Dinutuximab beta also has these adverse effects.More than 25% of children taking these drugs experienced pain, fever, hives, vomiting, diarrhea, bone marrow suppression causing loss of platelets, red blood cells, white blood cells, and albumin, hypotension, electrolyte imbalance including low sodium, potassium, and calcium, elevated transaminases, infusion reactions, and capillary leak syndrome.Other common adverse effects include retention or urine for weeks to months after receiving the drugs, protein in urine, blurred vision or dilated pupils, infections, edema, high blood pressure, bleeding that wont stop, tachycardia, and weight gain. Pharmacology
Dinutuximab and dinutuximab beta each work by binding to GD2, a glycolipid found on cells originating from the neuroectoderm during prenatal development, including neurons in the central nervous system and in the peripheral nervous system. Neuroblastoma cells have this as well. When dinutuximab binds to any cell that has GD2, that cell is destroyed via cell-mediated cytotoxicity and complement-dependent cytotoxicity.In clinical trials of dinutuximab, the maximum plasma concentration was 11.5 mcg/mL; the mean steady state volume distribution was 5.4 L; the clearance rate was 0.21 L/day; and the average half-life was 10 days. Chemistry
Ch14.18 is a chimeric monoclonal antibody in which the variable heavy and light chain regions come from a mouse, with a human constant region for the heavy chain IgG1 and light chain kappa.The version of dinutuximab made by United Therapeutics, and marketed under the brand name Unituxin, is manufactured via industrial fermentation using a murine myeloma cell line, SP2/0.
The version marketed by EUSA for Apeiron is called generically dinutuximab beta and is marketed under the brand name Isquette, and is manufactured in Chinese hamster ovary cells. History
Dinutuximab (originally called Ch14.18) was discovered by a group at University of California San Diego led by Alice Yu; this antibody and several others were brought into clinical trials funded by the National Cancer Institute. The NCI manufactured the mAbs for the Phase III trial of Ch14.18 in combination with GM-CSF and IL-2, which was halted due to clear efficacy; the results published in 2009. No company had offered by that time to get FDA approval and commercialize the drug, so the NCI kept manufacturing it and making it available under compassionate use. In 2010, the NCI signed an agreement with United Therapeutics under which the company took over manufacturing and would bring the drug to market.In the meantime in Europe, oncologists and patient advocates wanted to have the drug available in Europe, and made efforts to obtain the cell line used to make it from United Therapeutics and the originating lab at the NCI itself; when those efforts failed they reached out to a group at Memorial Sloan Kettering that had generated an anti-GD2 mAb and was making at MSK for administration to patients there, but this didnt work out either.