HAWK and HARRIER: 96-Week outcomes from the phase 3 trials of brolucizumab for neovascular age-related macular degeneration.

PURPOSE To report the 96-week outcomes from HAWK and HARRIER DESIGN: Phase III, prospective, randomized, double-masked, multicenter studies comparing the efficacy and safety of brolucizumab 3mg (HAWK only) and 6mg with aflibercept 2mg in eyes with neovascular AMD (nAMD) PARTICIPANTS: Treatment naive eyes with nAMD were randomized 1:1:1 to brolucizumab 3mg (n=358), brolucizumab 6mg (n=360) or aflibercept 2mg (n=360) [HAWK], or 1:1 to brolucizumab 6mg (n=370) or aflibercept 2mg (n=369) [HARRIER]. METHODS After three monthly loading doses, brolucizumab patients received every 12 week (q12w) dosing with the possibility of adjusting to every 8 week (q8w) dosing if disease activity was present at predefined disease activity assessment (DAA) visits. Aflibercept was dosed in a fixed q8w regimen. Visual and anatomical parameters were assessed throughout. The primary endpoint was at Week 48 (W48), with treatment and follow-up until W96. MAIN OUTCOME MEASURES Mean best corrected visual acuity (BCVA) change from baseline, proportion of patients on q12w, retinal thickness, retinal fluid changes, and safety; all to W96 RESULTS: Mean change (LS mean ±SE) in BCVA (ETDRS letters) from baseline to W96 in HAWK was 5.6 (0.79) for brolucizumab 3mg, 5.9 (0.78) for brolucizumab 6mg and 5.3 (0.78) for aflibercept and in HARRIER was 6.1 (0.73) for brolucizumab 6mg and 6.6 (0.73) for aflibercept. Greater central subfield thickness (CST) reductions were observed with brolucizumab 6mg vs aflibercept in HAWK (LS mean; -174.8 vs -148.7 μm; 95% CI for treatment difference -46.2, -5.9; p=0.0115) and HARRIER (LS mean; -197.7 vs -155.1 μm; 95% CI for treatment difference, -62.0, -23.3; p<0.0001). The proportion of eyes with intraretinal fluid and/or subretinal fluid (IRF/SRF) at W96 in HAWK were 31% (p=0.0688) and 24% (p=0.0002) for brolucizumab 3mg and 6mg, and 37% for aflibercept, while in HARRIER it was 24% for brolucizumab 6mg (p<0.0001) and 39% for aflibercept. At W92 (the last DAA), there was a 45.4% and 38.6% probability for brolucizumab 6mg patients of maintaining on q12w in HAWK and HARRIER, respectively. Brolucizumab exhibited an overall well-tolerated safety profile. CONCLUSIONS Visual outcomes from W48 to W96 confirm the efficacy achieved at W48. Brolucizumab continued to demonstrate greater fluid resolution compared to aflibercept. The q12w potential for brolucizumab observed up to W48 was maintained up to W96.