Identification
- Summary
Naxitamab is a GD2-targeted IgG1 monoclonal antibody for the treatment of high-risk relapsed/refractory neuroblastoma of the bone or bone marrow.
- Brand Names
- Danyelza
- Generic Name
- Naxitamab
- DrugBank Accession Number
- DB15965
- Background
Naxitamab (humanized 3F8, hu3F8) is an IgG1 monoclonal antibody directed against the oncofetal differentiation antigen GD2 disialoganglioside.6,4 Normally expressed during fetal development and in mature neurons, pain fibers, and skin cells, GD2 constitutes a highly efficient target in the treatment of neuroblastoma - it is widely expressed across and within neuroblastomas (and other neuroectodermal tumors),5 and is rarely subject to antigen loss.4
The first anti-GD2-monoclonal IgG antibody to be approved by the FDA for the treatment of neuroblastoma was dinutuximab under the brand name Unituxin in 2015.2 One stark disadvantage of this therapy is the requirement for concurrent use of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and 13-cis-retinoic acid (RA).7
Naxitamab-gqgk (Danyelza) was granted accelerated approval by the FDA in November 2020 for the treatment of high-risk relapsed/refractory neuroblastoma of the bone or bone marrow.6 This approval requires naxitamab to be co-administered only with GM-CSF, a factor known to enhance the granulocyte-mediated antibody-dependent cytotoxicity of anti-GD2 therapies,4 making the administration of naxitamab therapy markedly simpler than that of its predecessor.
- Type
- Biotech
- Groups
- Approved
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Chemical Formula
- Not Available
- Protein Average Weight
- 144000.0 Da (non-glycosylated)
- Sequences
- Not Available
- Synonyms
- Anti-Gd2 igg3 monoclonal antibody 3F8 humanized
- Anti-Gd2 monoclonal antibody 3F8 humanized
- HU3F8
- Humanized 3F8
- Humanized anti-Gd2 monoclonal antibody 3F8
- Humanized monoclonal antibody HU3F8-IGG1
- Monoclonal antibody HU3F8
- Naxitamab
- naxitamab-gqgk
Pharmacology
- Indication
Naxitamab-gqgk is indicated, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), for the treatment of patients 1 year of age and older with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response, or stable disease to prior therapy.6
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat High risk, refractory neuroblastomas of the bone or bone marrow •••••••••••• •••••• ••••••• ••••• •• ••••••• ••••••••• Used in combination to treat High risk, refractory neuroblastomas of the bone or bone marrow •••••••••••• ••••••• •• ••••• •••••••• •• ••••• ••••••• ••••••••• Used in combination to treat High risk, relapsed neuroblastomas of the bone or bone marrow •••••••••••• •••••• ••••••• ••••• •• ••••••• ••••••••• Used in combination to treat High risk, relapsed neuroblastomas of the bone or bone marrow •••••••••••• ••••••• •• ••••• •••••••• •• ••••• ••••••• ••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
In targeting cell surface glycoproteins (GD2) that occur on the surface of neuroendocrine tumors, naxitamab directs the immune system towards these cancerous cells and induces the activation of both complement-dependent and antibody-dependent cytotoxicity.6
Naxitamab can cause serious infusion reactions - including hypotension, hypoxia, anaphylaxis, and cardiac arrest - that necessitate careful monitoring during therapy. All patients should be pre-medicated with intravenous corticosteroids (e.g. methylprednisolone) as well as an antihistamine, H2 receptor antagonist, acetaminophen, and an antiemetic prior to therapy to mitigate the risk and severity of infusion-related reactions. Naxitamab may also cause severe neurotoxicity, including significant neuropathic pain, transverse myelitis, reversible posterior leukoencephalopathy syndrome (RPLS), and ocular toxicities. Pain management should be implemented prior to and during therapy - patients should take a 12-day course of neuropathic pain prophylaxis (e.g. gabapentin) starting 4 days prior to infusion, and should receive oral opioids 45-60 minutes prior to infusion and intravenous opioids and/or ketamine as needed thereafter.6
- Mechanism of action
Neuroblastomas are neuroendocrine tumors occurring in immature and developing cells of the nervous system and are the most common malignancy diagnosed in children <1 year of age.4 The GD2 disialoganglioside is a glycolipid found highly expressed on the surface of neuroectodermal tumors,5 including neuroblastomas. GD2 exhibits high density and homogeneity across neuroblastomas and a rare occurrence of antigen loss,4 making it a desirable target in the treatment of these cancers.
Naxitamab is an IgG1 monoclonal antibody directed against GD2 disialogangliosides - it binds to GD2 on the surface of neuroblastoma cells and induces both complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC),6 the latter of which is enhanced by co-administration with GM-CSF.4
Target Actions Organism AGD2 disialoganglioside binderantibodyHumans - Absorption
The mean plasma concentration of naxitamab following an intravenous infusion of 3 mg/kg over 30 minutes was 57.4 μg/mL.6 The AUC of naxitamab appears to correlate with body size.2
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
While the metabolism of naxitamab has not been studied directly,6 monoclonal antibodies as a class are principally metabolized to smaller peptides via catabolic processes.6,3
- 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.3
- Half-life
The mean terminal half-life of naxitamab is 8.2 days.6
- Clearance
The clearance of naxitamab appears to be correlated inversely with body weight.6
- Adverse Effects
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Data regarding overdose of naxitamab are unavailable. In the event of an overdose, patients should be treated with symptomatic and supportive measures.
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAcebutolol Naxitamab may decrease the antihypertensive activities of Acebutolol. Aceclofenac The risk or severity of hypertension can be increased when Aceclofenac is combined with Naxitamab. Acemetacin The risk or severity of hypertension can be increased when Acemetacin is combined with Naxitamab. Acetophenazine Acetophenazine may increase the neurotoxic activities of Naxitamab. Acetylsalicylic acid The risk or severity of hypertension can be increased when Acetylsalicylic acid is combined with Naxitamab. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Danyelza
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Danyelza Injection 40 mg/10mL Intravenous Y-mAbs Therapeutics, Inc. 2020-11-25 Not applicable US 
Categories
- ATC Codes
- L01FX21 — Naxitamab
- Drug Categories
- Agents that produce hypertension
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Blood Proteins
- Carbohydrates
- Globulins
- Glycoconjugates
- Glycolipid Disialoganglioside-directed Antibody
- Glycolipid Disialoganglioside-directed Antibody Interactions
- Immunoglobulins
- Immunoproteins
- Immunotherapy
- Lipids
- MONOCLONAL ANTIBODIES AND ANTIBODY DRUG CONJUGATES
- Neurotoxic agents
- Proteins
- Serum Globulins
- 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
Chemical Identifiers
- UNII
- 9K8GNJ2874
- CAS number
- 1879925-92-4
References
- General References
- Kushner BH, Cheung IY, Modak S, Basu EM, Roberts SS, Cheung NK: Humanized 3F8 Anti-GD2 Monoclonal Antibody Dosing With Granulocyte-Macrophage Colony-Stimulating Factor in Patients With Resistant Neuroblastoma: A Phase 1 Clinical Trial. JAMA Oncol. 2018 Dec 1;4(12):1729-1735. doi: 10.1001/jamaoncol.2018.4005. [Article]
- Cheung IY, Kushner BH, Modak S, Basu EM, Roberts SS, Cheung NV: Phase I trial of anti-GD2 monoclonal antibody hu3F8 plus GM-CSF: Impact of body weight, immunogenicity and anti-GD2 response on pharmacokinetics and survival. Oncoimmunology. 2017 Jul 31;6(11):e1358331. doi: 10.1080/2162402X.2017.1358331. eCollection 2017. [Article]
- 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]
- Cheung NK, Dyer MA: Neuroblastoma: developmental biology, cancer genomics and immunotherapy. Nat Rev Cancer. 2013 Jun;13(6):397-411. doi: 10.1038/nrc3526. [Article]
- Zhao Q, Ahmed M, Guo HF, Cheung IY, Cheung NK: Alteration of Electrostatic Surface Potential Enhances Affinity and Tumor Killing Properties of Anti-ganglioside GD2 Monoclonal Antibody hu3F8. J Biol Chem. 2015 May 22;290(21):13017-27. doi: 10.1074/jbc.M115.650903. Epub 2015 Apr 7. [Article]
- FDA Approved Drug Products: Danyelza (naxitamab-gqgk) for intravenous infusion [Link]
- FDA Approved Drug Products: Unituxin (dinutuximab) for intravenous injection [Link]
- FDA Drug Approvals and Databases: FDA grants accelerated approval to naxitamab for high-risk neuroblastoma in bone or bone marrow [Link]
- External Links
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Not Yet Recruiting Prevention Neuroblastoma (NB) 1 2 Active Not Recruiting Treatment Neuroblastoma (NB) 1 2 Recruiting Treatment Ewing's Sarcoma 1 2 Recruiting Treatment High Risk Neuroblastoma 1 2 Recruiting Treatment Neuroblastoma (NB) 2
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravenous 40 mg/10mL - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
References
- FDA Approved Drug Products: Danyelza (naxitamab-gqgk) for intravenous infusion [Link]
Drug created at November 28, 2020 01:24 / Updated at July 02, 2021 03:58