Sidney M. Crago, editor of Modern Retina, discusses expanded efficacy data from the GATHER 2 trial in geographic atrophy (GA) by Arshad M. Kanani, MD, PhD, MSc, FASRS. These data were presented on Saturday, February 3, at the Angiogenesis, Exudates, and Degeneration 2024 Conference, a virtual event sponsored by the Bascom Palmer Eye Institute and University of Miami Health System in Miami.
video transcript
Editor’s note – This transcript has been edited for clarity.
Sidney M. Crago: Hello, I’m Sydney Crago with Modern Retina. Today I’m joined by Dr. Arshad Hanani to talk about his presentation at the upcoming conference. He will discuss his two-year expanded efficacy data from the GATHER 2 trial. Dr. Hanani, could you tell us a little bit about your presentation?
Arshad M. Hanani, MD, MA, FASRS: Thank you, Sydney. So, my talk at the Angioplasty 2024 Virtual Conference is about expanding the efficacy of avasincaptad pegol (ACP). As you know, ACP is a small pegylated RNA aptamer designed to be a specific inhibitor of complement C-5. Based on his two important positive studies, GATHER-1 and GATHER-2, ACP received FDA approval last August. In my talk, I actually share expanded efficacy data, but there are a few points. [that] There was something I wanted to emphasize from my presentation. First, we see that running ACP monthly and bimonthly reduces the increase in GA compared to the GATHER-2 sham case. As you may recall, in an international, multicenter, randomized study, patients received either monthly ACP or a sham dose for the first year, and then were actually randomized to receive monthly or They received one of the bimonthly doses, and the sham group continued on the sham dose. injection.
So the idea was to see if bimonthly would have the same effect as monthly, and that’s what we found. Another thing we’re looking at is therapeutic efficacy. The therapeutic effects of ACP have been shown to be visible as early as 6 months. And what we saw was more than double the treatment effect over 2 years compared to ACP, 2 milligrams over 1 year compared to sham. Next, we also looked at the pooled analysis of GATHER-1 and GATHER-2. As you may recall, GATHER-1 was a pivotal Phase 2/3 study, lasting 18 months. So we know that GA is a highly variable and multifactorial disease, so by getting data from GATHER-1 and GATHER-2 in terms of efficacy, we’re trying to figure out how to treat it. We wanted to see if we could get more information about the effects. So what we saw was that in that analysis, we found strong efficacy for ACP, with an 18-month pooled analysis that showed almost a doubling of the treatment effect every six months, and growth in GA compared to sham. This is an overall decrease of 19%. Again, this is a postdoc analysis. Finally, we present the first results of a match-adjusted indirect comparison analysis, or what we call the Medac analysis. These analyzes are then performed when level 1 evidence is missing in direct comparison studies. This means that pegcetacoplan is also a drug approved for the treatment of GA.
That trial enrolled patients with central and noncentral involvement of the GA, and all patients in the ACP study enrolled patients with noncentral involvement. So each trial will have different baseline characteristics, but what we can do is match her baseline BCVA and GA lesion growth across trials to examine efficacy. So he took all the published data from the pegcetacoplan DERBY and OAKS studies and used data from the important GATHER-1 and GATHER-2 studies to match the BCVA GA parameters with other parameters. And we actually ended up with a very well matched population. Again, this is not Level 1 evidence done for payers and regulators, especially when Level 1 direct evidence is missing. So what we saw was a greater doubling of the direction of treatment effect when using ACP monthly compared to using pegcetacoplan monthly. So I think this is very beneficial for the field. Given similar baseline characteristics, we observed a 26% reduction at 12 months in ACP and spurious growth in GA, as we are comparing efficacy. It’s a fake from the same study. So we’re not comparing fake studies from different studies. Meanwhile, a similar group saw a 14% reduction with pegcetacoplan.
So I got all the data from DERBY and OAKS. And in this analysis he matched patients with ACP. Therefore, it was of great significance that the matched-medac analysis revealed a greater benefit for ACP compared with pegcetacoplan. Of course, keep in mind all the caveats regarding limitations.
Another point that is most important to patients is visual acuity. Therefore, we examined the visual acuity of the sham group and the ACP matched group. Derby and Oakes’ vision was then checked monthly and bimonthly. And when we compared pegcetacoplan with a placebo, we found that her monthly ACP showed better vision preservation compared to the placebo. Looking at the data, 47% of visual acuity is preserved compared to ACP. And if you look at the pegcetacoplan, there’s a 17% decrease in vision retention in the month-to-month group. And in the bimonthly group, vision retention is 65% lower. Therefore, this is another interesting finding that visual acuity was better preserved in patients treated with ACP, which is clearly the ultimate goal of long-term treatment of these patients with these therapies.
Therefore, I hope that this summary of my talk will be useful to you. Also, thank you for inviting me to share the summary of my talk.
