NAV

Axicabtagene ciloleucel

Identification

Summary

Axicabtagene ciloleucel is a CAR T-cell therapy used to treat adults with large B-cell lymphomas and follicular lymphoma.

Brand Names
Yescarta
Generic Name
Axicabtagene ciloleucel
DrugBank Accession Number
DB13915
Background

Axicabtagene ciloleucel is an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy. The drug has a unique mechanism of action, as it utilizes the patient's own T cells, which play a central role in immune response to cancer.3 Once T-cells are collected from the patient, they are genetically engineered to express anti-CD19 CARs that recognize and kill cancer cells, and are infused back into the patient.2 Each dose of axicabtagene ciloleucel represent the patient's genetically modified T-cells.4 The development of resulted from early preclinical studies conducted by a group of researchers at the National Cancer Institute (NCI), who demonstrated that T cells expressing an anti-CD19 CAR can produce cytokines that efficiently kill leukemic cells in vitro.3

Axicabtagene ciloleucel was approved by the FDA on October 18th, 2017. It is marketed under the brand name Yescarta and is used to treat large B-cell lymphomas and follicular lymphoma in adults.4 Axicabtagene ciloleucel was later approved by the EMA on August 23, 2018.5

Type
Biotech
Groups
Approved
Biologic Classification
Cell transplant therapies
Autologous cell transplant
Synonyms
  • Autologous T cells transduced with retroviral vector encoding an anti-CD-19 CD28/CD3-zeta chimeric antigen receptor
  • Axicabtagene ciloleucel
External IDs
  • KTE-C19
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Pharmacology

Indication

In the US, axicabtagene ciloleucel is indicated for the treatment of adults with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy.4

In the US and Europe, it is used to treat adults with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.4,5

Axicabtagene ciloleucel is also used to treat adults with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy in the US,4 or three or more lines of systemic therapy in Europe.5

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofRefractory diffuse large b cell lymphoma (dlbcl)•••••••••••••••••••••••••••
Treatment ofRefractory diffuse large b-cell lymphoma (dlbcl)•••••••••••••••••••••••••••
Treatment ofRefractory follicular lymphoma••••••••••••••••••••••••• •• ••••• ••••• ••••• ••••• •• •••••••• •••••••
Treatment ofRefractory follicular lymphoma•••••••••••••••••••••••••••
Treatment ofRefractory large b-cell lymphoma••••••••••••••••••••••••••• •• ••••••••••••• •••••••• •••••••••• ••••••••••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Axicabtagene ciloleucel transiently increases the levels of chemokines, such as IL-6, IL-8, IL-10, IL-15, TNF-α, IFN-γ, and sIL2Rα. Peak elevation was observed within the first 14 days after infusion, and levels generally returned to baseline within 28 days.4 As an off-target effect, axicabtagene ciloleucel can cause B-cell aplasia.4

Mechanism of action

The CD 19 antigen is an integral membrane glycoprotein normally expressed in B cells during differentiation; however, it is often aberrantly expressed on B cells that have undergone a neoplastic transformation. Distinctive expression of CD19 in lymphomas and leukemias makes this glycoprotein a good immunotherapeutic target.1

Axicabtagene ciloleucel is a CD19-directed chimeric antigen receptor (CAR) T-cell therapy. It consists of genetically modified T cells of the patient receiving the immunotherapy. The manufacturing of axicabtagene ciloleucel begins with the collection of peripheral blood mononuclear cells from the patient, followed by the harvesting and genetic modification of T cells ex vivo. Retroviral transduction is used to express a CAR on T cells, creating anti-CD19 CAR T cells that are then expanded. Axicabtagene ciloleucel, a suspension of anti-CD19 CAR T cells, is infused back into the patient during treatment.4 Axicabtagene ciloleucel is made up of two components: a single-chain variable fragment targets the CD19 proteins, and there are intracellular domains - CD28 and CD3-zeta co-stimulatory domains - that signal T-cell activation.2,4 Once administered into the patient's bloodstream, axicabtagene ciloleucel recognizes the CD19-expressing target cells and the intracellular domains of the drug activate the downstream signalling cascades that lead to T-cell activation, proliferation, acquisition of effector functions, and secretion of inflammatory cytokines and chemokines that kill cancer cells.4 Axicabtagene ciloleucel binds to CD19-expressing cancer cells and normal B cells.4

TargetActionsOrganism
AB-lymphocyte antigen CD19
antibody
Humans
Absorption

Following intravenous infusion, anti-CD19 CAR T cells rapidly expands, followed by a decline to near baseline levels by three months. Peak levels of anti-CD19 CAR T cells occurred within the first seven to 14 days following infusion.4

The median peak level of anti-CD19 CAR T cells in the blood (Cmax) was 38.3 cells/µL (range: 0.8 to 1513.7 cells/μL), which decreased to a median of 2.1 cells/µL by one month (range: 0 to 167.4 cells/μL) and to a median of 0.4 cells/µL by three months (range: 0 to 28.4 cells/μL) after drug infusion.5

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

There is no information regarding the LD50 and overdose of axicabatagene ciloleucel.5 Axicabatagene ciloleucel is reported to induce cytokine release syndrome (CRS) and neurotoxicity. No carcinogenicity, genotoxicity, or reproductive toxicity studies have been conducted with axicabatagene ciloleucel.4

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
Integrate drug-drug
interactions in your software
AmbroxolThe risk or severity of methemoglobinemia can be increased when Axicabtagene ciloleucel is combined with Ambroxol.
ArticaineThe risk or severity of methemoglobinemia can be increased when Axicabtagene ciloleucel is combined with Articaine.
BenzocaineThe risk or severity of methemoglobinemia can be increased when Axicabtagene ciloleucel is combined with Benzocaine.
Benzyl alcoholThe risk or severity of methemoglobinemia can be increased when Axicabtagene ciloleucel is combined with Benzyl alcohol.
BupivacaineThe risk or severity of methemoglobinemia can be increased when Axicabtagene ciloleucel is combined with Bupivacaine.
Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
YescartaSuspension200000000 cells / bagIntravenousGilead Sciences2019-11-27Not applicableCanada flag
YescartaSuspension2000000 1/68mLIntravenousKite Pharma, Inc.2017-10-18Not applicableUS flag
YescartaSuspension120000000 CellsIntravenousKite Pharma Eu B.V.2020-12-22Not applicableEU flag

Categories

ATC Codes
L01XL03 — Axicabtagene ciloleucel
Drug Categories
Classification
Not classified
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
U2I8T43Y7R
CAS number
Not Available

References

General References
  1. Scheuermann RH, Racila E: CD19 antigen in leukemia and lymphoma diagnosis and immunotherapy. Leuk Lymphoma. 1995 Aug;18(5-6):385-97. [Article]
  2. Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY: Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. N Engl J Med. 2017 Dec 28;377(26):2531-2544. doi: 10.1056/NEJMoa1707447. Epub 2017 Dec 10. [Article]
  3. Roberts ZJ, Better M, Bot A, Roberts MR, Ribas A: Axicabtagene ciloleucel, a first-in-class CAR T cell therapy for aggressive NHL. Leuk Lymphoma. 2018 Aug;59(8):1785-1796. doi: 10.1080/10428194.2017.1387905. Epub 2017 Oct 23. [Article]
  4. FDA Approved Drug Products: YESCARTA (axicabtagene ciloleucel) suspension for intravenous infusion (December 2023) [Link]
  5. EMA Approved Drug Products: Yescarta (axicabtagene ciloleucel) intravenous infusion [Link]
PubChem Substance
347911476
RxNav
1987398
Wikipedia
Axicabtagene_ciloleucel

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentRelapsed or Refractory Diffuse Large B Cell Lymphoma (DLBCL)1
3RecruitingTreatmentHigh-risk Large B-cell Lymphoma (LBCL)1
3RecruitingTreatmentRelapsed or Refractory Follicular Lymphoma1
2Active Not RecruitingTreatmentFollicular Lymphoma ( FL) / Indolent Non Hodgkin's Lymphoma (iNHL) / Marginal Zone Lymphoma (MZL)1
2Active Not RecruitingTreatmentHematopoietic and Lymphoid System Neoplasm / Recurrent Diffuse Large B-Cell Lymphoma / Recurrent High Grade B-Cell Lymphoma / Recurrent Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma / Recurrent Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma / Refractory Diffuse Large B Cell Lymphoma (DLBCL) / Refractory High Grade B-cell Lymphoma (HGBCL) / Refractory Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma / Refractory Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
SuspensionIntravenous120000000 Cells
SuspensionIntravenous2000.000 cells/68ml
SuspensionIntravenous2000000 1/68mL
SuspensionIntravenous200000000 cells / bag
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Targets

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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
References
  1. Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY: Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. N Engl J Med. 2017 Dec 28;377(26):2531-2544. doi: 10.1056/NEJMoa1707447. Epub 2017 Dec 10. [Article]
  2. Roberts ZJ, Better M, Bot A, Roberts MR, Ribas A: Axicabtagene ciloleucel, a first-in-class CAR T cell therapy for aggressive NHL. Leuk Lymphoma. 2018 Aug;59(8):1785-1796. doi: 10.1080/10428194.2017.1387905. Epub 2017 Oct 23. [Article]
  3. FDA Approved Drug Products: YESCARTA (axicabtagene ciloleucel) suspension for intravenous infusion (December 2023) [Link]

Drug created at October 19, 2017 15:01 / Updated at February 14, 2024 00:55