Arshad M. Khanani, Carl J. Danzig, Jeffrey S. Heier, Glenn J. Jaffe, Peter K. Kaiser, David R. Lally, Sunil Patel, Lejla Vajzovic, Christina Y. Weng, Hersh Patel, Julie Clark, Dhaval Desai, Don Luo, Erin C. Henry, Frank G. Holz, Arturo Alezzandrini, Anibal Andres Francone, Joaquín Bafalluy, Silvina Bainttein, Jose Luna Pinto, Mario Saravia, Matko Vidosevich, Carlos Zeolite, Federico Furno Sola, Andrew Chang, Elisa Eleanor Guida Cornish, Thanh Nguyen, Oliver Findl, Anton Haas, Martina Kralinger, Stefan Sacu, Laurence Dominique Postelmans, Michel Farah, Mauricio Maia, Marcio Nehemy, Fareed Ali, Michael Brent, Michael Dollin, John Gonder, Amin Kherani, Andrew Merkur, Raman Tuli, Monica Marie Lopera, Francisco Rodriguez, Mario Bradvica, Jan Ernest, Kuldar Kalijurand, Kai Noor, Yves Cohen, Catherine Creuzot-Garcher, Flore De Bats, François Devin, Catherine Français-Maury, Laurent Kodjikian, Jean François Korobelnik, Yannick Le Mer, Maddalena Quaranta El Maftouhi, Sam Razavi, Eric Souied, Ramin Tadayoni, Michel Weber, Nicole Eter, Nicolas Feltgen, Salvatore Grisanti, Peter Walter, Raffael Liegl, Katrin Lorenz, Georg Spital, Siegfried Priglinger, Martin Spitzer, Michael Volker, Tim Krohne, Claudia Jochmann, Chris Patrick Lohmann, Carsten Framme, Agnes Kerenyi, Andras Papp, Andras Seres, Edit Toth-Molnar, Alexis Tsorbatzoglou, Atilla Vajas, Balázs Varsanyi, Gabor Vogt, Asaf Bar, Eva Eting, David Hauser, Jamie Levy, Nurit Mathalone, Haia Morori-Katz, Irit Rosenblatt, Shiri Soudry-Zayit, Omert Trivizky, Francesco Bandello, Antonio Pasquale Ciardella, Michele Figus, Fabrizio Giansanti, Paolo Lanzetta, Cesare Mariotti, Leonardo Mastropasqua, Edoardo Midena
Purpose Avacincaptad pegol (ACP) is a pegylated RNA aptamer that inhibits complement C5. The efficacy and safety of ACP 2mg was investigated in GATHER2, with positive Year 1 results published. Here, 2-year results are reported. Design Phase 3, 2-year, randomized, double-masked, sham-controlled study (NCT04435366). Participants Patients with non-center point-involving geographic atrophy (GA). Methods Eligible patients were randomized 1:1 to monthly ACP 2mg (N=225) or sham (N=222) for 1 year. At Month 12, patients who received ACP 2mg and completed Year 1 were re-randomized 1:1 to monthly (EM; n=96) or every-other-month (EOM; n=93) ACP 2mg. Patients who had received monthly sham continued with sham (n=203). Main Outcome Measures To evaluate the safety and efficacy of ACP 2mg vs sham over 2 years, and to assess the effect of ACP 2mg EM or EOM dosing in Year 2. Results Overall, 175 and 184 patients in the ACP 2mg and sham group completed the study at Year 2, respectively. At 2 years, treatment with ACP 2mg demonstrated a continued reduction in GA growth (slope) with both ACP 2mg EM and EOM vs sham. From baseline to Year 2, the mean rate of GA area growth was 4.46mm 2 (standard error [SE]: 0.25) with ACP 2mg EM and 5.18mm 2 (SE: 0.17) with sham, a difference in growth of 0.724mm 2 (95% confidence interval [CI]: 0.133,1.315; P =0.0165), representing a 14% difference. From baseline to Year 2, the mean rate of GA area growth was 4.20mm 2 (SE: 0.25) with ACP 2mg EOM, a difference in growth of 0.976mm 2 (95% CI: 0.377,1.575; nominal P =0.0015) vs sham, representing a 19% difference. Over 2 years, ocular treatment-emergent adverse events (study eye) occurred in 64.0% and 48.2% of patients with ACP 2mg (all treated) and sham, respectively. The incidence of choroidal neovascularization (study eye) was 11.6% with ACP 2mg (all treated) vs 9.0% with sham over 2 years. No events of retinal vasculitis, ischemic optic neuropathy, or serious intraocular inflammation occurred over 2 years. Conclusions Dosing of ACP 2mg, either EM or EOM, continued to reduce GA growth vs sham over 2 years with no new safety signals compared with Year 1.