NAV

Dinutuximab

Identification

Summary

Dinutuximab is an immunotherapeutic agent used in combination with other immunomodulating agents to treat high-risk neuroblastoma in pediatric patients who achieve at least a partial response to prior first-line multiagent, multimodality therapy.

Brand Names
Unituxin
Generic Name
Dinutuximab
DrugBank Accession Number
DB09077
Background

Dinutuximab is an IgG1 monoclonal human/mouse chimeric antibody against GD2, a disialoganglioside expressed on tumors of neuroectodermal origin, including human neuroblastoma and melanoma, with highly restricted expression on normal tissues. It is composed of the variable heavy- and light-chain regions of the murine anti-GD2 mAb 14.18 and the constant regions of human IgG1 heavy-chain and kappa light-chain. By binding to GD2, dinutiximab induces antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity of tumor cells thereby leading to apoptosis and inhibiting proliferation of the tumour. It is indicated, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and 13-cis-retinoic acid (RA), for the treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to prior first-line multiagent, multimodality therapy. Despite a high clinical response seen after first-line treatment, the complete eradication of neuroblastoma is rarely achieved and the majority of patients with advanced disease suffer a relapse. Current strategies for treatment include immunotherapy with drugs such as dinutuximab to target surviving neuroblastoma cells and to prevent relapse.

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
C6422H9982N1722O2008S48
Protein Average Weight
145000.0 Da
Sequences
Not Available
Synonyms
  • CHIMERIC ANTI-DISIALOGANGLIOSIDE (GD2) MONOCLONAL ANTIBODY (CH14.18/CHO)
  • Dinutuximab
  • Dinutuximab beta
  • IMMUNOGLOBULIN G1, ANTI-(GANGLIOSIDE GD2) (HUMAN-MUS MUSCULUS MONOCLONAL CH14.18 HEAVY CHAIN), DISULFIDE WITH HUMAN-MUS MUSCULUS MONOCLONAL CH14.18 LIGHT CHAIN, DIMER
  • IMMUNOGLOBULIN G1, ANTI-(GANGLIOSIDE GD2) (HUMAN-MUS MUSCULUS MONOCLONAL CH14.18/CHO HEAVY CHAIN), DISULFIDE WITH HUMAN-MUS MUSCULUS MONOCLONAL CH14.18/CHO LIGHT CHAIN, DIMER
  • Monoclonal antibody ch14.18
External IDs
  • APN 311
  • APN-311
  • APN311
  • CH-14.18
  • CH-14.18-UTC
  • ch14.18
  • ch14.18-UTC
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Pharmacology

Indication

Dinutuximab is indicated, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and 13-cis-retinoic acid (RA), for the treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to prior first-line multiagent, multimodality therapy. Despite a high clinical response seen after first-line treatment, the complete eradication of neuroblastoma is rarely achieved and the majority of patients with advanced disease suffer a relapse. Current strategies for treatment include immunotherapy with drugs such as dinutuximab to target surviving neuroblastoma cells and to prevent relapse.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination to treatHigh risk neuroblastomaRegimen in combination with: Aldesleukin (DB00041), Sargramostim (DB00020), Isotretinoin (DB00982)•••••••••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

In vitro dinutuximab binds to neuroblastoma tumour cells and mediates the lysis of tumour cells via cell-mediated and complement-mediated cytotoxicity.

Mechanism of action

Dinutuximab is an IgG1 monoclonal human/mouse chimeric antibody against GD2, a disialoganglioside expressed on tumors of neuroectodermal origin, including human neuroblastoma and melanoma, with highly restricted expression on normal tissues. It is composed of the variable heavy- and light-chain regions of the murine anti-GD2 mAb 14.18 and the constant regions of human IgG1 heavy-chain and kappa light-chain. By binding to GD2, dinutiximab induces antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity of tumor cells thereby leading to apoptosis and inhibiting proliferation of the tumour.

TargetActionsOrganism
AGD2 disialoganglioside
inhibitor
Humans
Absorption

Not Available

Volume of distribution

The mean volume of distribution at steady state (Vdss) is 5.4 L

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

The terminal half-life is 10 days

Clearance

The clearance is 0.21 L/day and increases with body size

Adverse Effects
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Toxicity

The most common (incidence 15 %) grade 3 or 4 treatment-related adverse events in dinutuximab compared with standard therapy recipients were neuropathic pain (52 vs. 6 %), fever without neutropenia (39 vs. 6 %), any in-fection (39 vs. 22 %), hypokalaemia (35 vs. 2 %), hypersensitivity reactions (25 vs. 1 %), hyponatraemia (23 vs. 4 %), elevation of alanine transferase levels (23 vs. 3 %) and hypotension (18 vs. 0 %). Based on its mechanism of action, dinutuximab may cause fetal harm when administered to a pregnant woman however, there are no studies in pregnant women and no reproductive studies in animals to inform the drug-associated risk. Non-clinical studies suggest that dinutuximab-induced neuropathic pain is mediated by binding of the antibody to the GD2 antigen located on the surface of peripheral nerve fibers and myelin and subsequent induction of cell- and complement-mediated cytotoxicity. In clinical trials, 114 (85%) patients treated in the dinutuximab/RA group experienced pain despite pre­-treatment with analgesics including morphine sulfate infusion. Severe (Grade 3) pain occurred in 68 (51%) patients in the dinutuximab/RA group compared to 5 (5%) patients in the RA group. Pain typically occurred during the dinutuximab infusion and was most commonly reported as abdominal pain, generalized pain, extremity pain, back pain, neuralgia, musculoskeletal chest pain, and arthralgia.

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
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interactions in your software
AbaloparatideThe risk or severity of adverse effects can be increased when Abaloparatide is combined with Dinutuximab.
AbataceptThe risk or severity of adverse effects can be increased when Abatacept is combined with Dinutuximab.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Dinutuximab.
AcebutololThe risk or severity of adverse effects can be increased when Acebutolol is combined with Dinutuximab.
AcenocoumarolThe risk or severity of bleeding can be increased when Acenocoumarol is combined with Dinutuximab.
Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
QarzibaInjection, solution, concentrate4.5 mg/mlIntravenousRecordati Netherlands B.V.2020-12-16Not applicableEU flag
UnituxinInjection3.5 mg/1mLIntravenousUnited Therapeutics Corporation2015-03-10Not applicableUS flag
UnituxinInjection, solution, concentrate3.5 mg/mlIntravenousUnited Therapeutics Europe Ltd2021-01-122017-04-28EU flag
UnituxinSolution3.5 mg / mLIntravenousUnited Therapeutics Corporation2019-05-01Not applicableCanada flag

Categories

ATC Codes
L01FX06 — Dinutuximab beta
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
7SQY4ZUD30
CAS number
1363687-32-4

References

General References
  1. Dhillon S: Dinutuximab: first global approval. Drugs. 2015 May;75(8):923-7. doi: 10.1007/s40265-015-0399-5. [Article]
  2. Ahmed M, Cheung NK: Engineering anti-GD2 monoclonal antibodies for cancer immunotherapy. FEBS Lett. 2014 Jan 21;588(2):288-97. doi: 10.1016/j.febslet.2013.11.030. Epub 2013 Dec 1. [Article]
  3. Barker E, Mueller BM, Handgretinger R, Herter M, Yu AL, Reisfeld RA: Effect of a chimeric anti-ganglioside GD2 antibody on cell-mediated lysis of human neuroblastoma cells. Cancer Res. 1991 Jan 1;51(1):144-9. [Article]
  4. Aixinjueluo W, Furukawa K, Zhang Q, Hamamura K, Tokuda N, Yoshida S, Ueda R, Furukawa K: Mechanisms for the apoptosis of small cell lung cancer cells induced by anti-GD2 monoclonal antibodies: roles of anoikis. J Biol Chem. 2005 Aug 19;280(33):29828-36. Epub 2005 May 26. [Article]
KEGG Drug
D10559
PubChem Substance
347910402
RxNav
1606274
ChEMBL
CHEMBL3137342
Drugs.com
Drugs.com Drug Page
Wikipedia
Dinutuximab
FDA label
Download (446 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount
4RecruitingTreatmentNeuroblastoma (NB)1
3Active Not RecruitingTreatmentGanglioneuroblastoma / Neuroblastoma (NB)1
3Active Not RecruitingTreatmentLocalized, resectable Neuroblastoma (NB) / Localized, unresectable Neuroblastoma (NB) / Recurrent Neuroblastoma / Regional Neuroblastoma / Stage 4 Neuroblastoma / Stage 4S Neuroblastoma1
3CompletedTreatmentHigh Risk Neuroblastoma1
3Not Yet RecruitingTreatmentGanglioneuroblastoma / Neuroblastoma (NB)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solution, concentrateIntravenous4.5 mg/ml
Injection, solution, concentrateIntravenous; Parenteral4.5 MG/ML
InjectionIntravenous3.5 mg/1mL
Injection, solution, concentrateIntravenous3.5 MG/ML
SolutionIntravenous3.5 mg / mL
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US20140170155No2014-02-182038-02-18US flag

Properties

State
Solid
Experimental Properties
Not Available

Targets

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Details1. GD2 disialoganglioside
Kind
Small molecule
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
GD2 is a disialoganglioside that is overexpressed on neuroblastoma cells and other cells of neuroectodermal origin, including the central nervous system and peripheral nerves.
References
  1. Barker E, Mueller BM, Handgretinger R, Herter M, Yu AL, Reisfeld RA: Effect of a chimeric anti-ganglioside GD2 antibody on cell-mediated lysis of human neuroblastoma cells. Cancer Res. 1991 Jan 1;51(1):144-9. [Article]

Drug created at June 18, 2015 17:47 / Updated at July 18, 2023 22:56