Tositumomab is a murine monoclonal antibody which targets the CD20 antigen produced in mammalian cell.[1] It was combined with iodine-131 to produce a radiopharmaceutical for unsealed source radiotherapy, Iodine-131 Tositumomab (branded as Bexxar), for the treatment of non-Hodgkins lymphoma. It is classified as a IgG2a lambda antibody.[2]
The drug combination was developed by Corixa which was purchased by GlaxoSmithKline in 2005.[3] It was sold for about $25,000 for one round of treatment.[4] Bexxar competed with Zevalin,[5] until the former's discontinuation in 2014.[6]
A personalized regimen using Bexxar was approved for the treatment of relapsed or chemotherapy/rituxan-refractory Non-Hodgkin lymphoma in 2003.[7] [8]
The radioactive dose was adjusted for each patient in order to maximize the radiation delivered to the tumor and minimize the exposure of other organs.[9] Bexxar combined separate administration of unlabelled and iodine-labelled (i.e. covalently bonded to 131I) tositumomab. A first dose of labelled antibody was given once, and whole-body radiation was measured with a gamma camera over seven days. Analysis of that imaging data allowed an optimal dose of labelled antibody to be calculated, which was then administered once a day, for up to seven days.[9] Each time the labelled antibody was administered, it was always preceded by unlabelled (non-radioactive) antibody. Early clinical trials had shown that total body residence times of radioactivity were longer in people who first received unlabelled antibody, so that a lower dose of labelled antibody was needed to deliver the required total dose of radiation; additionally labelled antibody targeted tumors better in people pre-treated with unlabelled antibody.[9]
Following a first investigational new drug application in 1989 and biologics license application in 2000, Bexxar was approved by the FDA in 2003.[10] Sale of Bexxar was discontinued and marketing approval was withdrawn in February 2014 due to a decline in usage (fewer than 75 patients in 2012). One possible explanation for the lack of demand, despite a claimed 70% response rate, was that oncologists could not sell it directly to patients but had to refer patients to third party specialist centers, however a "muddled clinical trials strategy", supply chain issues, reimbursement problems, and emergence of non-radioactive competitors has also been blamed.[5] [11]
The European Medicines Agency granted tositumomab and 131I-tositumomab orphan drug status, for the treatment of follicular lymphoma, to Amersham plc in 2003. This was withdrawn in October 2015 at the request of the new owner, GlaxoSmithKline.[12] [13]