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.

Off-label intravitreal brolucizumab for recalcitrant diabetic macular edema: A real-world case series

“…Based on the promising results of the phase 3 trials evaluating IVI brolucizumab in the treatment of nAMD, 19 prospective phase 3 studies (KITE and KESTREL) are underway to assess its role in the management of DME. 6 The interim results of KITE and KESTREL study released in the end of 2020 confirmed non-inferiority of brolucizumab to aflibercept in mean change in visual acuity at one year. 7 , 8 Moreover, patients in KESTREL study showed significant improvement in central subfield thickness (CST) from baseline over the period of week 40 through 52 with brolucizumab, while in the KITE study, it demonstrated superior improvement in CST over aflibercept from week 40 through week 52.…”

“…The concurrent anatomical improvement persists up to 12 weeks after a single dose, with early recurrence of fluid noted at 16 weeks. The long-term results of the phase 3 trials, KITE and KESTREL, 6 will provide us with a better insight into the role of brolucizumab in the treatment of DME.…”

“… 5 Likewise, two phase 3 clinical trials, KESTREL and KITE, are underway at 200 sites in 36 countries to evaluate the non-inferiority of Brolucizumab 6 mg to Aflibercept 2 mg in terms of functional and morphological improvement for management of DME over 2 years. 6 The interim results of these trials have shown encouraging visual acuity and anatomical outcomes at the end of one year. 7 , 8…”

Future Perspectives for Antiangiogenic Therapy in Retinal Diseases

“…По сравнению с полным антителом или Fab-фрагментом бролуцизумаб представляет собой одноцепочечный фрагмент антитела, наименьшую функциональную субъединицу антитела, которая все еще сохраняет полную связывающую способность с намеченной мишенью. Бролуцизумаб имеет молекулярную массу 26 кДа, что, в свою очередь, намного меньше, чем бевацизумаб (149 кДа), афлиберцепт (115 кДа) или ранибизумаб (48 кДа) [6,10,11].…”

“…Более подробные сведения представлены на веб-сайте www.brolucizumab.info. Рекомендуется тщательная оценка риска воспаления и постоянное наблюдение за пациентами, получающими препарат бролуцизумаб [6,10,11].…”