KESTREL and KITE: 52-Week Results From Two Phase III Pivotal Trials of Brolucizumab for Diabetic Macular Edema.

Abstract

PURPOSE:

To compare the efficacy and safety of brolucizumab with aflibercept in patients with diabetic macular edema (DME).

DESIGN:

Double-masked, 100-week, multicenter, active-controlled, randomized trials.

METHODS:

Subjects were randomized 1:1:1 to brolucizumab 3 mg/6 mg or aflibercept 2 mg in KESTREL (n = 566) or 1:1 to brolucizumab 6 mg or aflibercept 2 mg in KITE (n = 360). Brolucizumab groups received 5 loading doses every 6 weeks (q6w) followed by 12-week (q12w) dosing, with optional adjustment to every 8 weeks (q8w) if disease activity was identified at predefined assessment visits; aflibercept groups received 5 doses every 4 weeks (q4w) followed by fixed q8w dosing. The primary endpoint was best-corrected visual acuity (BCVA) change from baseline at Week 52; secondary endpoints included the proportion of subjects maintained on q12w dosing, change in Diabetic Retinopathy Severity Scale score, and anatomical and safety outcomes.

RESULTS:

At Week 52, brolucizumab 6 mg was noninferior (NI margin 4 letters) to aflibercept in mean change in BCVA from baseline (KESTREL: +9.2 letters vs +10.5 letters; KITE: +10.6 letters vs +9.4 letters; P < .001), more subjects achieved central subfield thickness (CSFT) <280 µm, and fewer had persisting subretinal and/or intraretinal fluid vs aflibercept, with more than half of brolucizumab 6 mg subjects maintained on q12w dosing after loading. In KITE, brolucizumab 6 mg showed superior improvements in change of CSFT from baseline over Week 40 to Week 52 vs aflibercept (P = .001). The incidence of ocular serious adverse events was 3.7% (brolucizumab 3 mg), 1.1% (brolucizumab 6 mg), and 2.1% (aflibercept) in KESTREL; and 2.2% (brolucizumab 6 mg) and 1.7% (aflibercept) in KITE.

CONCLUSION:

Brolucizumab 6 mg showed robust visual gains and anatomical improvements with an overall favorable benefit/risk profile in patients with DME.

• Authors: David M Brown, Andrés Emanuelli, Francesco Bandello, Jose Juan Escobar Barranco, João Figueira, Eric Souied, Sebastian Wolf, Vishali Gupta, Nor Fariza Ngah, Gerald Liew, Raman Tuli, Ramin Tadayoni, Dilsher Dhoot, Lixin Wang, Emmanuel Bouillaud, Ying Wang, Lidija Kovacic, Nicolas Guerard, Justus G Garweg
• Journal: American journal of ophthalmology (Am J Ophthalmol) Vol. 238 Pg. 157-172 (06 2022) ISSN: 1879-1891 [Electronic] United States
• PMID: 35038415 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022. Published by Elsevier Inc.

Chemical References

• Angiogenesis Inhibitors
• Antibodies, Monoclonal, Humanized
• Recombinant Fusion Proteins
• Receptors, Vascular Endothelial Growth Factor
• brolucizumab

Topics

• Angiogenesis Inhibitors
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Diabetes Mellitus
• Diabetic Retinopathy (diagnosis, drug therapy)
• Humans
• Intravitreal Injections
• Macular Edema (diagnosis, drug therapy)
• Receptors, Vascular Endothelial Growth Factor (therapeutic use)
• Recombinant Fusion Proteins (therapeutic use)
• Treatment Outcome
• Visual Acuity