Annexon Adds Month 24 Endpoint to Phase 3 ARCHER II Trial of Vonaprument in Geographic Atrophy

Annexon has expanded the primary endpoint strategy for vonaprument in geographic atrophy (GA), adding a Month 24 assessment alongside the existing Month 15 endpoint in the Phase 3 ARCHER II trial (NCT06510816). The company also launched an open-label extension study to evaluate the long-term safety and clinical benefit of monthly vonaprument treatment.

Dual Primary Endpoint Strategy Extends ARCHER II Assessment

ARCHER II is a global, randomized, double-masked, sham-controlled Phase 3 trial evaluating intravitreal vonaprument in 659 patients with GA associated with dry age-related macular degeneration. The study is assessing whether treatment can reduce clinically meaningful vision loss in a disease that progressively destroys retinal tissue and can lead to irreversible visual impairment.

The trial’s primary functional endpoint is the proportion of patients who experience confirmed best-corrected visual acuity (BCVA) loss of at least 15 letters at two consecutive visits. A 15-letter decline corresponds to approximately three lines on the Early Treatment of Diabetic Retinopathy Study (ETDRS) eye chart and represents an established functional endpoint in ophthalmic drug development.

The Month 15 and Month 24 assessments are independent efficacy timepoints. Under the revised strategy, ARCHER II can demonstrate success by meeting the primary endpoint at either timepoint.

All eligible patients have now received at least 12 months of treatment. Masked event accrual remains consistent with projections, while the trial has maintained a discontinuation rate below 10% and treatment compliance above 95%.

Vonaprument Targets the Classical Complement Pathway

Vonaprument, formerly known as ANX007, is an investigational antigen-binding fragment (Fab) administered by intravitreal injection. It selectively inhibits C1q, the initiating molecule of the classical complement pathway.

Complement activation has been implicated in retinal inflammation and neurodegenerative processes associated with GA. By blocking C1q and the classical pathway while preserving the lectin and alternative complement pathways, vonaprument is being evaluated as a targeted approach to protecting photoreceptors and maintaining retinal function.

The candidate has received Fast Track designation from the U.S. Food and Drug Administration and PRIME designation from the European Medicines Agency. EMA also selected vonaprument for its Product Development Coordinator pilot, which provides additional regulatory support to PRIME-designated programs.

Phase 2 Data Supported Progression into ARCHER II

The earlier Phase 2 ARCHER trial (NCT04656561) provided clinical evidence supporting further development. Vonaprument produced time- and dose-dependent protection against confirmed BCVA loss of at least 15 letters.

The study also showed benefits across additional prespecified measures of visual function, including low-luminance visual acuity and low-luminance visual deficit. Optical coherence tomography assessments further indicated preservation of photoreceptor-associated retinal structures.

Through Month 12, vonaprument was generally well tolerated. The trial reported no increase in choroidal neovascularization compared with sham treatment and no cases of retinal vasculitis.

Month 15 Data Expected in Fourth Quarter

An independent Data Monitoring Committee will assess the overall ARCHER II study at Month 15. Annexon expects this assessment in the fourth quarter of 2026.

If the DMC determines that ARCHER II has met its Month 15 primary endpoint, the trial’s planned two-sub study analyses can proceed, with results expected in the first quarter of 2027. If the Month 15 endpoint is not met, the study can continue to the Month 24 primary endpoint analysis.

The company expects to complete ARCHER II, including the Month 24 analyses, in the third quarter of 2027.

Following Month 24, eligible participants can enter the newly launched open-label extension and receive monthly vonaprument. The extension will provide longer-term data on safety and treatment benefit, potentially adding evidence relevant to the durability of vision preservation in GA.

Reference

Annexon Expands Vonaprument Phase 3 Program in Geographic Atrophy with Addition of Month 24 Dual Primary Endpoint Complementing Month 15 Primary Endpoint and Launch of Open-Label Extension Study | Annexon Inc.