Brolucizumab: Difference between revisions

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{{Drugbox
{{Short description|A monoclonal antibody used in the treatment of neovascular age-related macular degeneration}}
| type              = mab
| image            =
| alt              =
| mab_type          = scFv
| source            = zu
| target            = [[Vascular endothelial growth factor A|VEGFA]]
| tradename        =
| Drugs.com        =
| MedlinePlus      =
| pregnancy_AU      =
| pregnancy_US      =
| pregnancy_category= 
| legal_AU =
| legal_CA =
| legal_UK =
| legal_US =
| legal_status      =
| routes_of_administration = [[Intravitreal]]
| bioavailability  =
| protein_bound    =
| metabolism        =
| elimination_half-life =
| excretion        =
| CAS_number        = 1531589-13-5
| ATC_prefix        = S01
| ATC_suffix        = LA06
| PubChem          =
| ChemSpiderID = none
| DrugBank          =
| C = 1164 | H = 1768 | N = 310 | O = 372 | S = 7
| molecular_weight  = 26.31 kDa
| UNII = XSZ53G39H5
| KEGG = D11083
| synonyms = ESBA1008, RTH258
}}


'''Brolucizumab''' ([[International Nonproprietary Name|INN]]) is a humanized single-chain antibody fragment designed for the treatment of [[wet age-related macular degeneration]].<ref>[http://www.ama-assn.org/resources/doc/usan/x-pub/brolucizumab.pdf Statement On A Nonproprietary Name Adopted By The USAN Council - Brolucizumab], ''[[American Medical Association]]''.</ref><ref>{{cite journal | author = [[World Health Organization]] | title = International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed INN: List 112 | journal = WHO Drug Information | volume = 28 | issue = 4 | year = 2014 | url = http://www.who.int/medicines/publications/druginformation/innlists/PL111.pdf | format=PDF}}</ref>
'''Brolucizumab''' is a humanized single-chain antibody fragment (scFv) used in the treatment of [[neovascular age-related macular degeneration]] (nAMD). It is marketed under the brand name Beovu and was developed by [[Novartis]]. Brolucizumab is designed to inhibit [[vascular endothelial growth factor A]] (VEGF-A), a protein that plays a critical role in the formation of abnormal blood vessels in the eye, which can lead to vision loss.


This drug was developed by [[ESBATech]] (discovery to phase 2a), [[Alcon]] Laboratories (phase 2b) and [[Novartis]] (phase 3).
==Mechanism of Action==
Brolucizumab works by binding to and inhibiting the activity of VEGF-A. VEGF-A is a key mediator of angiogenesis, the process by which new blood vessels form from pre-existing vessels. In nAMD, overexpression of VEGF-A leads to the growth of abnormal blood vessels beneath the [[retina]], causing leakage, bleeding, and scarring. By inhibiting VEGF-A, brolucizumab reduces the growth of these abnormal vessels and decreases fluid leakage, thereby stabilizing or improving vision.


Laboratory development names are RTH258 (Novartis Compound Code) and ESBA1008 (ESBATech AG).
==Clinical Use==
Brolucizumab is administered via intravitreal injection, directly into the [[vitreous humor]] of the eye. The typical dosing regimen involves an initial loading phase of monthly injections for the first three months, followed by maintenance injections every 8 to 12 weeks, depending on the patient's response and the physician's assessment.


Brolucizumab successfully completed phase 3 development in wet age-related macular degeneration (AMD) meeting the primary efficacy endpoint of non-inferiority to [[aflibercept]] in mean change in best corrected [[visual acuity]] (BCVA) from baseline to week 48. Furthermore, brolucizumab demonstrated superiority to aflibercept in key secondary endpoint measures of disease activity in wet AMD, a leading cause of blindness in two head-to-head pivotal Phase III studies.
==Efficacy and Safety==
Clinical trials have demonstrated that brolucizumab is effective in improving visual acuity and reducing retinal fluid in patients with nAMD. It has been shown to have a similar efficacy to other anti-VEGF therapies, such as [[ranibizumab]] and [[aflibercept]], with the advantage of potentially longer dosing intervals.


Whilst brolucizumab was initially developed for ophthalmology, non-ophthalmology indications (to which Cell Medica hold development rights) are also under investigation, under the name DLX1008. DLX1008 is under preclinical development for [[Kaposi sarcoma]]<ref name="EasonSin2018">{{cite journal|last1=Eason|first1=Anthony B.|last2=Sin|first2=Sang-Hoon|last3=Szabó|first3=Emese|last4=Phillips|first4=Douglas J.|last5=Droste|first5=Miriam|last6=Shamshiev|first6=Abdijapar|last7=Dittmer|first7=Dirk P.|last8=Weller|first8=Michael|title=Abstract 4: Antitumor activity of DLX1008, a single chain antibody fragment binding to VEGF-A, in<!--not a mistake--> in vivo preclinical models of Kaposi sarcoma and glioblastoma|journal=Cancer Research|volume=78|issue=13 Supplement|year=2018|pages=4–4|issn=0008-5472|doi=10.1158/1538-7445.AM2018-4}}</ref> and [[glioblastoma]].<ref name="SzabóPhillips2018">{{cite journal|last1=Szabó|first1=Emese|last2=Phillips|first2=Douglas J.|last3=Droste|first3=Miriam|last4=Marti|first4=Andrea|last5=Kretzschmar|first5=Titus|last6=Shamshiev|first6=Abdijapar|last7=Weller|first7=Michael|title=Antitumor Activity of DLX1008, an Anti-VEGFA Antibody Fragment with Low Picomolar Affinity, in Human Glioma Models|journal=Journal of Pharmacology and Experimental Therapeutics|volume=365|issue=2|year=2018|pages=422–429|issn=0022-3565|doi=10.1124/jpet.117.246249}}</ref>
The safety profile of brolucizumab is generally consistent with other anti-VEGF agents, with the most common adverse events being conjunctival hemorrhage, eye pain, and vitreous floaters. However, there have been reports of rare but serious adverse events, such as retinal vasculitis and retinal vascular occlusion, which require careful monitoring and management.


==References==
==Development and Approval==
<references/>
Brolucizumab was developed by Novartis and received approval from the [[U.S. Food and Drug Administration]] (FDA) in October 2019 for the treatment of nAMD. It has since been approved in several other countries and is considered a valuable addition to the therapeutic options available for managing this condition.
 
==Related pages==
* [[Neovascular age-related macular degeneration]]
* [[Vascular endothelial growth factor]]
* [[Monoclonal antibody]]
* [[Intravitreal injection]]


[[Category:Monoclonal antibodies]]
[[Category:Monoclonal antibodies]]
 
[[Category:Ophthalmology]]
{{monoclonals for bone, musculoskeletal, circulatory, and neurologic systems}}
[[Category:Drugs acting on the sensory organs]]
{{monoclonal-antibody-stub}}
{{dictionary-stub1}}
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Latest revision as of 19:08, 22 March 2025

A monoclonal antibody used in the treatment of neovascular age-related macular degeneration


Brolucizumab is a humanized single-chain antibody fragment (scFv) used in the treatment of neovascular age-related macular degeneration (nAMD). It is marketed under the brand name Beovu and was developed by Novartis. Brolucizumab is designed to inhibit vascular endothelial growth factor A (VEGF-A), a protein that plays a critical role in the formation of abnormal blood vessels in the eye, which can lead to vision loss.

Mechanism of Action[edit]

Brolucizumab works by binding to and inhibiting the activity of VEGF-A. VEGF-A is a key mediator of angiogenesis, the process by which new blood vessels form from pre-existing vessels. In nAMD, overexpression of VEGF-A leads to the growth of abnormal blood vessels beneath the retina, causing leakage, bleeding, and scarring. By inhibiting VEGF-A, brolucizumab reduces the growth of these abnormal vessels and decreases fluid leakage, thereby stabilizing or improving vision.

Clinical Use[edit]

Brolucizumab is administered via intravitreal injection, directly into the vitreous humor of the eye. The typical dosing regimen involves an initial loading phase of monthly injections for the first three months, followed by maintenance injections every 8 to 12 weeks, depending on the patient's response and the physician's assessment.

Efficacy and Safety[edit]

Clinical trials have demonstrated that brolucizumab is effective in improving visual acuity and reducing retinal fluid in patients with nAMD. It has been shown to have a similar efficacy to other anti-VEGF therapies, such as ranibizumab and aflibercept, with the advantage of potentially longer dosing intervals.

The safety profile of brolucizumab is generally consistent with other anti-VEGF agents, with the most common adverse events being conjunctival hemorrhage, eye pain, and vitreous floaters. However, there have been reports of rare but serious adverse events, such as retinal vasculitis and retinal vascular occlusion, which require careful monitoring and management.

Development and Approval[edit]

Brolucizumab was developed by Novartis and received approval from the U.S. Food and Drug Administration (FDA) in October 2019 for the treatment of nAMD. It has since been approved in several other countries and is considered a valuable addition to the therapeutic options available for managing this condition.

Related pages[edit]