Belantamab mafodotin

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Belantamab mafodotin
Mafodotin ADCs.svg
Monoclonal antibody
Type Whole antibody
Source Humanized
Target B-cell maturation antigen (BCMA) (CD269)
Clinical data
Trade names Blenrep
Other namesbelantamab mafodotin-blmf, GSK2857916
AHFS/Drugs.com Monograph
License data
Routes of
administration 		Intravenous
Drug class Antineoplastic agent
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
UNII
KEGG
Chemical and physical data
Formula C6484H10008N1728O2030S44. (C49H66N6O11)4

Belantamab mafodotin, sold under the brand name Blenrep, is a monoclonal antibody for the treatment of relapsed and refractory multiple myeloma. [2] [5] [6] [3]

Contents

The most common adverse reactions include keratopathy (corneal epithelium change on eye exam), decreased visual acuity, nausea, blurred vision, pyrexia, infusion-related reactions, and fatigue. [2] [5]

Belantamab mafodotin is a humanized IgG1κ monoclonal antibody against the B-cell maturation antigen (BCMA) conjugated with a cytotoxic agent, maleimidocaproyl monomethyl auristatin F (mcMMAF). [3] The antibody-drug conjugate binds to BCMA on myeloma cell surfaces causing cell cycle arrest and inducing antibody-dependent cellular cytotoxicity. [3]

Belantamab mafodotin was approved for medical use in the United States and in the European Union in August 2020. [5] [6] [3] The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. [7] [8]

In November 2022, GSK plc initiated the process for withdrawal of the United States marketing authorization for belantamab mafodotin following the request of the US FDA. [9] This request was based on the outcome of the DREAMM-3 phase III confirmatory trial, [10] which did not meet the requirements of the US FDA accelerated approval regulations. [11]

Medical uses

Belantamab mafodotin is indicated for the treatment of adults with relapsed or refractory multiple myeloma who have received at least four prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. [2] [5] [3] However, the phase III DREAMM-3 trial published in 2023, comparing patients with relapsed or refractory multiple myeloma receiving belantamab mafodotin to pomalidimide and dexamethasone did not demonstrate a clinical benefit for belantamab mafodotin. Due to this trial results, the manufacturer is voluntarily withdrawing belantamab mafodotin from the market. [10]

Adverse effects

The prescribing information includes a boxed warning stating belantamab mafodotin causes changes in the corneal epithelium resulting in alterations in vision, including severe vision loss and corneal ulcer, and symptoms, such as blurred vision and dry eyes. [5] [2]

History

Belantamab mafodotin was evaluated in DREAMM-2 (NCT 03525678), an open-label, multicenter trial. [5] Participants received either belantamab mafodotin, 2.5 mg/kg or 3.4 mg/kg intravenously, once every three weeks until disease progression or unacceptable toxicity. [5]

Efficacy was based on overall response rate (ORR) and response duration, as evaluated by an independent review committee using the International Myeloma Working Group uniform response criteria. [5] The ORR was 31% (97.5% CI: 21%, 43%). Seventy-three percent of responders had response durations ≥6 months. [5] These results were observed in participants receiving the recommended dose of 2.5 mg/kg. [5]

The US Food and Drug Administration (FDA) granted the application for belantamab mafodotin priority review, orphan drug, and breakthrough therapy designations. [5]

In 2023, the confirmatory phase III DREAMM-3 trial aimed to compare belantamab mafodotin versus pomalidomide plus low-dose dexamethasone in participants with relapsed or refractory multiple myeloma. Due to the trial results, the manufacturer is voluntarily withdrawing belantamab mafodotin from the market. [10]

Society and culture

Belantamab mafodotin was approved for medical use in the United States and in the European Union in August 2020. [5] [6] [3] [8]

Belantamab mafodotin is withdrawn in the United States [12] and the European Union. [3]

Names

Belantamab mafodotin is the international nonproprietary name (INN). [13]

Related Research Articles

<span class="mw-page-title-main">Multiple myeloma</span> Cancer of plasma cells

Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, anemia, renal insufficiency, and infections may occur. Complications may include hypercalcemia and amyloidosis.

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<span class="mw-page-title-main">B-cell maturation antigen</span> Protein-coding gene in the species Homo sapiens

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Daratumumab, sold under the brand name Darzalex among others, is an anti-cancer monoclonal antibody medication. It binds to CD38, which is overexpressed in multiple myeloma cells. Daratumumab was originally developed by Genmab, but it is now being jointly developed by Genmab along with the Johnson & Johnson subsidiary Janssen Biotech, which acquired worldwide commercialization rights to the drug from Genmab.

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<span class="mw-page-title-main">Ixazomib</span> Chemical compound

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<span class="mw-page-title-main">Nirogacestat</span> Chemical compound

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Ciltacabtagene autoleucel, sold under the brand name Carvykti, is an anti-cancer medication used to treat multiple myeloma. Ciltacabtagene autoleucel is a BCMA -directed genetically modified autologous chimeric antigen receptor (CAR) T-cell therapy. Each dose is customized using the recipient's own T-cells, which are collected and genetically modified, and infused back into the recipient.

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Elranatamab, sold under the brand name Elrexfio, is a medication used for the treatment of multiple myeloma. Elranatamab is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager. Elranatamab is administered subcutaneously.

References

  1. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA . Retrieved 22 October 2023.
  2. 1 2 3 4 5 "Blenrep- belantamab injection, powder, lyophilized, for solution". DailyMed. 5 August 2020. Archived from the original on 27 October 2020. Retrieved 11 August 2020.
  3. 1 2 3 4 5 6 7 8 "Blenrep EPAR". European Medicines Agency (EMA). 23 July 2020. Archived from the original on 1 November 2020. Retrieved 24 September 2020.
  4. ↑ "Blenrep Product information". Union Register of medicinal products. Archived from the original on 5 March 2023. Retrieved 3 March 2023.
  5. 1 2 3 4 5 6 7 8 9 10 11 12 "FDA granted accelerated approval to belantamab mafodotin-blmf for multiple myeloma". U.S. Food and Drug Administration (FDA). 5 August 2020. Archived from the original on 6 August 2020. Retrieved 6 August 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  6. 1 2 3 "FDA Approves GSK's Blenrep (belantamab mafodotin-blmf) for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma" (Press release). GlaxoSmithKline. 6 August 2020. Archived from the original on 6 August 2020. Retrieved 6 August 2020– via Business Wire.
  7. ↑ "New Drug Therapy Approvals 2020". U.S. Food and Drug Administration (FDA). 31 December 2020. Archived from the original on 18 January 2021. Retrieved 17 January 2021.
  8. 1 2 "Drug Approval Package: Blenrep". U.S. Food and Drug Administration (FDA). 1 August 2020. Archived from the original on 21 January 2021. Retrieved 17 January 2021.
  9. ↑ "GSK provides an update on Blenrep (belantamab mafodotin-blmf) US marketing authorization" (Press release). GSK. 22 November 2022. Archived from the original on 23 November 2022. Retrieved 23 November 2022.
  10. 1 2 3 "GSK provides update on DREAMM-3 phase III trial for Blenrep in relapsed/refractory multiple myeloma" (Press release). GSK. 11 July 2022. Archived from the original on 23 November 2022. Retrieved 23 November 2022.
  11. ↑ "GlaxoSmithKline Intellectual Property Development Ltd. England; Announcement of the Revocation of the Biologics License for Blenrep". Federal Register. 30 March 2023. Archived from the original on 30 March 2023. Retrieved 15 August 2024.
  12. ↑ "FDA granted accelerated approval to belantamab mafodotin-blmf for multiple myeloma". U.S. Food and Drug Administration. 20 March 2023. Archived from the original on 15 August 2024. Retrieved 15 August 2024.
  13. ↑ World Health Organization (2018). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 80". WHO Drug Information. 32 (3): 431–2. hdl: 10665/330907 . License: CC BY-NC-SA 3.0 IGO.

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