Expert opinions on benefit-risk profile and clinical use of brolucizumab

Authors

  • Nicholas Fung
  • Danny Ng
  • Ian YH Wong
  • Raymond Wong
  • Pui Pui Yip
  • Alvin Kwok
  • Wai Ching Lam
  • Timothy Lai The Chinese University of Hong Kong https://orcid.org/0000-0002-7832-6428
  • Ramin Khoramnia

Keywords:

Brolucizumab, Injections, intraocular, Macular degeneration, Vascular endothelial growth factor A

Abstract

Brolucizumab is a next-generation anti–vascular endothelial growth factor (VEGF) agent for the treatment of neovascular age-related macular degeneration. It is highly potent and thus appropriate for those unresponsive to other anti-VEGF agents and those undertreated owing to the low adherence or the heavy burden of repeated injections. An expert panel of 10 retina specialists from Hong Kong and Germany convened in February 2021 to discuss the benefit-risk profile and clinical use of brolucizumab. Evidence suggests that brolucizumab provides comparable visual outcomes to aflibercept at a more relaxed injection schedule. Brolucizumab is superior to aflibercept in resolving intraretinal and subretinal fluids and decreasing disease activity. Brolucizumab is suitable for patients unresponsive to other anti-VEGF agents, especially for those with persistent intraretinal and subretinal fluids or disease activity. Injection intervals of brolucizumab can be extended to 8 to 12 weeks. However, brolucizumab has higher risk of adverse events such as intraocular inflammation, retinal vasculitis, and retinal occlusion, compared with aflibercept. Thus, regular monitoring for signs of intraocular inflammation and prompt management are important before and during treatment.

References

Novartis Pharma AG. Core Submission Dossier PTJA09. Available from: https://www.eunethta.eu/wp-content/uploads/2020/03/PTJA09-brolucizumab-Core-Submission-Dossier-by-Novartis-v1.0.pdf.

Flaxel CJ, Adelman RA, Bailey ST, et al. Age-Related Macular Degeneration Preferred Practice Pattern®. Ophthalmology 2020;127:P1-P65.

Regeneron. Eylea ® prescribing information. Available from: https://www.regeneron.com/downloads/eylea_fpi.pdf.

Genentech. Lucentis ® prescribing information. Available from: https://www.gene.com/download/pdf/lucentis_prescribing.pdf.

Lynch SS, Cheng CM. Bevacizumab for neovascular ocular diseases. Ann Pharmacother 2007;41:614-25.

Kiss S, Liu Y, Brown J, et al. Clinical monitoring of patients with age-related macular degeneration treated with intravitreal bevacizumab or ranibizumab. Ophthalmic Surg Lasers Imaging Retina 2014;45:285-91.

Boulanger-Scemama E, Querques G, About F, et al. Ranibizumab for exudative age-related macular degeneration: a five year study of adherence to follow-up in a real-life setting. J Fr Ophtalmol 2015;38:620-7.

Holz FG, Tadayoni R, Beatty S, et al. Multi-country real-life experience of anti-vascular endothelial growth factor therapy for wet age-related macular degeneration. Br J Ophthalmol 2015;99:220-6.

Kim LN, Mehta H, Barthelmes D, Nguyen V, Gillies MC. Metaanalysis of real-world outcomes of intravitreal ranibizumab for the treatment of neovascular age-related macular degeneration. Retina 2016;36:1418-31.

Ehlken C, Helms M, Böhringer D, Agostini HT, Stahl A. Association of treatment adherence with real-life VA outcomes in AMD, DME, and BRVO patients. Clin Ophthalmol 2017;12:13-20.

MacCumber MW. Real-world injection intervals in wet AMD. Retina Today 2020:20-2.

Buckle M, Donachie PH, Johnston RL. Long-term outcomes of intravitreal ranibizumab for neovascular age-related macular degeneration in a well defined region of the UK. Br J Ophthalmol 2016;100:240-5.

Freund KB, Mrejen S, Gallego-Pinazo R. An update on the pharmacotherapy of neovascular age-related macular degeneration. Expert Opin Pharmacother 2013;14:1017-28.

Novartis. BEOVU ® prescribing information. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761125s000lbl.pdf.

Nelson AL. Antibody fragments: hope and hype. MAbs 2010;2:77-83.

Tadayoni R, Sararols L, Weissgerber G, Verma R, Clemens A, Holz FG. Brolucizumab: a newly developed anti-VEGF molecule for the treatment of neovascular age-related macular degeneration. Ophthalmologica 2021;244:93-101.

Gaudreault J, Gunde T, Floyd HS, et al. Preclinical pharmacology and safety of ESBA1008, a single-chain antibody fragment, investigated as potential treatment for age related macular degeneration. Invest Ophthalmol Vis Sci 2012;53:3025.

Tietz J, Spohn G, Schmid G, et al. Affinity and potency of RTH258 (ESBA1008), a novel inhibitor of vascular endothelial growth factor A for the treatment of retinal disorders. Invest Ophthalmol Vis Sci 2015;56:1501.

Holz FG, Dugel PU, Weissgerber G, et al. Single-chain antibody fragment VEGF inhibitor RTH258 for neovascular age-related macular degeneration: a randomized controlled study. Ophthalmology 2016;123:1080-9.

Szabó E, Phillips DJ, Droste M, et al. Antitumor activity of DLX1008, an anti-VEGFA antibody fragment with low picomolar affinity, in human glioma models. J Pharmacol Exp Ther 2018;365:422-9.

Nimz EL, Van’t Land CW, Yáñez JA, Chastain JE. Intraocular and systemic pharmacokinetics of brolucizumab (RTH258) in nonhuman primates. Invest Ophthalmol Vis Sci 2016;57:4996.

Dugel PU, Koh A, Ogura Y, et al. HAWK and HARRIER: phase 3, multicenter, randomized, double-masked trials of brolucizumab for neovascular age-related macular degeneration. Ophthalmology 2020;127:72-84.

Dugel PU, Singh RP, Koh A, et al. HAWK and HARRIER: ninety-six-week outcomes from the phase 3 trials of brolucizumab for neovascular age-related macular degeneration. Ophthalmology 2021;128:89-99.

Lally D. An assessment of BCVA and CST outcomes with brolucizumab and aflibercept in patients with early persistent retinal fluid: 96 week pooled data from HAWK and HARRIER. Presented at: EURETINA 2020 congress. October 2020.

Sharma A, Kumar N, Parachuri N, et al. Brolucizumab—early real-world experience: BREW study. Eye (Lond) 2021;35:1045-7.

Bulirsch LM, Saßmannshausen M, Nadal J, Liegl R, Thiele S, Holz FG. Short-term real-world outcomes following intravitreal brolucizumab for neovascular AMD: SHIFT study. Br J Ophthalmol 2022;106:1288-94.

Chakraborty D, Maiti A, Sheth JU, et al. Brolucizumab in neovascular age-related macular degeneration: Indian real-world experience: the BRAILLE study. Clin Ophthalmol 2021;15:3787-95.

Panigrahi PK. A case of recalcitrant neovascular wet age-related macular degeneration treated with intravitreal brolucizumab. Photodiagnosis Photodyn Ther 2021;35:102450.

Bilgic A, Kodjikian L, March de Ribot F, et al. Real-world experience with brolucizumab in wet age-related macular degeneration: the REBA study. J Clin Med 2021;10:2758.

Avaylon J, Lee S, Gallemore RP. Case series on initial responses to intravitreal brolucizumab in patients with recalcitrant chronic wet age-related macular degeneration. Int Med Case Rep J 2020;13:145-52.

Member update: Novartis-appointed safety review committee reports initial brolucizumab findings. Available from: https://www.brolucizumab.info/sites/brolucizumab_info/files/2020-07/ASRS_SRC_report.pdf.

Monés J, Srivastava SK, Jaffe GJ, et al. Risk of inflammation, retinal vasculitis, and retinal occlusion-related events with brolucizumab: post hoc review of HAWK and HARRIER. Ophthalmology 2021;128:1050-9.

Baumal CR, Bodaghi B, Singer M, et al. Expert opinion on management of intraocular inflammation, retinal vasculitis, and vascular occlusion after brolucizumab treatment. Ophthalmol Retina 2021;5:519-27.

Sharma A, Kumar N, Parachuri N, et al. Brolucizumab; foreseeable workflow in the current scenario. Eye (Lond) 2021;35:1548-50.

Khoramnia R, Figueroa MS, Hattenbach LO, et al. Manifestations of intraocular inflammation over time in patients on brolucizumab for neovascular AMD. Graefes Arch Clin Exp Ophthalmol 2022;260:1843-56.

Baumal CR, Spaide RF, Vajzovic L, et al. Retinal vasculitis and intraocular inflammation after intravitreal injection of brolucizumab. Ophthalmology 2020;127:1345-59.

Haug SJ, Hien DL, Uludag G, et al. Retinal arterial occlusive vasculitis following intravitreal brolucizumab administration. Am J Ophthalmol Case Rep 2020;18:100680.

Khanani AM, Zarbin MA, Barakat MR, et al. Safety outcomes of brolucizumab in neovascular age-related macular degeneration: results from the IRIS Registry and Komodo Healthcare Map. JAMA Ophthalmol 2022;140:20-28.

Maruko I, Okada AA, Iida T, et al. Brolucizumab-related intraocular inflammation in Japanese patients with age-related macular degeneration: a short-term multicenter study. Graefes Arch Clin Exp Ophthalmol 2021;259:2857-9.

Ogura Y, Jaffe GJ, Cheung CMG, et al. Efficacy and safety of brolucizumab versus aflibercept in eyes with polypoidal choroidal vasculopathy in Japanese participants of HAWK. Br J Ophthalmol 2022;106:994-9.

Downloads

Published

2023-07-14

How to Cite

1.
Fung N, Ng D, Wong IY, Wong R, Yip PP, Kwok A, Lam WC, Lai T, Khoramnia R. Expert opinions on benefit-risk profile and clinical use of brolucizumab. Hong Kong J Ophthalmol [Internet]. 2023Jul.14 [cited 2024Oct.14];27(1). Available from: https://hkjo.hk/index.php/hkjo/article/view/353

Issue

Section

Perspective