A Randomized, Double-Masked, Multicenter, Phase III Study Assessing the Efficacy and Safety of Brolucizumab versus Aflibercept in Patients with Visual Impairment due to Diabetic Macular Edema (KITE)

Abstract

Background Brolucizumab is a single-chain variable antibody fragment (scVF) that specifically binds to VEGF-A. The results of two large phase III, multicentre, randomized clinical trials comparing intravitreal treatment with Brolucizumab and Aflibercept in neovascular age-related degeneration demonstrated its potency in the treatment of neovascular age-related macular degeneration (nAMD).

Methods The currently tested injected dose of 6 mg Brolucizumab results in a 11.2 – 13.3 times higher equivalent molar dose compared to Aflibercept 2 mg. Thus, it is conceivable that the effect of Brolucizumab in DME exceeds that of other currently used anti-VEGF agents with regards to effect durability; this was confirmed for nAMD in a phase I/II study.

Results Approved anti-VEGF drugs have shown unprecedented success compared to laser treatment with regards to restoration of visual acuity and improvement of diabetic retinopathy severity scores for up to 5 years. The visual gains were sustained after the loading phase and a reduced number of injections were required after the first year independent of the treatment strategy. Compared to pan-retinal laser photocoagulation, the time to progression of DRP was markedly extended and was proven by better preservation of the visual field, prevention of severe vision loss, hemorrhagic complications, and the need for intraocular surgery.

Conclusions The ongoing prospective, randomized, phase III clinical studies in DME, KITE, and KESTREL aim to confirm the non-inferiority of Brolucizumab 6 mg compared to Aflibercept 2 mg on a functional and morphological level as well as durability effect over 2 years.

Zusammenfassung

Hintergrund Brolucizumab ist ein sogenanntes „Single-chain variable Antibody Fragment“ (scVF), das spezifisch an VEGF-A bindet. Zwei große randomisierte, klinische, multizentrische Phase-III-Studien haben die intravitreale Therapie mit Brolucizumab und Aflibercept bei feuchter altersbedingter Makuladegeneration verglichen und die Wirksamkeit von Brolucizumab bei dieser Erkrankung gezeigt.

Methoden Mit einer intravitrealen Injektion von 6 mg Brolucizumab wird eine 11,2- bis 13,3-fach höhere molekulare Äquivalentdosis als mit Aflibercept 2 mg erreicht. Deshalb geht man davon aus, dass die Wirkdauer von Brolucizumab auch bei diabetischer Makulopathie (DME) länger ist als die von anderen derzeit eingesetzten Medikamenten, da sich dies in einer Phase-I/II-Studie bei feuchter AMD bereits betätigt hat.

Resultate Die bisher zugelassenen Anti-VEGF-Medikamente haben eine weit über die Lasertherapie hinausgehende Wirkung bezüglich der Erholung des Visus und der Rückbildung diabetischer Netzhautveränderungen über bis zu 5 Jahre gezeigt. Der anfängliche Visusgewinn konnte trotz einer abnehmenden Zahl intravitrealer Injektionen unabhängig von der gewählten Behandlungsstrategie über das 1. Jahr hinaus erhalten werden. Gleichzeitig konnte im Vergleich zur panretinalen Laserkoagulation die Zeit bis zur Progression der diabetischen Retinopathie markant verlängert werden, ein deutlich besseres Gesichtsfeld erhalten, das Risiko eines schweren Visusverlustes und schwerer Komplikationen reduziert und das Risiko operativer Eingriffe deutlich gesenkt werden.

Schlussfolgerung Es ist zu erwarten, dass die laufenden randomisierten, klinischen Phase-III-Studien bei DME mit den Namen KITE und KESTREL die Noninferiorität von Brolucizumab 6 mg im Vergleich zu Aflibercept 2 mg bezüglich funktioneller und anatomischer Endpunkte über einen Zeitraum von bis zu 2 Jahren bestätigen.

Key words

diabetic macular edema - DME - Brolucizumab - Aflibercept - intravitreal therapy - randomized clinical trial

Schlüsselwörter

diabetische Makulopathie - Makulaödem - DME - Brolucizumab - Aflibercept - intravitreale Therapie - randomisierte klinische Studie

Publication History

Received: 24 September 2019

Accepted: 21 December 2019

Article published online:
04 March 2020

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