Naxitamab API Manufacturers

General Description:

Naxitamab, identified by CAS number 1879925-92-4, is a notable compound with significant therapeutic applications. Naxitamab (humanized 3F8, hu3F8) is an IgG1 monoclonal antibody directed against the oncofetal differentiation antigen GD2 disialoganglioside. 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), and is rarely subject to antigen loss. The first anti-GD2-monoclonal IgG antibody to be approved by the FDA for the treatment of neuroblastoma was under the brand name Unituxin in 2015. 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). 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. 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, making the administration of naxitamab therapy markedly simpler than that of its predecessor.

Indications:

This drug is primarily indicated for: 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. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Naxitamab undergoes metabolic processing primarily in: While the metabolism of naxitamab has not been studied directly, monoclonal antibodies as a class are principally metabolized to smaller peptides via catabolic processes. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Naxitamab are crucial for its therapeutic efficacy: The mean plasma concentration of naxitamab following an intravenous infusion of 3 mg/kg over 30 minutes was 57.4 μg/mL. The AUC of naxitamab appears to correlate with body size. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Naxitamab is an important consideration for its dosing schedule: The mean terminal half-life of naxitamab is 8.2 days. This determines the duration of action and helps in formulating effective dosing regimens.

Route of Elimination:

The elimination of Naxitamab from the body primarily occurs through: 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. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Clearance:

The clearance rate of Naxitamab is a critical factor in determining its safe and effective dosage: The clearance of naxitamab appears to be correlated inversely with body weight. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Naxitamab exerts its therapeutic effects through: 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. 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. ) 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. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Naxitamab functions by: 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. The GD2 disialoganglioside is a glycolipid found highly expressed on the surface of neuroectodermal tumors, including neuroblastomas. GD2 exhibits high density and homogeneity across neuroblastomas and a rare occurrence of antigen loss, 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), the latter of which is enhanced by co-administration with GM-CSF. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Naxitamab belongs to the None, classified under the direct parent group Peptides. This compound is a part of the Organic Compounds, falling under the Organic Acids superclass, and categorized within the Carboxylic Acids and Derivatives class, specifically within the Amino Acids, Peptides, and Analogues subclass.

Categories:

Naxitamab is categorized under the following therapeutic classes: Agents that produce hypertension, Amino Acids, Peptides, and Proteins, Antibodies, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Blood Proteins, Carbohydrates, Globulins, Glycoconjugates, Glycolipid Disialoganglioside-directed Antibody, Glycolipid Disialoganglioside-directed Antibody Interactions, Immunoglobulins, Immunoproteins, Immunotherapy, Lipids, Neurotoxic agents, Proteins, Serum Globulins. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Naxitamab include:

• Molecular Weight: 144000.0