The following transcript has been edited for clarity.

Hi, this is Ashkan “Ash” Abbey, MD, from Texas Retina Associates in Dallas, Texas. I’m here at the Retina Society annual meeting in Los Angeles. Today, I just presented the baseline characteristics of the patients that were being placed into the ARCHER II phase 3 clinical trial. The reason why this presentation is important is because we are now looking at a patient population in geographic atrophy (GA) that is having their visual function possibly truly being affected by the drug. Instead of looking just at anatomical outcomes, we were actually focusing on functional outcomes.

How we came to this point is the story of the presentation. The ARCHER trial was a phase 2 trial looking at vonaprument (ANX007; Annexon Biosciences), which is a C1q inhibitor intravitreally injected for patients with both foveal and nonfoveal GA. In that trial, patients were randomized 1:1:1 to either sham treatment, every-other-month dosing with vonaprument, or monthly dosing with vonaprument. The primary endpoint for that phase 2 trial was an anatomical outcome looking at the change in GA lesion area over time through the 12-month endpoint. And there were secondary endpoints that were more functional in terms of best-corrected visual acuity and also low-luminance visual acuity.

The key takeaway from the trial was that the anatomy, based upon autofluorescence, wasn’t actually the important part that we saw. We saw an interesting functional signal, and that signal was that vonaprument had a dose-dependent protective effect on severe vision loss, and it reduced the proportion of patients that actually experienced severe vision loss at 1 year. And how we quantified severe vision loss was a ≥15 letter loss at 1 year. So in the 12-month data from that phase 2 trial, we saw that in the sham group, 16.9% of patients lost ≥15 letters at month 12, whereas in the monthly vonaprument treatment group, it was only 4.5%. That was a significant reduction in the number of severe vision loss patients that were there, and the relative risk reduction was 73% for these monthly dosed patients compared to sham.

So we took that information and we created the phase 3 trial based upon those learnings from the phase 2. One of the things we noted from the phase 2 trial is that the patients who had “healthier eyes” in the phase 2 trial tended to have an even more pronounced effect of reducing the risk of severe vision loss. And what we mean by healthier eyes are those patients who have a low-luminance visual deficit of less than 30 letters. So those patients tend to have a little bit more macular functional reserve in their vision that can be preserved even better, potentially, with vonaprument.

When we look at the phase 3 trial, which is called ARCHER II, they took a larger population, 659 patients, that were randomized 2:1 to either monthly dosing with vonaprument or sham injections. In that trial, the primary endpoint is no longer an anatomical outcome; it is a functional outcome: the proportion of patients who have lost ≥15 letters at either month 15 or month 24. It’s a dual-endpoint trial. Either one of those endpoints could be enough to confirm the trial.

The patient population that was included in ARCHER II is something that’s important to recognize, because there was a larger effect on patients who had that low-luminance visual deficit that was less than 30 letters. And also the foveal lesions tended to have a more pronounced effect as well in terms of preserving vision for patients. So in the inclusion of the patients for the trial for ARCHER II, which is now fully enrolled, they included roughly a little over half of patients with foveal-involving lesions in order to see that more pronounced effect from the treatment on the vision. They also had about 60% of the patients have the low-luminance visual deficit of less than 30 letters. And this actually is roughly the same as what was in the initial ARCHER phase 2 trial as well.

So they’re expecting that based upon ARCHER II, including this same proportion of patients that I think have more of a substantial treatment effect from the vonaprument, that they will have a significant outcome in terms of the reduction in severe vision loss in these patients, which is the primary outcome of the trial.

We will stay tuned for what the outcome will actually be. Right now, we know that the month 15 primary endpoint data should be presented by the end of the year. So I’m looking forward to that. RP