Author’s Disclosure Block: Wai-Ching Lam: Roche, Grant/research support, Apellis, Membership on an advisory panel, standing committee or board of directors, Bayer, Employment/honoraria/consulting fees, Novartis, Membership on an advisory panel, standing committee or board of directors, Amgen, Membership on an advisory panel, standing committee or board of directors; Timothy Lai: Research grants from Bayer, Chengdu Kanghong, Novartis, and Roche; consulting fees from Bayer, Boehringer Ingelheim, Iveric Bio, Novartis, Oculis, and Roche; and lecture fees from Bayer, Chengdu Kanghong, Novartis, and Roche; Xiaodong Sun: Consulting fees from Alcon, Allergan, Bayer, Innovent Biologics Inc, Chengdu Kanghong Biotech Inc, Novartis, Roche, and Carl Zeiss Meditec Inc; Shih-Jen Chen: Consultant fee from Bayer and Roche; and lecture fees from Alcon, Novartis, and Bausch & Lomb; Xin Zhang: Employees of Bayer Consumer Care AG; Andrea Schulze: Employees of Bayer AG.; Tobias Machewitz: Employees of Bayer AG.; Min Zhao: Employee of Bayer Healthcare; Sergio Leal: Employees of Bayer Consumer Care AG

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Purpose: In the PULSAR double-masked, 96-week, Phase 3 trial in patients with neovascular age-related macular degeneration (nAMD), aflibercept 8 mg every 12 weeks (8q12) and every 16 weeks (8q16) demonstrated non-inferior (NI) gains versus aflibercept 2 mg every 8 weeks (2q8) in best-corrected visual acuity (BCVA; NI margin of 4 letters) from baseline at Week 48 (primary endpoint). Evaluation of the primary endpoint in a subpopulation of Asian patients was pre-specified at Week 48 and evaluated through Week 96 in a post hoc analysis. Study Design: PULSAR was a double-masked, 96-week, Phase 3 trial investigating the safety and efficacy of aflibercept 8 mg compared to aflibercept 2 mg in patients with treatment-naïve nAMD. Methods: Patients were randomly assigned 1:1:1 to receive aflibercept 8q12, 8q16, or 2q8, each after three initial monthly injections. Dosing intervals for patients in the aflibercept 8q12 and 8q16 groups could be shortened from Week 16 and extended from Week 52 based on protocol criteria. Outcomes for Asian patients were assessed at Weeks 48, 60, and 96 using a last observation carried forward approach. Outcome measures included change in BCVA and central subfield retinal thickness (CRT) from baseline, last assigned dosing intervals, number of injections and safety. Results: Of 1009 patients treated, 234 patients were Asian (8q12: n=74; 8q16: n=77; 2q8: n=83; baseline BCVA±SD: 57.7±13.9, 58.1±12.2, and 59.2±14.1 letters, respectively). At Week 48, 8q12 and 8q16 groups demonstrated comparable BCVA gains to 2q8, with mean (95%CI) BCVA gains from baseline of 9.3 (5.7, 12.9), 8.8 (6.8, 10.8), and 7.5 (4.7, 10.3) letters, in the 8q12, 8q16 and 2q8 groups, respectively. At Week 60, mean (95%CI) BCVA gains from baseline for the 8q12, 8q16 and 2q8 groups were 9.4 (5.8, 13.1), 8.7 (6.7, 10.7), and 8.2 (5.4, 11.0) letters, respectively, and at Week 96 were 8.9 (5.1, 12.8), 7.2 (4.8, 9.6) and 7.5 (4.8, 10.3) letters, respectively. Mean change (95% CI) in CRT from baseline to Week 96 for 8q12, 8q16 and 2q8 was –147 (–179, –115) μm, –140 (–169, –112) μm, and –144
(–176, –111) μm, respectively. At Week 96, 90% (8q12) and 84% (8q16) of Asian patients were assigned dosing intervals ≥12 and ≥16 weeks, respectively; 55% of patients receiving aflibercept 8 mg had treatment intervals extended to ≥20 weeks and 33% to 24 weeks. Aflibercept 8 mg and 2 mg had similar safety profiles in the Asian subpopulation. Conclusions: In Asian patients with nAMD, aflibercept 8 mg demonstrated comparable BCVA gains and decrease in CRT from baseline at Week 48 versus aflibercept 2 mg. The outcomes with aflibercept 8 mg were achieved and maintained with fewer injections and no new safety signals through Week 96, consistent with the overall PULSAR population.