Melanoma Patient Support (Topic #1) & Psoriasis (Topic #2)

Posted by Jeff Berk, BOLT International;

 

Desert Man Haiku:

Obama dearest,

What’s best way to wipe my ass?

Can you show me how?

 

Desert Man Toilet Paper

 

 

Melanoma Patient Support:

 

I get a ton of contacts from this blog.  50% of them are from melanoma patients.  Interestingly, about 10% in addition are from treaters who are looking for pieces of insight from our Advisory Boards; aka BOLT Thought Leader Panels.  Our rules of engagement are that if you’re a patient or treater, we try to share what we’ve got.  And if you’re Pharma or The Dark Side (you know, you have a signed portrait of you and Jon Corzine hanging on your wall), well use your Amex.  Or PO #’s are good too.  So many of the notes that I get from patients read something like these, posted below, from “Herb” (may or may not be his real name.  But what do you smoke when you’re trying to think of creative things to write in your blog?  ps…  IT’S A JOKE.  I get drug tested more than you do.  Word.)  Now, back to Herb, and all my other “Herbivores”.  You guys all need to hear from each other.  It doesn’t do a lot of good to email me with your responses to comment posts from Herb.  Please post your responses to the blog, so all the Herbivores can benefit from your personal experience.

 

 

So here are some comments from Herb…

 

I was diagnosed with Stage IV Metastatic Melanoma and it looks like I will be starting the Phase 2 of PD-1 within two weeks.  Do you have any heads-up or do/don’t info from your experience?

 

Thanks for your reply,

 

Herb

 

If it can help anyone else I’d be happy to post.  Looks like I’ll get my first infusion of PD-1 in Phase 2 of the study in 2 weeks.  Again, if anyone has any heads-up for the newbe I appreciate hearing it.

Herb

 

I started with Dr. Ribas and UCLA has not been approved for PD-1.

Herb

 

 

 

 

BOLT’s Psoriasis Thought Leader Panel #21 2011-11

 

Desert Man just published BOLT’s Psoriasis Thought Leader Panel #21 2011-11.  For you “instant gratification” types, go to the “Buy Now” link on BOLT’s Home Page.  As with other Panels we’ve been putting out recently for public consumption, this was a “Fantasy Formulary” thought exercise.  We run them the same as Fantasy Football works.  Players (drugs) cost currency, and our Panel has limited resources.  So they have to rank their favorite pipeline products.

 

Following is an alphabetical list by company of the drugs that were discussed.  Mind you, some were discussed in glowing terms, and some were discussed in disgusting terms:

 

Company Generic Name or Mechanism Brand Name(s)
Abbott (Eisai) adalimumab Humira (with Eisai)
Allostera / Unigene APG2305
Amgen AMG-827AMG-108
Amgen / Pfizer / Wyeth etanercept Enbrel
Anacor AN-2728
AnaptysBio / VLST somatic hypermutation anti-IL17
Array / Celgene TYK2
Astellas ASP015K
Astellas / Biogen-Idec alefacept Amevive
Biogen-Idec BG-12 Fumaderm
Boehringer-Ingelheim AbGn-168
Bristol-Myers Squibb / Alder BMS-945429 / ALD-518
Celgene apremilast (CC-100044)
Cephalon / Arana ART-621
Covagen / Roche COVA-301
DermiPsor DPS-101
Forward Pharmaceuticals FP-187
generic etanerceptmethotrexate
Genentech rontalizumabefalizumab Raptiva
Hybrigenics inecalcitol
Idera IMO-3100
IncyteIncyte / Lilly ruxolitinib, INCB-18424INCB-28050; LY-3009104
Janssen / J&J / Centocor / Schering-Plough / Essex ustekinumab; CNTO-1275IL22p19 Stelara
Leo LEO-22811
Lilly LY2439821LY-2525623
Medimmune sifalimumab
Merck anti-IL-17IL22SCH-900222
Novartis AIN-457; secukinumabNVP-AEB-071canakinumab Ilaris
NovImmune / Genentech NI-1401
Pfizer tofacitinib oral, topicalIL22
Roche tocilizumab Actemra/RoActemra
Roche / Actelion R3477 / ACT-128800
S*Bio / Onyx TYK2
UCB certolizumabCDP-6038 Cimzia
Vascular Biogenics VB-201
Vertex VX-509

 

 

Everybody likes something for nothing.  So here’s a couple of little sumpin’ sumpin’s from the report.  The first has to do with innate immunity; IL-I, IFNa, TLR, Dendritic, T-Cell.

 

  • All of the cells that are needed to cause psoriasis are present in uninvolved skin.  All you need to do is tickle the right thing.  That right thing is the innate immune system.  There are a couple of receptors that are very key to this.  They are now being identified as we speak.  One of them clearly is interferon alpha and another is IL-1. Other approaches mentioned by the Panel include TLR7,9, dendritic cell antibodies and T-cell regulators.

 

“Number five on your list are some of these immune pathways, the interferon alphas.  A lot of other panelists have mentioned that.  IL-1 not as many.  But talk to me about the importance of targeting?  So something I can’t share with you some other information that I am privy to and I am the primary investigator worldwide.  We just saw our data the other day and all I can say is that the innate immune system is going to become front and center for an approach of treating psoriasis and its comorbidities.  And what we know to support that at this point is that if you knock down interferon alpha in the best model that there is, and that is transplanting uninvolved skin patients with psoriasis to athymic mice, those uninvolved patches will turn into full fledged psoriasis both histologically as well as by mutant mediated.  What this is telling us is that all of the cells that are needed to cause psoriasis are present in uninvolved skin.  All you need to do is tickle the right thing, that right thing is the innate immune system.  There are a couple of receptors that are very key to this.  They are now being identified as we speak.  One of them clearly is interferon alpha and another is IL-1.  And so just how that is going to get used I don’t know.  I am predicting that the idea of clearing it with something and then putting it back into a non-lesional status would allow us to possibly keep it there by using one of these innate immune system blockers.  But the innate immune system blockers I predict are going to work to knock down primary disease as well.  Pretty interesting.  Yeah, so I think you are going to hear more about that within the next four or five months”.

 

 

 

The second is a cute reason to consider using apremilast in psoriasis – Weight Loss.  Come to think of it, in Scottsdale I expect that all the derms will be dispensing this – regardless of whether their patients have psoriasis.

 

 

  • The first differentiating benefit of apremilast in psoriasis patients will be its positive effect on weight loss.  The mechanistic rationale for this is related to the action of phosphodiesterase 4 in the composition and generation of fatty tissue.  PDE4 regulates the proliferation of adipocytes.

 

“So number two on your list is apremilast.  Give me the pros and cons.  There is one very interesting pro.  During apremilast treatment patients are losing weight.  Oh interesting.  Yes, this is extremely interesting.  It is therefore interesting because you know the psoriasis patient population is mostly overweight.  And from this aspect this is the first and only drug I know about which has a weight losing effect.  And you know that the first data and I think all data about TNF alpha antagonists show that patients gain weight under treatment.  This is one of the small drawbacks of the TNF-alpha antagonists.  But during apremilast treatment they obviously lose weight.

Categories: dermatology, IMMUNOLOGY, melanoma, psoriasis, psoriasis, psoriatic arthritis
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3 Responses to Melanoma Patient Support (Topic #1) & Psoriasis (Topic #2)

  1. alan kravitz says:

    An important breakthrough on a biomarker for anti-Pd-1:

    Both cytoplasmic and membranous B7-H1 staining have been reported in multiple tumor types; however, B7-H1 is a type I transmembrane molecule (6). Cytoplasmic staining may represent intracellular stores of B7-H1, which may be deployed to the cell surface depending on appropriate stimulation. Our previous study describing B7-H1 expression in various human cancers included a small sample size of melanomas (n = 22), among which all were deemed at least focally positive in frozen sections (5); however, the previous study assessed both cytoplasmic and membranous positivity, whereas the current study assesses only membranous expression. We hypothesize that cell surface expression of B7-H1 is the most immediately biologically relevant as a potential biomarker predicting clinical response to PD-1 blockade (29).
    These findings highlight a therapeutic opportunity in administering agents blocking the PD-1/B7-H1 pathway to patients with metastatic melanoma. B7-H1 is a critical immunomodulating component within the melanoma microenvironment. Expression of B7-H1 on tumor cells at the interface with immune infiltrates, in comparison to constitutive tumor expression in areas devoid of infiltrates, may represent distinct underlying immune resistance mechanisms and warrant further study on the molecular level. A deeper understanding of mechanisms driving the observed expression patterns is essential for developing rational treatment combinations with mAbs blocking PD-1 or B7-H1, which are already in clinical trials, and other potentially synergistic therapeutic agents.
    Citation: J. M. Taube, R. A. Anders, G. D. Young, H. Xu, R. Sharma, T. L. McMiller, S. Chen, A. P. Klein, D. M. Pardoll, S. L. Topalian, L. Chen, Colocalization of Inflammatory Response with B7-H1 Expression in Human Melanocytic Lesions Supports an Adaptive Resistance Mechanism of Immune Escape. Sci. Transl. Med. 4, 127ra37 (2012).

  2. Susan Steel says:

    Alan, As a Stage IV melanoma patient on her 6th clinical trial (BMS PD1 with Peptide Vaccines at Moffitt), how does one go about getting tested for the B7 H1 surface marker? I shall present this question to my PI, Jeff Weber too.
    Thanks for sharing your work. – ss

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