NAV

Ublituximab

Identification

Summary

Ublituximab is a low-fucose CD20-targeted monoclonal antibody used in the treatment of relapsing forms of multiple sclerosis.

Brand Names
Briumvi
Generic Name
Ublituximab
DrugBank Accession Number
DB11850
Background

CD20, an antigen expressed by various B and T cells, is an attractive therapeutic target in various cancers and autoimmune conditions.1,2,3 Monoclonal antibodies for B cell depletion rely on their binding affinity and ability to clear bound cells through mechanisms such as antibody-dependent cellular cytotoxicity (ADCC), mediated by interactions between an antibody and Fcγ receptors on natural killer cells or macrophages.4 Ublituximab is a chimeric anti-CD20 IgG1κ antibody produced in the rat YB2/0 cell line to target a unique epitope and enhance ADCC compared to other approved anti-CD20 antibodies such as rituximab, ofatumumab, obinutuzumab, and ocrelizumab.4,5,7

Ublituximab was initially developed by LFB Group but was licensed to TG Therapeutics in 2012. It has been investigated for use in numerous B cell-dependent conditions, including chronic lymphocytic leukemia, non-Hodgkin's lymphoma, and relapsing multiple sclerosis.7 In December 2022, ublituximab was approved by the US FDA for the treatment of relapsing forms of multiple sclerosis, becoming the first and only anti-CD20 monoclonal antibody for multiple sclerosis allowing for administration in a one-hour infusion twice-a-year following the starting dose.9

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
Not Available
Protein Average Weight
147000.0 Da
Sequences
>SUBUNIT_1
QAYLQQSGAELVRPGASVKMSCKASGYTFTSYNMHWVKQTPRQGLEWIGGIYPGNGDTSY
NQKFKGKATLTVGKSSSTAYMQLSSLTSEDSAVYFCARYDYNYAMDYWGQGTSVTVSSAS
TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL
YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS
VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST
YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELT
KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ
GNVFSCSVMHEALHNHYTQKSLSLSPGK
>SUBUNIT_2
QAYLQQSGAELVRPGASVKMSCKASGYTFTSYNMHWVKQTPRQGLEWIGGIYPGNGDTSY
NQKFKGKATLTVGKSSSTAYMQLSSLTSEDSAVYFCARYDYNYAMDYWGQGTSVTVSSAS
TKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGL
YSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPS
VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST
YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELT
KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ
GNVFSCSVMHEALHNHYTQKSLSLSPGK
>SUBUNIT_3
QIVLSQSPAILSASPGEKVTMTCRASSSVSYMHWYQQKPGSSPKPWIYATSNLASGVPAR
FSGSGSGTSYSFTISRVEAEDAATYYCQQWTFNPPTFGGGTRLEIKRTVAAPSVFIFPPS
DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL
SKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
>SUBUNIT_4
QIVLSQSPAILSASPGEKVTMTCRASSSVSYMHWYQQKPGSSPKPWIYATSNLASGVPAR
FSGSGSGTSYSFTISRVEAEDAATYYCQQWTFNPPTFGGGTRLEIKRTVAAPSVFIFPPS
DEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL
SKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
References:
  1. NIH Inxight: Ublituximab [Link]
Download FASTA Format
Synonyms
  • Ublituximab
External IDs
  • TG-1101

Pharmacology

Indication

Ublituximab is indicated in adult patients for the treatment of relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.8

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Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Treatment with ublituximab reduces CD19+ B-cell counts - used as a surrogate marker for CD20+ B-cells due to ublituximab's interference with the CD20 assay - within 24 hours of the initial infusion.8 The median time for B-cell counts to return to either baseline or the lower limit of normal (LLN) was 70.3 weeks following the final infusion, and within 1.5 years of the final infusion approximately 58% of patients had returned to baseline or LLN.8

Mechanism of action

B-cell dysregulation underlies the pathogenesis of various cancers and autoimmune conditions such as multiple sclerosis, neuromyelitis optica spectrum disease, and myelin oligodendrocyte glycoprotein IgG-associated disease.1,2,3 CD20 is an antigen expressed on pre-B cells, immature/mature B-cells, memory B-cells, and a subpopulation of CD3-positive T cells.2 Anti-CD20 antibodies can therefore induce B-cell depletion through direct cell death, induction of complement pathways, and Fc-gamma receptor (FcγR)-mediated phagocytosis (antibody-dependent cellular cytotoxicity, ADCC).4

Although several anti-CD20 antibodies have been developed, therapy has been hampered by low CD20 expression by malignant cells in diseases such as B-cell chronic lymphocytic leukemia and suboptimal antibody-dependent cytotoxicity.5 Ublituximab binds to an epitope on CD20 distinct from that bound by other approved antibodies such as rituximab, ofatumumab, obinutuzumab, and ocrelizumab, with a similar binding constant to rituximab.4,5 Uniquely, ublituximab is produced in the rat YB2/0 cell line such that it has a low fucose content (24% compared to 93% for rituximab), improving its interaction with FcγR, especially FcγRIIIA (CD16) expressed by natural killer cells and macrophages.4,5 This difference grants ublituximab enhanced ADCC, including for low CD20-expressing malignant cells.5,6

The precise mechanism of action of ublituximab in the treatment of multiple sclerosis is unclear, but is presumed to involve CD20 binding and subsequent cell lysis as described above.8

TargetActionsOrganism
AB-lymphocyte antigen CD20
binder
antibody
Humans
Absorption

Following the administration of the approved recommended dosage of ublituximab, the geometric mean steady-state AUC was 3000 mcg/mL per day and the mean Cmax was 139 mcg/mL.8 In patients with relapsing multiple sclerosis, ublituximab exposure increases proportionally over a dose range of 150mg to 600mg.8

Volume of distribution

The estimated central volume of distribution of ublituximab-xiiy was 3.18 L.8

Protein binding

Not Available

Metabolism

As with other therapeutic proteins, the metabolism of ublituximab likely occurs via degradation to smaller peptides and amino acids by non-specific proteolytic enzymes.8

Route of elimination

Not Available

Half-life

The estimated mean terminal half-life of ublituximab-xiiy was 22 days.8

Clearance

Not Available

Adverse Effects
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Toxicity

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.
DrugInteraction
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interactions in your software
AbataceptThe risk or severity of infection can be increased when Ublituximab is combined with Abatacept.
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Ublituximab.
AdalimumabThe risk or severity of infection can be increased when Ublituximab is combined with Adalimumab.
AducanumabThe risk or severity of adverse effects can be increased when Ublituximab is combined with Aducanumab.
AlclometasoneThe risk or severity of infection can be increased when Ublituximab is combined with Alclometasone.
AldesleukinThe risk or severity of infection can be increased when Ublituximab is combined with Aldesleukin.
AlefaceptThe risk or severity of infection can be increased when Ublituximab is combined with Alefacept.
AlemtuzumabThe risk or severity of infection can be increased when Ublituximab is combined with Alemtuzumab.
AlirocumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Ublituximab.
AltretamineThe risk or severity of infection can be increased when Ublituximab is combined with Altretamine.
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Food Interactions
Not Available

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
BriumviInjection, solution, concentrate150 mg/6mLIntravenousTg Therapeutics, Inc.2022-12-28Not 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
  • Humans and other mammals

Chemical Identifiers

UNII
U59UGK3IPC
CAS number
1174014-05-1

References

General References
  1. Babiker HM, Glode AE, Cooke LS, Mahadevan D: Ublituximab for the treatment of CD20 positive B-cell malignancies. Expert Opin Investig Drugs. 2018 Apr;27(4):407-412. doi: 10.1080/13543784.2018.1459560. Epub 2018 Apr 3. [Article]
  2. Graf J, Mares J, Barnett M, Aktas O, Albrecht P, Zamvil SS, Hartung HP: Targeting B Cells to Modify MS, NMOSD, and MOGAD: Part 1. Neurol Neuroimmunol Neuroinflamm. 2020 Dec 16;8(1). pii: 8/1/e918. doi: 10.1212/NXI.0000000000000918. Print 2021 Jan. [Article]
  3. Graf J, Mares J, Barnett M, Aktas O, Albrecht P, Zamvil SS, Hartung HP: Targeting B cells to modify MS, NMOSD, and MOGAD: Part 2. Neurol Neuroimmunol Neuroinflamm. 2020 Dec 16;8(1). pii: 8/1/e919. doi: 10.1212/NXI.0000000000000919. Print 2021 Jan. [Article]
  4. Fox E, Lovett-Racke AE, Gormley M, Liu Y, Petracca M, Cocozza S, Shubin R, Wray S, Weiss MS, Bosco JA, Power SA, Mok K, Inglese M: A phase 2 multicenter study of ublituximab, a novel glycoengineered anti-CD20 monoclonal antibody, in patients with relapsing forms of multiple sclerosis. Mult Scler. 2021 Mar;27(3):420-429. doi: 10.1177/1352458520918375. Epub 2020 Apr 30. [Article]
  5. de Romeuf C, Dutertre CA, Le Garff-Tavernier M, Fournier N, Gaucher C, Glacet A, Jorieux S, Bihoreau N, Behrens CK, Beliard R, Vieillard V, Cazin B, Bourel D, Prost JF, Teillaud JL, Merle-Beral H: Chronic lymphocytic leukaemia cells are efficiently killed by an anti-CD20 monoclonal antibody selected for improved engagement of FcgammaRIIIA/CD16. Br J Haematol. 2008 Mar;140(6):635-43. doi: 10.1111/j.1365-2141.2007.06974.x. [Article]
  6. Le Garff-Tavernier M, Herbi L, de Romeuf C, Nguyen-Khac F, Davi F, Grelier A, Boudjoghra M, Maloum K, Choquet S, Urbain R, Vieillard V, Merle-Beral H: Antibody-dependent cellular cytotoxicity of the optimized anti-CD20 monoclonal antibody ublituximab on chronic lymphocytic leukemia cells with the 17p deletion. Leukemia. 2014 Jan;28(1):230-3. doi: 10.1038/leu.2013.240. Epub 2013 Aug 20. [Article]
  7. Kaplon H, Reichert JM: Antibodies to watch in 2021. MAbs. 2021 Jan-Dec;13(1):1860476. doi: 10.1080/19420862.2020.1860476. [Article]
  8. FDA Approved Drug Products: Briumvi (ublituximab-xiiy) for intravenous injection [Link]
  9. TG Therapeutics Press Release: TG Therapeutics Announces FDA Approval of BRIUMVI™ (ublituximab-xiiy) [Link]
PubChem Substance
347911248
RxNav
2626349
Wikipedia
Ublituximab

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentChronic Lymphocytic Leukemia1
3CompletedTreatmentChronic Lymphocytic Leukemia1
3CompletedTreatmentRelapsing Multiple Sclerosis (RMS)2
3Enrolling by InvitationTreatmentRelapsing Multiple Sclerosis (RMS)1
2Active Not RecruitingTreatmentChronic Lymphocytic Leukemia / Chronic Lymphocytic Leukemia (CLL) - Refractory / Relapsed Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma1
2Active Not RecruitingTreatmentMantle Cell Lymphoma (MCL)1
2CompletedTreatmentMultiple Sclerosis1
2CompletedTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)1
2RecruitingTreatmentChronic Lymphocytic Leukemia / Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) / CLL Progression1
2SuspendedTreatmentFollicular Lymphoma ( FL) / Marginal Zone Lymphoma (MZL)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solution, concentrateIntravenous150 mg/6mL
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Targets

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Details1. B-lymphocyte antigen CD20
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Binder
Antibody
General Function
Mhc class ii protein complex binding
Specific Function
This protein may be involved in the regulation of B-cell activation and proliferation.
Gene Name
MS4A1
Uniprot ID
P11836
Uniprot Name
B-lymphocyte antigen CD20
Molecular Weight
33076.99 Da
References
  1. Fox E, Lovett-Racke AE, Gormley M, Liu Y, Petracca M, Cocozza S, Shubin R, Wray S, Weiss MS, Bosco JA, Power SA, Mok K, Inglese M: A phase 2 multicenter study of ublituximab, a novel glycoengineered anti-CD20 monoclonal antibody, in patients with relapsing forms of multiple sclerosis. Mult Scler. 2021 Mar;27(3):420-429. doi: 10.1177/1352458520918375. Epub 2020 Apr 30. [Article]
  2. de Romeuf C, Dutertre CA, Le Garff-Tavernier M, Fournier N, Gaucher C, Glacet A, Jorieux S, Bihoreau N, Behrens CK, Beliard R, Vieillard V, Cazin B, Bourel D, Prost JF, Teillaud JL, Merle-Beral H: Chronic lymphocytic leukaemia cells are efficiently killed by an anti-CD20 monoclonal antibody selected for improved engagement of FcgammaRIIIA/CD16. Br J Haematol. 2008 Mar;140(6):635-43. doi: 10.1111/j.1365-2141.2007.06974.x. [Article]
  3. Le Garff-Tavernier M, Herbi L, de Romeuf C, Nguyen-Khac F, Davi F, Grelier A, Boudjoghra M, Maloum K, Choquet S, Urbain R, Vieillard V, Merle-Beral H: Antibody-dependent cellular cytotoxicity of the optimized anti-CD20 monoclonal antibody ublituximab on chronic lymphocytic leukemia cells with the 17p deletion. Leukemia. 2014 Jan;28(1):230-3. doi: 10.1038/leu.2013.240. Epub 2013 Aug 20. [Article]
  4. FDA Approved Drug Products: Briumvi (ublituximab-xiiy) for intravenous injection [Link]

Drug created at October 20, 2016 20:53 / Updated at January 05, 2023 10:09