Brolucizumab Explained

Type:mab
Mab Type:scFv
Source:zu
Target:Vascular endothelial growth factor A (VEGFA)
Tradename:Beovu
Dailymedid:Brolucizumab
Pregnancy Au:D
Routes Of Administration:Intravitreal
Atc Prefix:S01
Atc Suffix:LA06
Legal Au:S4
Legal Au Comment:[1]
Legal Ca:Rx-only
Legal Ca Comment:/ Schedule D[2] [3]
Legal Uk:POM
Legal Uk Comment:[4]
Legal Us:Rx-only
Legal Eu:Rx-only
Legal Status:Rx-only
Cas Number:1531589-13-5
Pubchem:252827371
Iuphar Ligand:8713
Drugbank:DB14864
Chemspiderid:none
Unii:XSZ53G39H5
Kegg:D11083
Synonyms:brolucizumab-dbll, RTH258, DLX1008
C:1164
H:1768
N:310
O:372
S:7

Brolucizumab sold under trade name Beovu among others, is a humanized single-chain antibody fragment for the treatment of neovascular (wet) age-related macular degeneration (AMD).[5]

The most common side effects are reduced visual acuity, cataract (clouding of the lens in the eye), conjunctival haemorrhage (bleeding at the front of the eye) and vitreous floaters (spots in the vision). The most serious side effects are blindness, endophthalmitis (an infection inside the eye), retinal artery occlusion (blockage of the artery in the retina) and retinal detachment (separation of the retina from the back of the eye).

Brolucizumab was designed to attach to and block a substance called vascular endothelial growth factor A (VEGF-A). VEGF-A is a protein that makes blood vessels grow and leak fluid and blood, damaging the macula. By blocking VEGF-A, brolucizumab reduces the growth of the blood vessels and controls the leakage and swelling.

History

Brolucizumab is approved by the US Food and Drug Administration (FDA) for use in ophthalmology.[6] [7]

Brolucizumab successfully completed phase III 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 age-related macular degeneration, a leading cause of blindness in two head-to-head pivotal Phase III studies.[8] [9]

In October 2019, Novartis announced that the US Food and Drug Administration (FDA) approved brolucizumab injection for the treatment of wet age-related macular degeneration.

The FDA approved brolucizumab based on evidence from two clinical trials (Trial 1/ NCT02307682 and Trial 2/NCT02434328) of 1459 participants, 50–97 years old, with wet AMD. The trials were conducted at 336 sites in the United States, Canada, Central and South America, European countries, Israel, Turkey, Australia, New Zealand, Japan, South Korea, Singapore, Taiwan, and Vietnam.[10]

Brolucizumab was approved for use in the European Union in February 2020.[11]

Society and culture

Safety concerns

In February 2020, the American Society of Retina Specialists reported side effects of brolucizumab, specifically in 14 cases of retinal vasculitis reported in people using brolucizumab, 11 of the cases were occlusive retinal vasculitis that can lead to vision loss.[12] [13] Novartis responded with a statement standing behind the efficacy of Beovu.[14] [15]

In June 2020, the FDA approved an updated prescription label for brolucizumab that included additional safety information—specifically including the characterization of adverse events, retinal vasculitis and retinal vascular occlusion, as part of the spectrum of intraocular inflammation observed in HAWK (NCT02307682) and HARRIER (NCT02434328) clinical trials and noted in the original prescribing information.[16]

Names

Brolucizumab is the International Nonproprietary Name (INN) and the United States Adopted Name (USAN)[17] [18]

Research

Non-ophthalmology indications are under investigation, under the name DLX1008. DLX1008 is under preclinical development for Kaposi sarcoma[19] and glioblastoma.[20]

Notes and References

  1. https://www.tga.gov.au/resources/prescription-medicines-registrations/beovu-novartis-pharmaceuticals-australia-pty-ltd-0 Medicine registrations
  2. Web site: Beovu Product information . Health Canada . 25 April 2012 . 29 May 2022 . 8 August 2024 . https://web.archive.org/web/20240808043549/https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=98686 . live .
  3. Web site: Summary Basis of Decision (SBD) for Beovu . Health Canada . 23 October 2014 . 29 May 2022 . 23 June 2023 . https://web.archive.org/web/20230623152537/https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00489&lang=en . live .
  4. Web site: Beovu 120 mg/ml solution for injection in pre-filled syringe - Summary of Product Characteristics (SmPC) . (emc) . 9 March 2020 . 3 May 2020 . 24 September 2020 . https://web.archive.org/web/20200924192447/https://www.medicines.org.uk/emc/product/11145/smpc . live .
  5. Web site: Beovu- brolucizumab injection, solution . DailyMed . 13 January 2020 . 3 May 2020 . 9 January 2021 . https://web.archive.org/web/20210109214913/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5d1dc1fa-a2d3-46ed-9e9a-c1a036590d3d . live .
  6. Web site: Novartis receives FDA approval for Beovu, offering wet AMD patients vision gains and greater fluid reductions vs aflibercept. Novartis. 16 October 2019. 13 September 2021. https://web.archive.org/web/20210913133920/https://www.novartis.com/news/media-releases/novartis-receives-fda-approval-beovu-offering-wet-amd-patients-vision-gains-and-greater-fluid-reductions-vs-aflibercept. live.
  7. Web site: Drug Approval Package: Beovu (brolucizumab-dbll) . U.S. Food and Drug Administration (FDA) . 4 November 2019 . https://web.archive.org/web/20191117230240/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/761125_Orig1_toc.cfm . 17 November 2019 . live . 17 November 2019.
  8. Dugel PU, Koh A, Ogura Y, Jaffe GJ, Schmidt-Erfurth U, Brown DM, Gomes AV, Warburton J, Weichselberger A, Holz FG . HAWK and HARRIER: Phase 3, Multicenter, Randomized, Double-Masked Trials of Brolucizumab for Neovascular Age-Related Macular Degeneration . Ophthalmology . 127. 1. 72–84. April 2019 . 30986442 . 10.1016/j.ophtha.2019.04.017 . free . doi .
  9. Holz FG, Dugel PU, Weissgerber G, Hamilton R, Silva R, Bandello F, Larsen M, Weichselberger A, Wenzel A, Schmidt A, Escher D, Sararols L, Souied E . Single-Chain Antibody Fragment VEGF Inhibitor RTH258 for Neovascular Age-Related Macular Degeneration: A Randomized Controlled Study . Ophthalmology . 123 . 5 . 1080–9 . May 2016 . 26906165 . 10.1016/j.ophtha.2015.12.030 . free . doi .
  10. Web site: Drug Trials Snapshots: BEOVU . . 7 October 2019 . https://web.archive.org/web/20191117202234/https://www.fda.gov/drugs/development-approval-process-drugs/drug-trials-snapshots-beovu . 17 November 2019 . live . 17 November 2019.
  11. Web site: Beovu EPAR . European Medicines Agency (EMA) . 10 December 2019 . 3 May 2020 . 8 November 2020 . https://web.archive.org/web/20201108143531/https://www.ema.europa.eu/en/medicines/human/EPAR/beovu . live .
  12. Web site: Novartis Responds to ASRS Note Raising Safety Concerns With Wet AMD Drug Beovu. Eyewire News. 27 April 2020. 25 February 2020. 4 November 2021. https://web.archive.org/web/20211104155146/https://eyewire.news/news/novartis-responds-to-asrs-note-raising-safety-concerns-of-beovu. live.
  13. Web site: Novartis' hot new eye drug Beovu tied to potential vision loss: experts. FiercePharma. 24 February 2020. 27 April 2020. 27 July 2021. https://web.archive.org/web/20210727213956/https://www.fiercepharma.com/pharma/retinal-society-flags-serious-side-effect-for-novartis-beovu. live.
  14. Web site: Sagonowsky E. Novartis stands behind Beovu's safety, benefits after vision-loss warning. FiercePharma. 2 March 2020. 27 April 2020. 1 November 2020. https://web.archive.org/web/20201101015814/https://www.fiercepharma.com/pharma/novartis-stands-behinds-beovu-s-risk-benefit-profile-after-safety-warning. live.
  15. Web site: Novartis provides update on use and safety of Beovu (brolucizumab). Novartis. 27 April 2020. 28 April 2020. 17 October 2021. https://web.archive.org/web/20211017221345/https://www.brolucizumab.info/. dead.
  16. News: 11 June 2020. BRIEF-U.S. FDA Approves Novartis' Updated Beovu Label - Statement. Reuters. 11 June 2020. 11 June 2020. https://web.archive.org/web/20200611125543/https://in.reuters.com/article/brief-us-fda-approves-novartis-updated-b-idINASN0007VL. dead.
  17. http://www.ama-assn.org/resources/doc/usan/x-pub/brolucizumab.pdf Statement On A Nonproprietary Name Adopted By The USAN Council - Brolucizumab
  18. ((World Health Organization)) . World Health Organization . International nonproprietary names for pharmaceutical substances (INN): proposed INN: list 112 . WHO Drug Information . 28 . 4 . 2014 . 10665/331100 . free . 493 .
  19. Eason AB, Sin SH, Szabó E, Phillips DJ, Droste M, Shamshiev A, Dittmer DP, Weller M . 6 . Abstract 4: Antitumor activity of DLX1008, a single chain antibody fragment binding to VEGF-A, in in vivo preclinical models of Kaposi sarcoma and glioblastoma. Cancer Research. 78. 13 Supplement. 2018. 4. 0008-5472. 10.1158/1538-7445.AM2018-4. doi . 81317833 .
  20. Szabó E, Phillips DJ, Droste M, Marti A, Kretzschmar T, Shamshiev A, Weller M . Antitumor Activity of DLX1008, an Anti-VEGFA Antibody Fragment with Low Picomolar Affinity, in Human Glioma Models . The Journal of Pharmacology and Experimental Therapeutics . 365 . 2 . 422–429 . May 2018 . 29507055 . 10.1124/jpet.117.246249 . doi . free .

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