Annexon's ANX007, an investigational drug, has shown promising results in preserving vision in patients with geographic atrophy (GA) due to dry age-related macular degeneration (AMD). The Phase 2 ARCHER study demonstrated that monthly injections of ANX007 significantly reduced the risk of vision loss and preserved key retinal structures essential for vision. These findings were presented at the American Academy of Ophthalmology (AAO) 2024 annual meeting, offering hope for a potential breakthrough in treating this debilitating condition.
Protection Against Vision Loss
The ARCHER trial data indicated that patients treated monthly with ANX007 experienced a significant level of vision protection. Specifically, in a subpopulation of patients with less advanced disease, 0% (0/56) of ANX007-treated patients lost 15 letters on an eye chart, compared to 17% (10/59) of sham-treated patients (Nominal p-value 0.0013). Overall, 6% (5/89) of ANX007 monthly-treated patients lost 15 letters versus 21% (19/89) of sham patients (Nominal p-value 0.0021).
Preservation of Photoreceptors
ANX007 also demonstrated enhanced protection against ellipsoid zone (EZ) loss in central subdomains in patients with more EZ intact at baseline. There was a 61% decrease in EZ loss between ANX007 and sham in patients with < 80% EZ loss at baseline (Nominal p-value 0.0575) and a 48% decrease in EZ loss between ANX007 and sham in patients with < 98% EZ loss at baseline (Nominal p-value 0.0218).
Douglas Love, president and chief executive officer of Annexon, stated, “Photoreceptors near the foveal center are necessary for high acuity vision like reading an eye chart or seeing faces. Protecting these cells is essential to preserving vision and we are encouraged by ANX007’s consistent and robust effect on this structural element of the eye.”
Mechanism of Action
ANX007 is a first-in-kind, non-pegylated antigen-binding fragment (Fab) designed to selectively inhibit C1q, the initiating molecule of the classical complement pathway and a key driver of neurodegeneration. In dry AMD and GA, C1q binds to photoreceptor synapses, causing aberrant activation of the classical pathway, leading to synapse loss, inflammation, and neuronal damage that results in vision loss. Intravitreal administration of ANX007 fully stopped C1q and classical pathway activation.
Current Treatment Landscape and Future Directions
Geographic atrophy affects an estimated one million people in the United States and eight million people globally. Currently, effective treatments that preserve vision are lacking. While the FDA has approved treatments to slow the progression of GA, ANX007 offers a potential breakthrough by directly protecting vision.
Annexon anticipates Phase 3 ARCHER II data in the second half of 2026. ANX007 has been granted Fast Track designation by the FDA and Priority Medicine (PRIME) designation in the EU, highlighting its potential to address a significant unmet medical need.
