Identification

Summary

Tafasitamab is a CD19-directed cytolytic monoclonal antibody used in the treatment of B-cell malignancies.

Brand Names
Monjuvi
Generic Name
Tafasitamab
DrugBank Accession Number
DB15044
Background

Tafasitamab is a humanized, CD19-directed cytolytic monoclonal antibody intended for the treatment of B-cell malignancies.6 It is produced using recombinant DNA technology in Chinese hamster ovary cells, and contains an IgG1/2 hybrid Fc-domain which has been modified with 2 amino acid substitutions to enhance its cytotoxicity relative to non-engineered anti-CD19 antibodies.5,1

The CD19 surface protein is highly expressed on the surface of B-cells, where it appears to play a role in enhancing B-cell receptor signaling.6 Its relative ubiquity across different stages of B-cell development, including pre-B and mature B-lymphocytes,5 as well as its presence in several B-cell malignancies (e.g. chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), diffuse large B-cell lymphoma (DLBCL))6 has made it a desirable target in the treatment these B-cell malignancies. Tafasatimab is designed to bind to and block the activity of the CD19 surface antigen, which ultimately results in the lysis of B-cells (both healthy and malignant).5

Having previously received Breakthrough Therapy, Fast Track, and Orphan designations from the FDA,1 tafasatimab-cxix (Monjuvi®) received an accelerated approval on July 31st, 2020, for the treatment of relapsed or refractory DLBCL in adult patients who cannot receive autologous stem cell transplants.7 It must be used in combination with lenalidomide, as this combination results in greater efficacy as compared to either agent alone.5

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
Not Available
Protein Average Weight
150000.0 Da
Sequences
Not Available
Synonyms
  • Tafasitamab
  • tafasitamab-cxix
External IDs
  • MOR-00208
  • MOR-208
  • MOR00208
  • WHO 10835
  • XmAb 5574
  • XmAb-5574
  • XmAb5574

Pharmacology

Indication

Tafasitamab is indicated, in combination with lenalidomide, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified whom are ineligible for autologous stem cell transplant (ASCT).5

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Tafasitamab induces a reduction in circulating B-cell counts by binding to a surface antigen, CD19, which is important for their survival.6 Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) experienced a 97% reduction in peripheral blood B-cell counts following 8 days of treatment, with a 100% reduction reached within 16 weeks of treatment.5

Tafasitamab can cause infusion-related reactions, particularly during the initial cycles of therapy. Symptoms may include chills, flushing, dyspnea, and hypertension. Patients may be administered premedications (such as acetaminophen, antihistamines, or glucocorticoids) 0.5 - 2 hours prior to infusion to minimize infusion-related reactions.5 Tafasitamab may also cause significant myelosuppression, and subsequent infection, due to its mechanism of action - patients should undergo monitoring throughout therapy for signs of myelosuppression and/or infection.5

Mechanism of action

The CD19 surface antigen is a protein expressed on the surface of pre-B and mature B-lymphocytes5 that appears to play a role in enhancing B-cell receptor signaling and is considered integral to their survival.6 These surface proteins are also highly expressed on several B-cell malignancies, such as chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and diffuse large B-cell lymphoma (DLBCL).6

Tafasitamab is a CD19-directed cytolytic monoclonal antibody that, upon binding and blocking the activity of CD19, causes lysis of B-cells. This process is mediated through both direct apoptosis and immune-mediated effector mechanisms, such as antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).5

TargetActionsOrganism
UB-lymphocyte antigen CD19
binder
antibody
Humans
Absorption

Following intravenous administration of tafasitamab 12 mg/kg on Days 1, 8, 15, and 22 in cycle(s) 1-3 (with an additional dose on Day 4 of cycle 1), mean trough concentrations were 179 (± 53) μg/mL. From cycle 4 onwards, which involve the administration of tafasitamab 12 mg/kg on Days 1 and 15, mean trough concentrations were 153 (± 68) μg/mL.5

The overall maximum tafasitamab serum concentrations reached were 483 (± 109) μg/mL.5

Volume of distribution

The total volume of distribution of tafasitamab following intravenous injection is approximately 9.3 L.5

Protein binding

Not Available

Metabolism

The biotransformation of tafasitamab has not been elucidated. Most monoclonal antibodies undergo intracellular catabolism via lysosomal degradation to smaller amino acids and peptides.3,4

Route of elimination

Monoclonal antibodies are typically eliminated via uptake into cells and subsequent catabolism via lysosomal degradation. Due to their large size, they are only eliminated renally under pathologic conditions.4

Half-life

The terminal elimination half-life of tafasitamab is approximately 17 days.5

Clearance

The clearance of tafasitamab is approximately 0.41 L/day.5

Adverse Effects
Adverseeffects
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Toxicity

Data regarding overdose of tafasitamab are unavailable. Symptoms of overdosage are likely to be consistent with its adverse effect profile, and may therefore involve significant infusion-related reactions and/or myelosuppression.5

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 Tafasitamab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Tafasitamab.
AducanumabThe risk or severity of adverse effects can be increased when Aducanumab is combined with Tafasitamab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Tafasitamab.
AlirocumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Tafasitamab.
AmivantamabThe risk or severity of adverse effects can be increased when Tafasitamab is combined with Amivantamab.
AnifrolumabThe risk or severity of adverse effects can be increased when Anifrolumab is combined with Tafasitamab.
AnsuvimabThe risk or severity of adverse effects can be increased when Tafasitamab is combined with Ansuvimab.
Anthrax immune globulin humanThe risk or severity of adverse effects can be increased when Anthrax immune globulin human is combined with Tafasitamab.
Antilymphocyte immunoglobulin (horse)The risk or severity of adverse effects can be increased when Antilymphocyte immunoglobulin (horse) is combined with Tafasitamab.
Interactions
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Food Interactions
No interactions found.

Products

Products2
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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
MinjuviPowder, for solution200 mg / vialIntravenousIncyte CorporationNot applicableNot applicableCanada flag
MinjuviInjection, powder, for solution200 mgIntravenousIncyte Biosciences Distribution B.V.2021-10-06Not applicableEU flag
MonjuviInjection, powder, lyophilized, for solution200 mg/5mLIntravenousMorphoSys US Inc.2020-08-05Not 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
QQA9MLH692
CAS number
1422527-84-1

References

Synthesis Reference

패트릭 가리델, 안드레아스 란게르, 마틴 헤슬링, 다니엘 바인퍼트너, 보도 브록스. Anti-CD19 antibody preparation. South Korean Patent KR20190021373A. Published March 5, 2019.

General References
  1. Kaplon H, Muralidharan M, Schneider Z, Reichert JM: Antibodies to watch in 2020. MAbs. 2020 Jan-Dec;12(1):1703531. doi: 10.1080/19420862.2019.1703531. [Article]
  2. 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]
  3. Keizer RJ, Huitema AD, Schellens JH, Beijnen JH: Clinical pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet. 2010 Aug;49(8):493-507. doi: 10.2165/11531280-000000000-00000. [Article]
  4. Temrikar ZH, Suryawanshi S, Meibohm B: Pharmacokinetics and Clinical Pharmacology of Monoclonal Antibodies in Pediatric Patients. Paediatr Drugs. 2020 Apr;22(2):199-216. doi: 10.1007/s40272-020-00382-7. [Article]
  5. FDA Approved Drug Products: Monjuvi (tafasitamab-cxix) for intravenous injection [Link]
  6. Morphosys Proprietary Portfolio: Tafasitamab (MOR208) [Link]
  7. FDA Drug Approvals: FDA grants accelerated approval to tafasitamab-cxix for diffuse large B-cell lymphoma [Link]
RxNav
2387334
Wikipedia
Tafasitamab

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3RecruitingTreatmentDiffuse Large B-Cell Lymphoma (DLBCL)1
3RecruitingTreatmentFollicular Lymphoma ( FL) / Marginal Zone Lymphoma (MZL)1
2Active Not RecruitingTreatmentB-Cell Chronic Lymphocytic Leukemia (B-CLL) / Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma1
2Active Not RecruitingTreatmentChronic Lymphocytic Leukemia (CLL) - Refractory / Contiguous Stage II Small Lymphocytic Lymphoma / Noncontiguous Stage II Small Lymphocytic Lymphoma / Prolymphocytic Leukaemia (PLL) / Recurrent Small Lymphocytic Lymphoma / Stage I Chronic Lymphocytic Leukemia / Stage I Small Lymphocytic Lymphoma / Stage II Chronic Lymphocytic Leukemia / Stage III Chronic Lymphocytic Leukemia / Stage III Small Lymphocytic Lymphoma / Stage IV Chronic Lymphocytic Leukemia / Stage IV Small Lymphocytic Lymphoma1
2Active Not RecruitingTreatmentDiffuse Large B-Cell Lymphoma (DLBCL)1
2Active Not RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)1
2Not Yet RecruitingTreatmentDiffuse Large B-Cell Lymphoma (DLBCL)2
2RecruitingTreatmentMarginal Zone Lymphoma (MZL)1
2TerminatedTreatmentAcute Lymphoblastic Leukemia (ALL)1
2, 3Active Not RecruitingTreatmentDiffuse Large B-Cell Lymphoma (DLBCL)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, powder, for solutionIntravenous200 mg
Powder, for solutionIntravenous200 mg / vial
Injection, powder, lyophilized, for solutionIntravenous200 mg/5mL
CapsuleOral150 MG
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
Antibody
General Function
Receptor signaling protein activity
Specific Function
Assembles with the antigen receptor of B-lymphocytes in order to decrease the threshold for antigen receptor-dependent stimulation.
Gene Name
CD19
Uniprot ID
P15391
Uniprot Name
B-lymphocyte antigen CD19
Molecular Weight
61127.985 Da
References
  1. FDA Approved Drug Products: Monjuvi (tafasitamab-cxix) for intravenous injection [Link]

Drug created at May 20, 2019 14:44 / Updated at August 05, 2021 01:52