Q&A: The ARCHER trial and the importance of continued GA research

In conversation with Sydney M. Crago, Managing Editor of Ophthalmology Times, David R. Lally, MD, spoke about his presentation at the 2025 Retina Society meeting, which highlighted the results from the ARCHER trial (NCT04656561) of ANX007 for the treatment of age-related macular degeneration (AMD) and geographic atrophy (GA). Notably, Lally spoke to the need to continue research and develop next generation treatments for GA to ensure that patients have the best possible vision outcomes.

Note: The following conversation has been lightly edited for clarity.

Ophthalmology Times: You shared data on the ARCHER trial at the 2025 Retina Society meeting. What are the highlights from this research you presented?

David R. Lally, MD: It starts with C1q, and C1q is the initiating molecule of the complement cascade, and this is a key driver in neuroinflammation. We know that in the retina, C1q localizes to photo receptor synapses, and that leads to activation and removal of these synapses by microglial cells. It leads to local neuroinflammation and can result in photo receptor loss. There's a drug that's been developed called vonaprument [ANX007] that is an inhibitor of C1q, and it's an antibody fragment that's injected into the vitreous that inhibits C1q. By inhibiting C1q, we hope to block that initiation of the classical complement cascade and all the downstream effects of that cascade to protect or preserve photoreceptors.

This medicine was studied in a multi-centered randomized, what we call phase 2 trial, looking at monthly or every-other-month, injections of vonaprument over the course of 12 months compared to sham. After 12 months, there was a 6-month off treatment observational period through month 18. The primary endpoint for this study was the rate of change in the GA lesion area growth at month 12. There was also pre-specified functional analysis measures that included best-corrected and low luminance visual acuity changes. So what we saw, interestingly, was that vonaprument significantly reduced the rate of 15 or more letter loss compared to sham when we looked at month 12, and that was in both the monthly and every-other-month dosing arms. So what does 15 letter loss mean? Well, greater than or equal to 15 letter loss, it represents a doubling of the visual angle. This measure has been used as a primary outcome measure in many pivotal trials for retinal vascular disease over the years. This amount of vision change is often noticeable to our patients. It can affect their activities of their daily living, such as reading or driving or recognizing faces. So we think it's a meaningful change in the vision of these patients.

We saw with vonaprument in the monthly treatment arm that there was a risk reduction of 73% again, against losing 15 letters compared to sham at month 12, and it was about a 50% risk reduction in the every-other-month dosing arms. So these, these are not insignificant differences between these treatment groups and the sham in a relatively short time period of 1 year. We also saw that during that 6-month off treatment period, those eyes that were previously treated with vonaprument, their rates of 15 letter loss, appeared similar to the sham group during that time, and that further suggests that when the patients were receiving the vonaprument in the first 12 months, there was a real effect at slowing and protecting against that vision loss. We also saw that vonaprument showed significant reductions in both the foveal lesion types and also the non-foveal lesion types. This is exciting that we're seeing in different pathologies of geographic atrophy, significant reductions in protecting against significant vision loss over time.

OT: What impact did of the results from the ARCHER study have on the continued research for this therapeutic candidate?

Lally: The results of the ARCHER study led to the design of the ARCHER 2 study, which is the only global pivotal phase 3 trial ongoing right now for geographic atrophy with vision protection as its primary endpoint. This trial is now fully enrolled, and results are anticipated later next year. But why this is important is the previous complement inhibitor therapies that are currently FDA-approved for the treatment geographic atrophy, they were approved based on an anatomical endpoint change. That change is significant, and I do think that it's important and meaningful for our patients, but we can't forget about functional changes for our patients, not just how the picture changes of their retina over time. We want to know, "is it helping the patient's vision?" The measurement of visual acuity is probably the most unambiguous visual outcome measure we have. We've been using it for a long time in ophthalmology. So if we can demonstrate significance in protecting against vision loss, I think that would be very meaningful and reassuring to me as a provider, that this medicine is really of true, big benefit for my patients.

OT: When you consider the longterm future of GA and where we are at this moment, what do you think is still to come?

Lally: I think we're still in the early phases of, the first inning of the ball game, if you were to think of it as a baseball game. We're still in the early innings of the of the ball game in figuring out the treatment of geographic atrophy. The recent approvals of 2 products that are complement inhibitors for the treatment of GA was a landmark time in our field. It was the first time ever that we had therapies that demonstrated benefit for our patients. So that was a big shift a few years ago. But those therapies, they don't stop the disease, they don't make patients better. At the end of the day, we want to be able to stop the disease. We want to be able to prevent the disease. We want to be able to make the disease better, if the disease exists. What's encouraging is that now, with this ARCHER 2 study, we're going to that next step of the development in this field, which is now saying, we're looking for therapies that are going to preserve and protect the actual vision of the patient. It's an exciting time in geographic atrophy treatment and development. I think there's a lot more we have to learn. All of these trials that are ongoing and all these results and programs that are coming through, they're giving our community a wealth of information that's valuable in terms of developing the next generation therapies to reach our ultimate goal of protecting against this ever happening, or at least being able to reverse the disease.