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Zimura shows promise in treatment of geographic atrophy in AMD
TREVISO, Italy — Complement C5 is a viable target for inhibition to potentially prevent or slow retinal pigment epithelial cell death in patients with geographic atrophy, according to one specialist.
“The role of complement in age-related macular degeneration has been well established. Downstream in the complement cascade, cleavage of complement C5 leads to the generation of C5a and C5b. C5a is involved in priming and activation of inflammasomes, while the generation of C5b may lead to the formation of membrane attack complex (MAC). Inflammasome activation or MAC accumulation both lead to RPE degeneration and cell death,” Marco Zarbin, MD, PhD, said at the Retina 2020: New Trends meeting.
Zimura (avacincaptad pegol, Iveric bio) is a novel C5 inhibitor that was evaluated in a pivotal phase 2b trial for the treatment of patients with geographic atrophy secondary to AMD. The trial included 286 patients and compared the outcomes of Zimura at different dosages in two stages, namely 1 mg and 2 mg vs. sham and 2 mg and 4 mg vs. sham.
“Dose-response analysis showed that the benefit from 1 mg was less than from 2 mg, but the benefit from the 2 mg and 4 mg doses was quite similar, leading to a 27% reduction in the rate of expansion of GA,” Zarbin said.
One of the important details of the study is that almost only patients who had atrophy not involving the fovea were enrolled.
“The reason is that we want to treat the patients before the fovea is involved in the atrophy to preserve central vision. And we know that the atrophy is inexorably progressing once it starts, with an average time of about 2.5 years from the first signs until it involves the center of the fovea,” Zarbin said.
Another interesting finding was that patients who received the complement inhibitor seemed to have a higher chance to develop choroidal neovascularization than the control group (9% vs. 2%).
“These new vessels, however, don’t seem to be leaking fluid. Whether they will in the long term, we do not know yet, but at least during the 12 months of the study, they were well tolerated and may in fact be a homeostatic response to the ischemia associated with GA,” Zarbin said. “Further studies will clarify this point. However, we speculate that if these vessels show to cause problems, we could actually treat them with anti-VEGF.”
Iveric recently announced the design of a second pivotal trial testing Zimura 2 mg vs. sham over 24 months. The company plans to involve approximately 400 patients and will also compare monthly and bimonthly administration. – by Michela Cimberle
Reference:
Zarbin M. Zimura reduces the growth rate of GA in AMD: a phase 2 study. Presented at: Retina 2020: New Trends; Jan. 24-25, 2020; Treviso, Italy.
Disclosure: Zarbin reports he is a member of the scientific advisory board of Iveric.