Author’s Disclosure Block: David Wong: Alcon, Employment/honoraria/consulting fees, Abbviw, Employment/honoraria/consulting fees, Apellis, Employment/honoraria/consulting fees, Astellas, Employment/honoraria/consulting fees, Bayer, Grant/research support, Roche, Employment/honoraria/consulting fees, Zeiss, Employment/honoraria/consulting fees, Regeneron, Employment/honoraria/consulting fees, Biogen, Employment/honoraria/consulting fees, Ripple Therepeutics, Employment/honoraria/consulting fees; Praveen Patel: : Honoraria/attendance at advisory boards for Bayer, Boehringer Ingelheim and Roche, and speaker fees from Bayer and Roche. Educational travel grants from Roche and Bayer.; Paolo Lanzetta: Consultant for Aerie Pharmaceuticals, Allergan, Apellis, Bausch + Lomb, Bayer, Biogen, Boehringer Ingelheim, I-Care, Genentech, Novartis, Ocular Therapeutix, Outlook Therapeutics, and Roche.; Jean-François Korobelnik: : Consultant for AbbVie, Apellis, Bayer, Janssen, Nano Retina, Roche, Théa Pharmaceuticals, and Carl Zeiss Meditec AG; and member of a data safety monitoring board or advisory board for Alexion, Novo Nordisk, and Oxular. ; Sobha Sivaprasad: Receives funding/fees from Allergan, Apellis, Bayer, Biogen, Boehringer Ingelheim, EyeBiotech, Novartis, Optos, and Roche.; Sergio Leal: Employee of Bayer Consumer Care AG; Tobias Machewitz: Employees of Bayer AG; Xin Zhang: Employees of Bayer Consumer Care AG

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Purpose: To evaluate fluid control with aflibercept 8mg and 2mg at W16, W48 and, W96 in neovascular age-related macular degeneration (nAMD) patients stratified by clinically relevant baseline characteristics (central retinal thickness [CRT] and best-corrected visual acuity [BCVA]). Study Design: A double-masked, 96-week, non-inferiority Phase 3 trial Methods: The PULSAR study, a phase 3 clinical trial in patients with nAMD, patients were randomized 1:1:1 to aflibercept 8mg every 12 (8q12) or 16 (8q16) weeks or aflibercept 2mg every 8 weeks after 3 initial monthly injections. The dosing regimens for patients in the 8q12 and 8q16 groups could be shortened from W16 to 96 (to a minimum 8-week interval) and extended from W52 to 96 (to a maximum 24-week interval), based on protocol criteria. The proportions of participants who had fluid resolution at W16, W48, and W96 were evaluated according to baseline CRT (<400μm, ≥400μm) and BCVA letter score (≤54, 55–73, and ≥74 letters), using a last observation carried forward approach. Subgroups were determined post hoc, and analyses were exploratory. Results: At W96 in the full analysis set, 66.6% (444/667) and 66.5% (222/334) of patients receiving aflibercept 8mg and aflibercept 2mg were fluid-free in the central subfield. In patients with baseline CRT<400μm, 67.7% (306/452), 70.3% (317/451), and 66.2% (299/452) receiving aflibercept 8mg and 54.3% (125/230), 61.3% (141/230), and 64.8% (149/230) receiving 2mg were fluid-free at W16, W48, and W96, respectively. In patients with baseline CRT≥400μm, 54.0% (116/215), 65.6% (141/215), and
67.4% (145/215) receiving aflibercept 8mg, and 45.2% (47/104), 54.8% (57/104), and 69.9% (72/103) receiving 2mg were fluid-free at W16, W48, and W96, respectively. In patients with baseline BCVA ≤54 letters, 60.5% (118/195), 65.1% (127/195), and 68.9% (135/196) receiving aflibercept 8mg, and 54.3% (57/105), 58.1% (61/105), and 69.2% (72/104) receiving 2mg were fluid-free at W16, W48, and W96, respectively. In patients with baseline BCVA 55–73 letters, 65.8% (252/383), 69.7% (267/383), and 65.3% (250/383) receiving aflibercept 8mg, and 48.6% (88/181), 60.2% (109/181), and 65.2% (118/181) receiving 2mg were fluid-free at W16, W48, and W96, respectively. In patients with baseline BCVA ≥74 letters, 58.4% (52/89), 72.7% (64/88), and 67.0% (59/88) receiving aflibercept 8mg, and 57.1% (28/49), 59.2% (29/49), and 65.3% (32/49) receiving 2mg were fluid-free at W16, W48, and W96, respectively. Conclusions: Similar fluid control was achieved at W16 and sustained through W96 with aflibercept 8mg with extended dosing intervals compared to aflibercept 2mg every 8 weeks. Results in patients stratified by baseline BCVA and CRT are consistent with these findings. The observed data suggest rapid and sustained fluid control is achievable with aflibercept 8mg in patients with treatment-naïve nAMD with extended dosing intervals.