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{{Short description|Chemical compound}}
{{drugbox
{{drugbox
| type = mab
| verifiedrevid = 439543462
| type = mab
| mab_type = mab
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| source = zu
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| image =
| target = [[Interleukin 6|IL6]]
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| source = zu
| image =
| target = [[interleukin-6|IL-6]]
| CAS_number =
| alt =
| caption =
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| ATC_prefix = none
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| PubChem =
| Drugs.com =
| ChemSpiderID = NA
| MedlinePlus =
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| legal_status = investigational
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| routes_of_administration = infusion
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| elimination_half-life =
| elimination_half-life =
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| CAS_number = 1236278-28-6
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| pregnancy_US =
| UNII = 4S38Z8RA9O
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| legal_status = investigational
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| DrugBank =
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| routes_of_administration = infusion
| KEGG = D10312
| C=6426 | H=9972 | N=1724 | O=2032 | S=42
| synonyms = ALD518, BMS-945429
}}
}}
'''BMS-945429''' (formerly '''ALD518''') is an [[aglycosylated]], humanized [[monoclonal antibody]] against [[interleukin-6]].<ref name=June2010/> It is an [[investigational drug]] for cancer and [[rheumatoid arthritis]] due to its anti-inflammatory properties.


'''Clazakizumab''' (formerly '''ALD518''' and '''BMS-945429'''), an [[investigational drug]], is an [[aglycosylated]], humanized rabbit [[monoclonal antibody]] against [[interleukin-6]].<ref name="Handbook">{{cite book|title=Handbook of Therapeutic Antibodies, Volume 2|date=2007|publisher=Wiley Blackwell|page=987|isbn=9783527329373|url=https://books.google.com/books?id=svHsBQAAQBAJ&q=Clazakizumab,+BMS-945429+ALD518&pg=PA987|access-date=January 23, 2017}}</ref> Clazakizumab was developed by [[Bristol Myers Squib]] and [[Alder Biopharmaceuticals]]. A preliminary randomized, double-blind, [[placebo]]-controlled, [[phase 2 clinical trial|phase 2]] dose-ranging study of clazakizumab in [[psoriatic arthritis]] patients, funded by the manufacturer, suggested that clazakizumab may be an effective treatment option for musculoskeletal aspects of [[psoriatic arthritis]]; however, the antibody lacked a [[dose-response effect]].<ref name="ArthRheum1">{{cite journal|vauthors=Mease PJ, Gottlieb AB|display-authors=etal|title=The efficacy and safety of clazakizumab, an anti-interleukin-6 monoclonal antibody, in a phase IIb study of adults with active psoriatic arthritis.|journal=Arthritis Rheumatol|date=September 2016|volume=68|issue=9|pages=2163–73|doi=10.1002/art.39700|pmid=27059799|s2cid=3644962}}</ref>
The relatively long half-life of about 30 days should allow less frequent and subcutaneous injections.<ref name=XCFF>http://www.xconomy.com/seattle/2008/09/18/alder-sets-stage-for-showdown-with-roche-with-fast-follower-antibody-drug-strategy/</ref>

It is made using [[yeast]] cells rather than the standard [[Chinese hamster ovary cell]]s.<ref name=XCFF/>

==Clinical trials==
===Cancer===
A phase I clinical trial showed ALD518 was well tolerated and could reverse [[Cancer-related fatigue|fatigue in cancer patients]].<ref>{{cite web |url=http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=65&abstractID=32916 |title=A phase I, pharmacokinetic (PK), and preliminary efficacy assessment of ALD518, a humanized anti-IL-6 antibody, in patients with advanced cancer. |year=2009 }}</ref>

A phase II trial for advanced cancer is due to end in Oct 2009.<ref>http://www.boliven.com/clinical_trial/NCT00866970 Phase II: "Safety, Efficacy and Pharmacokinetics of ALD518 in Patients With Non-Small Cell Lung Cancer-Related Fatigue and Cachexia"</ref> Results due June 2010.<ref>http://www.xconomy.com/seattle/2010/05/13/alder-seeks-to-treat-cancer-patients-in-a-radical-way-fighting-inflammation-not-tumors/?single_page=true</ref> Results from 124 [[non-small cell lung cancer]] (NSCLC) patients were favourable (e.g. 1/10 the weight loss).<ref name=June2010>{{cite web|url=http://www.empr.com/phase-2a-study-of-ald518-for-treatment-of-non-small-cell-lung-cancer-nsclc-symptoms/article/171887/ |title=Phase 2a study of ALD518 for treatment of non small cell lung cancer (NSCLC) symptoms |date=June 2010 }}</ref>

It may be trialled in a dual therapy with [[Tarceva]] owing to a likely synergy.<ref>http://www.nature.com/scibx/journal/v3/n35/full/scibx.2010.1056.html Inflaming resistance to Tarceva. 2010</ref>

===Rheumatoid arthritis===
The Phase IIa trial for [[rheumatoid arthritis]]<ref>http://clinicaltrials.gov/ct2/show/NCT00867516</ref> has completed with promising results leading to a licencing deal allowing phase III trials.<ref>{{cite web |url=http://www.smartbrief.com/news/aanp/industryBW-detail.jsp?id=9279E59B-9E2A-4823-9476-17782B175A34 |title=Bristol-Myers Squibb and Alder Biopharmaceuticals Enter Global Agreement on Rheumatoid Arthritis Biologic |date=10 Nov 2009 }}</ref> The results are to be presented in June 2010 at the European League Against Rheumatism (EULAR) meeting in Rome.<ref>http://www.xconomy.com/seattle/2010/03/19/innovation-northwest-wrapup-alder-tekmira-acucela-other-emerging-little-biotechs/ March 2010</ref>
<ref>{{cite web|url=http://www.pymnts.com/new-data-for-investigational-antibody-blocking-il-6-in-rheumatoid-arthritis-patients-to-be-presented-at-annual-congress-of-european-league-against-rheumatism-20100615007245 |title=New Data for Investigational Antibody Blocking IL-6 in Rheumatoid Arthritis Patients to be Presented at Annual Congress of European League Against Rheumatism |date=June 2010}}</ref> Results showed that ALD518 in addition to [[Methotrexate|MTX]] performs markedly better
than MTX + placebo with a maximum ACR score, ([[ACR score for rheumatoid arthritis|ACR70]], i.e. >70% of joints improved), after 16 weeks .<ref>{{cite web |url=http://www.eular.org/myUploadData%5Cfiles%5CEMEUNET_Do_Not_Miss_EULAR_2010.pdf |title=EULAR 2010 Do not miss. |year=2010 }}</ref>

June 2011 : Due to start Phase 2b clinical trial in rheumatoid arthritis.<ref>{{cite news |url=http://gamutnews.com/20110620/30031/alder-biopharmaceuticals-to-receive-15-million-milestone-payment-from-bristol-myers-squibb-for-initiation-of-phase-2b-clinical-trial-in-rheumatoid-arthritis-of-ald518bms-945429-antibody-therapeutic.html |title=Initiation of Phase 2b Clinical Trial in Rheumatoid Arthritis. |Date=June 2011 }}</ref>

===Crohn's disease===
A phase II trial for [[Crohn's disease]] is due to run until 2015.<ref name=crohn2012>{{cite news |url=http://www.xconomy.com/seattle/2012/08/27/alder-gets-3-5m-milestone-as-bristol-myers-starts-crohns-study/ |title=Alder Gets $3.5M Milestone as Bristol-Myers Starts Crohn’s Study |date=27 Aug 2012 }}</ref>


==See also==
==See also==
*[[Tocilizumab]] (Actemra) an anti-IL-6 receptor mAb
* [[Tocilizumab]] (Actemra) an anti-IL-6 receptor mAb
*[[Anti-IL-6]], other anti-interleukin-6 agents
* [[Anti-IL-6]], other anti-interleukin-6 agents


==References==
==References==
{{reflist}}
{{Reflist}}

⚫
[[Category:Unnamed monoclonal antibodies]]



{{Monoclonals for immune system}}
{{monoclonal-antibody-stub}}
{{Interleukin receptor modulators}}
{{antineoplastic-drug-stub}}


[[Category:Drugs developed by Bristol Myers Squibb]]
[[it:ALD518]]
[[Category:Antibodies]]
⚫
[[Category:Experimental monoclonal antibodies]]

Latest revision as of 07:01, 2 December 2023

Clazakizumab
Monoclonal antibody
TypeWhole antibody
SourceHumanized
TargetIL6
Clinical data
Other namesALD518, BMS-945429
Routes of
administration		infusion
ATC code
  • none
Legal status
Legal status
  • investigational
Identifiers
CAS Number
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
FormulaC6426H9972N1724O2032S42
Molar mass145239.02 g·mol−1

Clazakizumab (formerly ALD518 and BMS-945429), an investigational drug, is an aglycosylated, humanized rabbit monoclonal antibody against interleukin-6.[1] Clazakizumab was developed by Bristol Myers Squib and Alder Biopharmaceuticals. A preliminary randomized, double-blind, placebo-controlled, phase 2 dose-ranging study of clazakizumab in psoriatic arthritis patients, funded by the manufacturer, suggested that clazakizumab may be an effective treatment option for musculoskeletal aspects of psoriatic arthritis; however, the antibody lacked a dose-response effect.[2]

See also

[edit]

References

[edit]
  1. ^ Handbook of Therapeutic Antibodies, Volume 2. Wiley Blackwell. 2007. p. 987. ISBN 9783527329373. Retrieved January 23, 2017.
  2. ^ Mease PJ, Gottlieb AB, et al. (September 2016). "The efficacy and safety of clazakizumab, an anti-interleukin-6 monoclonal antibody, in a phase IIb study of adults with active psoriatic arthritis". Arthritis Rheumatol. 68 (9): 2163–73. doi:10.1002/art.39700. PMID 27059799. S2CID 3644962.
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