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| Primary information |
|---|
| ID | 15990 |
| Therapeutic ID | Th1660 |
| Protein Name | Naxitamab |
| Sequence | NA
|
| Molecular Weight | 144000 |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | The mean terminal half-life of naxitamab is 8.2 days.[L24454] |
| Description | Naxitamab (humanized 3F8, hu3F8) is an IgG1 monoclonal antibody directed against the oncofetal differentiation antigen GD2 disialoganglioside.[L24454,A224604] 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),[A224609] and is rarely subject to antigen loss.[A224604] 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.[A224474] 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).[L24929] 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.[L24454] 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,[A224604] making the administration of naxitamab therapy markedly simpler than that of its predecessor. |
| Indication/Disease | 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.[L24454] |
| 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.[L24454] 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.[L24454] |
| 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.[A224604] The GD2 disialoganglioside is a glycolipid found highly expressed on the surface of neuroectodermal tumors,[A224609] including neuroblastomas. GD2 exhibits high density and homogeneity across neuroblastomas and a rare occurrence of antigen loss,[A224604] 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),[L24454] the latter of which is enhanced by co-administration with GM-CSF.[A224604] |
| Toxicity | Data regarding overdose of naxitamab are unavailable. In the event of an overdose, patients should be treated with symptomatic and supportive measures. |
| Metabolism | While the metabolism of naxitamab has not been studied directly,[L24454] monoclonal antibodies as a class are principally metabolized to smaller peptides via catabolic processes.[L24454,A216712] |
| Absorption | The mean plasma concentration of naxitamab following an intravenous infusion of 3 mg/kg over 30 minutes was 57.4 µg/mL.[L24454] The AUC of naxitamab appears to correlate with body size.[A224474] |
| NA |
| Clearance | The clearance of naxitamab appears to be correlated inversely with body weight.[L24454] |
| Categories | Agents that produce hypertension |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | GD2 disialoganglioside |
| Brand Name | Danyelza |
| Company | Y-mAbs Therapeutics, Inc. |
| Brand Description | Y-mAbs Therapeutics, Inc. |
| Prescribed For | Intravenous |
| Chemical Name | 40 mg/10mL |
| Formulation | DANYELZA is contraindicated in patients with a history of severe hypersensitivity reaction to naxitamab-gqgk. Reactions have included anaphylaxis [see WARNINGS AND PRECAUTIONS]. |
| Physical Appearance | infusion-related reactions occurring on the day of infusion or the day following an infusion (low blood pressure, bronchospasm, flushing, wheezing, stridor, hives, shortness of breath, fever, swelling of the face/lips/tongue, respiratory tract edema, chills, low blood oxygen, itching, and rash) pain (abdominal pain, pain in extremity, bone pain, neck pain, back pain, and musculoskeletal pain), fast heart rate, vomiting, cough, nausea, diarrhea, decreased appetite, high blood pressure (hypertension), fatigue, erythema multiforme, numbness and tingling of extremities, hives not occurring on the day of infusion or the day following an infusion, fever not occurring on the day of infusion or the day following an infusion, headache, injection site reaction, fluid retention (edema), anxiety, localized swelling, irritability, decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased platelet count, decreased potassium, increased alanine aminotransferase, decreased glucose, decreased calcium, decreased albumin, decreased sodium, and decreased phosphate |
| Route of Administration | NA |
| Recommended Dosage | DANYELZA is indicated, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), for the treatment of pediatric patients 1 year of age and older and adult patients 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. |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |