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| Primary information |
|---|
| ID | 10865 |
| Therapeutic ID | Th1226 |
| Protein Name | Dinutuximab |
| Sequence | NA
|
| Molecular Weight | 145000 |
| Chemical Formula | C6422H9982N1722O2008S48 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | The terminal half-life is 10 days |
| Description | 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. |
| Indication/Disease | 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. |
| 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. |
| 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. |
| Metabolism | NA |
| Absorption | NA |
| The mean volume of distribution at steady state (Vdss) is 5.4 L |
| Clearance | The clearance is 0.21 L/day and increases with body size |
| Categories | Antibody, Immunosuppresive agent, Antineoplastic agent |
| Patents Number | US20140170155 |
| Date of Issue | 18-02-2014 |
| Date of Expiry | 18-02-2038 |
| Drug Interaction | Severity of adverse effect can be increased while combining Dinutuximab with Acebutolol, Acetazolamide, Acetyldigitoxin, Aldesleukin, Aliskiren, Amifostine, Amiloride, Amiodarone, Amlodipine etc |
| Target | GD2 disialoganglioside |
| Brand Name | unituxin |
| Company | NA |
| Brand Description | NA |
| Prescribed For | Unituxin (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. |
| Chemical Name | NA |
| Formulation | 1 mL of concentrate contains 3.5 mg of dinutuximab |
| Physical Appearance | sterile, preservative-free, clear/colorless to slightly opalescent solution |
| Route of Administration | Intravenous |
| Recommended Dosage | The recommended dose of Unituxin is 17.5 mg/m2/day administered as an intravenous infusion over 10 to 20 hours for 4 consecutive days for a maximum of 5 cycles. |
| Contraindication | History of anaphylaxis to dinutuximab. |
| Side Effects | The most common serious adverse reactions (≥ 5%) are infections, infusion reactions, hypokalemia, hypotension, pain, fever, and capillary leak syndrome. |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |