Preparations for the 2012 ACR Meeting in Washington

These are my preparations for the the 2012 ACR Meeting in Washington. It lists the topics and what I already know about different therapies or emerging therapies. There are also some dead end streets!

Anakinra - IL-1Ra-Receptor antagonist

Anakinra and Pseudogout (calcium pyrophosphate crystal arthritis) - what has changed since the EULAR 2012? http://rheumatologe.blogspot.de/2012/07/anakinra-and-pseudogout-calcium.html

Ankylosing Spondylitis

New drugs? New developments?

Ankylosing Spondylitis refractory to TNF-inhibition had been addressed at the EULAR 2012. http://rheumatologe.blogspot.de/2012/07/ankylosing-spondylitis-refractory-to.html

Anti-CD-20 Monoclonal Antibody (like Rituximab)
Ofatumumab and/or ocrelizumab?

Some information at: http://rheumatologe.blogspot.de/2012/06/anti-cd-20-monoclonal-antibody.html 

Anti-CD-40 Monoclonal Antibody

Targeting CD-40 – Preliminaries at the EULAR 2012. Link: http://rheumatologe.blogspot.de/2012/08/targeting-cd-40-preliminaries-at-eular.html

ARRY-371797

ARRY-371797 is a p38 inhibitor. There are some studies on the way:

• A Study of ARRY-371797 in Patients With Rheumatoid Arthritis

• A Study of ARRY-371797 in Patients With Active Ankylosing Spondylitis

• A Study of ARRY-371797 in Patients With Osteoarthritis of the Knee

All three studies have been completed by July 2012, but nothing has been published at the EULAR 2012 meeting in Berlin. I guess the results will be presented at the ACR 2012 in Washington.

Atacicept

Has atacicept [works on BLys(B-lymphocyte stimulator) and APRIL (A PRoliferation Inducing Ligand)] shown new efficacy? Older information at: http://rheumatologe.blogspot.de/2012/06/atacicept.html. If I don´t see anything at the ACR 2012 I´ll erase Atacicept from my list.

B10 cells
I've got interested to look, if research on rodents for IL-10 activated B-cells already has made the ACR meeting.

 

Baricitinib

Baricitinib (also known as INCB28050, LY3009104) is an oral JAK1 and JAK2 inhibitor.Any new developmen? For results presented at EULAR 2012 look here: http://rheumatologe.blogspot.de/2012/06/baricitinib-ly3009104-at-eular-2012-in.html

Belimumab

Belimumab in RA???

Biosimilars

Celltrion will most probably launch an infliximab biosimilar in 2013. Anything on other drugs in the pipeline. How about other pharmaceutical companies? How about biosimilars that are already marketed to come to other markets? http://rheumatologe.blogspot.de/2012/06/biosimilars.html

BMS-582949
BMS-582949 is a dual action p38 kinase inhibitor. There is a study of G. Schieven and colleagues, which has been published at the 2010 ACR meeting (Arthritis Rheum 2010;62 Suppl 10 :1513 DOI: 10.1002/art.29279). There has been a study, http://clinicaltrials.gov/show/NCT00605735, which has been completed, but no study result have been published (updated: January 24, 2011). So I guess, this is another dead end. Or we shall see some new developments at the ACR2011

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 yet. If I don´t see anything at the ACR 2012 I´ll erase Brodalimumab from my list.

BT061

Target CD4, “Dose-finding of Multiple Dose of BT061 in Patients With Active Rheumatoid Arthritis Incompletely Controlled on Stable Methotrexate (MTX)”, Estimated Study Completion Date: December 2013. http://clinicaltrials.gov/ct2/show/NCT01481493

Mabe we shall see some preliminary results.

Canakinumab (ACZ885)

Canakinumab (ACZ885), target IL-1 beta, has been developed for the treatment of rheumatoid arthritis, but this indication has been abandoned. IL-1 beta isn’t a successful target in rheumatoid arthritis. Novartis tries desperately to find indications for its’ drug like gout as cryopyrin-associated periodic syndromes (CAPS) are orphan diseases.

CCX354-C

CCX354-C did better than expected. Maybe half a year is long enough for more results. For EULAR 2012 look at: http://rheumatologe.blogspot.de/2012/07/ccx-354-c-at-eular-2012.html

Cetrorelix

Cetrorelix is a gonadotropin-releasing hormone antagonist (GnRH antagonist). I expect some niew results. Older results here: http://rheumatologe.blogspot.de/2012/07/cetrorelix-at-eular-2012.html

Clazakizumab
Clazakizumab targets the interleukin-6 (IL-6). So it would be much like tocilizumab (Actemra). I don’t know of any study. If I don´t see anything at the ACR 2012 I´ll erase Clezakizumab from my list.

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. Who knows which dead man comes to life again?

Co-Stimulation-Inhibition

Subcutaneous abatacept, when will it be available?
I hope to confirm the date.

Dekavil

Dekavil - fibronectin-A-chain connected to IL-10 http://rheumatologe.blogspot.de/2012/07/dekavil-at-eular-2012.html

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. If I don´t see anything at the ACR 2012 I´ll erase fezakinumab from my list.

Fibromyalgia

Fibromyalgia will be an important issue for me.

Fostamatinib

Concerning fostamatinib (a SYK inhibitor), how far have we come during the the time since EULAR 2012? Any date for launching the drug? http://rheumatologe.blogspot.de/2012/07/fostamatinib-at-eular-2012.html

Iguratimod

Iguratimod, a new DMARD, is under way from Japan. A new DMARD is of interest as some patients have contraindications for biologics. Result presented at EULAR 2012 are here: http://rheumatologe.blogspot.de/2012/06/iguratimod-at-eular-2012.html

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. But maybe Washington will be the place to present new results.

KB-003

Target GM-CSF, “The study was terminated upon completion of safety run-in due to program refocus.” http://clinicaltrials.gov/ct2/show/results/NCT00995449. If I don´t see anything at the ACR 2012 I´ll erase KB-003 from my list.

Mavrilimumab

Mavrilimumab is a human MAB for the treatment of rheumatoid arthritis. It targets the GMCSF receptor and alpha-chain. http://rheumatologe.blogspot.de/2012/07/mavrilimumab-at-eular-2012.html

MDX-1100

Target CXCL10, but doesn’t seem to be very effective: “The ACR50 and ACR70 response rates on day 85 did not differ between the groups.” http://www.ncbi.nlm.nih.gov/pubmed/22147649. The ACR20 response rate, however, was significantly higher among MDX-1100-treated patients. Let´s wait for further results!

Modified release prednisone

On modified release prednisone: http://rheumatologe.blogspot.de/2012/06/modified-release-prednisone.html. I had been very skeptical about this product from the very beginning. The studies presented at the EULAR 2012 nurtured this skepticism.

MOR103

Target GM-CSF, there is some interesting data, but only published by MorphoSys: http://www.morphosys.com/pressrelease/morphosyss-mor103-antibody-demonstrates-excellent-safety-and-efficacy-rheumatoid-arthritis-patients. Lets wait for the discussions at the ACR2012 next month!

Nerelimomab

Nerelimomab targets TNF-alpha and therefore might not be investigated further (enough TNF-alpha-inhibitors already on the market). Maybe I´ll have to erase this one, too.

NKG2a

NKG2A / NNC141-0100 at the EULAR 2012 Link: http://rheumatologe.blogspot.de/2012/07/nkg2a-nnc141-0100-at-eular-2012.html

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. If I don´t see anything at the ACR 2012 I´ll erase olokizumab from my list.

Pamapimod
R. Alten and colleagues presented a study on “Efficacy and safety of pamapimod in patients with active rheumatoid arthritis receiving stable methotrexate therapy” in April 2009. Sorry to say, but “pamapimod showed non-significant improvement in efficacy outcomes compared to placebo.” Actually, patients on pamapimod achieved poorer results than those on methotrexate. Some people already think that rheumatoid arthritis might be the wrong indication for this kind of drugs. Maybe I´ll have to erase this one, too.

Pateclizumab

Pateclizumab is an anti-Lymphotoxin-alpha Monoclonal Antibody. http://rheumatologe.blogspot.de/2012/06/pateclizumab-anti-lymphotoxin-alpha.html

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. If I don´t see anything at the ACR 2012 I´ll erase olokizumab from my list.

Psoriatic Arthritis
Non-anti-TNF Biologics in Psoriatic Arthritis at EULAR 2011. http://rheumatologe.blogspot.de/2012/07/non-anti-tnf-biologics-in-psoriatic.html. I hope for new results on new drugs as therapy for psoriatic arthritis still lags behind.

Ruxolitinib
Ruxolitinib is a JAK1/JAK2 inhibitor, which could be useful to treat rheumatoid arthritis. There has been a study being presented at the 2008 ACR meeting, here’s an article referring to this study. http://www.istockanalyst.com/article/viewiStockNews/articleid/2739159. Nothing new at the EULAR 2012 meeting in Berlin. Let´s see, if ruxolitinib is a hot topic at the ACR 2012.

Sarilumab

Sarilumab, another anti-IL-6 monoclonal antibody, has already been in a phase 2 study in 2011, what’s new? More than presented at the EULAR 2012? http://rheumatologe.blogspot.de/2012/06/sarilumab-news-from-eular-2012.html

SBI-087

SBI-087 is a SMIP (= small molecule immune pharmaceutical) binding to CD-20 http://rheumatologe.blogspot.de/2012/07/sbi-087-at-eular-2012.html

Secukinumab

Secukinumab (an Anti-Il17a Monoclonal Antibody). http://rheumatologe.blogspot.de/2012/06/secukinumab-anti-il17a-monoclonal.html

Sirukumab MAB against IL-6 –

Sirukumab (formerly known as CNTO 136) is a human MAB that binds to the cytokine IL-6, designed for the treatment of rheumatoid arthritis. So sirukumab will be competiting with tocilizumab. Link: http://rheumatologe.blogspot.de/2012/07/sirukumab-at-eular-2012.html

Small molecules / protein kinase inhibitors

Safety of different small molecules / protein kinase inhibitors http://rheumatologe.blogspot.de/2012/06/safety-of-different-small-molecules.html

Synavive

Synavive, a combination of 2 mgs of prednisolone and 200 mgs of dipyramidole: http://rheumatologe.blogspot.de/2012/07/synavive-crx-102-at-eular-2012.html. A new idea, what how much benefirt for our patients?

Tabalumab

Tabalumab is an anti-BAFF Monoclonal Antibody. http://rheumatologe.blogspot.de/2012/06/tabalumab-ly2127399-anti-baff.html. I´m very skeptical about benefit in RA.

Tocilizumab

In a head to head study tocilizumab monotherapy has been studied against humira monotherapy. http://rheumatologe.blogspot.de/2012/06/tocilizumab-monotherapy-vs-humira.html  
Concerning Tocilizumab, my most important question to solve at the EULAR 2012 has been: How about subcutaneous tocilizumab? http://rheumatologe.blogspot.de/2012/06/tocilizumab-at-eular-2012.html. The answer has been 2014. I hope for better news.

Tofacitinib

The oral jak inhibitor tofacitinib (CP-690,550) has attracted most attention. http://rheumatologe.blogspot.de/2012/07/tofacitinib-oral-jak-inhibitor-at-eular.html.Any late breaking news?

Ustekinumab

Ustekinumab and other options in psoriatic arthritis. http://rheumatologe.blogspot.de/2012/07/ustekinumab-and-other-options-in.html.

Veltuzumab

Target CD20, VELVET, a Dose Range Finding Trial of Veltuzumab in Subjects With Moderate to Severe Rheumatoid Arthritis – the study is ongoing. Let’s wait for results! And please check: http://rheumatologe.blogspot.de/2012/06/anti-cd-20-monoclonal-antibody.html

VX-702
About VX-702, a novel p38 MAPK inhibitor, not much better is to be said. N. Damjanov and colleagues of Belgrade University School of Medicine published two studies: “Efficacy, pharmacodynamics, and safety of VX-702, a novel p38 MAPK inhibitor, in rheumatoid arthritis: results of two randomized, double-blind, placebo-controlled clinical studies” and concluded: “The modest clinical efficacy plus the transient suppression of biomarkers of inflammation observed in this study suggest that p38 MAPK inhibition may not provide meaningful, sustained suppression of the chronic inflammation seen in RA.”

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.

Minor changes at 16.10.2012 and 24.10.2012

There are some more interesting small molecules like:
Masitinib (c-KIT - a tyrosine kinase inhibitor / yes, I know, it is in use in mast cell tumors of animals)
Imatinib (c-KIT/PDGF-R - another tyrosine kinase inhibitor, already approved for treatment of certain cancers)
Sunitinib (fit3 - another tyrosine kinase inhibitor, already approved for treatment of certain cancers)
Dasotinib (BCR/ABL and Src family tyrosine kinase inhibitor already approved for treatment of certain cancers)
26.10.2012