Brolucizumab

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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Definition
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Brolucizumab is an active substance from the group of VEGF inhibitors. The monoclonal antibody (MAK) is a humanised single-chain antibody fragment with a single Fv chain. The antibody belongs to the group of vascular endothelial growth factor inhibitors (VEGF inhibitors). VEGF is a group of proteins from different groups that act as signalling molecules and perform different tasks in human vascular tissues.

VEGF-A is important for angiogenesis (formation of new vessels) in the eye. Brolucizumab binds to all forms of VEGF-A and thus prevents the growth factor from binding to its receptor. By interrupting the VEGF/VEGFR signalling cascade, the formation of new retinal vessels and the development of retinal oedema is reduced. Brolucizumab has a low molecular weight of only 26 kilodaltons (kDa), which makes tissue penetration (which is of paramount importance for local application) and drug clearance particularly favourable.

Indication
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The drug is administered intravitreally. The most common possible adverse effects include blurred vision, cataracts, conjunctival hemorrhage, eye pain and mouche volantes

Undesirable effects
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The most common side effects of brolucizumab are: conjunctival hemorrhage; eye pain; cataracts; floaters; increased intraocular pressure; vitreous detachment; serious side effects are infections in the eye (endophthalmitis) and retinal detachment.

Note(s)
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In the pivotal trials, two randomized double-blind phase III studies enrolled 1817 patients with nAMD. The trials evaluated the efficacy of brolucizumab at a 12-week treatment interval compared to Aflibercept at an eight-week treatment interval. Initially, three injections were given monthly. When disease activity was detected with brolucizumab, the treatment interval was reduced to two months and thus maintained until the end of the study. The patients were treated with 6 mg brolucizumab or 2 mg aflibercept. The improvement in morphological parameters continued until 96 weeks.

Literature
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  1. Barmas-Alamdari D et al.(2019) Intravitreal Ziv- Aflibercept: A Comprehensive Review. Semin Ophthalmol 34:420-435.
  2. Cai S et al (2017) Aflibercept, bevacizumab or ranibizumab for diabetic macular oedema: recent clinically relevant findings from DRCR.net Protocol T. Curr Opin Ophthalmol 28:636-643.
  3. Dugel PU et al (2017) Brolucizumab Versus Aflibercept in Participants with Neovascular Age-Related Macular Degeneration: A Randomized Trial. Ophthalmology 124:1296-1304.
  4. Dugel PU et al (2019) HAWK and HARRIER: Phase 3, Multicenter, Randomized, Double-Masked Trials of Brolucizumab for Neovascular Age-Related Macular Degeneration. Ophthalmology 127:72-84.
  5. Yannuzzi NA et al (2019) Brolucizumab: evidence to date in the treatment of neovascular age-related macular degeneration. Clin Ophthalmol 13:1323-1329.

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Last updated on: 29.10.2020