Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Tositumomab: Difference between pages

{{Short description|Pharmaceutical drug}}

| verifiedrevid = 470611959

<!-- Monoclonal antibody data -->

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| tradename = Bexxar

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| ChemSpiderID = none

| CAS_number_Ref = {{cascite|changed|CAS}}

| CAS_number = 208921-02-2

| UNII_Ref = {{fdacite|correct|FDA}}

| ChEMBL = 1201604

<!-- Chemical data -->

| C=6416 | H=9874 | N=1688 | O=1987 | S=44

'''Tositumomab''' is a [[murine]] [[monoclonal antibody]] which targets the [[CD20]] antigen produced in mammalian cell.<ref name="GSK_FDA_Label">{{cite web |title=BEXXAR drug label |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/125011s0126lbl.pdf |website=FDA |publisher=GlaxoSmithKline |access-date=18 January 2016 |date=August 2012}}</ref> 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]].<ref name="GSK_FDA_Label" /> It is classified as a [[IgG]]2a lambda antibody.<ref name="GSK_FDA_Label" /><ref>{{cite web |title=Guide to Antibody structure and isotypes |url=https://www.abcam.com/protocols/antibody-structure-and-isotypes |website=Abcam |access-date=25 July 2020}}</ref>

The drug combination was developed by [[Corixa (company)|Corixa]] which was purchased by [[GlaxoSmithKline]] in 2005.<ref>{{Cite news |last=Mozee |first=Carla |date=29 April 2005 |title=Glaxo to acquire Corixa for $300 million |language=en-US |work=MarketWatch |url=https://www.marketwatch.com/story/corixa-agrees-to-glaxo-acquisition-for-300-million}}</ref> It was sold for about $25,000 for one round of treatment.<ref name=Srinivasan2011rev>{{cite journal | vauthors = Srinivasan A, Mukherji SK | title = Tositumomab and iodine I 131 tositumomab (Bexaar) | journal = AJNR. American Journal of Neuroradiology | volume = 32 | issue = 4 | pages = 637–8 | date = April 2011 | pmid = 21436340 | doi = 10.3174/ajnr.A2593 | pmc = 7965875 | doi-access = free }}</ref> Bexxar competed with [[Zevalin]],<ref name="Davies07">{{cite journal |last1=Davies |first1=A J |title=Radioimmunotherapy for B-cell lymphoma: Y90 ibritumomab tiuxetan and I131 tositumomab |journal=Oncogene |date=28 May 2007 |volume=26 |issue=25 |pages=3614–3628 |doi=10.1038/sj.onc.1210378 |pmid=17530015|doi-access=free}}</ref> until the former's discontinuation in 2014.<ref name="Timmerman2013">{{Cite news |last=Timmerman |first=Luke |date=26 August 2013 |title=Why Good Drugs Sometimes Fail: The Bexxar Story |work=Xconomy |url=http://www.xconomy.com/national/2013/08/26/why-good-drugs-sometimes-fail-in-the-market-the-bexxar-story/}}</ref>

==Clinical use==

A personalized regimen using Bexxar was approved for the treatment of relapsed or [[chemotherapy]]/[[rituxan]]-[[refractory]] [[Non-Hodgkin lymphoma]] in 2003.<ref name=Srinivasan2011rev /><ref>{{Cite news |date=1 July 2003 |title=Corixa and Glaxo's Cancer Drug Wins F.D.A. Approval |language=en-US |work=The New York Times |url=https://www.nytimes.com/2003/07/01/business/company-news-corixa-and-glaxo-s-cancer-drug-wins-fda-approval.html |issn=0362-4331}}New York Times. July 1, 2003 [https://www.nytimes.com/2003/07/01/business/company-news-corixa-and-glaxo-s-cancer-drug-wins-fda-approval.html Company News: Corixa and Glaxo's Cancer Drug Wins FDA Approval]</ref><ref name="FDAapproval">{{Cite web |date=2 July 2003 |title=Tositumomab - Product Approval Information - Licensing Action |url=https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2003/tosicor062703L.htm |website=FDA/Center for Drug Evaluation and Research}}</ref>

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.<ref name="GSK_FDA_Label" /><ref name="2002Descrip">{{Cite web |title=Tositumomab product description |url=https://www.fda.gov/ohrms/dockets/ac/02/briefing/3916B1_02_D-FDA%20-%20Product%20Description.htm |archive-url=https://web.archive.org/web/20180127032045/https://www.fda.gov/ohrms/dockets/ac/02/briefing/3916B1_02_D-FDA%20-%20Product%20Description.htm |archive-date=27 January 2018 |access-date=25 July 2020 |website=[[Food and Drug Administration]]}}</ref>{{rp|14–15}} 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.<ref name="GSK_FDA_Label" /><ref name=2002Descrip/>{{rp|14–15}} Each time the labelled antibody was administered, it was always preceded by unlabelled (non-radioactive) antibody. Early [[clinical trial]]s 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.<ref name=2002Descrip/>{{rp|21}}

==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.<ref>{{cite web |title=Briefing Information Iodine I-131 Tositumomab |url=https://www.fda.gov/ohrms/dockets/ac/02/briefing/3916b1.htm |website=[[Food and Drug Administration]] |access-date=25 July 2020 |archive-url=https://web.archive.org/web/20180125201355/https://www.fda.gov/ohrms/dockets/ac/02/briefing/3916b1.htm |archive-date=25 January 2018 |date=17 December 2002}}</ref><ref name="FDAapproval" /> 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 [[oncologist]]s 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.<ref name="Timmerman2013" /><ref name="Davies07"/><ref>{{Cite web |date=23 October 2013 |title=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 |url=https://www.federalregister.gov/documents/2013/10/23/2013-24840/glaxosmithkline-llc-withdrawal-of-approval-of-the-indication-for-treatment-of-patients-with-relapsed |website=Federal Register}} ({{Federal Register|78|63226}})</ref>

===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.<ref>{{cite web |title=EU/3/03/137 |url=https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu303137 |website=European Medicines Agency |access-date=25 July 2020 |language=en |date=17 September 2018}}</ref><ref>{{cite web |title=EU/3/03/136 |url=https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu303136 |website=European Medicines Agency |access-date=25 July 2020 |language=en |date=17 September 2018}}</ref>

==References==

{{Reflist}}

{{Extracellular chemotherapeutic agents}}

{{Monoclonals for tumors}}

{{Therapeutic radiopharmaceuticals}}

[[Category:Monoclonal antibodies]]

[[Category:Drugs developed by GSK plc]]