Findings from the phase 2 ARCHER trial suggest that a confirmed loss of ≥15 ETDRS letters represents a meaningful and consistent indicator of clinically relevant vision loss in patients with dry age-related macular degeneration (AMD) with geographic atrophy (GA), according to David Lally, MD, and the ARCHER study investigators, who presented the data at the 2025 Retina Society meeting.
In ARCHER, patients were randomized to monthly (every month; EM) or every-other-month (EOM) intravitreal injections of vonaprument (formerly ANX007; Annexon Biosciences), or to sham treatment, for 12 months. At study completion, persistent best-corrected visual acuity (BCVA) loss of ≥15 letters was observed in 5.6% of EM-treated eyes, 9.8% of EOM-treated eyes, and 21.3% of sham-treated eyes. Most patients who lost ≥15 letters failed to regain meaningful vision during follow-up.
When stricter criteria were applied—requiring ≥15-letter loss at 2 consecutive visits through month 12, verified at month 15—results were consistent: 4.5% of EM, 8.7% of EOM, and 16.9% of sham patients met this endpoint. Outcomes were similar in a subset of patients who would have qualified for the phase 3 ARCHER II trial, further reinforcing the reproducibility of the findings.
Importantly, the proportion of sham patients with ≥15-letter loss in ARCHER was generally aligned with external datasets such as CHROMA/SPECTRI and PROXIMA, which reported 25% to 35% of patients experiencing similar vision decline over 2 years.1,2 These findings support ≥15-letter loss as a clinically meaningful endpoint for evaluating functional decline in GA and informed the design of ARCHER II.
"Current therapeutics for the treatment of geographic atrophy may demonstrate meaningful effect in slowing disease progression with regards to anatomical parameters, most notably the area of atrophy," Dr. Lally told Retinal Physician. "Although the protection of loss of macular tissue would intuitively seem to correlate with visual benefit, the demonstration of such visual benefit has been challenging to date likely because of the phenotypic heterogeneity of this disease.
"Visual acuity is the most unambiguous measure of visual function. In the ARCHER trial, treatment with vonaprument demonstrated robust protection against a 3-line drop on the eye chart at 12 months. This level of vision loss is often noticeable to patients and can impact daily activities like reading, driving, or recognizing faces. A therapy like vonaprument designed to protect patients from losing significant vision would provide me confidence and reassurance in the therapy's benefit for patients." RP
References
-
Holz FG, et al. Efficacy and safety of lampalizumab for geographic atrophy due to age-related macular degeneration: Chroma and Spectri phase 3 randomized clinical trials. JAMA Ophthalmol. 2018;136(6):666–677. doi:10.1001/jamaophthalmol.2018.1544
-
Holekamp N, et al. Natural history of geographic atrophy secondary to age-related macular degeneration: results from the prospective Proxima A and B clinical trials. Ophthalmology. 2020;127(6):769-783. doi:10.1016/j.ophtha.2019.12.009.