BOLT / MedPredict Rheumatology Thought Leader Panels

Posted by Jeff Berk; BOLT International


Greetings from sunny Scottsdale, AZ.  But I repeat myself.  Here in the Desert we’re in the middle of AZ Bike Week.  There must be 100,000 motorcycles rumbling around town.  Organ-donor heaven, right?!  I recently got flamed by some kid who asked, matter of factly, who on Earth would ever want my crusty organs.  Ouch.  (Land the plane, Jeff.  What’s your point?) So the point is, given the option of riding Harleys or writing blogs, I confess I’ve been more interested in the former than the latter.  But in the spirit of not being unidimensional…

BOLT / MedPredict published two new RA reports this month, so today we’re going to talk a little bit about rheumatoid arthritis.  First, the sales pitch…  Both Rheumatology Thought Leader Panel #34 and Rheumatology Thought Leader Panel #35 are available to our Pharma customers for immediate purchase and download.  Just follow the link.  For patients and their physicians, email me to discuss whether you qualify for the freebies.


In Rheumatology Thought Leader Panel #34 we asked our esteemed Panel of US and European thought leaders to help us understand how rheumatologists and payers value the benefits that are delivered by existing products.  We use this as a foundation on which to predict how Pfizer will price tofacitinib in light of competitive dynamics in the rheumatology space.   These discussions shed light on how rheumatologists are compensated and how payers, both private and government, are shifting the responsibility for cost containment back to the physicians, patients and drug companies.



In Rheumatology Thought Leader Panel #35 our esteemed Panel of US and European thought leaders grappled with the challenge of how to rescue waning response to an immunosuppressant, while avoiding excessive immunosuppression.  Using anti-TNF therapy (usually with methotrexate also on board) as the foundation therapy, once response no longer is adequate the question becomes:  Is it better to augment with a third agent (anti-TNF + MTX + new agent) or to switch to another class of drugs?  Against this backdrop the Panel looks at a couple of Ph-III compounds (tofacitinib, fostamatinib) and a variety of Ph-II and earlier development drug classes (other JAKs, CCR1, NRF2/AIM, GM-CSF, CD4, PDE4, BTK, bifunctional monoclonals {TNF + IL17}), with an eye toward identifying compounds that may rescue anti-TNF therapy in the treatment of rheumatoid arthritis.


Since the publication of our tofacitinib pricing forecast, Rheumatology Thought Leader Panel #34, the Panel has had some time to think about the ramifications of the US extension of the etanercept patent lifespan.  Therefore we update slightly the section on Pfizer’s tofacitinib pricing strategy.


This report also focuses a fair amount of discussion on some of Abbott’s recent licensing forays, as they prepare for the loss of exclusivity for Humira (adalimumab).


Drugs mentioned in this report:


Company Drug Brand
Abbott adalimumab Humira
Amgen AMG-827anakinra Kineret
Amgen / Pfizer etanercept Enbrel
Astellas ASP015K
AstraZeneca / Medimmune mavrilimumab (CAM-3001
Biotest / Abbott BT-061
Caprecom etanercept biosimilar Etanar
Celgene apremilast
Dartmouth / Sporn CDDO
Galapagos / Abbott GLPG0634
Genentech / Tolerx MTRX1011A
GSK / ChemoCentryx CCX-354
Incyte / Lilly LY3009104 / INCB28050
KaloBios KB-003
Morphosys MOR-103
Mycenax Biotech etanercept biosimilar TuNEX
Pfizer tofacitinib; CP-690550
Pharmacyclics ibrutinib; PCI-32765
Reata / Abbott NRF2 / AIM
Rigel / AstraZeneca fostamatinib (R788)
Vertex VX-509




Along the lines of an agent that has the potential to address the non-immunosuppressive concomitant therapy need that I alluded to above are CD4 inhibitors from BioTest / Abbott and Genentech /Tolerx .  Here’s a little of the discussion that our Panel (Rheum TLP #35) had related to BT-061:



BT-061 (Abbott / Biotest)


  • BT-061 is a humanized monoclonal anti-CD4 antibody that binds and activates regulatory T-cells.  The principle is that this will be non-immunosuppressive because it just activates these Treg cells.  The target indications for the drug are rheumatoid arthritis and psoriasis.  Ph-II trials in both are ongoing.  Possible upside indications include systemic lupus erythematosus, inflammatory gastro-intestinal diseases, multiple sclerosis, type 1 diabetes and allergy.



“I tell you what was interesting to me the most striking talk of the entire conference was the new anti-CD4 agent by Biotest.  It is an anti-CD4 drug.  And it looks like it exclusively activates regulatory T-cells.  They presented some data in psoriasis.  Some patients switching close to PASI90, which is really surprising.  I had my great hesitations to believe in the clinical efficacy of targeting regulatory T-cells in autoimmune diseases in the human system because you may come too late, the disease is already ongoing or whatever, but these data looked very, very exciting.  The Biotest compound is called BT whatever; and Biotest is in Germany.  How will this drug be used?  I am not sure if it is subcutaneous or IV but it is also monoclonal antibody and probably could be used like many others.  I think they have just completed phase I/II in the US.  I saw that when I went to  I saw that just by chance.  I was quite surprised that companies are still working with anti-CD4.  I was even more surprised when I saw the rationale, which looks very exciting.  So talk to me about how you would envision it being used in therapeutic regimen.  Is this something that would be used after TNF failure?  Could it possibly be used concomitantly?  Given all we know with combining biologicals is this the kind of approach that you could see adding on?  Ideally it would be a non-suppressive agent because it just activates regulatory T-cells.  So it doesn’t interfere with any infectious issues or so.  On paper that looks extremely interesting so you could either use it as a first line drug potentially after methotrexate failure because it is a completely different mechanism.  And the safety looked very good but, of course, these were short term trials.  Is there a North American sponsor yet or co-development group?  I don’t know but I would think so because the initial trial was done in the US.  I will go looking after we talk.  It is not a huge company, Biotest.  It is located in Germany at Dreieich.  It is close to Frankfurt and it is a company which has some drugs in immunology but that in my eyes looked very interesting.  Not many people think that it might hit clinical practice in the end but the data looked very nice”.




“So I mean one agent is quite interesting, the anti-CD4 that Abbott also in-licensed from Biotest.  I have had people tell me that they have had such horrible experience from the anti-CD4s maybe ten years ago.  So what makes this one different?  Yeah, but this is apparently quite a safe agent from what I heard because it only hits regulatory T-cells. It doesn’t deplete. It just activates but doesn’t let’s say stimulate the growth of regulatory T-cells. We are also taking part in the trial. As I say, it has been in-licensed by Abbott, so they must have looked at it and they are smart people there, of course.  So I think that is quite interesting”.



“I think we don’t fully understand the ramifications of messing with regulatory T-cells.  I can’t for the life of me imagine that could ever make it out of a complicated autoimmune disease to be used somewhere where there is the potential for complication would be far less tolerated.  You opened the door early in the discussion about using the CCR1 antagonist in combination with anti-TNF.  What about BTO61 in combination with anti-TNF therapy?  I think it is highly unlikely unless they can hit a grand slam.  That is two biologics and it is basically I think the potential to mess things up in the immune system but good using a T-reg antibody and a TNF inhibitor together sounds profound to me”.


“You would have to really convince me about why I would want to go back into anti-CD4 therapy again.  A number of us were bloodied by this experience 13 years ago when we used monoclonal antibodies against CD4.  It was a terrible experience.  The stuff just did not work even with significant depletion.  So there was a suggestion you could get a non-depleting antibody.  GSK had one and you get some clinical response.  Some of us have long memories about this so I am having trouble here because it just didn’t work”.








Keep the paint side up!

– jb










Categories: ankylosing spondylitis, IMMUNOLOGY, psoriatic arthritis, Rheumatoid Arthritis
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