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To evaluate whether topical acrizanib (LHA510), a small-molecule vascular endothelial growth factor receptor inhibitor, could suppress the need for anti-vascular endothelial growth factor therapy over a 12-week period in patients with neovascular age-related macular degeneration.A phase 2 multicenter randomized double-masked, vehicle-controlled proof-of-concept study.Trial includes n = 90 patients with active choroidal neovascularization due to neovascular age-related macular degeneration and under anti-vascular endothelial growth factor treatment. All patients received an intravitreal injection of ranibizumab at baseline and were retreated when there was evidence of disease recurrence (rescue). Patients were randomized 1:1 to receive topical LHA510 or vehicle for 12 weeks. Drops were administered twice a day for 8 weeks and then 3 times a day for the last 4 weeks.The primary outcome was the number of patients requiring rescue over 84 days of topical dosing. Key secondary outcome measures were time to first rescue, total number of ranibizumab injections, changes in central subfield thickness, and changes of visual acuity from baseline to day 84.The extended per protocol set included 70 patients of whom 25 of 33 patients in the LHA510 group (75.8%) and 25 of 37 patients in the placebo group (67.6%) required rescue by day 84 (P = .8466). Secondary and subgroup analysis did not support evidence of efficacy. Twenty-one of 46 patients administered LHA510 developed a reversible corneal haze that resolved with cessation of treatment and did not recur in patients restarted at once daily frequency.In spite of extensive optimization for topical efficacy, LHA510 failed to demonstrate clinical efficacy.

Objective Post-hoc analysis to compare the outcomes of brolucizumab 6 mg vs. aflibercept 2 mg in neovascular age-related macular degeneration (nAMD) patients with early persistent retinal fluid in HAWK and HARRIER. Methods After 3 monthly loading doses, brolucizumab-treated eyes (N = 730) received injections every 12 weeks (q12w) or q8w if disease activity was detected. Aflibercept-treated eyes (N = 729) received fixed q8w dosing. Early persistent fluid was defined as the presence of subretinal fluid and/or intraretinal fluid up to Week 12. Results A lower proportion of brolucizumab patients had early persistent retinal fluid compared with aflibercept (11.2% (n = 82) vs. 19.2% (n = 140)). In these patients, 34.1% of the brolucizumab-treated group achieved a ≥ 15 ETDRS letter gain in best corrected visual acuity (BCVA) from baseline at Week 96 compared with 20.7% of the aflibercept-treated group. Brolucizumab achieved numerically better BCVA outcomes (Week 96: brolucizumab, +6.4 letters; aflibercept, +3.7 letters) and significantly greater central subfield thickness reductions versus aflibercept from baseline through Week 96 (Week 96: −202 µm vs. −145 µm; p = 0.0206). Brolucizumab demonstrated an overall favourable benefit/risk profile in this patient cohort. In their unmasked, post-hoc review, the Safety Review Committee identified two cases of retinal vasculitis and no cases of retinal vascular occlusion in the brolucizumab arm; no cases of retinal vasculitis or retinal vascular occlusion were identified in the aflibercept arm. Conclusion In this analysis, anatomical and visual outcomes were better with brolucizumab compared with aflibercept. Brolucizumab may therefore achieve greater disease control than aflibercept in nAMD patients with early persistent retinal fluid.

Purpose Determine associations between early residual fluid (ERF)-free status and improved long-term visual outcomes. Design Clinical cohort study from post hoc analysis of two phase 3 clinical trials’ data. Methods Independent of treatment allocation, patients from the multicenter, prospective, randomized, double-masked HAWK and HARRIER trials who received either brolucizumab 6 mg or aflibercept 2 mg were split into two cohorts dependent on presence or absence of ERF at week 12. Additionally, similar analyses were performed on presence or absence of early residual intraretinal fluid (IRF) and subretinal fluid (SRF) at week 12. The two groups, ERF-free (N=1051) and ERF (N=366) were compared. Changes from baseline in best-corrected visual acuity (BCVA) and central subfield thickness (CST) were determined. Results From week 12 to 96, patients who were ERF-free had greater least square (LS) mean increases from baseline for BCVA and CST compared to ERF patients. Greater LS mean differences in BCVA from week 12 to 96 were noted between ERF-free and ERF patients. A greater proportion of patients in the ERF-free cohort reported a ≥5, ≥10, or ≥15 letter improvement and a higher proportion reported BCVA ≥70 letters from baseline to week 96 compared to those with fluid. Conclusions Improvements in visual outcomes in ERF-free patients were greater than in ERF patients occurring as early as 4 weeks (week 12) following the last loading dose and continued to week 96. Therefore, ERF status may be a useful indicator of anti-vascular endothelial growth factor treatment response.

Background Ensovibep is a multi-specific DARPin (designed ankyrin repeat protein) antiviral in clinical development for treatment of COVID-19. In the Phase 2 EMPATHY study, ensovibep demonstrated greater viral load decline versus placebo. Here we report (1) the efficacy of ensovibep in patients with and without anti-SARS-CoV-2 antibodies at baseline and (2) SARS-CoV-2 mutation emergence data with treatment. Methods Eligible ambulatory patients with ≥2 COVID-19 symptoms (onset within 7 days) and positive SARS-CoV-2 rapid antigen test on day of dosing, were randomized (1:1:1:1) to ensovibep (600, 225 or 75 mg) or placebo as single, IV infusion. Chemiluminescent immunoassays were used for antibody detection (SARS-CoV-2 S1/S2 IgG and SARS-CoV-2 IgM). A pre-specified subgroup analysis was performed based on baseline anti-SARS-CoV-2 antibody status. Analysis of changes in viral genome from baseline to post baseline was performed to evaluate treatment-emergent mutations. Results Of the patients analyzed, 48.5% had anti-SARS-CoV-2 antibodies at baseline. Baseline log10 SARS-CoV-2 viral load (mean ±SD) was similar across groups [ensovibep (all doses) 6.5 ±1.5, placebo 6.2 ±1.5]; > 90% were infected with the Delta (B.1.617.2) variant. SARS-CoV-2 viral load reduction up to Day 8 showed similar effects in favor of ensovibep compared with placebo regardless of the presence of anti-SARS-CoV-2 antibodies (Figure 1). Patients in ensovibep 75 mg, 600 mg, and placebo groups had comparable incidences of emergent mutations, with a higher incidence in the 225 mg group. Based on analysis of 70% of the expected viral sequencing data, two mutations in the key binding residues of ensovibep were observed (Y489H and F486L) in a total of three patients treated with ensovibep. These patients either cleared virus by Day 8 or mutations were transient (occurred at a single time point but not later in the course of infection). Figure 1Forest plot of estimated treatment differences and associated 95% confidence intervals in time-weighted change from baseline in log10 SARS-CoV-2 viral load through Day 8 by subgroups for the presence of anti-SARS-CoV-2 antibodies (SARS-CoV-2 S1/S2 IgG and/or SARS-CoV-2 IgM) at baseline. Conclusion Ensovibep effectively reduces SARS-CoV-2 viral load regardless of the presence of anti-SARS-CoV-2 antibodies at baseline. Furthermore, there were no emerging mutations of concern, indicating that a single dose administration of ensovibep is associated with minimal selective pressure. Disclosures Marc Bonten, MD, PhD, Astra-Zeneca: Advisor/Consultant|Janssen: Advisor/Consultant|Merck: Advisor/Consultant|Novartis: Advisor/Consultant Richa Chandra, MD, Novartis Pharmaceuticals Corporation: Employee Damodaran Solai Elango, MD, Novartis Healthcare Pvt Ltd: Employee Pierre Fustier, PhD, Molecular Partners AG: Employee Kinfemichael Gedif, PhD, Novartis Pharmaceuticals Corporation: Employee Susana Goncalves, MD, Novartis Pharma AG: Employee Awawu Igbinadolor, MD, Novartis: Awawu Igbinadolor reports financial support from different pharmaceutical companies and organizations Jeff Kingsley, DO, MBA, CPI, FACRP, Centricity Research: Other Charles G. Knutson, PhD, Novartis Institutes for BioMedical Research: Employee Petra Kukkaro, PhD, Novartis Pharma AG: Employee Nagalingeswaran Kumarasamy, MD, Novartis: Nagalingeswaran Kumarasamy reports financial support from different pharmaceutical companies and organizations Philippe Legenne, MD, Molecular Partners AG: Employee Martha Mekebeb-Reuter, MD, Novartis: Martha Mekebeb-Reuter reports financial support from different pharmaceutical companies and organizations Krishnan Ramanathan, MD, Novartis Pharma AG: Employee Evgeniya Reshetnyak, PhD, Novartis Pharmaceuticals Corporation: Employee Michael Robinson, PhD, Novartis Institute for Tropical Disease: Employee Jennifer Rosa, MD, Novartis: Jennifer Rosa reports financial support from different pharmaceutical companies and organizations Marianne Soergel, MD, Molecular Partners AG: Employee Vaia Stavropoulou, PhD, Molecular Partners AG: Employee Nina Stojcheva, PhD, Molecular Partners AG: Employee Michael T. Stumpp, PhD, Molecular Partners AG: Employee Andreas Tietz, MD, Novartis Pharma AG: Employee Xiaojun Zhao, PhD, Novartis Institutes for BioMedical Research: Employee Zhaojie Zhang, PhD, 8. Novartis Institutes for BioMedical Research: Employee.

Various statistical models have been proposed to analyze fMRI data. The usual goal is to make inferences about the eects that are related to an external stimulus. The primary focus of this paper is on those statisti- cal methods that enable one to detect 'signicantly activated' regions of the brain due to event-related stimuli. Most of these methods share a common property, requiring estimation of the hemodynamic response function (HRF) as part of the deterministic component of the statistical model. We propose and investigate a new approach that does not require HRF ts to detect 'activated' voxels. We argue that the method not only avoids tting a specic HRF, but still takes into account that the unknown response is delayed and smeared in time. This method also adapts to dierential re- sponses of the BOLD response across dierent brain regions and experimen- tal sessions. The maximum cross-correlation between the kernel-smoothed stimulus sequence and shifted (lagged) values of the observed response is the proposed test statistic. Using our recommended approach we show through realistic simulations and with real data that we obtain better sensitivity than simple correlation methods using default values of SPM2. The simulation experiment incor- porates dierent HRFs empirically determined from real data. The noise models are also dierent AR(3) ts and fractional Gaussians estimated from real data. We conclude that our proposed method is more powerful than simple correlation procedures, because of its robustness to variation in the HRF.

Purpose To report the 96-week outcomes from HAWK and HARRIER. Design Phase 3, prospective, randomized, double-masked, multicenter studies comparing efficacy and safety of brolucizumab 3 mg (HAWK only) and 6 mg with aflibercept 2 mg in eyes with neovascular age-related macular degeneration (nAMD). Participants Treatment-naive eyes with nAMD were randomized 1:1:1 to brolucizumab 3 mg (n = 358), brolucizumab 6 mg (n = 360), aflibercept 2 mg (n = 360; HAWK) or 1:1 to brolucizumab 6 mg (n = 370), aflibercept 2 mg (n = 369; HARRIER). Methods After 3 monthly loading doses, brolucizumab patients received every (q)-12-week (w) dosing, possibly adjusting to q8w dosing if disease activity was present at predefined disease activity assessment (DAA) visits. Aflibercept was dosed in a fixed q8w regimen. Visual and anatomic parameters were assessed throughout. Primary end point was at week 48 (48w), confirmed at 96w. Main Outcome Measures Mean best-corrected visual acuity (BCVA) change from baseline, proportion of patients on an q12w regimen, retinal thickness, retinal fluid changes, and safety, all to 96w. Results Mean change (least squares [LS] mean ± standard error) in BCVA from baseline to 96w in HAWK was 5.6±0.79 Early Treatment Diabetic Retinopathy Study (ETDRS) letters for brolucizumab 3 mg, 5.90±0.78 letters for brolucizumab 6 mg, and 5.3±0.78 letters for aflibercept and in HARRIER was 6.1±0.73 letters for brolucizumab 6 mg and 6.6 ± 0.73 letters for aflibercept. Greater central subfield thickness reductions were observed with brolucizumab 6 mg versus aflibercept in HAWK (LS mean, −174.8 μm vs. −148.7 μm; 95% confidence interval for treatment difference, –46.2 to –5.9 μm; P = 0.0115) and HARRIER (LS mean, –197.7 μm vs. –155.1 μm; 95% confidence interval for treatment difference, –62.0 to –23.3 μm; P Conclusions Visual outcomes from 48w to 96w confirm the efficacy achieved at 48w. Brolucizumab demonstrated greater fluid resolution compared with aflibercept. The q12w potential for brolucizumab observed at 48w was maintained to 96w.

Introduction: This post hoc analysis applies a fixed dosing stratification approach to patient-level brolucizumab data from the phase III HAWK and HARRIER trials to determine the proportion of patients who would have been assigned to fixed dosing regimens with treatment intervals of 8, 12, or 16 weeks (q8w, q12w, or q16w) based on the presence/absence of disease activity (DA) following the loading phase. The analysis also simulates central subfield thickness (CSFT) data to estimate the anatomical outcomes if the patients had been thus assigned. Of note, the limitations of this analysis include the post hoc nature of the work and the inability to directly compare HAWK and HARRIER with TENAYA and LUCERNE due to the differences in design. Design: This study was a post hoc modelling analysis of patient-level data. Methods: Using patient-level data from HAWK and HARRIER, patients (n = 730) were allocated to a fixed q16w, q12w, or q8w regimen based on assessment of DA at weeks 16 and 20. Two definitions of DA were used: DA 1, based on a phase II study of faricimab, and DA 2, a definition derived from common clinical consideration including visual acuity and anatomical changes. CSFT simulations were performed using a pharmacokinetic/pharmacodynamic model describing CSFT response to anti-VEGF treatment. Outcome measures were modelled patient allocation to fixed regimens and mean CSFT reduction. Results: Using DA definitions 1 and 2, respectively, 78% and 76% of patients in the brolucizumab arm were allocated to a greater than or equal to q12w regimen, and 56% and 52% were allocated to a q16w regimen. Mean reduction in CSFT was similar between the two study drugs with both DA definition assumptions. Conclusions: This analysis demonstrates the potential durability of action and effectiveness of brolucizumab.

Post-hoc analysis to compare the outcomes of brolucizumab 6 mg vs. aflibercept 2 mg in neovascular age-related macular degeneration (nAMD) patients with early persistent retinal fluid in HAWK and HARRIER.After 3 monthly loading doses, brolucizumab-treated eyes (N = 730) received injections every 12 weeks (q12w) or q8w if disease activity was detected. Aflibercept-treated eyes (N = 729) received fixed q8w dosing. Early persistent fluid was defined as the presence of subretinal fluid and/or intraretinal fluid up to Week 12.A lower proportion of brolucizumab patients had early persistent retinal fluid compared with aflibercept (11.2% (n = 82) vs. 19.2% (n = 140)). In these patients, 34.1% of the brolucizumab-treated group achieved a ≥ 15 ETDRS letter gain in best corrected visual acuity (BCVA) from baseline at Week 96 compared with 20.7% of the aflibercept-treated group. Brolucizumab achieved numerically better BCVA outcomes (Week 96: brolucizumab, +6.4 letters; aflibercept, +3.7 letters) and significantly greater central subfield thickness reductions versus aflibercept from baseline through Week 96 (Week 96: -202 µm vs. -145 µm; p = 0.0206). Brolucizumab demonstrated an overall favourable benefit/risk profile in this patient cohort. In their unmasked, post-hoc review, the Safety Review Committee identified two cases of retinal vasculitis and no cases of retinal vascular occlusion in the brolucizumab arm; no cases of retinal vasculitis or retinal vascular occlusion were identified in the aflibercept arm.In this analysis, anatomical and visual outcomes were better with brolucizumab compared with aflibercept. Brolucizumab may therefore achieve greater disease control than aflibercept in nAMD patients with early persistent retinal fluid.

To compare the outcomes of brolucizumab versus aflibercept in patients with neovascular age-related macular degeneration with early residual fluid in the HAWK and HARRIER studies.Post hoc analysis using pooled data from the phase 3 studies HAWK (NCT02307682) and HARRIER (NCT02434328).The early residual fluid cohort for this post hoc analysis consisted of patients treated with either brolucizumab 6 mg (n = 730 patients) or aflibercept 2 mg (n = 729 patients) and who had the presence of intraretinal fluid (IRF), subretinal fluid (SRF), or both verified by spectral-domain OCT at the week 12 clinic visit.After 3 initial monthly doses, patients treated with brolucizumab received injections every 12 weeks (q12w) or every 8 weeks (q8w), depending on the neovascular age-related macular degeneration disease activity, whereas patients treated with aflibercept received fixed q8w dosing.The mean change in best-corrected visual acuity and central subfield thickness (CST) from the baseline to that at weeks 48 and 96, the proportion of patients treated with brolucizumab remaining on q12w dosing to week 96, and the change in fluid status at weeks 48 and 96.All analyses were based on 149 of 730 (20.4%) patients treated with brolucizumab and 217 of 729 (29.8%) patients treated with aflibercept with spectral-domain OCT-verified IRF, SRF, or both at their week 12 visit. The best-corrected visual acuity improvements from baseline at weeks 48 and 96 were numerically better for brolucizumab than for aflibercept (least square mean [standard error] 7.9 ± 1.1 vs. 4.6 ± 0.9 and 7.4 ± 1.3 vs. 2.9 ± 1.1 letters, respectively). The CST reductions from baseline at weeks 48 and 96 were consistently greater with brolucizumab than with aflibercept (least square mean [standard error], μm: -194.9 ± 13.7 vs. -123.9 ± 11.3; and -201.1 ± 14.5 vs. -134.2 ± 12.0, respectively). At weeks 48 and 96, patients treated with brolucizumab had a 40.4% and 31.3% probability of remaining on q12w dosing intervals, respectively. Fewer patients treated with brolucizumab had remaining IRF, SRF, or both at weeks 48 and 96 than patients treated with aflibercept (59.1% vs. 75.1% and 49.0% vs. 60.4%, respectively).In patients with early residual fluid, defined as spectral-domain OCT-verified IRF, SRF, or both at the week 12 clinic visit, brolucizumab resolved the early residual fluid and reduced CST more effectively than aflibercept, resulting in greater best-corrected visual acuity improvements through week 96 of anti-VEGF treatment.

Introduction: Neovascular age-related macular degeneration (nAMD) is characterized by exudation of fluid from abnormally growing blood vessels in the macula. Anti-vascular endothelial growth factor (VEGF) therapy is standard treatment for nAMD. Fluid resolution is used both as an indicator of disease control and to guide the frequency of treatment because of anti-VEGF therapy effectiveness in reducing neovascularization-related exudation. Herein reports a post hoc assessment of the HAWK and HARRIER trials comparing the efficacy and safety of brolucizumab with aflibercept in patients with nAMD. Materials and Methods: HAWK randomized 1,078 patients with untreated, active choroidal neovascularization due to AMD in the study eye to receive brolucizumab 3, 6 mg or aflibercept 2 mg. In HARRIER, 739 patients received brolucizumab 6 mg or aflibercept 2 mg. Brolucizumab was injected at weeks 0, 4, and 8, and thereafter q12w unless disease activity was identified (injection interval: q8w). Aflibercept was injected q8w after the loading phase, aligned with approved dosing at study initiation. The objective of this analysis was to assess effects of brolucizumab versus aflibercept on retinal fluid resolution during two phase 3 trials (HAWK and HARRIER) in patients with nAMD. Anatomical assessments for intraretinal fluid (IRF) and subretinal fluid (SRF) were performed every 4 weeks by spectral domain optical coherence tomography. Sustained dryness was defined as a patient being fluid-free (SRF and IRF) on ≥3 consecutive visits. Time to sustained dryness was determined by Kaplan-Meier estimates. Results: At week 96, fluid resolution (absence of IRF and SRF) was achieved by more brolucizumab- (6 mg; 76.1%) versus aflibercept-treated patients (63.1%; p = 0.0002, HAWK); 75.4% versus 61.8% (p < 0.0001, HARRIER). More patients achieved sustained dryness with brolucizumab versus aflibercept: at 96 weeks, 87.9% (brolucizumab 3 mg) and 86.1% (brolucizumab 6 mg) versus 82.0% (aflibercept) in HAWK, and 91.2% (brolucizumab) versus 78.0% (aflibercept) in HARRIER. Sustained dryness was achieved faster and hence with fewer brolucizumab injections. Discussion/Conclusion: Brolucizumab dried the macula in patients with nAMD faster and to a greater degree than aflibercept. Achieving sustained dryness faster, and therefore with fewer injections, provides an opportunity for earlier decisions relating to treatment interval extension potentially reducing treatment burden.

PurposeTo compare the efficacy and safety of brolucizumab versus aflibercept in eyes with polypoidal choroidal vasculopathy (PCV) over 96 weeks in the HAWK study.DesignHAWK was a global, 2-year, randomised, double-masked, multicentre phase III trial in participants with neovascular age-related macular degeneration.MethodsOf the Japanese participants with PCV, 39 received brolucizumab 6 mg and 30 received aflibercept 2 mg. After 3 monthly loading doses, brolucizumab-treated eyes received an injection every 12 weeks (q12w) but were adjusted to q8w if disease activity was detected. Aflibercept-treated eyes received fixed q8w dosing. Mean change in best-corrected visual acuity (BCVA), the proportion of participants on q12w, retinal thickness, retinal fluid changes and safety were assessed to Week 96.ResultsMean change in BCVA (early treatment diabetic retinopathy study (ETDRS) letters) from baseline to week 48/week 96 was+10.4/+11.4 for brolucizumab and +11.6/+11.1 for aflibercept. For brolucizumab-treated eyes, the probability of only q12w dosing after loading through week 48 was 76%, and 68% through week 96. Fluid resolution was greater with brolucizumab than aflibercept: respective proportions of eyes with intraretinal fluid and/or subretinal fluid were 7.7% and 30% at week 48% and 12.8% and 16.7% at week 96. Brolucizumab exhibited an overall well-tolerated safety profile despite a higher rate of intraocular inflammation compared with aflibercept.ConclusionIn Japanese eyes with PCV, brolucizumab q12w/q8w monotherapy resulted in robust and consistent BCVA gains that were comparable to q8w aflibercept dosing. Anatomical outcomes favoured brolucizumab over aflibercept, with 76% of brolucizumab participants maintained on q12w dosing after loading to week 48.

To report the 96-week outcomes from HAWK and HARRIER.Phase 3, prospective, randomized, double-masked, multicenter studies comparing efficacy and safety of brolucizumab 3 mg (HAWK only) and 6 mg with aflibercept 2 mg in eyes with neovascular age-related macular degeneration (nAMD).Treatment-naïve eyes with nAMD were randomized 1:1:1 to brolucizumab 3 mg (n = 358), brolucizumab 6 mg (n = 360), aflibercept 2 mg (n = 360; HAWK) or 1:1 to brolucizumab 6 mg (n = 370), aflibercept 2 mg (n = 369; HARRIER).After 3 monthly loading doses, brolucizumab patients received every (q)-12-week (w) dosing, possibly adjusting to q8w dosing if disease activity was present at predefined disease activity assessment (DAA) visits. Aflibercept was dosed in a fixed q8w regimen. Visual and anatomic parameters were assessed throughout. Primary end point was at week 48 (48w), confirmed at 96w.Mean best-corrected visual acuity (BCVA) change from baseline, proportion of patients on an q12w regimen, retinal thickness, retinal fluid changes, and safety, all to 96w.Mean change (least squares [LS] mean ± standard error) in BCVA from baseline to 96w in HAWK was 5.6±0.79 Early Treatment Diabetic Retinopathy Study (ETDRS) letters for brolucizumab 3 mg, 5.90±0.78 letters for brolucizumab 6 mg, and 5.3±0.78 letters for aflibercept and in HARRIER was 6.1±0.73 letters for brolucizumab 6 mg and 6.6 ± 0.73 letters for aflibercept. Greater central subfield thickness reductions were observed with brolucizumab 6 mg versus aflibercept in HAWK (LS mean, -174.8 μm vs. -148.7 μm; 95% confidence interval for treatment difference, -46.2 to -5.9 μm; P = 0.0115) and HARRIER (LS mean, -197.7 μm vs. -155.1 μm; 95% confidence interval for treatment difference, -62.0 to -23.3 μm; P0.0001). The proportions of eyes with intraretinal fluid and/or subretinal fluid (IRF/SRF) at 96w in HAWK were 31% (P = 0.0688) and 24% (P = 0.0002) for brolucizumab 3 mg and 6 mg and 37% for aflibercept, whereas in HARRIER, they were 24% for brolucizumab 6 mg (P0.0001) and 39% for aflibercept. At 92w (last DAA), a 45.4% and 38.6% probability was observed for brolucizumab 6 mg patients of maintaining an q12w treatment regimen in HAWK and HARRIER, respectively. Brolucizumab exhibited an overall well-tolerated safety profile.Visual outcomes from 48w to 96w confirm the efficacy achieved at 48w. Brolucizumab demonstrated greater fluid resolution compared with aflibercept. The q12w potential for brolucizumab observed at 48w was maintained to 96w.