Belantamab mafodotin

Identification

Name
Belantamab mafodotin
Accession Number
DB15719
Description

Belantamab mafodotin, or GSK2857916, is an afucosylated monoclonal antibody that targets B cell maturation antigen conjugated to the microtubule distrupter monomethyl auristatin-F (MMAF).1

Belantamab mafodotin was granted FDA approval on 5 August 2020.10

Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
Not Available
Protein Average Weight
Not Available
Sequences
Not Available
Synonyms
  • Belantamab mafodotin
  • Belantamab Mafodotin-blmf
External IDs
  • GSK 2857916
  • GSK-2857916
  • GSK2857916
  • WHO 10754

Pharmacology

Indication

Belantamab mafodotin is indicated in the treatment of adults with relapsed or refractory multiple myeloma who have received at least 4 prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent.10

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
Pharmacodynamics

Belantamab mafodotin treats multiple myeloma through antibody dependant cell mediated cytotoxicity as well as G2/M cell cycle arrest.4 It has a narrow therapeutic index due to the incidence of adverse effects, and a long duration of action as it is given every 3 weeks.10 Patients should be counselled regarding the risk of keratopathy.10

Mechanism of action

Belantamab mafodotin, or GSK2857916, is an afucosylated monoclonal antibody that targets B cell maturation antigen (BCMA) conjugated to the microtubule distrupter monomethyl auristatin-F (MMAF).1 Afucosylation of the Fc region of monoclonal antibodies enhances binding to the Fc region, which enhances antibody dependant cell mediated cytoxicity.4

BCMA is uniquely expressed on CD138-positive myeloma cells.1 Targeting BCMA allows belantamab mafodotin to be highly selective in its delivery of MMAF to multiple myeloma cells.1 Belantamab mafodotin binds to BCMA, is internalised into cells, and releases MMAF.1

The MMAF payload binds to tubulin, stopping the cell cycle at the DNA damage checkpoint between the G2 and M phases, resulting in apoptosis.4

TargetActionsOrganism
UTumor necrosis factor receptor superfamily member 17
binder
Humans
Absorption

Belantamab mafodotin at a dose of 2.5mg/kg reaches a Cmax of 42 µg/mL, with a Tmax of 0.78 hours, and an AUC of 4666 µg*h/mL.10

Volume of distribution

The mean steady state volume of distribution of belantamab mafodotin was 11 L.10

Protein binding

Monoclonal antibodies are generally not protein bound5,6.

Metabolism

Monoclonal antibodies are expected to be metabolized to smaller peptides and amino acids.10 MMAF is expected to be metabolized by oxidation and demethylation, however further data is not readily available.9,8

Hover over products below to view reaction partners

Route of elimination

Monoclonal antibodies are eventually phagocytosed and broken down to smaller peptides and amino acids which are eliminated in a similar fashion to other proteins.5,6 Monoclonal antibodies are generally not eliminated in the urine, and only a small amount is excreted in bile.7

Half-life

The terminal half life of belantamab mafodotin was 12 days after the first dose and 14 days at steady state.10

Clearance

The clearance of belantamab mafodotin was 0.9 L/day after the first dose and 0.7 L/day at steady state.10

Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

Data regarding overdose is not readily available.10 However, keratopathy was seen in 71% of patients.1,2,3,10

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
No interactions found.

Products

International/Other Brands
BLENREP
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
BlenrepInjection, powder, lyophilized, for solution50 mg/1mLIntravenousGlaxoSmithKline LLC2020-08-05Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Chemical Identifiers

UNII
DB1041CXDG
CAS number
2050232-20-5

References

General References
  1. Trudel S, Lendvai N, Popat R, Voorhees PM, Reeves B, Libby EN, Richardson PG, Hoos A, Gupta I, Bragulat V, He Z, Opalinska JB, Cohen AD: Antibody-drug conjugate, GSK2857916, in relapsed/refractory multiple myeloma: an update on safety and efficacy from dose expansion phase I study. Blood Cancer J. 2019 Mar 20;9(4):37. doi: 10.1038/s41408-019-0196-6. [PubMed:30894515]
  2. Popat R, Warcel D, O'Nions J, Cowley A, Smith S, Tucker WR, Yong K, Esposti SD: Characterization of response and corneal events with extended follow-up after belantamab mafodotin (GSK2857916) monotherapy for patients with relapsed multiple myeloma: a case series from the first-time-in-human clinical trial. Haematologica. 2020 May;105(5):e261-e263. doi: 10.3324/haematol.2019.235937. Epub 2020 Feb 27. [PubMed:32107339]
  3. Authors unspecified: Anti-BCMA Therapy Endorsed, despite Eye Toxicity. Cancer Discov. 2020 Aug 5. pii: 2159-8290.CD-NB2020-074. doi: 10.1158/2159-8290.CD-NB2020-074. [PubMed:32759303]
  4. McMillan A, Warcel D, Popat R: Antibody-drug conjugates for multiple myeloma. Expert Opin Biol Ther. 2020 Jul 30. doi: 10.1080/14712598.2020.1802422. [PubMed:32729730]
  5. Tabrizi MA, Tseng CM, Roskos LK: Elimination mechanisms of therapeutic monoclonal antibodies. Drug Discov Today. 2006 Jan;11(1-2):81-8. doi: 10.1016/S1359-6446(05)03638-X. [PubMed:16478695]
  6. Lobo ED, Hansen RJ, Balthasar JP: Antibody pharmacokinetics and pharmacodynamics. J Pharm Sci. 2004 Nov;93(11):2645-68. doi: 10.1002/jps.20178. [PubMed:15389672]
  7. Ryman JT, Meibohm B: Pharmacokinetics of Monoclonal Antibodies. CPT Pharmacometrics Syst Pharmacol. 2017 Sep;6(9):576-588. doi: 10.1002/psp4.12224. Epub 2017 Jul 29. [PubMed:28653357]
  8. Doronina SO, Mendelsohn BA, Bovee TD, Cerveny CG, Alley SC, Meyer DL, Oflazoglu E, Toki BE, Sanderson RJ, Zabinski RF, Wahl AF, Senter PD: Enhanced activity of monomethylauristatin F through monoclonal antibody delivery: effects of linker technology on efficacy and toxicity. Bioconjug Chem. 2006 Jan-Feb;17(1):114-24. doi: 10.1021/bc0502917. [PubMed:16417259]
  9. Park MH, Lee BI, Byeon JJ, Shin SH, Choi J, Park Y, Shin YG: Pharmacokinetic and Metabolism Studies of Monomethyl Auristatin F via Liquid Chromatography-Quadrupole-Time-of-Flight Mass Spectrometry. Molecules. 2019 Jul 29;24(15). pii: molecules24152754. doi: 10.3390/molecules24152754. [PubMed:31362431]
  10. FDA Approved Drug Products: Blenrep Belantamab Mafodotin-blmf Intravenous Injection [Link]
RxNav
2387833
Wikipedia
Belantamab_mafodotin

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Not Yet RecruitingTreatmentMultiple Myeloma (MM)2
3RecruitingTreatmentMultiple Myeloma (MM)2
2Active Not RecruitingTreatmentMultiple Myeloma (MM)1
2RecruitingTreatmentMultiple Myeloma (MM)3
1Active Not RecruitingTreatmentMultiple Myeloma (MM)1
1CompletedTreatmentMultiple Myeloma (MM)1
1Not Yet RecruitingTreatmentMultiple Myeloma (MM)2
1RecruitingTreatmentMultiple Myeloma (MM)2
1, 2RecruitingTreatmentRelapsed and/or Refractory Multiple Myeloma1
Not AvailableAvailableNot AvailableMultiple Myeloma (MM)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous50 mg/1mL
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Receptor for TNFSF13B/BLyS/BAFF and TNFSF13/APRIL. Promotes B-cell survival and plays a role in the regulation of humoral immunity. Activates NF-kappa-B and JNK.
Specific Function
Signaling receptor activity
Gene Name
TNFRSF17
Uniprot ID
Q02223
Uniprot Name
Tumor necrosis factor receptor superfamily member 17
Molecular Weight
20165.065 Da
References
  1. FDA Approved Drug Products: Blenrep Belantamab Mafodotin-blmf Intravenous Injection [Link]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. FDA Approved Drug Products: Blenrep Belantamab Mafodotin-blmf Intravenous Injection [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. FDA Approved Drug Products: Blenrep Belantamab Mafodotin-blmf Intravenous Injection [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Transporter activity
Specific Function
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotre...
Gene Name
ABCC1
Uniprot ID
P33527
Uniprot Name
Multidrug resistance-associated protein 1
Molecular Weight
171589.5 Da
References
  1. FDA Approved Drug Products: Blenrep Belantamab Mafodotin-blmf Intravenous Injection [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
References
  1. FDA Approved Drug Products: Blenrep Belantamab Mafodotin-blmf Intravenous Injection [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Organic anion transmembrane transporter activity
Specific Function
May act as an inducible transporter in the biliary and intestinal excretion of organic anions. Acts as an alternative route for the export of bile acids and glucuronides from cholestatic hepatocyte...
Gene Name
ABCC3
Uniprot ID
O15438
Uniprot Name
Canalicular multispecific organic anion transporter 2
Molecular Weight
169341.14 Da
References
  1. FDA Approved Drug Products: Blenrep Belantamab Mafodotin-blmf Intravenous Injection [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. FDA Approved Drug Products: Blenrep Belantamab Mafodotin-blmf Intravenous Injection [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. FDA Approved Drug Products: Blenrep Belantamab Mafodotin-blmf Intravenous Injection [Link]

Drug created on August 06, 2020 13:10 / Updated on September 03, 2020 17:44

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Logo pink
Stay in the know!
As part of our commitment to providing the most up-to-date drug information, we will be releasing #DrugBankUpdates with our newly added curated drug pages.
#DrugBankUpdates