LAUSR

PURPOSE To evaluate available rationale and outcomes of randomized trial results for complement inhibition for geographic atrophy. METHODS Data from recently completed randomized trials of complement inhibition, particularly for pegcetacoplan and avacincaptad pegol, were evaluated for both the outcome, area of autofluorescence loss, and functional vision tests. RESULTS Pegcetacoplan 2 mg showed statistically significant reduction in expansion of area of autofluorescence loss with monthly, but not every-other-month dosing, in a 12-month phase 2 trial. Nearly 40% of patients recruited for the monthly arm did not complete the trial. In two parallel phase 3 studies there was a statistically significant reduction in the area of atrophy in one but not both studies. Data released at 24 months follow-up showed statistically significant reduction in area of autofluorescence detected atrophy in both studies compared with sham. Patients did not show functional difference in best corrected visual acuity, maximum reading speed, Functional Reading Independence Index, and mean microperimetry threshold sensitivities in the treatment versus sham arms. Avacincaptad pegol was evaluated in 2 randomized pivotal studies and showed a statistically significant reduction in expansion of autofluorescence loss at 12 months. Patients in the treatment arms did not show any difference as compared with sham in best corrected visual acuity or low luminance visual acuity, the only functional outcomes mentioned. Both drugs increased the risk of macular neovascularization. CONCLUSIONS Both avacincaptad pegol and pegcetacoplan show significant differences compared with sham in autofluorescence imaging but no benefit in visual function at 12 and 24 months, respectively.