Annexon, Inc. (Nasdaq: ANNX) is set to present detailed analyses of ANX007 from the completed Phase 2 ARCHER trial in geographic atrophy (GA) at the Retina Society’s 57th annual scientific meeting in Lisbon, Portugal (September 11-15), and the 24th annual Euretina Congress in Barcelona, Spain (September 19–22). ANX007, a non-pegylated antigen-binding fragment (Fab), is designed to selectively inhibit C1q in the eye via intravitreal administration.
Douglas Love, president and chief executive officer of Annexon, stated, “The randomized ARCHER data for ANX007 in GA demonstrated broad-based protection of vision in standard and low light conditions, along with significant protection of visual structures in key regions of the eye important to visual acuity. Based on these data, we have initiated a Phase 3 pivotal ARCHER II trial to further evaluate the potential of ANX007 to be the first treatment to protect vision in GA.”
ARCHER Trial Results
The Phase 2 ARCHER trial was a randomized, multi-center, double-masked, sham-controlled study. Results indicated that ANX007 provided statistically significant, time and dose-dependent protection from vision loss, as measured by ≥ 15 letter loss on reading an eye chart with best corrected visual acuity (BCVA). Additional measures of BCVA and visual function, including low luminance visual acuity (LLVA) and low luminance visual deficit (LLVD), also showed significant protection from vision loss.
The treatment effect of ANX007 increased over the on-treatment portion of the study, suggesting a growing and durable effect over time. While the benefit against vision loss was maintained during the six-month off-treatment period, the rate of decline for BCVA ≥ 15-letter vision after treatment termination began to parallel that of sham, further supporting the observed on-treatment protection.
Protection of Retinal Structures
Optical coherence tomography (OCT) measurements showed that ANX007 protected key retinal structures, including photoreceptors. Fundus autofluoresence (FAF) measurements supported these findings by indicating a slowing of retinal pigment epithelial (RPE) cell loss in the fovea.
ANX007 was generally well-tolerated through month 12, with no increase in choroidal neovascularization (CNV) rates between the treated and sham arms and no events of retinal vasculitis reported.
About Geographic Atrophy
Geographic atrophy (GA) is an advanced form of dry age-related macular degeneration (AMD), a leading cause of blindness in the elderly. GA is characterized as a chronic, progressive neurodegenerative disorder of the retina, involving the loss of photoreceptor synapses and cells in the outer retina. It affects an estimated one million people in the United States and eight million people globally.
Mechanism of Action
ANX007 is designed to selectively inhibit C1q, the initiating molecule of the classical complement pathway, which is a key driver of neurodegeneration. In GA, C1q binds to photoreceptor synapses early in the disease process, causing aberrant activation of the classical pathway, leading to synapse loss, inflammation, and neuronal damage, ultimately resulting in vision loss. Intravitreal administration of ANX007 fully stops C1q and classical pathway activation. Preclinical studies in animal models have shown that a murine analog of ANX007 protects against the loss of photoreceptor synapses and cells, preserving function.
ANX007 has been granted Fast Track designation by the FDA and PRIME designation in the EU.
