Belantamab mafodotin

Identification

Summary

Belantamab mafodotin is an anti B-cell maturation antigen antibody conjugated to a microtubule inhibitor to treat relapsed or refractory multiple myeloma.

Brand Names
BLENREP
Generic Name
Belantamab mafodotin
DrugBank Accession Number
DB15719
Background

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

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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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

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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
Adverseeffects
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Toxicity

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

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.
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Belantamab mafodotin.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Belantamab mafodotin.
AcetylcysteineThe excretion of Belantamab mafodotin can be decreased when combined with Acetylcysteine.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Belantamab mafodotin.
AducanumabThe risk or severity of adverse effects can be increased when Aducanumab is combined with Belantamab mafodotin.
AfatinibThe serum concentration of Belantamab mafodotin can be increased when it is combined with Afatinib.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Belantamab mafodotin.
AlirocumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Belantamab mafodotin.
AmbrisentanThe serum concentration of Belantamab mafodotin can be increased when it is combined with Ambrisentan.
Aminohippuric acidThe excretion of Belantamab mafodotin can be decreased when combined with Aminohippuric acid.
Interactions
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Food Interactions
No interactions found.

Products

Products2
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International/Other Brands
BLENREP
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
BlenrepInjection, powder, for solution100 mgIntravenousGlaxo Smith Kline (Ireland) Limited2020-12-16Not applicableEU flag
BlenrepInjection, powder, lyophilized, for solution50 mg/1mLIntravenousGlaxoSmithKline LLC2020-08-05Not applicableUS flag

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
Affected organisms
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  10. FDA Approved Drug Products: Blenrep Belantamab Mafodotin-blmf Intravenous Injection [Link]
RxNav
2387833
Wikipedia
Belantamab_mafodotin

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentMultiple Myeloma (MM)1
3RecruitingBasic ScienceMultiple Myeloma (MM)1
3RecruitingTreatmentMultiple Myeloma (MM)2
2Active Not RecruitingTreatmentMultiple Myeloma (MM)1
2Not Yet RecruitingTreatmentMultiple Myeloma (MM)1
2Not Yet RecruitingTreatmentPlasma Cell Myeloma1
2RecruitingTreatmentAL Amyloidosis1
2RecruitingTreatmentAnaplastic Lymphoma Kinase Positive Large B-Cell Lymphoma / Refractory Plasmablastic Lymphoma / Relapsed Plasmablastic Lymphoma1
2RecruitingTreatmentMultiple Myeloma (MM)1
2RecruitingTreatmentPlasma Cell Myeloma1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, powder, for solutionIntravenous100 MG
Injection, powder, lyophilized, for solutionIntravenous50 mg/1mL
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Targets

Drugtargets2
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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 19:10 / Updated on February 21, 2021 18:55