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

Tadayoni, Ramin; Sararols, Laura; Weissgerber, Georges; Verma, Rohini Kumar; Clemens, Andreas; Holz, Frank G.

doi:10.1159/000513048

Cited by 108 publications

(111 citation statements)

References 26 publications

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“…Brolucizumab is a humanized single chain antibody fragment weighing just 26kDa. 18 Due to its smaller size, it binds to VEGF-A in 2:1 ratio initially, which may reduce to 1:1 with decreased concentration of the drug. 18 However, even at 1:1 ratio, a complete blockage of VEGF-A is maintained by brolucizumab.…”

Section: Discussionmentioning

confidence: 99%

“… 18 Due to its smaller size, it binds to VEGF-A in 2:1 ratio initially, which may reduce to 1:1 with decreased concentration of the drug. 18 However, even at 1:1 ratio, a complete blockage of VEGF-A is maintained by brolucizumab. 18 Additionally, with a low molecular weight of brolucizumab, that is 4 times lower than aflibercept and 1.8 times lower than ranibizumab, it is possible to deliver a 12-fold higher molar dose as compared to aflibercept and 22-fold higher molar dose as compared with ranibizumab.…”

Section: Discussionmentioning

confidence: 99%

“… 18 However, even at 1:1 ratio, a complete blockage of VEGF-A is maintained by brolucizumab. 18 Additionally, with a low molecular weight of brolucizumab, that is 4 times lower than aflibercept and 1.8 times lower than ranibizumab, it is possible to deliver a 12-fold higher molar dose as compared to aflibercept and 22-fold higher molar dose as compared with ranibizumab. 18 , 19 With these molecular characteristics, brolucizumab has been shown to have longer durability in the initial trials on nAMD.…”

Section: Discussionmentioning

confidence: 99%

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

Chakraborty¹,

Sheth²,

Boral³

et al. 2021

American Journal of Ophthalmology Case Reports

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Purpose To report the efficacy of intravitreal injection (IVI) of brolucizumab for recalcitrant diabetic macular edema (DME) in a real-world setting. Observations This was a single-center, prospective uncontrolled non-randomized case series. Three eyes with recalcitrant DME, who have received a minimum of ten intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections, underwent IVI brolucizumab and were followed-up for minimum of 16 weeks. Patients underwent best-corrected visual acuity (BCVA) testing, ophthalmic examination, and optical coherence tomography at baseline and all the scheduled follow-up visits (Weeks 4, 8, 12, and 16). All three patients demonstrated notable improvement in BCVA and reduction in the fluid on SD-OCT lasting up to week 12. At week 16, all three eyes maintained the visual acuity gains. However, early increase in fluid was noted in all the three cases, for which second dose of IVI brolucizumab was planned. No ocular or systemic adverse events were noted in any of the cases. Conclusions and Importance In this real-world case series, treatment with IVI brolucizumab exhibited excellent visual acuity outcomes lasting up to 16 weeks for the treatment of recalcitrant DME. Single dose IVI brolucizumab achieves good anatomical improvement based on SD-OCT persisting up to 12 weeks, followed by early recurrence of fluid at week 16. The results did not show any ocular or systemic safety concerns for IVI brolucizumab.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Chakraborty¹,

Sheth²,

Boral³

et al. 2021

American Journal of Ophthalmology Case Reports

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“…Brolucizumab (Beovu ® , Novartis Pharmaceuticals, Ottawa, ON, Canada) is a single-chain antibody fragment of 26 kDa, characterized by the absence of the Fc portion and specifically developed to minimize molecule size and to improve the affinity for VEGF-A isoforms, compared with the other molecules [ 46 , 47 ]. Brolucizumab has been recently approved for use in neovascular age-related macular degeneration, showing non-inferiority and higher penetrance within the retina and the choroid compared with the other anti-VEGF molecules [ 48 , 49 ].…”

Section: Anti-vegf Moleculesmentioning

confidence: 99%

Molecular Features of Classic Retinal Drugs, Retinal Therapeutic Targets and Emerging Treatments

Arrigo

Bandello

2021

Pharmaceutics

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The management of exudative retinal diseases underwent a revolution due to the introduction of intravitreal treatments. There are two main classes of intravitreal drugs, namely anti-vascular endothelial growth factors (anti-VEGF) and corticosteroids molecules. The clinical course and the outcome of retinal diseases radically changed thanks to the efficacy of these molecules in determining the regression of the exudation and the restoration of the macular profile. In this review, we described the molecular features of classic retinal drugs, highlighting the main therapeutic targets, and we provided an overview of new emerging molecules. We performed a systematic review of the current literature available in the MEDLINE library, focusing on current intravitreal molecules and on new emerging therapies. The anti-VEGF molecules include Bevacizumab, Pegaptanib, Ranibizumab, Aflibercept, Conbercept, Brolucizumab, Abicipar-pegol and Faricimab. The corticosteroids approach is mainly based on the employment of triamcinolone acetonide, dexamethasone and fluocinolone acetonide molecules. Many clinical trials and real-life reports demonstrated their efficacy in exudative retinal diseases, highlighting differences in terms of molecular targeting and pharmacologic profiles. Furthermore, several new molecules are currently under investigation. Intravitreal drugs focus their activity on a wide range of therapeutic targets and are safe and efficacy in managing retinal diseases.

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“…Бролуцизумаб -одноцепочечный фрагмент гуманизированного антитела (ScFv, single-chain variable fragment), который с высокой аффинностью связывается с различными изоформами VEGF-A (в частности, с VEGF110, VEGF121 и VEGF165), тем самым препятствуя связыванию VEGF-A с его рецепторами VEGFR-1 и VEGFR-2. Бролуцизумаб является наименьшей функциональной единицей антитела с молекулярной массой 26 кДа, в то время как молекулярная масса афлиберцепта -115 кДа, а ранибизумаба -48 кДа [13]. Малая масса бролуцизумаба позволяет создавать бóльшую молярную концентрацию в единице объема, вводимого при интравитреальной инъекции, c потенциальной возможностью более высокой пенетрации тканей, более длительного действия, что подтверждается доклиническими данными [14,15].…”

Section: резюмеunclassified

New Qualitative Methods for Assessing the “Fluid” in the Retina in Age-Related Macular Degeneration

Будзинская

Плюхова

2021

Oftalʹmologiâ

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Age-related macular degeneration (AMD) is a chronic disease of the central retina and one of the main causes of blindness in patients over 60 years of age in industrialized countries. Currently, anti-vascular endothelial growth factor therapy (anti-VEGF therapy) has become the standard of neovascular AMD treatment, leading to the prevention of progressive vision loss in more than 90 % of treated patients during a two-year follow-up period. In the modern world there are transition from quantitative assessment of “fluid” according to optical coherence tomography (OCT) — the thickness of the central retinal zone, to qualitative — the presence of IRF, SRF, fluid under RPE. The data obtained by Zinkernagel have shown that, despite good functional results (an increase in visual acuity), the administration of the drug once every 2 months leads not only to fluctuations in IRF and SRF, but also to serous PED [4]. The existing qualitative and quantitative analysis is not perfect. Fluctuation is a new qualitative marker of the study of disease activity, it is defined as the sum of all types of fluid (IRF + SRF + fluid under RPE) in a certain time interval (with monthly measurement of the indicator). The fluctuation index was determined from the cumulative change in the thickness of the retina in the fovea over time [6]. Thus, the fluid is considered as a key morphological criterion for the activity of nVMD and an indication for (initiation or continuation) of antiangiogenic therapy. At the same time, there is evidence that a lower level of each type of fluid (IRF, SRF, fluid under RPE) is associated with better BCVA results against the background of anti-VEGF therapy [17]. The stability of retinal thickness during anti-VEGF therapy is no less important parameter than the statement of fluid resolution at a certain time, and it appears that better control of the central retinal thickness was associated with higher overall NEI VFQ-25 scores and individual scales reflecting important daily activities of the patient [16].

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

Cited by 108 publications

References 26 publications

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

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

Molecular Features of Classic Retinal Drugs, Retinal Therapeutic Targets and Emerging Treatments

New Qualitative Methods for Assessing the “Fluid” in the Retina in Age-Related Macular Degeneration

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