Other Complement Inhibitors for Geographic Atrophy Treatment

Eleonora M. Lad, MD, PhD: Nancy, there’s another drug targeting the complement pathway. Please tell us a little bit about the GATHER1 and GATHER2 studies and your impression of the efficacy, safety data, and how you think these programs will move forward.

Nancy M. Holekamp, MD, FASRS: This drug is called avacincaptad pegol, and they took a slightly different strategy with the clinical trials. It started out as a phase 2 trial that was grandfathered into phase 3. It’s a small trial, not as large as the Apellis [Pharmaceuticals]-sponsored trials with over 1200 patients; we’re looking more in the 400-patient category for GATHER2 and 200 patients for GATHER1. In this clinical trial they used only extrafoveal GA [geographic atrophy] lesions in their inclusion criteria, and they only dosed monthly. Right there, we have a different drug, we have different inclusion criteria, and we have a different way of dosing in both clinical trials. In the GATHER1, which started out as a phase 2 and then went to phase 3, they looked at 2 different doses of avacincaptad pegol, a 2-mg dose and a 4-mg dose, versus a sham [treatment]. The natural history of the sham arm is important to all of these clinical trials. It showed that both doses, the 2 and the 4 mg, had roughly a 27% reduction in the growth rate, which was outstanding, very encouraging. This led to the GATHER2 clinical trial, which used only the 2-mg dose, and again, only used monthly dosing and only included extrafoveal lesions.

That data set was recently presented at the American Academy of Ophthalmology meeting, and it showed that they were able to decrease the growth rate, not quite by 27%, it was more in the realm of 17%, but it did meet statistical significance for the size of the study compared to sham. What’s encouraging now that we have GATHER1 and GATHER2, in light of what we just discussed, is that this validates complement as a viable target for treating GA. It may not be the complete story because we’re not able to stop the disease, but we are slowing the growth rate for the very first time. What’s also exciting about the GATHER1, GATHER2 data is the safety; the safety for these injections was pristine. They also had a slightly increased rate of corneal neovascularization, whether it was exudative or nonexudative, but the IOI [intraocular inflammation] rates were very low, and there were no instances of retinal vasculitis or occlusive vasculitis. There was a case in both the studies that David reviewed and this of optic neuropathy, like an anterior ischemic optic neuropathy, which I’d like to know how the panel feels about that. I feel that’s more age-related, and we’re following people in this age group over 2 years. I think that the safety profile is excellent. This program is a bit behind, we’re still looking at an IND [investigational new drug] submission and then time for the FDA to review it. But I am happy now to have 2 clinical trial approaches targeting complement C3 and C5 that seem to be giving me the same or at least similar results.

Transcript edited for clarity