Brolucizumab: A Newly Developed Anti-VEGF Molecule for the Treatment of Neovascular Age-Related Macular Degeneration.


Journal

Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde
ISSN: 1423-0267
Titre abrégé: Ophthalmologica
Pays: Switzerland
ID NLM: 0054655

Informations de publication

Date de publication:
2021
Historique:
received: 11 06 2020
accepted: 13 11 2020
pubmed: 17 11 2020
medline: 18 9 2021
entrez: 16 11 2020
Statut: ppublish

Résumé

Despite the success of anti-vascular endothelial growth factors (anti-VEGFs), currently, there is a need for highly effective compounds that can alleviate the burden of managing neovascular age-related macular degeneration (nAMD). To review the milestones in the molecular and clinical development of brolucizumab, the first single-chain antibody fragment (scFv) designed specifically for intraocular use in humans. In this article, we summarize the preclinical and current clinical evidence of brolucizumab administration with an overview of the other treatment regimens and additional indications under investigation. The unique molecular design of brolucizumab led to a low molecular weight of only 26 kDa, allowing for a concentrated molar dose of 1 intravitreal injection compared with other anti-VEGF agents. Phase I and II clinical trial outcomes validated the efficacy of brolucizumab in the treatment of nAMD with signals of a more durable treatment effect. The pivotal phase III trials, HAWK and HARRIER, which included a total of 1,817 patients, established that brolucizumab can be administered every 3 months while maintaining disease control. The preclinical and clinical data on brolucizumab provide evidence of sustained disease control with longer injection intervals, thus potentially reducing the treatment burden in patients with nAMD.

Sections du résumé

BACKGROUND BACKGROUND
Despite the success of anti-vascular endothelial growth factors (anti-VEGFs), currently, there is a need for highly effective compounds that can alleviate the burden of managing neovascular age-related macular degeneration (nAMD).
PURPOSE OBJECTIVE
To review the milestones in the molecular and clinical development of brolucizumab, the first single-chain antibody fragment (scFv) designed specifically for intraocular use in humans.
METHODS METHODS
In this article, we summarize the preclinical and current clinical evidence of brolucizumab administration with an overview of the other treatment regimens and additional indications under investigation.
RESULTS RESULTS
The unique molecular design of brolucizumab led to a low molecular weight of only 26 kDa, allowing for a concentrated molar dose of 1 intravitreal injection compared with other anti-VEGF agents. Phase I and II clinical trial outcomes validated the efficacy of brolucizumab in the treatment of nAMD with signals of a more durable treatment effect. The pivotal phase III trials, HAWK and HARRIER, which included a total of 1,817 patients, established that brolucizumab can be administered every 3 months while maintaining disease control.
CONCLUSIONS CONCLUSIONS
The preclinical and clinical data on brolucizumab provide evidence of sustained disease control with longer injection intervals, thus potentially reducing the treatment burden in patients with nAMD.

Identifiants

pubmed: 33197916
pii: 000513048
doi: 10.1159/000513048
doi:

Substances chimiques

Angiogenesis Inhibitors 0
Antibodies, Monoclonal, Humanized 0
brolucizumab XSZ53G39H5

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

93-101

Informations de copyright

© 2021 S. Karger AG, Basel.

Auteurs

Ramin Tadayoni (R)

Université de Paris, Ophthalmology Department, AP-HP, Hôpital Lariboisière, Paris, France.

Laura Sararols (L)

Hospital General de Catalunya, Barcelona, Spain.

Georges Weissgerber (G)

Novartis Pharma AG, Basel, Switzerland.

Rohini Verma (R)

Novartis Pharma AG, Basel, Switzerland.

Andreas Clemens (A)

Novartis Pharma AG, Basel, Switzerland, andreas.clemens@novartis.com.
Department of Cardiology and Angiology I, Heart Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany, andreas.clemens@novartis.com.

Frank G Holz (FG)

Department of Ophthalmology, University of Bonn, Bonn, Germany.

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Classifications MeSH