Clazakizumab: Difference between revisions

Clazakizumab
Monoclonal antibody
Type	Whole antibody
Source	Humanized
Target	IL6
Clinical data
Other names	ALD518, BMS-945429
Routes of; administration	infusion
ATC code	none;
Legal status
Legal status	investigational;
Identifiers
CAS Number	1236278-28-6;
ChemSpider	none;
UNII	4S38Z8RA9O;
KEGG	D10312;
Chemical and physical data
Formula	C6426H9972N1724O2032S42
Molar mass	145239.02 g·mol−1

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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]

References

^ Handbook of Therapeutic Antibodies, Volume 2. Wiley Blackwell. 2007. p. 987. ISBN 9783527329373. Retrieved January 23, 2017.
^ 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.

[Handbook-1] Handbook of Therapeutic Antibodies, Volume 2. Wiley Blackwell. 2007. p. 987. ISBN 9783527329373. Retrieved January 23, 2017.

[ArthRheum1-2] 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.

[1]

[2]

@@ Line 1: / Line 1: @@
+{{Short description|Chemical compound}}
 {{drugbox
 | type = mab
@@ Line 25: / Line 26: @@
 | excretion =
 | CAS_number = 1236278-28-6
+| UNII_Ref = {{fdacite|correct|FDA}}
+| UNII = 4S38Z8RA9O
 | ATCvet =
 | ATC_prefix = none
@@ Line 31: / Line 34: @@
 | ChemSpiderID = none
 | DrugBank          =
+| KEGG = D10312
 | C=6426 | H=9972 | N=1724 | O=2032 | S=42
+| synonyms = ALD518, BMS-945429
-| molecular_weight = 145.2 kg/mol
 }}
+'''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>
-'''Clazakizumab''' (formerly '''ALD518''' and '''BMS-945429''')<ref name=Claz-2B>[http://news.bms.com/press-release/financial-news/promising-phase-iib-data-clazakizumab-patients-moderate-severe-rheumato Promising Phase IIb Data On Clazakizumab In Patients With Moderate-To-Severe Rheumatoid Arthritis To Be Presented At The 2013 Annual Meeting Of The American College Of Rheumatology ]</ref> 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.
-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://web.archive.org/web/20110708082411/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 trialed 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>
-{{update-section|date=December 2015}}
-===Rheumatoid arthritis===
-The Phase IIa trial for [[rheumatoid arthritis]]<ref>http://clinicaltrials.gov/ct2/show/NCT00867516 Safety, Efficacy and Pharmacokinetics Study of ALD518 in Patients With Active Rheumatoid Arthritis (ALD518-003)</ref> has completed with promising results leading to a licensing 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>
-: A phase 2 trial reported good results in patients not responsive to [[methotrexate]] (MTX).<ref name=Mease2012>{{cite journal |url=http://ard.bmj.com/content/early/2012/02/09/annrheumdis-2011-200704.abstract |title=A phase II, double-blind, randomised, placebo-controlled study of BMS945429 (ALD518) in patients with rheumatoid arthritis with an inadequate response to methotrexate |year=2012 |doi=10.1136/annrheumdis-2011-200704 }}</ref>
-Oct 2013 : A phase 2B clinical trial has met its primary endpoint ([[ACR score for rheumatoid arthritis|ACR20]] response at 12 weeks).<ref name=Claz-2B/> [[Adalimumab]] with [[Methotrexate|MTX]] was included as a comparison in the trial.<ref name=Claz-2B/>
-: A dose ranging phase 2B trial was running.<ref name=NCT02015520>[https://www.clinicaltrials.gov/ct2/show/NCT02015520 Phase IIB Dose Ranging Study in Subjects With Moderate to Severe Rheumatoid Arthritis]</ref>
-===Crohn's disease===
-A phase II trial for [[Crohn's disease]] initially 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> has been prematurely discontinued after having recruited 71 patients out of 288.<ref>http://www.clinicaltrials.gov/ct2/show/study/NCT01545050?show_locs=Y</ref>
 ==See also==
@@ Line 71: / Line 47: @@
 ==References==
 {{Reflist}}
-==Further reading==
-* [http://acrabstracts.org/abstract/anti-il-6-antibody-clazakizumab-is-more-potent-than-tocilizumab-in-blocking-in-vitro-and-ex-vivo-il-6-induced-functions/ Anti-IL-6 Antibody Clazakizumab Is More Potent Than Tocilizumab In Blocking In Vitro and Ex Vivo IL-6-Induced Functions. 2013]
 {{Monoclonals for immune system}}
 {{Interleukin receptor modulators}}
-[[Category:Bristol-Myers Squibb]]
+[[Category:Drugs developed by Bristol Myers Squibb]]
 [[Category:Antibodies]]
-[[Category:Anti-inflammatory agents]]
+[[Category:Experimental monoclonal antibodies]]
-[[Category:Experimental drugs]]
-[[Category:Experimental cancer drugs]]