Tuesday, May 14, 2013

EULAR 2013 Meeting in Madrids

This is the list of topics, I'm interested in. I'll look at all of the posters and try to be in as many of the sessions duiscussing these topics. More information on the drugs/topics look for the links.

Anti-IL-6 Receptor Nanobody (ALX-0061) – anything new?

Anakinra - IL-1Ra-Receptor antagonist
New fields of action?
Link to the EULAR evaluation: http://rheumatologe.blogspot.de/2012/07/anakinra-and-pseudogout-calcium.html

Ankylosing Spondylitis
New drugs? New developments?
Link to the EULAR 2012 blog post: http://rheumatologe.blogspot.de/2012/07/ankylosing-spondylitis-refractory-to.html  

Anti-CD20 Monoclonal Antibody (like Rituximab)
Ocrelizumab, ocaratuzumab, which will be looked at below.
More information on other agents at: http://rheumatologe.blogspot.de/2012/06/anti-cd-20-monoclonal-antibody.html  

Anti-CD-40 Monoclonal Antibody
There´s no anti-CD40 agent, but my guess is that there will be. So I keep it on the list. – Well let’s see if EULAR has something this year.
Link to preliminaries at the EULAR 2012: http://rheumatologe.blogspot.de/2012/08/targeting-cd-40-preliminaries-at-eular.html

ARRY-371797 / ARRY-797
Still sceptic!

"An oral Janus kinase (JAK) inhibitor with selectivity for JAK1/3.

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

"Belimumab is a recombinant, human Ig-G1 monoclonal antibody that binds and antagonizes the biological activity of soluble B-lymphocyte stimulator protein."  

Still problems getting them to market approval.

Brodalumab targets the interleukin-17 (IL-17) and is therefore much like ixekizumab, see below. How about PsA?

Target is CD4. Maybe we shall see some preliminary results. – If there isn’t any new data, I’ll erase this one from my list. Though: Estimated Study Completion Date: December 2013. http://clinicaltrials.gov/ct2/show/NCT01481493  
Mabe we shall see some preliminary results.

Canakinumab (ACZ885)
More on orphan diseases?

CCX354-C should come up with some new data.
For EULAR 2012 look at: http://rheumatologe.blogspot.de/2012/07/ccx-354-c-at-eular-2012.html

Cetrorelix is a gonadotropin-releasing hormone antagonist (GnRH antagonist). http://rheumatologe.blogspot.de/2012/07/cetrorelix-at-eular-2012.html

Dekavil - fibronectin-A-chain connected to IL-10. Still progressing slowly?

Fibromyalgia – anything on the hype of “change of paradigm”?

Concerning fostamatinib (a SYK inhibitor) it’s getting tight? http://rheumatologe.blogspot.de/2012/07/fostamatinib-at-eular-2012.html  

Selective JAK1 inhibitor. Better than tofacitinib or not as efficacious?

Iguratimod, a new DMARD, is under way from Japan. Maybe something new presented in Europe?! http://rheumatologe.blogspot.de/2012/06/iguratimod-at-eular-2012.html

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.
But after this introduction - no further use. It should be an interesting target (maybe more in PsA), but perhaps ixekizumab is failing to hit the target.

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  
GMCSF? I'm very sceptical.

Modified release prednisone
On modified release prednisone: http://rheumatologe.blogspot.de/2012/06/modified-release-prednisone.html.
To sum it up: I'm even more sceptic about modified release prednisone after the ACR 2012! Will this scepticism be reduced at the EULAR?

Target GMCSF, there had been some interesting data, but only published by MorphoSys: http://www.morphosys.com/pressrelease/morphosyss-mor103-antibody-demonstrates-excellent-safety-and-efficacy-rheumatoid-arthritis-patients.
There has been a late breaking poster at the ACR on MOR103. Link:  http://rheumatologe.blogspot.de/2012/12/mor103-at-acr-2012-in-washington.html
I think the paper left open lots of questions.

There hasn't been too much on NKG2A / NNC141-0100 both at the EULAR 2012 and the ACR 2012. Link: http://rheumatologe.blogspot.de/2012/07/nkg2a-nnc141-0100-at-eular-2012.html and http://rheumatologe.blogspot.de/2012/12/nkg2a-at-acr-2012-in-washington.html  
I hope to see more.

NNC0114-0005 is a recombinant anti-IL-21 monoclonal antibody. Link: http://rheumatologe.blogspot.de/2012/12/nnc0114-0005-at-acr-2012-in-washington.html  

"NNC0109-0012 (anti-IL-20 mAb) is a novel human monoclonal IgG4 antibody which binds to and neutralizes the activity of IL-20." And the word still ring in my ear: "The data from this trial support further clinical development of NNC0109-0012 (anti-IL-20 mAb) in RA." Link to more information: http://rheumatologe.blogspot.de/2012/12/nnc0109-0012-at-acr-2012-in-washington.html  
How much is there to be expected within half a year?

Ocaratuzumab is a Fc- and Fab engineered anti-CD20 antibody, which showed rapid and sustained depletion of circulating B-cells in rheumatoid arthritis patients (No. 835). A. O'Reilly and colleagues also discussed the possibility of using ocaratuzumab subcutaneously.
Link to more information: http://rheumatologe.blogspot.de/2012/12/ocaratuzumab-at-acr-2012-in-washington.html  
Will s.c. cause problems because of missed follow-ups?

Olokizumab targets 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. But I have seen some results on olokizumab at the ACR 2012. Link to more information: http://rheumatologe.blogspot.de/2012/12/olokizumab-at-acr-2012-in-washington.html  
If there won't be any results ... maybe it's going to be abandoned.

Ozoralizumab (ATN-103)
R. M. Fleischmann and colleagues presented: "A Novel Individualized Treatment Approach in Open-Label Extension Study of Ozoralizumab (ATN-103) in Subjects with Rheumatoid Arthritis On a Background of Methotrexate" (No. 1311). "Ozoralizumab (ATN-103), a novel TNF-inhibitor, is a trivalent, bispecific Nanobody (R) that potently neutralises TNF ..." Results: " ... EULAR good/moderate response rate was 97% ...". Conclusions: " ... This treatment approach could prove beneficial to patients and minimize treatment costs."
Link: http://rheumatologe.blogspot.de/2012/12/ozoralizumab-atn-103-at-acr-2012-in.html
If I hear nano, I think of hype; but maybe I'm too sceptical.

Pateclizumab is an anti-Lymphotoxin-alpha Monoclonal Antibody. http://rheumatologe.blogspot.de/2012/06/pateclizumab-anti-lymphotoxin-alpha.html
Nothing at the ACR 2012, but I´ll wait until the EULAR 2013 before I´ll erase pateclizumab from my list of interests.
Anti-Lymphotoxin might not work alone. So dropping the development of a new drug now and use it in the future in some combination would be still an option.

Pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, used in diabetes, has been tested in rheumatoid arthritis: "A Proof-of-Concept Randomized Controlled Trial" by M. J. Ormseth and colleagues (No. 832). Pioglitazone "modestly reduces RA disease activity measured by DAS28 CRP and CRP levels". If you want more, then here's the link: http://rheumatologe.blogspot.de/2012/12/pioglitazone-at-acr-2012-in-washington.html
Modestly ... honestly I doubt that pioglitazone will be a success.

PRTX-100 (Staphylococcal Protein A)
E. Bernton et al. presented: "A Phase 1, Randomized, Double-Blind, Placebo-Controlled Multiple-Dose Study of Intravenous Staphylococcal Protein A in Patients with Active Rheumatoid Arthritis On Methotrexate: Safety, Pharmacokinetics and Efficacy" No. 833). As I had been part in testing immunoadsorption, I´m not too confident in PRTX-100. But it´s still too early for skepticism.You find more here: http://rheumatologe.blogspot.de/2012/12/prtx-100-staphylococcal-protein-a.html
The EULAR might still be too early.

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. Maybe Brodalumab.
I've found some data on apremilast in psoriatic arthritis:

Ruxolitinib is a JAK1/JAK2 inhibitor, which could be useful to treat rheumatoid arthritis. Nothing new at the EULAR 2012 and the ACR 2012. But there has been a study mentioning the drug (No. 1807). http://rheumatologe.blogspot.de/2012/12/ruxolitinib-at-acr-2012-in-washington.html
Time is pressing, ruxolitinib!

Sarilumab is another anti-IL-6 monoclonal antibody. http://rheumatologe.blogspot.de/2012/06/sarilumab-news-from-eular-2012.html  
At the ACR 2012 sarilumab failed to present the final results of the phase 2 study and nothing on a phase 3 study. And here are the details:
So the 2013 meetings might be cricial.

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  
Nothing at the ACR 2012. If there isn´t anything at the EULAR2013, I´ll erase this one, too.

Secukinumab is an Anti-Il17a Monoclonal Antibody. http://rheumatologe.blogspot.de/2012/06/secukinumab-anti-il17a-monoclonal.html  
There have been two studies at the ACR 2012: http://rheumatologe.blogspot.de/2012/12/secukinumab-at-acr-2012-in-washington.html  
I'll have to check results against brodalumab.

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  
I'll have a look at other PK inhibitors as well, which aren't mentioned or which surface at the EULAR meeting.

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 benefit for our patients? As there hasn't been anythin at the ACR 2012, I might erase this one, too.

Tabalumab is an anti-BAFF Monoclonal Antibody. http://rheumatologe.blogspot.de/2012/06/tabalumab-ly2127399-anti-baff.html. I'm very skeptical about benefits in RA. Here are the details:
I might erase this MAB, too.

There might be something on tocilizumab and amyloidosis. http://rheumatologe.blogspot.de/2012/06/tocilizumab-at-eular-2012.html.
How about subcutaneous tocilizumab? When will it be available?

The oral JAK 1 and 3 inhibitor tofacitinib (CP-690,550) had already attracted most attention at the EULAR 2012. See here: http://rheumatologe.blogspot.de/2012/07/tofacitinib-oral-jak-inhibitor-at-eular.html.
At the ACR 2012 the real hit has been: tofacitinib has been approved by the FDA, with a black box warning on opportunistic infections, tuberculosis, cancers, lymphoma, and is available on the US market as Xeljanz. EMA approval has been postponed. See: http://rheumatologe.blogspot.de/2013/04/xeljanz-tofacitinib-and-negative.html 

Ustekinumab and other options in psoriatic arthritis. http://rheumatologe.blogspot.de/2012/07/ustekinumab-and-other-options-in.html.
Quite lot discussion you'll find here: http://rheumatologe.blogspot.de/2012/12/ustekinumab-at-acr-2012-in-washington.html
We have been discussing ustekinumab in a circle of rheumatologists at "Immunology & more", first impression is that it works better on the skin than on the joints. So, I'll be looking, if this hypothesis is addressed in any of the studies.

Target CD20, VELVET, a Dose Range Finding Trial of Veltuzumab in Subjects With Moderate to Severe Rheumatoid Arthritis – the study is ongoing. Please check: http://rheumatologe.blogspot.de/2012/06/anti-cd-20-monoclonal-antibody.html  
If you wait for results you have to join me. Nothing new elucidated at the ACR 2012 in Washington. If there isn´t some development until EULAR 2013, I´ll erase this one.

A JAK 3 inhibitor. I'd give some time.

There hasn't been anything new on VX-702, a novel p38 MAPK inhibitor, at the 2012 meetings. If there isn´t some development until EULAR 2013, I´ll erase this one, too. I'm not convinced that p38 MAPK is a good target.

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