Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

Posts by MaverickNY

Simplifying data capture and blog post workflow

By on July 15, 2010

Recently, I’ve had a lot of enquiries as to how I manage to write so many blog posts, either in terms of finding the time or staying current.

The answer is simple – I use tools to help simplify and minimise the effort involved.  You could also use this kind of web 2.0 approach for creating a database and tracking data, intelligence, keeping current if you work in the Pharma or Biotech industry, whether a scientist, a marketer or a PR professional.  Of course, you could spend hours Googling stuff or reading a few health sites online, but there are other ways to stay ahead of the pack.

The key parameters at play here can be summarised:

  • Gather data
  • Process and understand information
  • Perform analysis
  • Generate Insights

Far too many people often only do the first two tasks, but without analysis and insights, the data means very little.  So what are the tools of my trade?

 

1. Evernote

I’ve talked about Evernote in the past, which is a nifty data capture tool we use daily here at Icarus Consultants. They have both free and premium versions to suit everyone’s pocket.

When starting projects, we clip relevant information from the internet into a new Evernote Notebook and gather it all in one place. You can use a desktop or a smart phone for this task and dump as much information as you like into it for later searching. This makes it easier to digest when looking at the big picture and gathering ideas and seeing trends.  You can also search your own database for existing information, which is very useful for blog posts or writing reports around a topic.

I often create and write blog posts in Evernote too.  The research information is already there and it’s straightforward to use the editor as well, as backing up and synchronising the information across multiple platforms.  We’ve all written something in Word or a Blog Editor and lost the content >.< but l have found Evernote more reliable for saving information, which can then be cut/paste with minimal editing into the Blog platform or Office for reports. I also have a bunch of articles, reports and blog posts that get part drafted and finished later, acting as a useful repository for gathering ideas.

Other good uses? Need some information on the road while talking to someone? A quick search in the app my iPhone will usually bring it up.

The other side of the coin is generating and gathering data. I’ve mentioned that you can clip research to an app such as Evernote on the go, but I also have a LOT of information in RSS, whether it be news items, feeds for the latest articles in tens of cancer and science journals, blogs from a variety of sources, rss alerts by topic or keyword etc. Keeping track of this huge volume of information used to be unwieldy.

2. My 6 Sense

One tool I really love and have been using for a while is My 6 Sense.  This cool app takes all the rss feeds from my Google Reader, which is clumsy and awkward to read, and processes them into a more manageable fashion.

Several times a day I can check the app on my iPhone and see what’s new or relevant.  Over time the app algorithms learn what your particular interests are and creates a page of what it considers to be useful items of interest in your RSS feeds via the Relevance tab or as they come in (the Time tab) as shown below (left photo).

Data is social, though; it cries out to be shared with others. The M6S app allows you to add social media sites such as Twitter, Facebook etc and share any interesting items with your friends or colleagues too. Here, you can also see the items from my shared stream as an example of what I found interesting and streamed to others to read:

Over time, as you use the app more, it gets much better at predicting what you like or may find interesting. One thing I miss from the M6S app is a Search button – what happens if I want to find a bunch of interesting articles in my RSS database on a given topic, eg PI3K or something similar? At the moment, there’s no obvious way to do that as far as I can tell, but it would certainly be really useful to me.

3. SimpleNote

I confess that after years of losing data unexpectedly, I’ve become a bot of a plain text geek. On my Macs, TextEdit was something I use daily, especially when taking notes from market research interviews on the fly. Then one day, someone mentioned SimpleNote, which is a beautifully simple yet flexible tool for gathering text notes.

For some months now, I’ve been using the App on my iPhone, which allows me to jot down ideas, tasks, notes to self etc on the fly… essentially simple notes.

Then recently, I realised that the free iPhone app also gave me access to the desktop app, which opens up a whole new world of utility and practicality.  Here was something that could help me do multiple things efficiently:

  • Research and find interesting journal articles or news about say, PI3-kinase in My 6 Sense
  • Email article links to self via iPhone
  • On desktop, cut/paste multiple snippets of information to SimpleNote
  • Search SimpleNote for older articles
  • Write blog post in SimpleNote
  • Cut/paste blog post to TypePad for posting
  • Sync selected information with DropBox and read from any computer later

Take a look at the snapshot below for the basic SimpleNote concept:

You can see how neat and intuitive this is at first glance and how easy it is to find information, whether it be data or contact information or even the reference link months after clipping it by scrolling down in an individual note:

The DOI is really useful because when I blog about journal articles, I only have to cut/paste the DOI into the Research Blogging site and it generates a nifty bit of code that provides easy access to the article via a link for anyone interested in it.

Over time, I diligently put in tonnes of stuff into these tools, whether Evernote or SimpleNote and they come in very handy for research for blog posts and consulting reports. Essentially, I find that I tend to use Evernote for web clipping and SimpleNote for text processing.

Of course, the short answer to the blogging question is you either get more efficient and smarter at gathering, processing, analysing and generating insights or you work longer hours.  Being a good European, I’d rather work smarter and hope that people appreciate the insights generated either in the blog posts here or in client report :-).

What are your favourite tools and apps that make a difference to your daily workflow?

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The Long Tail of Cancer Research

By on July 14, 2010

"What's really amazing about the Long Tail is the sheer size of it. Combine enough nonhits on the Long Tail and you've got a market bigger than the hits." 

Source: Chris Anderson, Wired

The other other day, while barely lucid in the early hours of the morning, I was thinking about the herd instinct, the tendency to follow the masses and the counterpoint to that, i.e. the long tail.

If you're wondering what the long tail is, think of those statistical distribution plots where everything is bunched around the median, creating 50% on one side and 50% on the other.  At either end the plots tail off into infinity.  That's the long tail.  

The long tail looks small at first, but creative marketers realise that added up (as Chris Anderson's quote above shows), you can in effect still have quite a large niche market while every one else focuses on minute shares in the middle.

I first realised the long tail effect as a sales rep in the tough anti-cholesterol market.  You can spend fruitless hours chasing the majority of the primary care doctors who see reps but don't remember you when the relevant patient appears, or you can carefully invest time in the ones who don't see reps but are busy with appropriate patients and eventually crack if you try enough times. Once convinced, they often switch wholesale and your job is done with a smaller group of physicians who others can't see :-).

If we apply the principle of the long tail to cancer research, we can see things more clearly.  In the old days, the majority of patients got treated pretty much the same with various chemo doublets, irrespective of whether they might work or not.  In fact, in many cases, there wasn't even biomarkers such as ERCC1 to determine which patient should get platinum or not, but things are changing and now it's much easier to make these decisions and start segmenting patients according to their biochemical profile and make decisions based on the profile.

Today, we can take this niche idea to treatment a lot further.  

In colon cancer, for example, we now know that patients with wild type KRAS are more likely to respond to an EGFR therapy than those with mutant KRAS. However, in lung cancer, the old adage was that erlotinib (Tarceva) was best suited for patients who were female, asian, non-smokers with adenocarcinoma is giving way to a more precise definition, i.e. do they have the EGFR mutation or not? If they do, they're more likely to respond, irrespective of smoking status. Offering these patients maintenance treatment may also be an effective treatment strategy that impacts outcomes.  

We can see this effect in other cancer types too.  Trastuzumab (Herceptin) is approved for women with Her-2 breast cancer, imatinib (Gleevec) and other TKIs such as dasatinib (Sprycel) and nilotinib (Tasigna) for Philadelphia-chromosome positive chromic myeloid leukemia (CML).

Histology is a very crude way to select patients, but looking at the aberrant mutations essentially creates niche long tail opportunities to treatment for pharma and biotech companies.  Patients who are more likely to respond to a given therapeutic get appropriate treatment, without having to expose others who would not to unnecessary systemic effects. This is a win-win solution all around.  

Why?  

Well, it's good news for patients as you increase the chances of successful outcomes rather than relying on hope alone.  It's also good news for manufacturers because smaller patient populations ultimately involve fewer patients in clinical trials, thereby making clinical development more cost effective and as cancer therapy moves from an acute to chronic disease, so longer term revenues are generated despite a small patient base.

As more oncology companies start looking at their pipelines, we can see many asking the critical questions – which patients are more likely to respond to a given treatment and why?  As we learn more about the underlying biology of the disease, so companion diagnostics are also evolving in sophistication and sensitivity.

The other marketing advantage of developing niche targeted therapies and diagnostics is that often, you see less competition for smaller subsets of disease because it creates a high barrier to entry. Diagnostics also create barriers to entry because of the extra costs involved in their development.  For smaller biotechs this can be prohibitive, and many are more actively seeking Pharma and Biotech partners to fund late stage research and clinical trials.  Overall, the long tail opportunities offer big and small hurdles, depending on the circumstances.  

Roche's VEGF monoclonal antibody bevacizumab (Avastin) has a very high barrier to entry in colon cancer, for example, as other VEGF inhibitors have fallen by the wayside, unable to beat the results already obtained by the first to market drug.  

At the other end of the scale, the barrier to entry is much lower in renal cell cancer with numerous targeted therapies now approved for a relatively small niche indication, including sorafenib (Nexavar), sunitinib (Sutent), temsirolimus (Torisel), everolimus (Afinitor), pazopanib (Votrient) and bevacizumab (Avastin), probably reflecting the improvement over IL2, without completely reducing unwanted side effects or dramatically improving efficacy.

Some of the marketed therapies mentioned in this post are now billion dollar blockbusters despite cancer being a relatively niche market opportunity compared to the much bigger primary care markets such as metabolic or cardiovascular disease, proving that there are valuable nuggets to be found, even in the long tail.  

The future in cancer research is not in broad acting systemic chemotherapies that target normal cells as well as cancer cells, but in the niche development of better and less toxic targeted therapies based on the underlying biological abnormalities with easy to use diagnostic technology based on fluid-based biomarkers.  To achieve this though, will take a lot of bright smart people with expertise in oncology who dare to think differently and boldly, whether they be scientists, marketers or clinical research professionals.

Watch this space!

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Fluid-based early detection biomarkers in cancer

By on July 13, 2010

A really interesting idea that seems to be growing in popularity is the concept of fluid-based biomarkers from blood, urine, saliva etc, as opposed to invasive tumour biopsies. A recent paper in Cancer Research took a look at this novel and much needed concept (reference below). 

One of the biggest challenges in oncology at the moment is finding easier and more convenient ways of identifying appropriate patients who might be best suited for a given therapy.  In clinical trials, often tests are developed as useful biomarkers based on tumour biopsies.  However, once a drug is approved, Community Oncologists often find their patients older, frailer and with a poorer performance status or more advanced disease and thus unresectable. Earlier detection of asymptomatic patients would also be useful, since in general, the earlier the patient is diagnosed, the better their long term chances are.

There is a lot of potential value, therefore, in developing fluid-based biomarkers and tests since the majority of cancer patients are treated in the Community, rather than Academic, setting.

In leukemias, FISH and QT-PCR testing have become standard, largely because it is easy to compare a blood sample with that of a bone marrow sample to validate test results.  In solid tumours though, that has generally been less easy. Even the FISH test for HER-2 positive women with breast cancer has not been without it's controversies over the years.  

At recent cancer meetings such as ASCO and AACR, I have noticed an increasing number of early surrogate markers being explored in solid tumours such as circulating tumour cells (CTCs) in prostate cancer as a more viable marker than PSA, as the authors also discussed:

"Fluid sampling has advantages over imaging as it is widely accepted, readily repeated, convenient, noninvasive, and low cost. Biomarkers in body fluids have the potential to detect a wide variety of primary tumors and metastases located throughout the body. Fluid biomarkers include a variety of components in blood, urine, or other fluids that reflect the presence of a tumor in the body. These include circulating tumor cells (CTC) and macromolecules such as lipids, proteins, RNA, microRNA, and DNA that originate from tumor cells."

Source: Martin et al.,

It was interesting to see the development of Pfizer's crizotinib in non-small cell lung cancer (NSCLC) with ALK mutations emerge recently.  While Pfizer should be applauded for the speed with which they have developed the drug after the mutation was discovered, the development of the mutation test has clearly not been without its challenges. 

A number of patient blogs complained about the time taken to produce the results from the tumour biopsies (several weeks to a month compared to say, 48 hrs for blood tests) and also in some cases, that their own physician ordered tests were not accepted, requiring another test validated by a central laboratory, sometimes with differing results. This does not augur well for an easy to use commercial diagnostic test for ALK if there are variations in the results. 

Patients with advanced lung cancer often don't have a lot of time so this will be an issue to them and their physicians. Part of the reason for the delay is that tumour biopsy tests often require DNA sequencing to be performed, which inevitably takes time. A validated blood test would have a huge advantage in terms of time and convenience, but whether it is practically possible in an example like this, I don't know. 

Whether a validated blood test is being developed in parallel isn't yet clear, but lung biopsies in the community setting are not routine in the way they are for breast cancer, for example.  Finding suitable patients will therefore be akin to looking for needles in a haystack as the data so far suggests that the number of patients who were ALK positive in the NSCLC trials that looked for the mutation was around 5%.  I'm not sure if this will extrapolate to the broader lung cancer universe though, as patients in a clinical trial are typically different from those in the general cancer population.

Meanwhile, another other interesting trend that is emerging is microRNA:

"In addition to proteins, mRNAs are promising biomarkers, and microarrays represent a powerful approach for their discovery in blood.  A study using custom spotted arrays published in 2001 identified a signature of 12 genes whose mRNA expression was elevated in peripheral blood mononuclear cells (PBMC) of breast cancer patients." 

Source: Martin et al.,

The number of articles, papers, abstracts and presentations on microRNA has increased at a tremendous rate over the last 2 years.  At the AACR Molecular Targets meeting last November, it seemed as though 1 in 3 abstracts mentioned the subject in a variety of different ways from prognosis to early resistance. This is one area I'll be following to see what interesting new concepts emerge. I've had a few requests for more information on microRNA, so this will be the topic of a forthcoming blog post.

The ultimate question as always, though, is what does this all mean?

Clearly, earlier detection of disease is useful for prognosis, but predicting the impact of therapeutic intervention is also important. If we can develop biomarkers for determining which drug might work optimally for a given patient or subset, that would alleviate a lot of the pressure on healthcare systems and reducing patient exposure to drugs that would not work. At present, there are probably more tests developed than actually used in practice, but incorporating them into large scale clinical trials as part of a battery of tests may well provide more useful information in the near future across a variety of different cancer types. 

Time will tell, but it makes a lot of sense to incorporate a vast battery of surrogate biomarker tests upfront and then track what happens over time, as the Medivation trial with MDV3100 has shown with PSA and CTC's in prostate cancer, to offer a practical example.  You never know which of the biomarkers tested will emerge as useful in any given tumour type, so testing more rather than fewer may have a higher chance of hitting the bullseye.

ResearchBlogging.org
Martin, K., Fournier, M., Reddy, G., & Pardee, A. (2010). A Need for Basic Research on Fluid-Based Early Detection Biomarkers Cancer Research, 70 (13), 5203-5206 DOI: 10.1158/0008-5472.CAN-10-0987

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Monday Mumblings – Life in the fast lane

By on July 12, 2010

After taking a week off work decompressing without a laptop (yes really), I've been catching up on my reading over the weekend and browsing the long list of diverse blogs that I follow from tech to venture capital, sports, science, medicine and of course, cancer. One article in particular caught my eye – on preoccupations in the NY Times Jobs section from last Friday. You can get the gist of it from the quote below:

"SIX years ago, fresh out of Stanford with a degree in economics, I had what many would consider the perfect job. I was a management consultant at a prestigious firm, with an office overlooking the San Francisco Bay and a shiny new ThinkPad to boot.

My co-workers were intelligent, ambitious and fun, and I interacted with high-level executives at Fortune 500 companies. My perks included free concert tickets, ski trips and fancy dinners. I was on track to be earning six figures within three years. It was the good life I had been chasing along with my peers at Stanford. 

So why wasn’t I happy? 


After six months of living this supposed dream, my day-to-day life was far from satisfying. I was working 14-hour days, and most of my time seemed to be spent nudging boxes around in PowerPoint slides and agonizing over the wording of bullet-pointed items.
It felt wrong to be dreading work at such a young age. I wanted to wake up each morning excited about what was ahead. I wanted to create something of my own." 

Source: NY Times

image from www.flickr.comWhat was interesting was having just spent time away from the office decompressing and having fun in the real world away from computers, reports, PowerPoint, phone calls and meetings, the comments struck a chord with me about the Pharma treadmill. How many people go from meeting to meeting in a whirlwind, dashing off to catch a plane to yet another weekend Advisory Board or conference, creating endless reports for the higher ups, handling calls from sales reps, even pushing boxes around on PowerPoint? I'm willing to bet it's a lot of people. 

How many people have gone to a major medical conference, only to spend most of the time stuck in their hotel in meetings or writing slides for some deliverable, while the really interesting stuff being presented on the clinical data was missed?

One of the many questions I get as a consultant is would I go back to Pharma/Biotech land?  Maybe, for a truly unique and challenging opportunity to make a difference, but while I enjoyed the time I spent and the most of the people I worked with, work life balance in the US is a lot harder to attain than in Europe. It's gruelling and full of politics and consensus. This means making things happen takes a lot of time and energy, plus if you don't watch out the daily grind can be more driven by the immediacy and urgency of tactics rather than strategy. 

Think about it, those sales trimester meetings come round all too quickly! 

As someone running a small strategic consultancy firm, I can reach out and help more people, be my own boss, focus on the strategic impact, have more fun and be inspired by some wonderful people doing great things. Most important of all, it's like being a kid in the candy store again – full of excitement and exuberance for what's happening in cancer research, discovering what might have an impact on better patient outcomes and improved quality of life.  What's not to like?

Over the last few weeks, I've had the pleasure of meeting or talking with some really dynamic and creative people that stimulated my thinking and made me realise that the future in oncology is still bright and full of enthusiasm for the next big thing. Kudos to them for keeping the vision and inspiration going. Life tends to back winners with imagination, long may it continue.

If your drug, technology or device doesn't make a meaningful difference, what's the point?

Photo Credit: Geus2006

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On clinical trials, creativity and patient adherence in cancer

By on July 9, 2010

"Let us honour if we can

The vertical man

Though we value none

But the horizonatal one."


WH Auden 

Over the last few months, I've been having some interesting conversations with various people involved with cancer research and have been impressed with how many are going about looking at the clinical trial conundrum with a new and fresher lens.  Sometimes doing the same thing repeatedly isn't always in the best interests of everyone, the researchers, doctors, patients, manufacturers, regulatory authorities.

The good news is that there are some new initiatives being discussed that break the mould from just looking at either first-line metastatic or relapsed, refractory disease as the first port of call in a isolationist nihilistic approach.  This is good news and I'm hoping that more people taking on a broader, more holistic perspective will change the kaleidoscope of collective thinking.  

Think about it.  

What happens when patients stop adhering to therapy?  How does that affect outcomes?  What education is needed to help address this?  Who should provide the education?  Giving out pills boxes and chips in lids isn't going to change much without a link to why it matters. 

At the recent EHA meeting, Jan Geissler gave an excellent overview of the broader factors affecting patients in two different sessions from the patient perspective.  I hope it opened many physicians eyes to some of the underlying issues.  This issue is nowhere near as simple as many may think.  In a different session, David Mahon gave a fascinating talk on the impact of patient adherence on outcomes in CML based on some serious research.  As one might expect, they were affected negatively, but the shocking piece of information was how many physicians encouraged dose holidays or skipping a dose, saying it wouldn't matter.  This creates the wrong impression to start with.

More recently, the news that compliance with chronic tamoxifen therapy for treatment of hormone sensitive breast cancer is often poor, is not a surprise given the tolerability issues associated with the drug, but what is surprising is how little take-up this made in the medical news (HT Jody Schoger).  How many women had a poorer outcome from their hormone treatment as a result of less than 90% compliance?  What can be done about it?  Very little comment or analysis in the medical press or advocacy world ensued.

In the end, we need more creative leaders working on this problem, a greater synergy between translational and biology research with clinical practice, cross functional working groups that involve multiple stakeholders, including patient advocacy, working towards a common goal for the greater good. 

It is only when all of these factors come together in multi-functional teams that faster and better progress in cancer outcomes, in terms of both survival and quality of life, will ultimately be made. Where's that Cowbell when you need it?

What are you doing to help change things?

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Advancing the Use of Biomarkers in Cancer Drug Development

By on July 1, 2010

This was the title of a fascinating article I saw on Twitter a few minutes ago, courtesy of the American Association of Cancer Research (AACR).  They are providing access to the paper free of charge to the public using this link.  If you are on Twitter and interested in cancer related research, do follow them and keep track of the hot news items as they share quite a few important articles on translational research.  Of all the medical associations I've come across in social media, they are also very helpful and responsive to enquiries.

So, what of the Consensus Report?  Well, it's a collaborative effort from the AACR, FDA and NCI to create a position statement of the state of play so far:

"There is a growing imperative to modernize the drug development process by incorporating new techniques that can predict the safety and effectiveness of new drugs faster, with more certainty, and at lower cost."

As always, though, things are never as easy or simple as one might like.

Developing novel and useful biomarkers is an expensive and time consuming process driven largely by translational research and bioinformatics, often with a lot of diverse stakeholders involved in the process. 

The Cancer Biomarkers Collaboration covered recommendations in eight key areas:

  1. Biospecimens
  2. Analytical performance
  3. Standardisation and harmonisation
  4. Bioinformatics
  5. Collaboration and data sharing
  6. Regulatory issues
  7. Stakeholder education and communication
  8. Science policy

Ultimately, the goal of the collaboration is to:

"The AACR-FDA-NCI Cancer Biomarkers Collaborative is a stakeholder-driven effort to inform and accelerate the FDA Critical Path Initiative and the work of the broader cancer
community."

The paper is well worth reading for those interested in the area, so check it out.

Meanwhile, on a practical note, a new potential biomarker has emerged in small cell lung cancer (SCLC) – see link to the Journal of Thoracic Oncology below (subscription required).  The problem here is that while the majority of people with SCLC initially respond well to chemotherapy, resistance develops leading to relapse. The big question is why?

To answer this question, the researchers hypothesised that:

"… tumor microRNAs (miRNAs) could serve as predictive biomarkers for chemoresistance and prognostic biomarkers for survival of patients with SCLC treated with systemic chemotherapy."

The initial microRNA research on tumour samples (n=34) showed that:

"Higher tumor miR-92a-2* levels are associated with chemoresistance and with decreased survival in patients with SCLC.
Tumor miR-92a-2* may have application in screening patients with SCLC at risk for de novo chemoresistance in an effort to design more tailored clinical trials for this subpopulation."

In other words, microRNA (miR-92a-2*) could potentially be used as both a predictive and prognostic marker in SCLC.  These results will need to be validated in larger scale trials, but they offer a promising glimpse of what might be possible for future therapeutic interventions.

ResearchBlogging.org
Khleif, S., Doroshow, J., Hait, W., et al., (2010). AACR-FDA-NCI Cancer Biomarkers Collaborative Consensus Report: Advancing the Use of Biomarkers in Cancer Drug Development Clinical Cancer Research, 16 (13), 3299-3318 DOI: 10.1158/1078-0432.CCR-10-0880 

Ranade, A., Cherba, D., Sridhar, S., Richardson, P., Webb, C., Paripati, A., Bowles, B., & Weiss, G. (2010). MicroRNA 92a-2* Journal of Thoracic Oncology DOI: 10.1097/JTO.0b013e3181dea6be

Celgene buy Abraxis Bioscience for $2.9B

By on June 30, 2010

I did a double take at my inbox alerts this morning as things have been rather quiet of late in the Pharma and Biotech world.  You can read the financial aspects of the deal in Celgene's press release.

While the timing might be a little bit of a surprise, the strategic acquisition is not and makes a lot of commercial sense for Celgene.  There are a number of reasons for my thinking here:

  1. It continues to build out of hematology with the beginnings of a solid tumour franchise since Abraxane is approved for breast cancer and has trials ongoing in pancreatic, lung, melanoma and bladder cancers.
  2. The patent life for Abraxane is something like 2023, much longer than lenalidomide (Revlimid) and with few near term opportunities in the oncology pipeline, this adds extra protection.
  3. Abraxane, while more expensive than generic paclitaxel, has probably been underfunded in clinical development and marketing efforts to date, so Celgene's thorough and aggressive approach may well kick start things, especially as they have cash to do so.
  4. Buying Abraxis gives them access to nanotechnology, which I think will become more important in the future as an improved drug delivery system.

Late last year, while at the AACR Molecular Targets meeting in Boston, I wrote about nanoparticle technology and how it appears to offer a chance of improved outcomes in pancreatic cancer using Abraxane.  The concept described by the researchers at Mass General was solid and promising, as was the early phase I data.  Sometimes, it's not just about drug A being better or more potent than drug B, but the science and thinking behind solving a problem is elegant and well thought out.  This was one of those cases.  A couple of Phase II trials have so far yielded early but promising results in a devastating disease. The latest results, reported by the Abraxis in May this year, look encouraging so far.

Of course, most oncology specialists will know that melanoma, pancreatic and lung cancers as probably three of the four toughest cancers to get positive results in from phase III trials (the fourth is glioblastoma), but if any of them actually pan out with a significant difference in overall survival and FDA approval, then Celgene will have another winner on it's hands.  I say 'if' because the road to approval and cancer drug development is littered with promising phase II studies that flopped or were sadly cancelled for futility in phase III.  

Time will tell if this was a good acquisition or not, but for now, it's early but promising.  That's ultimately both the lure and the heartache that is oncology.

You have to make the big plays to win.

How cognitive surplus will change the world: Clay Shirky

By on June 29, 2010

Here's an interesting and informative TED video I just came across, where Clay Shirky talks about cognitive surplus and how it will change the world.

The idea behind the concept of "cognitive surplus" is that we use spare brain cycles while online to build a more cooperative world.  In other words, new technologies enable loose collaborations to evolve.

I'm not sure I like the term 'cognitive surplus' but Shirky is an eloquent, thoughtful and engaging speaker who is well worth listening to:

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Gefitinib or Chemotherapy for Non–Small Cell Lung Cancer with Mutated EGFR

By on June 28, 2010

AstraZeneca's Gefitinib (Iressa) has had a bit of a chequered history since it's fast track approval by the the Japanese Health Authority in 2002 and the FDA in 2003 for non-small cell lung cancer (NSCLC). However, since the phase III trials did not appear to generate a significant overall survival advantage, it has been available in the US, Canada and Switzerland under strict labelling restrictions based on the ISEL study since 2005.  A patient assistance program is available for suitable patients in the US:

"In the light of positive survival data with other agents including another oral EGFR inhibitor, physicians should use other treatment options in advanced non-small cell lung cancer patient populations who have received one or two prior chemotherapy and are refractory or intolerant to their most recent regimen." 

Source: US Iressa PI

The IPASS study (IRESSA Pan-ASia Study) subsequently demonstrated superiority of gefitinib's efficacy over doublet chemotherapy in EGFR mutation positive patients in 2008.  In Europe, this led to gefitinib being finally approved for the treatment of adults with locally advanced or metastatic NSCLC with activating mutations of EGFR-TK across all lines of therapy in 2009.

The latest data, from the North-East Japan Study Group, published in this weekend's NEJM, showed some interesting new results in a study of 239 newly diagnosed Asian patients with NSCLC and EGFR mutations when they compared standard chemotherapy of carboplatin plus paclitaxel to gefitinib as a single agent.

Essentially, in this front-line setting, treatment with the EGFR tyrosine kinase inhibitor gefitinib resulted in progression-free survival (PFS) that was twice as long as treatment with standard chemotherapy, ie PFS of 10.8 months in the gefitinib group compared with 5.4 months in the chemotherapy group. Response rates were also improved in the gefitinib arm compared to chemotherapy (73.7% vs. 30.7%). Side effects were as expected for the two treatments (rash and elevated aminotransferase in the gefinib group and neutropenia, anemia, loss of appetite and neuropathy in the chemotherapy group).

However, the median overall survival (OS) of 30.5 months vs 23.6 months was not significantly different between the two groups.  

It is clear from both IPASS and the NE Japan studies that in a select sub-population of lung cancer patients, patients could elect to receive biologic therapy such as gefitinib rather than chemotherapy and have a reasonable quality of life.  

However, given the lack of over survival benefit with Iressa but has been demonstrated with Tarceva (erlotinib) in other studies, I'm not sure where this leaves AstraZeneca. It is unlikely that the restrictions on the US or Canadian approvals will change as a result of this study. 

Why Tarceva led to a survival benefit in EGFR mutated NSCLC and Iressa does not is still unclear at this stage.

ResearchBlogging.org

Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H, Gemma A, Harada M, Yoshizawa H, Kinoshita I, Fujita Y, Okinaga S, Hirano H, Yoshimori K, Harada T, Ogura T, Ando M, Miyazawa H, Tanaka T, Saijo Y, Hagiwara K, Morita S, Nukiwa T, & North-East Japan Study Group (2010). Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. The New England journal of medicine, 362 (25), 2380-8 PMID: 20573926

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