NAV

Tisagenlecleucel

Identification

Summary

Tisagenlecleucel is a CAR T cell therapy for relapsed or refractory large B-cell lymphoma and diffuse large B-cell lymphoma.

Brand Names
Kymriah
Generic Name
Tisagenlecleucel
DrugBank Accession Number
DB13881
Background

Tisagenlecleucel is a CD19-directed genetically modified autologous T cell immunotherapy, or a CAR-T cell therapy for B-cell acute lymphoblastic leukemia. It was granted approval by FDA in August 2017 under the market name Kymriah. Tisagenlecleucel is an immunocellular therapy that involves autologous T cells that are collected from each individual patient and genetically engineered to express a specific protein called a chimeric antigen receptor (CAR) that specifically target CD19 antigens. Modified T cells are infused back into the patient's body. These CD19-directed chimeric antigen receptors (CD19 CAR-T cells) direct the T cells to target and kill leukemia cells that express CD19 on the cell surface.

In a multicenter clinical trial involving pediatric and young adult patients with relapsed or refractory B-cell precursor ALL, the overall remission rate within three months of treatment was 83 percent.4

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Cell transplant therapies
Autologous cell transplant
Synonyms
  • Adoptive immunotherapy agent CTL019
  • CAR.CD19-Redirected T cells
  • Tisagenlecleucel
  • Tisagenlecleucel-T
External IDs
  • CART-19
  • CART19
  • CTL-019
  • CTL019
Poor quality drug data slowing you down?
Unlock 38% more drug discovery time and eliminate decision-making doubts with this one-stop guide to quality drug data.
Download eBook
Poor quality drug data slowing you down?
Download eBook

Pharmacology

Indication

Tisagenlecleucel is indicated for use in individuals aged 25 years and younger with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse.5

It is also used to treat adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.5

Tisagenlecleucel is also indicated in adult patients with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy.5

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofRefractory diffuse large b cell lymphoma (dlbcl)•••••••••••••••••••••• •• ••••• •• •••••••• ••••••••••••••••• ••••••••••
Treatment ofRefractory follicular lymphoma•••••••••••••••••••••• •• ••••• •• •••••••• ••••••••••••••••• ••••••••••
Treatment ofRelapsed diffuse large b-cell lymphoma (dlbcl)•••••••••••••••••••••• •• ••••• •• •••••••• ••••••••••••••••• ••••••••••
Treatment ofRelapsed follicular lymphoma•••••••••••••••••••••• •• ••••• •• •••••••• ••••••••••••••••• ••••••••••
Treatment ofRefractory b-cell precursor acute lymphoblastic leukemia••••••••••••••••••••••• •••••• ••••••••••••••••••• ••••••••••
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
Pharmacodynamics

Tisagenlecleucel demonstrates efficacy in re-inducing remission in patients with refractory B-cell precursor acute lymphoblastic leukemia. The sole purpose of the therapy is to eliminate CD19-expressing malignant and normal cells with specificity and increased chance of remission.

Mechanism of action

Tisagenlecleucel is a CD19-directed genetically modified autologous T cell immunotherapy that involves genetically modified autologous T cells isolated from each individual patient. The reprogramming of the patient's T cells uses a lentiviral vector to encode an anti-CD19 chimeric antigen receptor (CAR). The CAR is comprised of a murine single-chain antibody fragment (scFv) specific for CD19, followed by a CD8 hinge and transmembrane region that is fused to the intracellular signaling domains from 4-1BB (CD137) and CD3 zeta.5 These intracellular costimulatory signaling domains increase the expansion, longer-term persistence and potency of CAR T cells1,3; the CD3 zeta component is critical for initiating T-cell activation and antitumor activity, while 4-1BB enhances the expansion and persistence of tisagenlecleucel.5,2 Upon binding to CD19-expressing cells, the CAR transmits a signal to promote T-cell expansion, activation, target cell elimination, and persistence of the tisagenlecleucel cells.5

TargetActionsOrganism
AB-lymphocyte antigen CD19
antibody
Humans
Absorption

In pediatric and young adult relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) patients receiving tisagenlecleucel infusion, the mean peak plasma concentration was approximately 34,700 copies/mcg with a median time of 9.91 days to reach this value (Tmax).5

Volume of distribution

The drug is found to be distributed in the blood as well as the bone marrow. Blood to bone marrow partitioning suggested that tisagenlecleucel distribution in bone marrow was 44% of that present in blood at Day 28 while at Months 3 and 6 tisagenlecleucel distributed at 67% and 69%, respectively, indicating high distribution to bone marrow.5

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

The mean half life was 16.8 days in pediatric and young adult relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) patients.5

Clearance

Not Available

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

Genotoxicity assay, carcinogenicitiy assay, and studies assesssing the effect of drug on fertility have not been conducted for tisagenlecleucel. According to in vitro T cell expansion studies involving transduced T cells from healthy donors and patients, there is no evidence of transformation and immortality.5

Pathways
Not Available
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
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
Integrate drug-drug
interactions in your software
AmbroxolThe risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Ambroxol.
ArticaineThe risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Articaine.
BenzocaineThe risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Benzocaine.
Benzyl alcoholThe risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Benzyl alcohol.
BupivacaineThe risk or severity of methemoglobinemia can be increased when Tisagenlecleucel is combined with Bupivacaine.
Food Interactions
No interactions found.

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
KymriahInjection, suspension60000000 1/1IntravenousNovartis Pharmaceuticals Corporation2018-05-01Not applicableUS flag
Kymriah300600000 cellsIntravenousNovartis Europharm Limited2020-12-16Not applicableEU flag
KymriahInjection, suspension2000000 1/1IntravenousNovartis Pharmaceuticals Corporation2017-08-30Not applicableUS flag
KymriahSuspension600000000 cellsIntravenousNovartis2019-05-24Not applicableCanada flag

Categories

ATC Codes
L01XL04 — Tisagenlecleucel
Drug Categories
Classification
Not classified
Affected organisms
Not Available

Chemical Identifiers

UNII
Q6C9WHR03O
CAS number
1823078-37-0

References

General References
  1. Tasian SK, Gardner RA: CD19-redirected chimeric antigen receptor-modified T cells: a promising immunotherapy for children and adults with B-cell acute lymphoblastic leukemia (ALL). Ther Adv Hematol. 2015 Oct;6(5):228-41. doi: 10.1177/2040620715588916. [Article]
  2. Wei G, Ding L, Wang J, Hu Y, Huang H: Advances of CD19-directed chimeric antigen receptor-modified T cells in refractory/relapsed acute lymphoblastic leukemia. Exp Hematol Oncol. 2017 Apr 14;6:10. doi: 10.1186/s40164-017-0070-9. eCollection 2017. [Article]
  3. Davila ML, Brentjens RJ: CD19-Targeted CAR T cells as novel cancer immunotherapy for relapsed or refractory B-cell acute lymphoblastic leukemia. Clin Adv Hematol Oncol. 2016 Oct;14(10):802-808. [Article]
  4. FDA Press Announcements: FDA approval brings first gene therapy to the United States [Link]
  5. FDA Approved Drug Products: Kymriah (tisagenlecleucel) suspension for intravenous infusion [Link]
PubChem Substance
347911451
RxNav
1986438
Wikipedia
Tisagenlecleucel
FDA label
Download (222 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)1
3CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL)1
3RecruitingTreatmentB-cell Acute Lymphoblastic Leukemia / Diffuse Large B-Cell Lymphoma (DLBCL)1
3RecruitingTreatmentFollicular Lymphoma ( FL)1
3WithdrawnTreatmentAcute Lymphoblastic Leukaemias (ALL)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, suspensionIntravenous2000000 1/1
Injection, suspensionIntravenous300600.000 cells
Injection, suspensionIntravenous60000000 1/1
SuspensionIntravenous600000000 cells
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Details1. B-lymphocyte antigen CD19
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
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

Drug created at September 01, 2017 18:43 / Updated at July 02, 2022 14:09