Tositumomab

Clinical use

A personalized regimen using Bexxar was approved for the treatment of relapsed or chemotherapy/rituxan-refractory Non-Hodgkin lymphoma in 2003.

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. 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. 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.

Availability

United States

Following a first investigational new drug application in 1989 and biologics license application in 2000, Bexxar was approved by the FDA in 2003. Sale of Bexxar was discontinued and marketing approval was withdrawn in February 2014 due to a decline in usage (fewer than 75 patients in 2012).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.

Europe

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 This was withdrawn in October 2015 at the request of the new owner, GlaxoSmithKline.

References

References

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4. (April 2011). "Tositumomab and iodine I 131 tositumomab (Bexaar)". AJNR. American Journal of Neuroradiology.
5. (28 May 2007). "Radioimmunotherapy for B-cell lymphoma: Y90 ibritumomab tiuxetan and I131 tositumomab". Oncogene.
6. Timmerman, Luke. (26 August 2013). "Why Good Drugs Sometimes Fail: The Bexxar Story". Xconomy.
7. (1 July 2003). "Corixa and Glaxo's Cancer Drug Wins F.D.A. Approval". The New York Times.
8. (2 July 2003). "Tositumomab - Product Approval Information - Licensing Action".
9. "Tositumomab product description".
10. (17 December 2002). "Briefing Information Iodine I-131 Tositumomab".
11. (23 October 2013). "GlaxoSmithKline LLC; Withdrawal of Approval of the Indication for Treatment of Patients With Relapsed or Refractory, Low Grade, Follicular, or Transformed CD20 Positive Non-Hodgkin's Lymphoma Who Have Not Received Prior Rituximab; BEXXAR".
12. (17 September 2018). "EU/3/03/137".
13. (17 September 2018). "EU/3/03/136".