Brolucizumab

Brolucizumab
Monoclonal antibody
TypeSingle-chain variable fragment
SourceHumanized
TargetVascular endothelial growth factor A (VEGFA)
Names
Trade namesBeovu, Vsiqq
Other namesBrolucizumab-dbll, ESBA1008, RTH258, DLX1008
Clinical data
Main usesWet age-related macular degeneration (AMD)[1]
Side effectsReduced visual acuity, cataracts, conjunctival bleeding, floaters[1]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • AU: D
  • US: N (Not classified yet)[2]
    Routes of
    use    		Intravitreal
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa620001
    Legal
    License data
    Legal status
    • AU: S4 (Prescription only)
    • UK: POM (Prescription only) [3]
    • US: ℞-only [4]
    • EU: Rx-only [1]
    • In general: ℞ (Prescription only)
    Chemical and physical data
    FormulaC1164H1768N310O372S7
    Molar mass26281.17 g·mol−1

    Brolucizumab, sold under the brand names Beovu and Vsiqq, is a medication used to treat wet age-related macular degeneration (AMD).[1][4] It is given by injection into the eye.[4]

    Common side effects include reduced visual acuity, cataracts, conjunctival bleeding, and floaters.[1] Other side effects may include blindness, infection inside the eye, retinal artery occlusion, and retinal detachment.[1] Use in pregnancy may harm the baby.[5] It is a piece of a monoclonal antibody that attaches to and block vascular endothelial growth factor A (VEGF-A).[1] VEGF-A is a protein that makes blood vessels grow and leak fluid.[1]

    Brolucizumab was approved for medical use in the United States in 2019 and Europe in 2020.[4][1] In the United Kingdom it costs the NHS about £820 per dose as of 2021.[6] This amount in the United States is about 1,950 USD.[7]

    Medical use

    Dosage

    It is given as a dose of 6 mg into the eye.[1] The first three doses are given once a month, followed by doses every 2 to 3 months.[1]

    Side effects

    On 23 February 2020, the American Society of Retina Specialists reported side effects of the drug, specifically in 14 cases of retinal vasculitis reported in Beovu patients, 11 of the cases were occlusive retinal vasculitis that can lead to vision loss.[8][9]

    Novartis responded with a statement standing behind the efficacy of Beovu.[10][11]

    On 11 June 2020, the FDA approved an updated Beovu label, 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)[12] and HARRIER (NCT02434328)[13] clinical trials and noted in the original prescribing information.[14]

    History

    This drug was developed by ESBATech[15][16] (discovery to phase 2a), Alcon Laboratories (phase 2b), and Novartis (phase 3).

    Brolucizumab is U.S. Food and Drug Administration (FDA) approved in ophthalmology as Beovu.[17][18]

    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 AMD, a leading cause of blindness in two head-to-head pivotal Phase III studies.[19][20][21] [22]

    On 8 October 2019, Novartis announced that the U.S. Food and Drug Administration (FDA) approved brolucizumab injection for the treatment of wet AMD.[17] Beovu is the first FDA approved anti-VEGF to offer both greater fluid resolution versus aflibercept and the ability to maintain eligible wet AMD patients on a three-month dosing interval immediately after a three-month loading phase[23] with uncompromised efficacy.

    The FDA approved Beovu based on evidence from two clinical trials (Trial 1/ NCT02307682 and Trial 2/NCT02434328) of 1459 patients, 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.[24]

    While 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[25] and glioblastoma.[26]

    Brolucizumab was approved for use in the European Union in February 2020.[1]

    Names

    Laboratory development names were RTH258 (Novartis Compound Code) and ESBA1008 (ESBATech AG).

    Brolucizumab is the International Nonproprietary Name (INN) and the United States Adopted Name (USAN)[27][28]

    References

    1. 1 2 3 4 5 6 7 8 9 10 11 12 "Beovu EPAR". European Medicines Agency (EMA). 10 December 2019. Archived from the original on 8 November 2020. Retrieved 3 May 2020. Public Domain This article incorporates text from this source, which is in the public domain.
    2. ↑ "Brolucizumab (Beovu) Use During Pregnancy". Drugs.com. 24 October 2019. Retrieved 3 May 2020.
    3. ↑ "Beovu 120 mg/ml solution for injection in pre-filled syringe - Summary of Product Characteristics (SmPC)". (emc). 9 March 2020. Archived from the original on 24 September 2020. Retrieved 3 May 2020.
    4. 1 2 3 4 "Beovu- brolucizumab injection, solution". DailyMed. 13 January 2020. Archived from the original on 9 January 2021. Retrieved 3 May 2020.
    5. ↑ "Brolucizumab (Beovu) Use During Pregnancy". Drugs.com. Retrieved 12 January 2022.
    6. ↑ BNF 81: March-September 2021. BMJ Group and the Pharmaceutical Press. 2021. p. 1235. ISBN 978-0857114105.
    7. ↑ "Beovu Prices, Coupons & Patient Assistance Programs". Drugs.com. Archived from the original on 18 April 2021. Retrieved 12 January 2022.
    8. ↑ "Novartis Responds to ASRS Note Raising Safety Concerns With Wet AMD Drug Beovu". Eyewire News. 25 February 2020. Archived from the original on 4 November 2021. Retrieved 27 April 2020.
    9. ↑ "Novartis' hot new eye drug Beovu tied to potential vision loss: experts". FiercePharma. Archived from the original on 27 July 2021. Retrieved 27 April 2020.
    10. ↑ "Novartis stands behind Beovu's safety, benefits after vision-loss warning". FiercePharma. Archived from the original on 1 November 2020. Retrieved 27 April 2020.
    11. ↑ "Novartis provides update on use and safety of Beovu (brolucizumab)". Novartis. 28 April 2020. Archived from the original on 17 October 2021. Retrieved 27 April 2020.
    12. ↑ "Efficacy and Safety of RTH258 Versus Aflibercept - Study 1 - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. Archived from the original on 15 May 2020. Retrieved 11 June 2020.
    13. ↑ "Efficacy and Safety of RTH258 Versus Aflibercept - Study 2 - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. Archived from the original on 15 May 2020. Retrieved 11 June 2020.
    14. ↑ "BRIEF-U.S. FDA Approves Novartis' Updated Beovu Label - Statement". Reuters. 11 June 2020. Archived from the original on 11 June 2020. Retrieved 11 June 2020.
    15. ↑ "ESBATech case story" (PDF). 6 July 2011. Archived (PDF) from the original on 17 November 2019. Retrieved 17 November 2019.
    16. ↑ "RTH258". Biomedtracker. Archived from the original on 17 November 2019. Retrieved 17 November 2019.
    17. 1 2 "Novartis receives FDA approval for Beovu, offering wet AMD patients vision gains and greater fluid reductions vs aflibercept". Novartis. Archived from the original on 13 September 2021. Retrieved 24 September 2021.
    18. ↑ "Drug Approval Package: Beovu (brolucizumab-dbll)". U.S. Food and Drug Administration (FDA). 4 November 2019. Archived from the original on 17 November 2019. Retrieved 17 November 2019.
    19. ↑ Dugel PU, Koh A, Ogura Y, Jaffe GJ, Schmidt-Erfurth U, Brown DM, Gomes AV, Warburton J, Weichselberger A, Holz FG (April 2019). "HAWK and HARRIER: Phase 3, Multicenter, Randomized, Double-Masked Trials of Brolucizumab for Neovascular Age-Related Macular Degeneration". Ophthalmology. 127 (1): 72–84. doi:10.1016/j.ophtha.2019.04.017. PMID 30986442.
    20. ↑ 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 (May 2016). "Single-Chain Antibody Fragment VEGF Inhibitor RTH258 for Neovascular Age-Related Macular Degeneration: A Randomized Controlled Study". Ophthalmology. 123 (5): 1080–9. doi:10.1016/j.ophtha.2015.12.030. PMID 26906165.
    21. ↑ "Efficacy and Safety of RTH258 Versus Aflibercept - Study 1 (HAWK)". ClinicalTrials.gov. 4 December 2014. Archived from the original on 15 May 2020. Retrieved 3 May 2020.
    22. ↑ "Efficacy and Safety of RTH258 Versus Aflibercept - Study 2 (HARRIER)". ClinicalTrials.gov. 5 May 2015. Archived from the original on 15 May 2020. Retrieved 3 May 2020.
    23. ↑ BEOVU [prescribing information] East Hanover, NJ. Novartis: 2019
    24. ↑ "Drug Trials Snapshots: BEOVU". U.S. Food and Drug Administration. 7 October 2019. Archived from the original on 17 November 2019. Retrieved 17 November 2019.Public Domain This article incorporates text from this source, which is in the public domain.
    25. ↑ Eason, Anthony B.; Sin, Sang-Hoon; Szabó, Emese; Phillips, Douglas J.; Droste, Miriam; Shamshiev, Abdijapar; Dittmer, Dirk P.; Weller, Michael (2018). "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): 4. doi:10.1158/1538-7445.AM2018-4. ISSN 0008-5472.
    26. ↑ Szabó E, Phillips DJ, Droste M, Marti A, Kretzschmar T, Shamshiev A, Weller M (May 2018). "Antitumor Activity of DLX1008, an Anti-VEGFA Antibody Fragment with Low Picomolar Affinity, in Human Glioma Models". J. Pharmacol. Exp. Ther. 365 (2): 422–9. doi:10.1124/jpet.117.246249. ISSN 0022-3565. PMID 29507055.
    27. ↑ Statement On A Nonproprietary Name Adopted By The USAN Council - Brolucizumab Archived 15 August 2016 at the Wayback Machine, American Medical Association.
    28. ↑ World Health Organization (2014). "International nonproprietary names for pharmaceutical substances (INN): proposed INN: list 112". WHO Drug Information. 28 (4): 493. hdl:10665/331100.
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