Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

Posts by MaverickNY

Fall cancer conference schedule

By on August 9, 2010

The dog days of summer are now here and looking ahead at my conference schedule over the next couple of months, things look quite busy already.

Here's a list of some of the meetings and events I plan to attend based on my public Plancast schedule:

Whew!

Come December there will also be ASH in Orlando and the San Antonio Breast Cancer Symposium back to back, so a busy season ahead awaits already.

If you would like to meet up at any of the meetings for coffee, a chat or networking, please let me know.  You can email me here or comment below.

 

An experiment on Pharma Strategy Blog

By on August 9, 2010

Over the last couple of months I've had a few grumbles from readers suggesting that the 13pt font was too small on the screen or the blog text in the emails was miniscule.

I've played around with the theme a bit and it seems the default goes from 13pt to 16pt, which for me as a scientist used to reading tiny text in journal papers is a bit like shouting, but we'll see what happens.

Over the next few months you'll see some UI and UX changes as we move from Typepad to WordPress for blog hosting.  I've resisted the move some time as I'm one of those people who aren't really interested in the nerdy bits inside the engine, preferring to set up a theme and just blog rather than fiddle with the innards.

Still, we are planning to evolve Pharma Strategy Blog with new services such as monthly newsletters and more extensive cancer reports that you can purchase, in addition to the daily snippets here on the blog. Setting up a commercial service is much easier and more professional in WordPress (WP), so that is pretty much driving the decision to move along with other cool tools such as Disqus and Backtype, which don't play at all well on the Typepad platform.

Converting the posts (over 700 of them along with comments) is not going to be easy by all accounts, especially transferring the precise urls, so you may see some old posts reappear in Twitter or the RSS feed as we convert them from the old Typepad Oncochat url to the Pharma Strategy Blog one before the move to WP. We do appreciate you patience during the transition to our new home.

A number of you have asked how to find old posts.

The Archives section has been added to the right hand column, which is useful if you can remember when (approximate month) it was posted or you can browse for anything interesting. Alternatively, the Lijit search widget on the right works like Google – you just type in what you're looking for and it will produce a list of posts on that specific topic if it has been covered.

If you have any other ideas or suggestions that you would like to see here, please add them in the comments.

Social media is NOT a strategy…

By on August 6, 2010

No, it is not a strategy in and of itself.

It is, however, a useful collection of tools that can be used tactically as part of an overall brand strategy… one element or part of the whole, if you like.  To make social media work well you need to integrate it with more traditional approaches that capture the imagination and inspire people.

New (digital) toys on their own will not do much for your brand or ROR, return on relationships.  Adding value, will however, make a huge difference.  Deep down, we all know this intuitively, but it’s easy to get distracted by shiny lures and forget the basics of marketing.

Joe Chernov and Valerie Maltoni illustrate this conundrum perfectly (see link below for the cartoon source):

Picture 2

Source: Eloqua Blog

If a consultant or agency comes to see you Pharma folks touting “social media strategy” you instantly know they’re a fake and don’t know what they’re talking about ;-).

Isolated tactical execution without a strong focused brand strategy is doomed to failure from the start so avoid that trap.

Think differently.

Somatic mutations and pathway alterations in cancer

By on August 5, 2010

"The systematic characterization of somatic mutations in cancer genomes is essential for understanding the disease and for developing targeted therapeutics."

So began today's journal article from a letter to Nature (link below) from scientists at Genentech.  They went on to state that they have looked at:

"The identification of 2,576 somatic mutations across 1,800 megabases of DNA representing 1,507 coding genes from 441 tumours comprising breast, lung, ovarian and prostate cancer types and subtypes. We found that mutation rates and the sets of mutated genes varied substantially across tumour types and subtypes.

Statistical analysis identified 77 significantly mutated genes including protein kinases, G-protein-coupled receptors such as GRM8, BAI3, AGTRL1 (also called APLNR) and LPHN3, and other druggable targets.

Integrated analysis of somatic mutations and copy number alterations identified another 35 significantly altered genes including GNAS, indicating an expanded role for Ga subunits in multiple cancer types."

The goal of this type of analysis is to look for patterns and alterations associated with disease and try to figure out which are potentially druggable targets for drug development.  The researchers went on to note:

"Our study represents a substantial expansion of the knowledge base of cancer somatic mutations. Of the 845 genes with proteinaltering mutations identified in this study, 361 (43%), including 13 significantly mutated genes like TLR4, SPOP and NRG3, have not previously been reported."

image from www.flickr.com That's great news. Of course, it should be noticed that theory is one thing, but until a pipeline compound enters into clinical trials and we see the results of extensive studies, we won't know whether the target is truly a relevant one in human cancers or not.

Not all mutations may occur in every person though, as we have seen in lung cancer where some people might have an EGFR mutation, some an ALK mutation and so on. The secret to this approach is to start documenting the likely targets and go looking to see how many exist, which ones might be a critical driver and which ones are merely passengers.

Clearly though, it does help to have an idea of what the needles in the haystack might look light before going hunting for them to increase the chances of success.

Photo Credit: Yellow Book

 

ResearchBlogging.orgKan, Z., Jaiswal, B., Stinson, J., Janakiraman, V., Bhatt, D., Stern, H., Yue, P., Haverty, P., Bourgon, R., Zheng, J., Moorhead, M., Chaudhuri, S., Tomsho, L., Peters, B., Pujara, K., Cordes, S., Davis, D., Carlton, V., Yuan, W., Li, L., Wang, W., Eigenbrot, C., Kaminker, J., Eberhard, D., Waring, P., Schuster, S., Modrusan, Z., Zhang, Z., Stokoe, D., de Sauvage, F., Faham, M., & Seshagiri, S. (2010). Diverse somatic mutation patterns and pathway alterations in human cancers Nature DOI: 10.1038/nature09208

Hedgehog (Hh) signaling in cancer: a new pipeline emerges

By on August 4, 2010

The other day I came across an interesting journal article on Hedgehog signalling, how it might be implicated in some cancers, and the potential issues associated with targeting the pathway:

“… several issues surrounding the basic biology of the Hh pathway in human cancers remain unclear. These include the influence of specific oncogenic events on Hh signal transduction, the precise mode of Hh signaling (i.e., autocrine or paracrine) that occurs within human tumors, and the best means to inhibit aberrant pathway activity in the clinical setting.

The cancer stem cell (CSC) hypothesis may explain a number of clinical phenomena, such as unchecked self-renewal and the development of metastatic disease, and to some extent, the Hh signaling pathway has been implicated in all of these processes.

Therefore, Hh pathway inhibitors may also represent some of the first agents to formally examine the CSC hypothesis in the clinical setting.”

3657524851_b1936f3830_mWe’ve covered a little about the basics on Hedgehog and Smoothened in the past on this blog (see here and here for examples), but the latest journal article covers some new topics of discussion. In particular, I loved Fig 4 but cannot reproduce it here for copyright reasons, but you can check it out through the Research Blogging for peer reviewed science articles link below.

In the past, it was thought that Hedgehog signalling was associated with basal cell carcinoma and medulloblastoma, both fairly rare cancers.

The new review provides some useful references for involvement in other cancers including:

  • Multiple myeloma
  • Pancreatic
  • Ewings sarcoma
  • Melanoma
  • Breast cancer
  • Ovarian cancer
  • Prostate cancer

And a few others as well.  Of course, it is still unclear whether Hedgehog is a critical driving aberration in these tumours, but as early clinical trials expand into new indications with pipeline drugs, so we will learn more.  It is possible that multiple combinations with a cocktail of therapies each aimed at different targets may be the way to go, but most likely an incremental and conservative approach will be reflective of the initial offerings.

In terms of agents targeting Hedgehog, a number of companies are active in this space:

  • Roche Genentech/Curis have GDC-0449, a small molecule inhibitor.
  • Curis have Debio-0932, a heat shock protein inhibitor, which they are developing with Debiopharm.
  • Another Hsp90 inhibitor that is in very early development for solid tumours and pancreatic cancer is IPI-926 from Infinity.
  • Novartis have LDE225, which targets Hedgehog and Smoothened.
  • Exelixis/BMS are testing XL139, which also targets Smoothened, in gastric and small cell lung cancers and multiple myeloma.

There are probably a few others, both those are the ones that jumped to mind just now.  If you know of any I’ve missed, please do add them in the comments section below.

The Pharma pipeline in this field is obviously burgeoning, but most are in fairly early trials having not long moved out of preclinical, so it will be a while before we know whether this is a useful target for therapeutic intervention or not.

 

Photo Credit: Dave-F

ResearchBlogging.orgMerchant, A., & Matsui, W. (2010). Targeting Hedgehog — a Cancer Stem Cell Pathway Clinical Cancer Research, 16 (12), 3130-3140 DOI: 10.1158/1078-0432.CCR-09-2846

 

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ArQule and Daiichi Sankyo move ARQ 197 into phase III trials in lung cancer

By on August 3, 2010

"ArQule, Inc. (Nasdaq: ARQL) and Daiichi Sankyo Co., Ltd. (TSE 4568) today announced that they will move forward with a Phase 3 clinical trial of ARQ 197, a small molecule inhibitor of the c-Met receptor tyrosine kinase, in patients with non-small cell lung cancer (NSCLC).

In connection with this decision, the sponsor company, Daiichi Sankyo, will file a Special Protocol Assessment (SPA) with the U.S. Food and Drug Administration (FDA) for a trial comparing ARQ 197 plus erlotinib against erlotinib plus placebo."

Source: ArQule

 

This is promising news from ArQule and their partner Daiichi Sankyo, which one of my Twitter buddies kindly alerted me to this morning (Thank You, you know who you are!).

Many of you may remember the blog post earlier this year discussing the phase II results. The data was a little odd in that they saw a fairly large improvement in PFS from 9.7 to 16.1 weeks when used in combination with erlotinib (Tarceva), which is clinically significant but without the P-value hitting significance.

Dr West from Swedish did a very nice overview of the data on his lung cancer site, GRACE, which is well worth reading for those interested.  I particularly loved this quote from his post:

"This work is also looking only at patients who haven’t received an EGFR inhibitor before. It may be that ARQ 197 and/or another c-MET inhibitor could restore activity and clinical benefit for patients who previously responded to an EGFR inhibitor and then progressed from acquired resistance. That concept remains to be demonstrated, but the concept is certainly appealing."

I'm also keen to see what the data from a larger sample size would show and whether there are any useful molecular markers involved.  There are a myriad of other interesting questions:

  • Must all the people entering the study have MET/EGFR or KRAS amplification?
  • Did any of the patients in the phase II trial have/develop the ALK or T790M mutation?
  • Was the EGFR mutation present as WT or mutated?
  • Were there any particular features of the people who responded versus those who did not?

The list could go on and on, but likely the study would be underpowered in phase II to tell us any of that important information.  If it does, I can't wait for more extensive analysis!

There are numerous other c-MET inhibitors in pipeline development (at least 11 or 12 that I know of), but ArQule's appears to be the most advanced to date.

 

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Turning frustration into positive change

By on August 3, 2010

The email and RSS feed for this blog suddenly and inexplicably stopped working on July 20th in a sort of this is the how the world ends, not with a bang but with a whimper moment.  Of course it doesn't stop in reality it just feels that way and the world goes on about it's business regardless.  Postings are still occurring, but the remote publication side of things are a little strangled for a bit while this frustrated blogger researches and fixes the problem between Typepad and Feedburner not playing nicely.

 

image from farm1.static.flickr.comMost probably, I will switch platforms and email service because while Google is great for many things, if you have a problem with their services they are frustratingly unhelpful and you're on your own. For now the feed is sadly borked if you were one of the nearly 1400 subscribers reading this by RSS or email and wondering what happened.  My sincere apologies.

Hopefully, the service will be fully functioning again soon, but at least you can still read the blog on the internet… at least the server isn't down.

Sometimes, it is moments of frustration like these when you realise that change can be for the better and a nicer, more effective service or strategy might evolve from a few unexpected teething problems.  I guess research and development and the commercialisation of pipelines can be a bit like that as well as the road to nirvana is never a smooth one.

Carpe Diem sounds a lot more positive than </rant> 🙂

 

Photo Credit: Joel Bedford

 

{UPDATE: the TypePad to Feedburner glitch has been fixed and normal email service for subscribers has now been restored. Thank you for your patience.}

Does lung cancer have a stigma attached to it?

By on August 2, 2010

At the recent American Association of Cancer Research (AACR) meeting in Washington DC, a press conference was held to discuss new treatments and options for people with lung cancer.  In a break with tradition, the briefing was held not only with some of the top researchers in the area including Drs Ed Kim and Roy Herbst from MD Anderson, but the local Georgetown doctor brought a couple of her patients with her to drive home some important messages:

  1. Clinical trials are important to provide access to new medicines
  2. It's a devastating disease
  3. Not all people with lung cancer smoke
  4. Not all people with lung cancer are elderly

It struck me at that moment that of all the main cancers (say breast, lung, colon, prostate), lung cancer unfortunately seems to have the most stigma associated with it.  Perhaps this is because of the smoking association, but quite frankly, one fifth of people with the disease will be never smokers, often younger with families.  This was illustrated by the two gentlemen at the press briefing – one had never smoked and one had smoked a little in his youth, yet both had lung cancer and both were young (they looked under 45 yo).

image from www.flickr.com

My Twitter buddy, Dr Jack West at Swedish illustrated this point well with his very sad but poignant blog post about a young (42 yo) woman who died over the weekend.  A tragic loss, and no, she had never smoked.

Looking at the American Cancer Society figures, you can get a better picture of how devastating this disease really is:

"About 222,520 new cases of lung cancer will be diagnosed (116,750 among men and 105,770 among women).

There will be an estimated 157,300 deaths from lung cancer (86,220 among men and 71,080 among women), accounting for about 28% of all cancer deaths.

Lung cancer is by far the leading cause of cancer death among both men and women. More people die of lung cancer than of colon, breast, and prostate cancers combined."

From those figures alone, you can see that many people will have maybe, 1-2 years from the time of diagnosis, unless they are lucky to be diagnosed very early and have a chance of cure with surgery and chemoradiation.  More people die from lung cancer than the other big solid tumours combined – that's an astonishing statistic in itself.

One of the other things I've noticed is how breast and prostate cancer groups are extremely active in advocacy, lung cancer not so much.  There are some great people doing good things though to address this gap, though.  Some examples include:

  • AACR have been very active in this field and are making great strides with increased efforts to harness the integration between basic research (including biomarkers) and clinical practice through their alliance with the International Association for the Study of Lung Cancer (IASLC) organisation. This will hopefully speed up new developments from bench to bedside.
  • If you haven't seen it, Dr West's website, GRACE, provides some truly excellent education resources and information for people with lung cancer – it's well worth checking out.
  • On Twitter, WTFlungcancer through the sterling efforts of Jennifer Windrum, are raising awareness of lack of funding for lung cancer initiatives through social media outreach.
  • Another great resource on Twitter is LUNGevity, which seeks to help raise funds for lung cancer research, as well as providing support for people.
  • Pharma and Biotech companies are also doing their bit with over 1,000 trials posted on the clinical trials database to help with access to new experimental therapies and pipeline agents.

There are many other examples like this, but changing the stigma associated with the disease, and more importantly, developing better methods of early detection, diagnosis and treatment is going to take some time.

What initiatives would you like to see in this area?  How can we help change things for the better?

 

{UPDATE: originally, I intended to link to Fard Johnmar's excellent post on lung cancer pessimism and the stigma associated with it after a Twitter discussion we had about the topic, but got distracted by some urgent client requests that came in.  My sincere apologies to Fard for forgetting!  The study with their non-profit partners, The Lung Cancer Alliance, is here – it's well written, nicely produced and worth checking out.}

 

Photo Credit: Andreia

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Pathwork Diagnostics and Novartis to pursue a research partnership

By on July 30, 2010

It was interesting to see my Diagnostics alert feed full of the news that Pathwork Diagnostics and the new Novartis molecular diagnostics group are entering a research partnership.

I first came across Pathwork Dx at ASCO last month when they presented an interesting poster on their tissue of origin gene based expression test to help in the diagnosis of poorly differentiated and metastatic tumours.  Clearly, an accurate diagnosis will lead to better optimisation of appropriate therapy and risk assessment/management.  The tissue based test has since received approval from the FDA.

According to Pathwork:

"The Tissue of Origin LDT uses a combination of microarray technology and advanced analytics to measure the gene expression patterns (comprising more than 1500 genes) of challenging tumors, including poorly differentiated, undifferentiated, and metastatic cancer. These data are compared with the gene expression patterns of a panel of 15 known tissue types—representing 58 morphologies and covering 90% of solid tumors—in order to identify the tumor."

The tissue test is based on gene arrays using DNA and RNA technology used in research, but with its approval, we will start to see more commercial applications evolve for diagnostic purposes.

More details about the deal and the financial background can be found in the WSJ.

What's interesting here is that:

1) We are seeing more sophisticated technology emerge for both tissue and blood biomarkers, which will hopefully help us improve not only diagnosis but also treatment and monitoring of drug responses over time.

2) More integration and collaborations between manufacturers and diagnostic companies means that the information and knowledge can be shared more easily and quickly rather than being bogged down in silos.

3) The companies that do well with integrating diagnostics into their cancer programs will not only have a huge commercial edge, but it will continue to raise the bar for new competitors and smaller companies in terms of funding and resources.

It's going to be fascinating watching this area of oncology develop.

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