KESTREL and KITE Phase 3 Studies: 100-Week Results with Brolucizumab in Patients with Diabetic Macular Edema

center dot PURPOSE: To report the 100-week outcomes from the KESTREL and KITE trials. center dot DESIGN: Two phase 3, double -masked, active-controlled, randomized trials. center dot METHODS: Patients with diabetic macular edema (DME) were randomized 1:1:1 to brolucizumab 3 mg/6 mg (BRO3/BRO6) or aflibercept 2 mg (AFL) in KESTREL (N = 566) or 1:1 to BRO6 or AFL in KITE (N = 360). BRO3/BRO6 arms received 5 loading doses every 6 weeks (q6w) followed by q12w dosing, with an option to adjust to q8w at predefined disease activity assessment visits. In KITE, at week 72, based on the disease stability assessment, treatment intervals could be extended by 4 weeks in the BRO6 arm. AFL arms received 5 monthly loading doses followed by fixed q8w dosing. center dot RESULTS: At week 100, change from baseline in BCVA (letters) was + 8.8 for BRO6 and + 10.6 for AFL in KESTREL; and + 10.9 for BRO6 and + 8.4 for AFL in KITE. In both studies, fewer BRO6 subjects had intraretinal fluid and/or subretinal fluid than AFL subjects. Results were achieved with 32.9% (KESTREL) and 47.5% (KITE) of BRO6 subjects maintained on q12w and q12w/q16w dosing, respectively. Intraocular inflammation rates for BRO6 vs AFL were 4.2% vs 1.1% (KESTREL) and 2.2% vs 1.7% (KITE), of which retinal vasculitis rates were 0.5% vs 0% in KESTREL, with no cases in KITE. Retinal vascular occlusion rates were 1.6% vs 0.5% (KESTREL) and 0.6% in both treatment arms in KITE. center dot CONCLUSIONS: Results show the long-term efficacy and durability of brolucizumab in improving visual and anatomical outcomes in DME; the overall safety profile of brolucizumab remained unchanged through year 2. (Am J Ophthalmol 2024;260: 70- 83. (c) 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ ))