ARCHER study demonstrated that the antibody ANX007 was time and dose dependent, robust, and not dependent on lesion growth.
A new study found monthly ANX007 geographic atrophy (GA) treatment leads to a 72% risk reduction with 15 lost letters at 12 months and every other month treatment leads to a 48% risk reduction.
David Lally, MD, from New England Retina Consultants, discussed his study at the presentation “Treatment of Geographic Atrophy Secondary to Age-related Macular Degeneration with Intravitreal ANX007, a Selective Classical Complement Inhibitor: Results of the ARCHER Study,” delivered November 3rd at the 127th Annual American Academy of Ophthalmology (AAO) Congress in San Francisco, California.
ARCHER was a phase 2 trial, with locations evenly randomized. Participants either received ANX007 monthly or every other month or Sham. ANX007 was a fab antibody fragment that selectively inhibited C1Q, a key driver of neurodegeneration which activates photoceptor cells to cause inflammation and loss, which was modeled after IBT fat antibodies like Ranibizumab. Participants received doses of 5 mg.
The primary endpoint was the best corrected visual mean change in geographic area lesion size of month 12. Secondary endpoints were best corrected visual acuity, low luminance, visual deficit, and low lumens of visual acuity. Lally said the baseline geographics were well-balanced.
Lally presented the audience with an image of a healthy retina compared to the retina of a patient with GA. In the GA retina, retinal pigment epithelium (RPE) cells were absent within the atrophic lesion, as well as a decreasing reading of the photoreceptor cells toward the atrial Elysian.
“What’s particularly striking is the loss of the red labeled photoreceptors synapses that extend quite distinct from the…lesion,” Lally said. “These synapses appear to be more negatively impacted than the photoreceptor cell bodies.”
By month 12, the monthly treatment showed a non-significant 6% reduction in lesion growth, but treatment revealed greater growth reductions in the second 6 months. Thus, the findings suggest longer therapy lesion reductions may grow over time. Lally and his colleagues found that while ANX007 did not significantly reduce lesion area, the treatment demonstrated a statistically significant protection from vision loss as measured by BCVA > 15 Letter Loss. Lally shared that 21.3% of participants in the sham group had persistent BCVA > 15 Letter Loss through month 12 while the monthly ANX007 group had 5.6%, and the ANX007 every other month group had 10.9%.
Lally noted another compelling finding in Archer’s pre-specified visual acuity analyses.
“ANX treatment demonstrated the significant dose dependent protection against vision loss to find [these] 15 letters are greater than two consecutive visits for month 12,” he said.
Lally and his team examined the proportion of subjects with 15 letter loss at each of the study visits in the first 12 months. ANX subjects stayed consistently under 10% while sham increased. Lally concluded by saying that ANX007 transforms the treatment options of GA, and they are preparing preparations for phase 3.
“ANX007 demonstrated a novel neuro protective mechanism for GA that consistently translated to a clinically meaningful protection of vision,” Lally said. “ANX007 protection showed us that it was significant, it was time and dose dependent, it was robust across multiple measures and patient subgroups, and importantly, it was not dependent on lesion growth.”
Lally, D. Treatment of Geographic Atrophy Secondary to Age-related Macular Degeneration with Intravitreal ANX007, a Selective Classical Complement Inhibitor: Results of the ARCHER Study. Presented at the 2023 American Academy of Ophthalmology Annual Meeting; November 3, 2023; California, San Francisco.