PMID- 33221326 OWN - NLM STAT- MEDLINE DCOM- 20211012 LR - 20211012 IS - 1549-4713 (Electronic) IS - 0161-6420 (Linking) VI - 128 IP - 7 DP - 2021 Jul TI - Two-Year Results of the Phase 3 Randomized Controlled Study of Abicipar in Neovascular Age-Related Macular Degeneration. PG - 1027-1038 LID - S0161-6420(20)31109-X [pii] LID - 10.1016/j.ophtha.2020.11.017 [doi] AB - PURPOSE: To report the 2-year efficacy and safety of abicipar every 8 weeks and quarterly (after initial doses) compared with monthly ranibizumab in patients with treatment-naive neovascular age-related macular degeneration (nAMD). DESIGN: Two multicenter, randomized, phase 3 clinical trials with identical protocols (CEDAR and SEQUOIA). Analyses used pooled trial data. PARTICIPANTS: The trials enrolled 1888 patients (1 eye/patient) with active choroidal neovascularization secondary to age-related macular degeneration and best-corrected visual acuity (BCVA) of 24 to 73 Early Treatment Diabetic Retinopathy Study letters. METHODS: At enrollment, patients were assigned to study eye treatment with abicipar 2 mg every 8 weeks after initial doses at baseline and weeks 4 and 8 (abicipar Q8, n = 630), abicipar 2 mg every 12 weeks after initial doses at baseline and weeks 4 and 12 (abicipar Q12, n = 628), or ranibizumab 0.5 mg every 4 weeks (ranibizumab Q4, n = 630). MAIN OUTCOME MEASURES: Efficacy measures included stable vision (<15-letter loss in BCVA from baseline) and change from baseline in BCVA and central retinal thickness (CRT). Safety measures included adverse events (AEs). RESULTS: For patients who completed the study, efficacy of abicipar after initial doses was maintained through week 104. At week 104, the proportion of patients with stable vision was 93.0% (396/426), 89.8% (379/422), and 94.4% (470/498); mean change in BCVA from baseline was +7.8 letters, +6.1 letters, and +8.5 letters, and mean change in CRT from baseline was -147 mum, -146 mum, and -142 mum in the abicipar Q8 (14 injections), abicipar Q12 (10 injections), and ranibizumab Q4 (25 injections) groups, respectively. The overall incidence of intraocular inflammation (IOI) AEs was 15.4%, 15.3%, and 0.3% from baseline through week 52 and 16.2%, 17.6%, and 1.3% from baseline through week 104 in the abicipar Q8, abicipar Q12, and ranibizumab Q4 groups, respectively. CONCLUSIONS: Two-year results show efficacy of abicipar Q8 and Q12 in nAMD. First onset of IOI events with abicipar was much reduced in the second year and comparable with ranibizumab (0.8% and 2.3% vs. 1.0%). The extended duration of effect of abicipar allows for quarterly dosing and reduced treatment burden. CI - Copyright (c) 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. FAU - Khurana, Rahul N AU - Khurana RN AD - Northern California Retina Vitreous Associates, Mountain View, California. Electronic address: rnkhurana@gmail.com. FAU - Kunimoto, Derek AU - Kunimoto D AD - Retinal Consultants of Arizona, Phoenix, Arizona. FAU - Yoon, Young Hee AU - Yoon YH AD - Asan Medical Center, University of Ulsan, Seoul, South Korea. FAU - Wykoff, Charles C AU - Wykoff CC AD - Retina Consultants of Houston, Houston, Texas. FAU - Chang, Andrew AU - Chang A AD - Sydney Retina Clinic, Sydney, Australia; Save Sight Institute, University of Sydney, Sydney, Australia. FAU - Maturi, Raj K AU - Maturi RK AD - Midwest Eye Institute, Indianapolis, Indiana; Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana. FAU - Agostini, Hansjurgen AU - Agostini H AD - Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany. FAU - Souied, Eric AU - Souied E AD - Centre Hospitalier Creteil, Service Universitaire d'Ophthalmologie, Creteil, France. FAU - Chow, David R AU - Chow DR AD - St Michael's Hospital, University of Toronto, Toronto, Canada; Toronto Retina Institute, North York, Canada. FAU - Lotery, Andrew J AU - Lotery AJ AD - University of Southampton, Southampton, United Kingdom. FAU - Ohji, Masahito AU - Ohji M AD - Department of Ophthalmology, Shiga University of Medical Science, Shiga, Japan. FAU - Bandello, Francesco AU - Bandello F AD - University Vita-Salute Scientific Institute, Hospital San Raffaele, Milan, Italy. FAU - Belfort, Rubens Jr AU - Belfort R Jr AD - Vision Institute, Federal University of Sao Paulo, Sao Paulo, Brazil. FAU - Li, Xiao-Yan AU - Li XY AD - Allergan, an AbbVie company, Irvine, California. FAU - Jiao, Jenny AU - Jiao J AD - Allergan, an AbbVie company, Irvine, California. FAU - Le, Grace AU - Le G AD - Allergan, an AbbVie company, Irvine, California. FAU - Kim, Kimmie AU - Kim K AD - Allergan, an AbbVie company, Irvine, California. FAU - Schmidt, Werner AU - Schmidt W AD - Allergan, an AbbVie company, Irvine, California. FAU - Hashad, Yehia AU - Hashad Y AD - Allergan, an AbbVie company, Irvine, California. CN - CEDAR and SEQUOIA Study Groups LA - eng PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20201119 PL - United States TA - Ophthalmology JT - Ophthalmology JID - 7802443 RN - 0 (Recombinant Fusion Proteins) RN - M55Q728KNA (abicipar pegol) SB - IM MH - Aged MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - Female MH - Follow-Up Studies MH - Humans MH - Intravitreal Injections MH - Macula Lutea/*pathology MH - Male MH - Recombinant Fusion Proteins/*administration & dosage MH - Time Factors MH - Tomography, Optical Coherence/methods MH - Treatment Outcome MH - *Visual Acuity MH - Wet Macular Degeneration/diagnosis/*drug therapy OTO - NOTNLM OT - Abicipar OT - Anti-VEGF OT - Choroidal neovascularization OT - DARPin therapeutic OT - Intravitreal injection OT - Neovascular age-related macular degeneration OT - Ranibizumab OT - Treatment burden OT - Visual acuity EDAT- 2020/11/23 06:00 MHDA- 2021/10/13 06:00 CRDT- 2020/11/22 20:33 PHST- 2020/08/27 00:00 [received] PHST- 2020/11/02 00:00 [revised] PHST- 2020/11/13 00:00 [accepted] PHST- 2020/11/23 06:00 [pubmed] PHST- 2021/10/13 06:00 [medline] PHST- 2020/11/22 20:33 [entrez] AID - S0161-6420(20)31109-X [pii] AID - 10.1016/j.ophtha.2020.11.017 [doi] PST - ppublish SO - Ophthalmology. 2021 Jul;128(7):1027-1038. doi: 10.1016/j.ophtha.2020.11.017. Epub 2020 Nov 19.