Avacincaptad pegol for geographic atrophy secondary to age-related macular degeneration: 18-month findings from the GATHER1 trial

• Published in: Eye (London) Vol. 37; no. 17; pp. 3551 - 3557
• Main Authors: Patel, Sunil S., Lally, David R., Hsu, Jason, Wykoff, Charles C., Eichenbaum, David, Heier, Jeffrey S., Jaffe, Glenn J., Westby, Keith, Desai, Dhaval, Zhu, Liansheng, Khanani, Arshad M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.12.2023; Nature Publishing Group
• Subjects: 692/308/409; 692/699/3161/3175; Age; Atrophy; Fluorescein Angiography; Geographic Atrophy - drug therapy; Geographic Atrophy - etiology; Humans; Intravitreal Injections; Laboratory Medicine; Macular degeneration; Macular Degeneration - complications; Macular Degeneration - drug therapy; Medicine; Medicine & Public Health; Ophthalmology; Pharmaceutical Sciences/Technology; Prospective Studies; Surgery; Surgical Oncology; Vascularization; Visual Acuity
• ISSN: 0950-222X; 1476-5454; 1476-5454
• DOI: 10.1038/s41433-023-02497-w

Background/Objectives To assess the safety and efficacy of avacincaptad pegol (ACP), a C5 inhibitor, for geographic atrophy (GA) secondary to age-related macular degeneration (AMD) over an 18-month treatment course. Subjects/Methods This study was an international, prospective, randomized, double-masked, sham-controlled, phase 2/3 clinical trial that consisted of 2 parts. In part 1, 77 participants were randomized 1:1:1 to receive monthly intravitreal injections of ACP 1 mg, ACP 2 mg, or sham. In part 2, 209 participants were randomized 1:2:2 to receive monthly ACP 2 mg, ACP 4 mg, or sham. The mean rate of change of GA over 18 months was measured by fundus autofluorescence. Results Compared with their respective sham cohorts, monthly ACP treatment reduced the mean GA growth (square root transformation) over 18 months by 28.1% (0.168 mm, 95% CI [0.066, 0.271]) for the 2 mg cohort and 30.0% (0.167 mm, 95% CI [0.062, 0.273]) for the 4 mg cohort. ACP treatment was generally well tolerated over 18 months, with most ocular adverse events (AEs) related to the injection procedure. Macular neovascularization (MNV) was more frequent in both 2 mg (11.9%) and 4 mg (15.7%) cohorts than their respective sham control groups (2.7% and 2.4%). Conclusions Over this 18-month study, ACP 2 mg and 4 mg showed continued reductions in the progression of GA growth compared to sham and continued to be generally well tolerated. A pivotal phase 3 GATHER2 trial is currently underway to support the efficacy and safety of ACP as a potential treatment for GA.