PMID- 36964259 OWN - NLM STAT- MEDLINE DCOM- 20231127 LR - 20240126 IS - 1476-5454 (Electronic) IS - 0950-222X (Print) IS - 0950-222X (Linking) VI - 37 IP - 17 DP - 2023 Dec TI - Avacincaptad pegol for geographic atrophy secondary to age-related macular degeneration: 18-month findings from the GATHER1 trial. PG - 3551-3557 LID - 10.1038/s41433-023-02497-w [doi] AB - 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. CI - (c) 2023. The Author(s). FAU - Patel, Sunil S AU - Patel SS AD - West Texas Retina Consultants, Abilene, TX, USA. FAU - Lally, David R AU - Lally DR AD - New England Retina Consultants, Springfield, MA, USA. FAU - Hsu, Jason AU - Hsu J AD - The Retina Service of Wills Eye Hospital, Wills Eye Physicians-Mid Atlantic Retina, Philadelphia, PA, USA. FAU - Wykoff, Charles C AU - Wykoff CC AD - Retina Consultants of Texas, Houston, TX, USA. FAU - Eichenbaum, David AU - Eichenbaum D AD - Retina Vitreous Associates of Florida, St. Petersburg, FL, USA. AD - Morsani College of Medicine at The University of South Florida, Tampa, FL, USA. FAU - Heier, Jeffrey S AU - Heier JS AD - Ophthalmic Consultants of Boston, Boston, MA, USA. FAU - Jaffe, Glenn J AU - Jaffe GJ AD - Department of Ophthalmology, Duke University, Durham, NC, USA. FAU - Westby, Keith AU - Westby K AD - IVERIC Bio, Inc, New York, NY, USA. FAU - Desai, Dhaval AU - Desai D AD - IVERIC Bio, Inc, New York, NY, USA. FAU - Zhu, Liansheng AU - Zhu L AD - IVERIC Bio, Inc, New York, NY, USA. FAU - Khanani, Arshad M AU - Khanani AM AD - Sierra Eye Associates and The University of Nevada, Reno School of Medicine, Reno, NV, USA. arshad.khanani@gmail.com. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial DEP - 20230324 PL - England TA - Eye (Lond) JT - Eye (London, England) JID - 8703986 SB - IM EIN - Eye (Lond). 2023 May 26;:. PMID: 37237234 MH - Humans MH - *Geographic Atrophy/drug therapy/etiology MH - Prospective Studies MH - Visual Acuity MH - *Macular Degeneration/complications/drug therapy MH - Intravitreal Injections MH - Fluorescein Angiography PMC - PMC10686386 COIS- The authors disclose the following conflicts of interest related to this manuscript: SSP has received grants/contracts from Apellis, Genentech-Roche, Ionis, IVERIC bio, and Stealth, consulting fees from IVERIC bio and Genentech-Roche, and has participated on a data safety monitoring board or advisory board for IVERIC bio. DRL has received investigator grants from Annexon, Apellis, IVERIC bio, and Stealth, consultant fees from Annexon, Apellis, IVERIC bio, and Stealth, honoraria from Annexon, Apellis, IVERIC bio, and Stealth, travel support from Annexon, Apellis, IVERIC bio, and Stealth, and served on steering committees for Annexon and IVERIC bio. JH has received institutional research grants from Genetech-Roche and IVERIC bio, and consulting fees from Gyroscope and IVERIC bio. CCW's research has been funded in part through grants or contracts from Annexon, Apellis, Genentech-Roche, Gyroscope, Ionis, IVERIC bio, and NGM, and has received consulting fees from Annexon, Apellis, Genentech-Roche, Gyroscope, IVERIC Bio, NGM, and Stealth. DE has received contracts or grants from Annexon, Genentech-Roche, Gyroscope, Ionis, IVERIC bio, and NGM, consulting fees from Apellis, Genentech-Roche, Gyroscope, and IVERIC bio, payment or honoraria from Apellis, Genentech-Roche, and has served on advisory boards for Genentech-Roche, IVERIC bio. JSH has received consulting fees from Allegro, Annexon, Apellis, Genentech-Roche, Gyroscope, IVERIC bio, NGM, Stealth, has participated on advisory boards for Annexon, Apellis, Genentech-Roche, Gyroscope, IVERIC bio, NGM, and holds stock/stock options in Allegro. GJJ has received institutional research grants or contracts from Annexon, Ionis, and Genentech-Roche, consulting fees from Genentech-Roche, and has participated on an advisory board for Annexon. KW, DD, and LZ are employees of IVERIC bio. AMK has received contracts or grants from Annexon, Apellis, Gyroscope, IVERIC bio, NGM, Genentech-Roche, consulting fees from Apellis, Genentech-Roche, Gyroscope, IVERIC bio, and Stealth, and honoraria from Apellis and Genentech-Roche. EDAT- 2023/03/26 06:00 MHDA- 2023/11/27 12:43 PMCR- 2023/03/24 CRDT- 2023/03/25 00:21 PHST- 2023/01/11 00:00 [received] PHST- 2023/03/07 00:00 [accepted] PHST- 2023/02/24 00:00 [revised] PHST- 2023/11/27 12:43 [medline] PHST- 2023/03/26 06:00 [pubmed] PHST- 2023/03/25 00:21 [entrez] PHST- 2023/03/24 00:00 [pmc-release] AID - 10.1038/s41433-023-02497-w [pii] AID - 2497 [pii] AID - 10.1038/s41433-023-02497-w [doi] PST - ppublish SO - Eye (Lond). 2023 Dec;37(17):3551-3557. doi: 10.1038/s41433-023-02497-w. Epub 2023 Mar 24.