other month (n=92), or sham monthly or every other month (pooled n=89) for 12 months, followed by a 6-month off-treatment period.

The study's primary outcome measure was the rate of change in GA lesion growth (slope) from baseline as measured by fundus autofluorescence through 12 months for the study eye.

Vonaprument provided statistically significant time- and dose-dependent protection from vision loss as measured by 15 or greater letter loss on reading an eye chart with BCVA of 15 or more. Significant protection from vision loss was also shown in other prespecified measures of BCVA and visual function, including LLVA and LL visual deficit.

While the benefit gained against vision loss was maintained during the subsequent 6-month off-treatment period, the rate of decline for BCVA of 15-letter or greater vision after treatment termination began to parallel that of sham, providing additional support for the observed on-treatment protection, stated the company.

References

1. Annexon announces completion of enrollment in pivotal phase 3 ARCHER II trial of vonaprument (formerly ANX007) for dry age-related macular degeneration (AMD) with geographic atrophy. News release. Annexon, Inc. July 24, 2025. Accessed July 24, 2025. https://ir.annexonbio.com/news-releases/news-release-details/annexon-announces-completion-enrollment-pivotal-phase-3-archer

2. Crago SM. Annexon announces topline results from ARCHER phase 2 trial of ANX007 for geographic atrophy. Ophthalmology Times. May 29, 2023. Accessed July 24, 2025. https://www.ophthalmologytimes.com/view/annexon-announces-topline-results-from-archer-phase-2-trial-of-anx007-for-geographic-atrophy