Friday, July 27, 2012

Fighting Rheumatoid Arthritis - Monoclonal Antibodies in the Pipeline


I have been wondering which monoclonal antibodies might be in the pipeline to emerge later a potent drugs fighting rheumatoid arthritis. I can’t be sure, what the pharma industry will decide, sometimes these monoclonal antibodies are abandoned for several reasons before becoming a potential drug. Here are a few candidates and also some candidates that didn’t make it..


Briakinumab (ABT-874)
Briakinumab (ABT-874) targets the interleukin-12 (IL-12) and interleukin-23 (IL-23). Briakinumab might be used to treat rheumatoid arthritis psoriasis, and other autoimmune diseases like ustekinumab.


Brodalumab
Brodalumab targets the interleukin-17 (IL-17) and is therefore much like ixekizumab, see below. I don’t know of any study.


Clazakizumab
Clazakizumab targets the interleukin-6 (IL-6). So it would be much like tocilizumab (Actemra). I don’t know of any study.


Clenoliximab
Clenoliximab targets CD4. There has been a study in 1999: http://www.ncbi.nlm.nih.gov/pubmed/10511060. Another study is dated 2002 (Antibody‐mediated stripping of CD4 from lymphocyte cell surface in patients with rheumatoid arthritis) by T. W. Hepburn and colleagues. I think clenoliximab has been abandoned.


Fezakinumab
Fezakinumab targets IL-13 an has been designed for the treatment of inflammatory diseases, but my guess is that it’s more against asthma. Nothing at the EULAR 2012 meeting in Berlin.


Ixekizumab
Ixekizumab targets the interleukin-17 (IL-17) and is also known as LY2439821. It has been introduced at the ACR 2011 in Chicago: http://rheumatologe.blogspot.de/2011/11/ly2439821-anti-il-17-monoclonal.html. There hasn’t been any new study at the EULAR 2012 meeting in Berlin. M. Genovese et al. showed the results already presented at the ACR 2011 meeting in Chicago.


Nerelimomab
Nerelimomab targets TNF-alpha and therefore might not be investigated further (enough TNF-alpha-inhibitors already on the market).


Olokizumab
Olokizumab is targets the interleukin-6 (IL-6). So it would be much like tocilizumab (Actemra). I haven’t seen any study at the EULAR 2012 meeting in Berlin.


Placulumab
Placulumab targets TNF-alpha and therefore might not be investigated further (enough TNF-alpha-inhibitors already on the market). Nothing on Placulumab at the EULAR 2012 meeting in Berlin.


Zanolimumab
Zanolimumab targets CD4 and has an expected trade name (HuMax-CD4). It should be used to treat rheumatoid arthritis, psoriasis, and more. Wikipedia: “The drug is currently undergoing Phase II trials[5].” When I looked further I’ve found a study: “Trial With HuMax-CD4 in Patients With Rheumatoid Arthritis Failing Treatment With Methotrexate and a TNF-Alpha Blocker”, which had been completed in 2005, but: “No publications provided”. So I guess, this drug also has been abandoned in the treatment of rheumatoid arthritis.


1 comment:

  1. Hallo Rheumatologe,
    es ist Wahnsinn, wieviel Antikörper Medikamente derzeit gegen RA untersucht werden, man könnte die Liste fortführen mit

    ACZ885 (Canakinumab), Target IL-1 beta
    MDX-1100, Target CXCL10
    MOR103, Target GM-CSF
    KB-003, Target GM-CSF
    Sirukumab, Target IL-6
    BT061, Target CD4
    Belimumab, Target BAFF
    Veltuzumab, Target CD20
    Golimumab, Target TNF-alpha
    Mavrilimumab, Target GM-CSF

    und wäre damit noch lange nicht vollständig.

    Auf Clinicaltrials findet man unter dem Stichwort "rheumatoid arthritis" allein 231 Studien der Phasen 1 bis 3.

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