brolucizumab

Brolucizumab, sold under the brand name Beovu, is a humanized single-chain antibody fragment that inhibits vascular endothelial growth factor A (VEGF-A). It is used for the treatment of neovascular, or wet, age-related macular degeneration (AMD) in adults and is administered by intravitreal injection.

Mechanism of action: Brolucizumab binds VEGF-A with high affinity, blocking its interaction with VEGF receptors. Its relatively small molecular size (about 26 kilodaltons for the scFv fragment) allows a higher molar concentration to be delivered in a given injection, which helps reduce pathological choroidal neovascularization and vascular permeability that contribute to vision loss in AMD.

Clinical use and dosing: Dosing commonly begins with three monthly loading injections, followed by injections at 8 to 12 week intervals, depending on disease activity. In phase 3 trials (HAWK and HARRIER), brolucizumab demonstrated noninferiority to aflibercept and permitted extended intervals up to 12 weeks after loading in some patients.

Approval and availability: Beovu was approved for wet AMD in 2019 and is marketed by Novartis. It has been explored for other retinal conditions, but regulatory approvals outside AMD are limited or absent in many jurisdictions.

Safety considerations: Postmarketing experience identified risks of intraocular inflammation, including retinal vasculitis and retinal vein occlusion, which can lead to vision loss. Regulatory agencies issued safety communications and labeling updates to emphasize monitoring for intraocular inflammation and to discontinue treatment if inflammation occurs. Endophthalmitis, while less common, remains a possible adverse event.

See also: Other anti-VEGF therapies for AMD include ranibizumab, aflibercept, and faricimab.