Author: Richard Gale (United Kingdom)
Co-authors: Rishi Singh, Chirag Jhaveri, Charles C. Wykoff, Giovanni Staurenghi, Tomohiro Iida, Adrian Koh
Purpose
Retinal fluid is a key biomarker of anti-vascular endothelial growth factor (VEGF) efficacy in neovascular age-related macular degeneration (nAMD). Despite an initial loading dose of three (monthly) anti-VEGF injections, early residual fluid (ERF) is evident in some patients at Week 12 (four weeks post final loading injection). We compare the efficacy of brolucizumab versus aflibercept to Week 96 in nAMD patients who had ERF at Week 12.
Setting/Venue
HAWK and HARRIER were two 96-week, 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 nAMD.
Methods
HAWK and HARRIER were two Phase III, prospective, randomized, double-masked, multicenter studies comparing the efficacy and safety of brolucizumab with aflibercept in treatment-naïve eyes with nAMD. In HAWK, patients were randomized 1:1:1 to brolucizumab 3 mg (n=358), brolucizumab 6 mg (n=360) or aflibercept 2 mg (n=360). In HARRIER, patients were randomized 1:1 to brolucizumab 6 mg (n=370) or aflibercept 2 mg (n=369). After three loading doses, brolucizumab patients received 12-weekly (q12w) dosing with an option to adjust to 8-weekly dosing (q8w) if disease activity (as identified by a masked investigator) was present; aflibercept was dosed q8w as per the label. This HAWK and HARRIER pooled analysis includes patients who were defined as having ERF (presence of intraretinal [IRF] and/or sub-retinal fluid [SRF] at Week 12) from the brolucizumab 6 mg (treated every 12 or 8 weeks; n=149) and aflibercept 2 mg (treated every 8 weeks; n=217) arms.
Results
The proportion of patients with ERF at Week 12 was lower in the brolucizumab 6 mg group (149/730; 20.4%) than with aflibercept 2 mg (217/729; 29.8%). In those patients with ERF, mean (SE) best corrected visual acuity (BCVA) change (letters) from baseline in the brolucizumab 6 mg group was 5.7 (0.9), 7.1 (1.1), 6.2 (1.2) and 6.5 (1.2) at Weeks 24, 48, 72 and 96, respectively, while in the aflibercept 2 mg group it was 4.8 (0.8), 5.2 (0.9), 4.0 (1.0) and 3.6 (1.0). Mean (SE) central subfield thickness (CST) change (µm) from baseline at Weeks 24, 48, 72 and 96 in the ERF brolucizumab 6 mg group was -162.2 (10.1) µm, -181.5 (10.2) µm, -184.5 (10.7) µm and -186.6 (10.8) µm, respectively, while in the ERF aflibercept 2 mg group it was -120.3 (8.3) µm, -133.1 (8.4) µm, -137.4 (8.9) µm and -144.1 (8.9) µm, respectively. The percentage of ERF brolucizumab 6 mg patients with IRF and/or SRF at Weeks 24, 48, 72 and 96 was 61%, 59%, 50% and 50%, respectively, while in the ERF aflibercept 2 mg group it was 76%, 76%, 62% and 58%.
Conlusions
In nAMD patients with ERF at Week 12, long-term vision gains and fluid resolution was higher in the brolucizumab-treated patients versus aflibercept.
Financial Disclosure
RG: Consultant and Financial Support: Novartis, Bayer, Roche, Alimera, Allergan
Comments
Co-authors: 7. Catherine Best - Novartis Pharma AG, Basel, Switzerland 8. Kinfemichael Gedif - Novartis Pharma AG, Basel, Switzerland 9. Guru Prasad - Novartis Pharmaceuticals, NJ, USA 10. Micael Singer - Medical Center Ophthalmology Associates, TX, USA
