Annexon Presents New Neuroprotection Data Showing ANX007 Protects Vision and Vision-Associated Structures in GA

Annexon presented new analyses of ANX007 from the phase 2 ARCHER trial in geographic atrophy (GA), and new preclinical data on the role of C1q in the pathogenic elimination of photoreceptor synapses and their protection with C1q blockade in GA.

ANX007 is a first-in-class, non-pegylated antigen-binding fragment (Fab) designed to block C1q and activation of the classical complement cascade locally in the eye with an intravitreal formulation, according to Annexon. It is the first therapeutic candidate for the treatment of GA to receive Priority Medicine (PRIME) designation by the European Medicines Agency (EMA). The data were presented at the Association for Research in Vision and Ophthalmology (ARVO) 2024 annual meeting.

“We are pleased to present additional clinical data from the ARCHER trial that are the first to show preservation of both vision and relevant anatomical structures following ANX007 treatment,” Douglas Love, president and chief executive officer of Annexon, said in a company news release. “These data combined with our robust preclinical work underscore the potential of ANX007’s neuroprotective mechanism of action to protect photoreceptor synapses and visual function and deliver differentiated functional benefit for millions of patients. We look forward to advancing ANX007 into registrational phase 3 trials in GA expected to initiate by mid- and second half of 2024.”

“These new data reinforce the impressive vision preservation observed with ANX007 treatment in GA which is demonstrated by multiple measures of visual acuity, including in foveal and non-foveal patients and in low light settings,” said David Boyer, MD, Retina-Vitreous Associates Medical Group, California. “Importantly, the statistically significant preservation of photoreceptor anatomy measured by ellipsoid zone change highlights protection of key retinal structures associated with vision. Moreover, protection of the RPE was more robust in lesions near the fovea, a region highly correlated with visual acuity, while slowing of RPE loss as a lagging indicator was more pronounced over time. These encouraging findings along with the generally well-tolerated safety profile with no incidence of vasculitis hold promise to impact loss of visual acuity within the current treatment landscape.”

Key Additional Phase 2 Analyses from ARCHER Study Show ANX007 Treatment:

Provided broad-based protection against vision loss

• Statistically significant and dose dependent protection in BCVA ≥15-letter loss
• 73% relative risk reduction in BCVA 15-letter loss, supporting time-dependent protection
• Statistically significant slowing of low luminance visual acuity (LLVA) loss at month 12
• Protection in both foveal and non-foveal patients from BCVA 15-letter loss

Protected key retinal structures important for vision

• Statistically significant reduction in photoreceptor loss through 12 months based on OCT Ellipsoid Zone assessment, a direct measure of photoreceptor anatomy
• Greater slowing of RPE loss in patients with baseline foveal involvement compared to overall population (Fundus Autofluorescence Photography Assessment)
• >50% reduction in the number of patients with substantial RPE loss in the fovea, a region highly correlated with visual acuity

Generally well-tolerated

• No choroidal neovascularization (CNV) increase in treated vs. sham
• No reported cases of vasculitis 

Additional Preclinical Analyses of Anti-C1q Neuroprotective Mechanism in GA

Annexon also presented first time preclinical evidence demonstrating the deposition of C1q on photoreceptor synapses and C1q mediated microglia engulfment in a nonclinical model of photoreceptor degeneration. In postmortem retina of patients with GA, C1q deposition on photoreceptor synapses and their loss is observed beyond the area of atrophy defined by the RPE, reaffirming neurodegeneration at sites outside the atrophic areas in the GA retina. Moreover, in an animal model of GA and photoreceptor damage, pharmacological inhibition of C1q protected photoreceptor synapses and preserved retinal function, supporting findings from the phase 2 ARCHER trial and enhancing the mechanistic understanding of how ANX007 protects photoreceptor synapses and provides visual function protection in GA.

Annexon’s Global Phase 3 Plans

Annexon plans to initiate a global pivotal phase 3 ARCHER II trial against sham control in mid-2024, and a pivotal phase 3 head-to-head ARROW trial against Syfovre (pegcetacoplan injection) in the second half of 2024. These two registrational trials are designed to confirm the phase 2 ARCHER findings of protection against vision loss and underscore the unique neuroprotective mechanism of action of ANX007 and its competitive differentiation in visual function.