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.
It is given in patients who have completed induction therapy and consolidation therapy (autologous bone marrow transplant and external beam radiation therapy), as part of standard-of-care therapy for newly-diagnosed high-risk neuroblastoma. It is given by intravenous infusion, over ten to twenty hours, four days in a row. It is also used second-line for relapsed/refractory neuroblastoma in combination with chemotherapy and GM-CSF. Dinutuximab beta is also used as a second line treatment for children with high-risk neuroblastoma; it was tested and is used with a longer and slower dosing regime, and is given on its own, although it may be combined with IL-2 if a stronger immune response is needed.Morphine is administered prior to, during, and for two hours after infusion of dinutuximab and dinutuximab beta to manage the severe pain that this drug causes. An antihistamine and an anti-inflammatory are also given before, during, and after to manage the infusion reaction.Women who are pregnant or who might become pregnant should not take dinutuximab or dinutuximab beta, because it is very likely to cause harm to a fetus. Adverse effects
The US label for dinutuximab carries black box warnings for life-threatening infusion reactions and neurotoxicity, as it causes severe neuropathic pain, and can cause severe sensory neuropathy and severe peripheral motor neuropathy.