KESTREL and KITE: 52-week results from two Phase III pivotal trials of brolucizumab for diabetic macular edema

Brown DM 1 , Emanuelli A 2 , Bandello F 3 , Barranco JJE 4 , Figueira J 5 , Souied E 6 Show all authors , Wolf S 7 , Gupta V 8 , Ngah NF 9 , Liew G 10 , Tuli R 11 , Tadayoni R 12 , Dhoot D 13 , Wang L 14 , Bouillaud E 14 , Wang Y 14 , Kovacic L 14 , Guerard N 14 , Garweg JG 15

Affiliations 

  • 1 Retina Consultants of Texas, Houston, TX, USA. Electronic address: dmbmd@retinaconsultantstexas.com
  • 2 Emanuelli Research and Development Center, Arecibo, Puerto Rico, USA; Department of Ophthalmology, Medical Sciences Campus, University of Puerto Rico, San Juan, Puerto Rico
  • 3 Department of Ophthalmology, University Vita-Salute, Scientific Institute San Raffaele, Milan, Italy
  • 4 Department of Ophthalmology, Hospital Dos de Maig, Barcelona, Spain
  • 5 AIBILI - Association for Innovation and Biomedical Research on Light and Image, Azinhaga de Santa Comba, Celas, Coimbra, Portugal; Faculty of Medicine, Coimbra Institute for Clinical and Biomedical Research (iCBR), University of Coimbra, Coimbra, Portugal
  • 6 Department of Ophthalmology, Hôpital Intercommunal de Creteil, Créteil, France
  • 7 Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
  • 8 Advanced Eye Center, Post Graduate Institute of Medical Education and Research, Chandigarh, India
  • 9 Hospital Shah Alam, Selangor, Malaysia
  • 10 Centre for Vision Research, Westmead Institute for Medical Research, University of Sydney, Sydney, Australia
  • 11 Department of Ophthalmology, University of Ottawa, Ottawa, Canada; The Retina Centre of Ottawa, Canada
  • 12 Université de Paris, Ophthalmology Department, AP-HP, Lariboisière, Saint Louis and Fondation Adolphe de Rothschild Hospitals, Paris, France
  • 13 California Retina Consultants/Retina Consultants of America, Santa Barbara, CA, USA
  • 14 Novartis Pharma AG, Basel, Switzerland
  • 15 Department of Ophthalmology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Berner Augenklinik am Lindenhofspital and Swiss Eye Institute, Bern, Switzerland
Am J Ophthalmol, 2022 Jan 13.
PMID: 35038415 DOI: 10.1016/j.ajo.2022.01.004

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 3mg/6mg or aflibercept 2mg in KESTREL (N=566) or 1:1 to brolucizumab 6mg or aflibercept 2mg in KITE (N=360). Brolucizumab groups received 5 loading doses every 6 weeks (q6w) followed by q12w dosing, with optional adjustment to q8w if disease activity was identified at pre-defined assessment visits; aflibercept groups received 5xq4w 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 DRSS score and anatomical and safety outcomes.

RESULTS: At Week 52, brolucizumab 6mg was noninferior (NI margin 4 letters) to aflibercept in mean change in BCVA from baseline (KESTREL: +9.2 letters versus +10.5 letters; KITE: +10.6 letters versus +9.4 letters; p<0.001), more subjects achieved central subfield thickness (CSFT) <280µm and fewer had persisting subretinal and/or intraretinal fluid versus aflibercept, with >50% of brolucizumab 6mg subjects maintained on q12w dosing after loading. In KITE, brolucizumab 6mg showed superior improvements in change of CSFT from baseline over Week 40-Week 52 versus aflibercept (p=0.001). The incidence of ocular serious adverse events was 3.7% (brolucizumab 3mg), 1.1% (brolucizumab 6mg), 2.1% (aflibercept) in KESTREL; 2.2% (brolucizumab 6mg), 1.7% (aflibercept) in KITE.

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

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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