Author: Arshad Khanani (United States)
Co-authors: Srinivas R. Sadda, David Sarraf, Ramin Tadayoni, David T. Wong, Anne-Sophie Kempf, Insaf Saffar
Purpose
The presence of pigment epithelial detachments (PEDs) and sub-retinal pigment epithelium (sub-RPE) fluid may be indicators of disease activity (DA) in neovascular age-related macular degeneration (nAMD). This post hoc analysis compares the efficacy of brolucizumab and aflibercept treatment in reducing the maximum thickness of PED and sub-RPE fluid in the macula in patients with nAMD in the HAWK & HARRIER studies.
Setting/Venue
HAWK (NCT02307682) and HARRIER (NCT02434328) were two 96-week, prospective, randomized, double-masked, active controlled, multicenter studies that enrolled 1,775 patients across 11 countries in HAWK and 1,048 patients across 29 countries in HARRIER.
Methods
Patients were randomized 1:1:1 to brolucizumab 3 mg, 6 mg or aflibercept 2 mg in HAWK or 1:1 to brolucizumab 6 mg or aflibercept 2 mg in HARRIER. After three monthly loading doses, brolucizumab patients received q12w dosing with an option to adjust to q8w at predefined DA assessment visits; aflibercept was dosed in a fixed q8w regimen. Here, we present a retrospective analysis of optical coherence tomography images from patients in the pooled HAWK & HARRIER studies treated with brolucizumab 6 mg (n=700) or aflibercept 2 mg (n=696). Images were assessed for the maximum thickness or height of PED (measured from the RPE inner border to the Bruch’s membrane) and sub-RPE fluid (between the RPE and Bruch’s membrane) across the macula at baseline through Week 96. In addition, PED and sub-RPE thickness from baseline to Week 96 were compared in the subgroup of patients in both treatment arms who had DA at Week 16, which was the first DA assessment visit after loading. As brolucizumab patients with DA were adjusted to q8w dosing until the end of the study, these two subgroups were matched in terms of number of injections and treatment interval.
Results
In this pooled analysis, least square mean (LSM) (±SE) PED thickness in the brolucizumab group was 202.8, 139.0 (3.7), 122.9 (3.7) and 116.0 (3.7) µm at baseline, Weeks 16, 48, and 96, respectively, whereas in the aflibercept group it was 202.8, 152.5 (3.7), 142.3 (3.8) and 134.0 (3.8) µm. For sub-RPE fluid, LSM thickness in the brolucizumab group was 64.3, 14.0 (2.2), 10.0 (2.1) and 10.8 (2.0) µm at baseline, Weeks 16, 48, and 96, respectively, whereas in the aflibercept group it was 64.3, 22.4 (2.2), 19.5 (2.1) and 15.5 (2.1) µm. The observed better reductions in the pooled analysis were also seen in the individual studies. In patients with DA at Week 16, LSM PED thickness in the brolucizumab arm (n=152) was 234.4, 200.0 (9.3), 173.1 (9.5) and 156.8 (10.0) µm at baseline, Weeks 16, 48 and 96 respectively; in the aflibercept-treated subgroup (n=215), it was 234.4, 208.7 (7.8), 198.3 (8.1) and 180.9 (8.5) µm. LSM sub-RPE thickness in the brolucizumab arm was 76.7, 20.0 (6.1), 8.9 (5.9) and 7.3 (5.0) µm at baseline, Weeks 16, 48 and 96 respectively whereas in the aflibercept-treated subgroup, it was 76.7, 40.2 (5.1), 31.3 (5.0) and 21.0 (4.3) µm.
Conlusions
The results of this analysis show that brolucizumab achieved greater reductions in PED and sub-RPE fluid thickness in the macula than aflibercept over the 96-week study period in both the overall pooled treatment arms and in the matched subgroups with DA at Week 16 in HAWK & HARRIER.
Financial Disclosure
Consultant for Adverum, Aerpio, Alcon, Allergan, Dutch Ophthalmic Research Center, Genentech, Inc., Kato Pharmaceuticals, Kodiak Sciences Inc., Novartis, Gemini Therapeutics, Graybug, Gyroscope, Opthea, Oxurion, PolyPhotonix, Recens Medical, Regenxbio; Research support from Adverum, Alkahest, Allergan, Allegro, Gemini Therapeutics, Genentech, Inc., Gyroscope, Iveric Bio, NGM pharmaceuticals, Kodiak Sciences Inc., Novartis, Opthea, Ophthotech, Oxurion, Regenxbio; Recens Medical; and lecture fees from Allergan, Genentech and Novartis.
Comments
Additional Co-authors: 7. Kinfemichael Gedif - Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA 8. Andrew Chang - Sydney Retina Clinic, Sydney Eye Hospital, Sydney University, NSW, Australia
