Pharma Strategy Blog

Novartis' Afinitor approved by the FDA

While live tweeting the Eye for Pharma Oncology Summit, I noticed a tweet from CNBC's Mike Huckman that Novartis' Afinitor had been approved by the FDA in renal cell cancer:

A short while later it was confirmed on the Novartis website. Twitter is certainly useful for breaking news. If you're not Twittering yet, check it out. There is even a Pharma wiki created by Jon Richman which is updated regularly as more Pharma join Twitter.

Eye for Pharma Oncology Summit

Today and tomorrow I'm microblogging the Eye for Pharma Oncology Summit meeting in Boston. You can follow the meeting from the widget below, from my Twitterstream or on the Eye for Pharma website. We'll be using the #EFP code to track live tweets from anyone commenting at the event. 

The program looks to be a really good one, so do join us during the event and catch up on the news and views for what's hot and what's not in the cancer arena!

 

Posted by MaverickNY on March 30, 2009 at 07:58 AM in Conferences, Market Trends, Marketing, Networking, Oncology, Technology | Permalink | Comments (0) | TrackBack (0)

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Approaches to improve the efficacy of radiotherapy and chemotherapy in treating various cancers have begun to include the addition of radio- and chemo-sensitisers to the existing regimen. 

One such drug is motexafin gadolinium (MGd, Xcytrin®).  Motexafin is an aromatic macrocycle that has a strong affinity for electrons, i.e., it is easily reduced.  In the presence of oxygen, motexafin accepts electrons from various cellular reducing metabolites and forms superoxide and other reactive oxygen species.  The molecular target for the drug appears to be thioredoxin reductase, which when inhibited, results in cellular redox stress, cytotoxicity and an increase in tumour responsiveness to a variety of treatments. Previous research has shown that motexafin increases cytotoxicity of ionizing radiation and various chemotherapy agents and may be directly cytotoxic to tumour cells under certain conditions.

This latest phase III study was an international large randomised trial. The researchers observed increased median time to neurologic progression from 10 to 15 months with motexafin gadolinium/WBRT over WBRT alone, and a more pronounced increase in those treated promptly after diagnosis (median, 8.8 to 24.2 months).  An interesting finding was found to be crucial for interpreting multicenter studies: delays in randomization (particularly long for EU/Australian contributors) produced statistically worse results.

Overall, the trial demonstrated the benefit of motexafin gadolinium added to whole brain radiotherapy (WBRT) and now offers a treatment option for non-small cell lung cancer (NSCLC) patients who develop brain metastases. Approximately 50% of such lung cancer patients get brain mets.

Mehta, M., Shapiro, W., Phan, S., Gervais, R., Carrie, C., Chabot, P., Patchell, R., Glantz, M., Recht, L., & Langer, C. (2009). Motexafin Gadolinium Combined With Prompt Whole Brain Radiotherapy Prolongs Time to Neurologic Progression in Non–Small-Cell Lung Cancer Patients With Brain Metastases: Results of a Phase III Trial International Journal of Radiation OncologyBiologyPhysics, 73 (4), 1069-1076 DOI: 10.1016/j.ijrobp.2008.05.068

Well, that was an attention grabbing headline for those of us interested in CML.
   
Whilst the majority of patients do well on treatment with imatinib (Gleevec), a small number will not respond to the drug initially (primary resistance), and a few will develop secondary resistance as new mutations occur.  Other tyrosine kinase inhibitors such as dasatinib (Sprycel) and nilotinib (Tasigna) are now available that cover most mutations except for  T315i.  There are also kinase inhibitors in develop for blocking the activity of T315i.

One theory that has been proposed for the development of resistance is that Gleevec does not eradicate cancer stem cells in this group.  Without a doubt, those that achieve a complete cytogenetic or molecular response do very well.

Zhao et al., looked at the stem cell issue in a letter to Nature.  They suggested that Hedgehog (Hh) signalling might well play an important part in CML because it is a critical regulator of oncogenesis.  They tested this idea in mice in whom smoothened (SMO), a protein necessary for Hh signal transduction, had been conditionally deleted in hematopoeitic cells and found that the loss of SMO impaired hematapoeitic stem cell renewal. 

They also found something very interesting.  Namely, that transplantation of Smo cells transduced with the BCR-ABL oncoprotein that causes CML into irradiated mice significantly reduced the frequency of cancer stem cells compared to controls.  Transgenic expression of Smo, hwoever, increased the frequency of cancer stems cells, leading to disease progression.

Blocking the Hh pathway chemically with cyclopamine produced different results in the experimental group compared to the controls.  Overall, the results suggest that Hh signalling inhibitors might possibly be useful in both normal and imatinib-resistant CML.  Some of these small molecules are already in phase I development, including one from Genentech, but it should be noted that none of them appear to target the Hh proteins themselves.

Zhao, C., Chen, A., Jamieson, C., Fereshteh, M., Abrahamsson, A., Blum, J., Kwon, H., Kim, J., Chute, J., Rizzieri, D., Munchhof, M., VanArsdale, T., Beachy, P., & Reya, T. (2009). Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia Nature DOI: 10.1038/nature07737

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Yesterday, Jade Goody the UK reality tv star sadly passed away from cervical cancer.  She was 27 years old.

Source: Daily Telegraph

Whatever else one may think about the furore and PR that accompanied her last few months, we cannot deny that she was very brave and probably did more for raising awareness of the condition than any other individual.

Cervical cancer is linked to the Human Papillomavirus (HPV) and vaccines such as Gardasil (Merck) and Cervarix (GSK) are now available to prevent the disease occurring in young women.  Currently, there are 11,000 new cases a year in the US with 3,800 deaths.  In the UK, over 700 women a year die from cervical cancer.  The condition can be picked up early by PAP smears.

What was fascinating about the Jade story was that she got the conservative and shy Brits talking about death and dying in an open way that has rarely been seen in the country before.  Even my mother discussed it despite not being able to talk about my father's death from prostate cancer a few years ago.  Some cancers are slow growing, some recur, Jade Goody's battle was a short and very brutal one.

Cancer is devastating. It's not just a life-threatening illness. It can make you poor, it can collapse your family life and it can have huge emotional consequences.  But most of all, it can leave you isolated and alone. 

In the end, perhaps we should think more holistically about about the patient as a whole and not just treat the tumour.  If more young (sexually active) women consider getting annual PAP smears and parents vaccinate their under 21 yo's, we may well see a decline in the death rate for cervical cancer in the future.  If that happens, it may not bring the Jade Goody's of this world back, but at least the publicity and raised awareness will have achieved something lasting and impactful.

Today we will be covering the above meeting via live microblogging from Princeton, New Jersey.  It's an interesting lineup of some of the top business and competitive intelligence professionals in pharma and biotechnology.

You can follow the meeting via the widget below or join us on Twitter and contribute to the discussion remotely by ending your tweets with #eyeforpharma so we can pick up any comments and questions you may have.

Eye for Pharma, the excellent organisers of the meeting are also on Twitter as @eyeforpharma, while this contributor is @MaverickNY.

We hope to see you at the meeting or on Twitter - do join us!

I'm looking forward to the Eye For Pharma Business Intelligence Summit tomorrow in Princeton, NJ.

We'll be live tweeting and blogging the conference so anyone can follow in Twitter using the #eyeforpharma hashtag in Twitter search, via Cover It Live on this blog or on the Eye For Pharma blog.

Hopefully, the speakers will have some new and interesting trends to talk about!

I was reading Clay Shirky's rather long yet illuminating article on the rise and fall of newspapers as a modern viable business.  In it he says:

"When reality is labeled unthinkable, it creates a kind of sickness in an industry. Leadership becomes faith-based, while employees who have the temerity to suggest that what seems to be happening is in fact happening are herded into Innovation Departments, where they can be ignored en masse. This shunting aside of the realists in favor of the fabulists has different effects on different industries at different times."

In different ways, the same revolution is happening in Pharma and Biotechnology.  Many saw the lack of pipelines eons ago and investigated ways of addressing it, but of course, like newspapers, the unthinkable worse case scenario happened.  The drugs failed before they made it market and many were slow to catch onto innovations such as targeted therapies, focusing instead on me-too chemotherapies, for example.  Now, just about every major oncology company has targeted therapies in their R&D and the market is suddenly becoming very competitive and crowded. 

It does beg the big question though; which targets are absolutely critical to the tumour and will different approaches in how they might be used make a difference in long term survival to patients?

Darwin's survival of the fittest is also at play in the background here.  Those that fail to adapt, adopt and modify will be left behind as dinosaurs, just like the newspapers.  In times like these, it's new innovations and game changing approaches that will win out rather than following the herd and making yet more me-too copies.  The next 18 months may well see a bloodbath in the industry with patent expiries, desperate corporations and a lengthy credit crunch strangling access to cash flow.

Innovate or die.

The WSJ Health blog has an interesting post this morning on "The Great Biotech Shakeout is Near".  Now, that may sound a little alarmist, but since November, 15 have already gone to the wall and the suspicion of a VC firm is that:

"120 out of 360 publicly traded biotechs have less than six months of cash left. A year ago, only 12 companies were in that position."

Burrill & Co.

In theory, this should be a good time for cash rich pharma and biotech to be shopping for good deals to replenish their pipelines.  In reality, our experience is that many are looking keenly, but hoping for a better deal by waiting.  Who knows where the bottom of the market might be?

For some baby biotechs, help in the form of licensing deals or buyouts may not come soon enough as their cash dwindles fast and the credit crunch continues to impact business.

The answer is in their genes.

Chronic obstructive pulmonary disease (COPD) is characterised by progressive decline in lung function, and encompasses both chronic bronchitis and emphysema. Almost 90% of COPD is caused by chronic cigarette smoking, but only 25% of long-term tobacco smokers will go on to develop COPD.

New research published yesterday in Respiratory Research from the Wake Forest School of Medicine and Saint Louis University, may shed some light on why.

The researchers looked at a disintegrin and metalloprotease (ADAM) gene known as ADAM33 in 880 long-term heavy smokers. ADAM33 is located on chromosome 20 and has been linked with asthma in previous research. This study is unique in comparing long-term smokers with COPD versus a control group of long-term smokers without COPD.

Five single nucleotide polymorphisms (SNPs), which are human DNA sequence variations, were found in ADAM33 that were more frequent in the COPD group than in the group of smokers without COPD. One particular SNP, known as S1, had a particularly strong link to lung abnormalities.

Functional studies will now be needed to evaluate the biologic significance of these polymorphisms in the pathogenesis of COPD, but the early results suggest that the abnormalities may affect the chances of developing chronic obstructive pulmonary disease (COPD) in later life.

Sadeghnejad, A., Ohar, J., Zheng, S., Sterling, D., Hawkins, G., Meyers, D., & Bleecker, E. (2009). ADAM33 polymorphisms are associated with COPD and lung function in long-term tobacco smokers Respiratory Research, 10 (1) DOI: 10.1186/1465-9921-10-21

Roche and Genentech have announced the latest results from the HERA study performed by the Breast International Group (BIG).

Historically, HER2 positive breast cancer has been associated with a poor prognosis, but the first analysis of the HERA trial, released in 2005, established unprecedented benefits in terms of lowering the risk of cancer returning (disease-free survival).

The latest HERA (HERceptin Adjuvant) study analysis showed that women treated with Herceptin (trastuzumab) had a 25% reduction in the risk of their cancer coming back compared to women who did not receive Herceptin, and after an average of four years, almost 90% of the Herceptin-treated women were still alive.  In addition to the significant treatment benefit, the analysis confirmed the long-term safety profile of Herceptin, with good cardiac safety and tolerability maintained throughout the four-year follow-up period.

There are now data from four large studies – HERA, NSABP B-31, NCCTG N9831 and BCIRG 006 that have consistently demonstrated that Herceptin prolongs survival in women with HER2 positive early breast cancer.

Herceptin is approved for the adjuvant treatment of HER2-overexpressing, node-positive or node-negative (ER/PR-negative or with one high-risk feature) breast cancer.  These results are reassuring to HER2-positive women that their lives are significantly prolonged on treatment with the therapy.

Yesterday, I met the lovely Joanne Gere from the Bioanalytics Group, who pointed me in the direction of an interesting abstract on Herceptin from 2005 at the San Antonio Breast Cancer Symposium, which demonstrated the effective combination of computer modeling and immunohistochemistry to predict the most likely patient outcomes after treatment with Herceptin.  The data suggested that efficacy could be drastically improved from 41.67% to 74.07% by selecting patients most likely to respond using a panel of biomarkers.  This would add to the weight of evidence for personalised medicine and appropriate therapy by pre-selecting women most like to respond to Herceptin.

An interesting paper in Nature revealed why some some tumours are resistant to dietary restriction. Normally, restricting food intake will lead to tumour shrinkage but some tumours grow despite limiting calorific intake.  The answer?  PI3K activation is permanently turned "on" via a mutation, so the tumours grow and proliferate independent of the amount of food consumed:

"Substitution of an activated mutant allele of PI3K with wild-type PI3K in otherwise isogenic cancer cells, or the restoration of PTEN expression in a PTEN-null cancer cell line, is sufficient to convert a dietary-restriction-resistant tumour into one that is dietary-restriction-sensitive."

Further information can be found on the institution's website at MIT:

Meanwhile, there are a number of PI3K and PTEN inhibitors in development, but if these only affect the wild-type, not mutant, mutation, then they may only have a limited effect in overcoming the proliferation.  This blog has covered PI3 Kinase and PTEN in tumourigenesis in the past.   Companies with active research in PI3 kinase pr PTEN inhibitors include Genentech, Exelixis, Calistoga, Semafore, EMD and others.  It will be interesting to see how the research pans out. 

Finally, some thoughts from the researchers on what they found from their studies:

“We already know that the United States has an epidemic of obesity and that obesity is probably the biggest contributor to cancer in the U.S., even more so than smoking. Does this research have anything to do with that correlation between obesity and cancer, that if we make animals really obese, that this pathway is also involved in determining their sensitivity to cancer?  Answering that question is the next step.”

Kalaany, N., & Sabatini, D. (2009). Tumours with PI3K activation are resistant to dietary restriction Nature DOI: 10.1038/nature07782

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Approximately 80% of lung cancers are of the non-small cell (NSCLC) type and these can be differentiated further, i.e. squamous or non-squamous histology.  One of the challenges facing oncologists is that up to a third of squamous cell carcinomas are misclassified, which is important because increasingly, different treatments may be selected depending upon the histology.

An interesting study that may address this issue has just been e-published in the Journal of Clinical Oncology by researchers from NYU Langone Medical Center at New York University School of Medicine.  In it, they reported that a microRNA-based diagnostic test can objectively identify squamous lung cancer with 96% sensitivity. 

Squamous lung cancer carries increased risk of severe or fatal bleeding from vascular endothelial growth factor receptor (VEGF) inhibitors such as bevacizumab (Avastin) and other similar drugs in development. In addition, other approved therapies such as pemetrexed (Alimta) are indicated for non-squamous lung cancer only, so accurately defining a patient's histology is crucial.

According to the Institution press release, Dr Harvey Pass, one of the lead investigators reported that:

"The study has demonstrated that a microRNA biomarker successfully identifies squamous lung cancer with high reproducibility, sensitivity and specificity. The study certainly demonstrates the power of microRNAs in correctly classifying lung cancer and hopefully can immediately translate into more accurate choices of targeted therapies as well as cytotoxics for the disease."

The test involves use of qRT-PCR assays, a standard process in testing for various cancer markers.  While is it likely that most academic institutions will be able to perform the test quickly and easily, use of the assay may take a little while to filter out to the network of community oncologists who treat the vast majority of lung cancer patients in the US and order tests from commercial diagnostic companies. 

 
Lebanony, D., Benjamin, H., Gilad, S., Ezagouri, M., Dov, A., Ashkenazi, K., Gefen, N., Izraeli, S., Rechavi, G., Pass, H., Nonaka, D., Li, J., Spector, Y., Rosenfeld, N., Chajut, A., Cohen, D., Aharonov, R., & Mansukhani, M. (2009). Diagnostic Assay Based on hsa-miR-205 Expression Distinguishes Squamous From Non-Squamous Non-Small-Cell Lung Carcinoma Journal of Clinical Oncology DOI: 10.1200/JCO.2008.19.4134

It is a bit of a shock to realise that this is my 200th blog post and 25,000 views since the first one, how time flies!

This month sees a couple of really interesting conferences that I'll be attending, Twittering and live blogging.  Both are from Eye for Pharma.  The first one is on March 18-19th in Princeton and will cover the 2nd Global Business Intelligence Summit meeting, including areas such as drug pipelines, emerging markets and the global economic downturn.

A number of industry speakers in the competitive intelligence field will be speaking on key topics including representatives from Merck, sanofi-aventis, Amgen, Wyeth, Bayer, Genzyme and Shire among others.  It looks to be a very topical and interesting conference overall.

The second meeting I'm looking forward to covering live is also from Eye for Pharma, this time the first Oncology Summit from Boston on March 30-31.  Topics covered include a range of subjects from product commercialisation strategies, regulatory environment, reimbursement, pricing and market access.

I've already interviewed Steve Heller from Johnson & Johnson on how biomarkers can influence and add value to the new product commercialisation of cancer drugs and will be posting the interview here on the blog this week, so watch this space.

Two things crossed my thoughts this week.  One was chancing upon Senator John McCain's Twitter account and finding a series of tweets ranting about earmarks, presumably in the new stimulus bill.  One the tweets amused me:

Now, I'm no expert on catfish or genetics, but I do know that in science and medical research you can never predict where and how discoveries will be made or in what form the research may benefit people. 

Image via Wikipedia

Harold Varmus, the former head of the NIH, illustrated some great examples of serendipity in his book, The art and politics of Science. 

For example, the studies of retrovirus-induced breast cancer in mice lead to the discovery of the wnt genes.  Now, while these have no role in breast cancer, abnormalities in the wnt signalling pathway were found to exist in virtually every case of colon cancer.  In another example, Bob Weinstein's laboratory discovered the HER2 gene while researching rat neuroblastoma.  The gene plays no role in brain cancer, but is critically aberrant in about 30% of breast cancers, causing poorer prognosis.  This lead to the development of Herceptin, a monoclonal antibody that targets the HER2 gene and the rest is history.

Of course, Varmus made no mention of earmarks in his book other than repudiating Nancy Pelosi, while head of the NIH, for an increase in the HIV/AIDS budget because the funding would have to come from other projects.  After all, scientists grab what budget they can because not every Administration sees science and research as an important priority, especially if they are military-minded.

Which brings me onto the second thought this week.  What's happening to the $10B windfall being doled out to the NIH from the stimulus bill?  Mostly, it seems that it's being allocated back to projects that were put on hold from previous budget cuts.  There was a heartening story in the The Scientist though (free registration is required to access it):

"The National Institutes of Health is inviting researchers to apply for newly created grants, funded by the $10 billion that the agency netted in the recently-signed economic stimulus legislation.

The new initiative, called the NIH Challenge Grants in Health and Science Research, will make a pot of $200 million of that stimulus cash available for projects focusing on a broad array of more than one hundred topics, from behavioral sciences and genomics to stem cells and translational science. These areas, according to the NIH, reflect a 'focus on specific knowledge gaps, scientific opportunities, new technologies, data generation, or research methods that would benefit from an influx of funds to quickly advance the area in significant ways.'  The agency said on its website that it expects to fund 200 or more projects over the next two years."

Wow, well that is something - at least it's focused towards areas of need, even if some of the best medical research has come from serendipity.  Submissions for grants from the American Recovery and Reinvestment Act of 2009 are due by April 27 and any scientists interested can find the application information here.  Some of the key topics include stem cell research, genomics, regenerative medicine, translational research, biomarkers and biomaterials etc. 

So, going back to McCain's rant against pork, is the NIH funding necessary?  I don't know, but like all scientists I would rather see more funding in science than less, so up to $200M on new grants for science can't be all a bad thing and it's hardly a huge pot but 200 new research projects in one go is a rare and beautiful thing and I applaud the Obama Administration for including the NIH in the bill.

If you're a scientist or medical researcher, better get going on those grant applications - who knows what great new discoveries will come out of this important legislation?

Motexafin with whole brain radiotherapy prolongs time to neurologic progression in lung cancer patients with brain metastases

Approaches to improve the efficacy of radiotherapy and chemotherapy in treating various cancers have begun to include the addition of radio- and chemo-sensitisers to the existing regimen. 

One such drug is motexafin gadolinium (MGd, Xcytrin®).  Motexafin is an aromatic macrocycle that has a strong affinity for electrons, i.e., it is easily reduced.  In the presence of oxygen, motexafin accepts electrons from various cellular reducing metabolites and forms superoxide and other reactive oxygen species.  The molecular target for the drug appears to be thioredoxin reductase, which when inhibited, results in cellular redox stress, cytotoxicity and an increase in tumour responsiveness to a variety of treatments. Previous research has shown that motexafin increases cytotoxicity of ionizing radiation and various chemotherapy agents and may be directly cytotoxic to tumour cells under certain conditions.

This latest phase III study was an international large randomised trial. The researchers observed increased median time to neurologic progression from 10 to 15 months with motexafin gadolinium/WBRT over WBRT alone, and a more pronounced increase in those treated promptly after diagnosis (median, 8.8 to 24.2 months).  An interesting finding was found to be crucial for interpreting multicenter studies: delays in randomization (particularly long for EU/Australian contributors) produced statistically worse results.

Overall, the trial demonstrated the benefit of motexafin gadolinium added to whole brain radiotherapy (WBRT) and now offers a treatment option for non-small cell lung cancer (NSCLC) patients who develop brain metastases. Approximately 50% of such lung cancer patients get brain mets.

Mehta, M., Shapiro, W., Phan, S., Gervais, R., Carrie, C., Chabot, P., Patchell, R., Glantz, M., Recht, L., & Langer, C. (2009). Motexafin Gadolinium Combined With Prompt Whole Brain Radiotherapy Prolongs Time to Neurologic Progression in Non–Small-Cell Lung Cancer Patients With Brain Metastases: Results of a Phase III Trial International Journal of Radiation OncologyBiologyPhysics, 73 (4), 1069-1076 DOI: 10.1016/j.ijrobp.2008.05.068

Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukemia

Well, that was an attention grabbing headline for those of us interested in CML.
   
Whilst the majority of patients do well on treatment with imatinib (Gleevec), a small number will not respond to the drug initially (primary resistance), and a few will develop secondary resistance as new mutations occur.  Other tyrosine kinase inhibitors such as dasatinib (Sprycel) and nilotinib (Tasigna) are now available that cover most mutations except for  T315i.  There are also kinase inhibitors in develop for blocking the activity of T315i.

One theory that has been proposed for the development of resistance is that Gleevec does not eradicate cancer stem cells in this group.  Without a doubt, those that achieve a complete cytogenetic or molecular response do very well.

Zhao et al., looked at the stem cell issue in a letter to Nature.  They suggested that Hedgehog (Hh) signalling might well play an important part in CML because it is a critical regulator of oncogenesis.  They tested this idea in mice in whom smoothened (SMO), a protein necessary for Hh signal transduction, had been conditionally deleted in hematopoeitic cells and found that the loss of SMO impaired hematapoeitic stem cell renewal. 

They also found something very interesting.  Namely, that transplantation of Smo cells transduced with the BCR-ABL oncoprotein that causes CML into irradiated mice significantly reduced the frequency of cancer stem cells compared to controls.  Transgenic expression of Smo, hwoever, increased the frequency of cancer stems cells, leading to disease progression.

Blocking the Hh pathway chemically with cyclopamine produced different results in the experimental group compared to the controls.  Overall, the results suggest that Hh signalling inhibitors might possibly be useful in both normal and imatinib-resistant CML.  Some of these small molecules are already in phase I development, including one from Genentech, but it should be noted that none of them appear to target the Hh proteins themselves.

Zhao, C., Chen, A., Jamieson, C., Fereshteh, M., Abrahamsson, A., Blum, J., Kwon, H., Kim, J., Chute, J., Rizzieri, D., Munchhof, M., VanArsdale, T., Beachy, P., & Reya, T. (2009). Hedgehog signalling is essential for maintenance of cancer stem cells in myeloid leukaemia Nature DOI: 10.1038/nature07737

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• Mutations, good and bad, are the natural order of species (pharmastrategyblog.com)

Jade Goody and cervical cancer

Yesterday, Jade Goody the UK reality tv star sadly passed away from cervical cancer.  She was 27 years old.

Source: Daily Telegraph

Whatever else one may think about the furore and PR that accompanied her last few months, we cannot deny that she was very brave and probably did more for raising awareness of the condition than any other individual.

Cervical cancer is linked to the Human Papillomavirus (HPV) and vaccines such as Gardasil (Merck) and Cervarix (GSK) are now available to prevent the disease occurring in young women.  Currently, there are 11,000 new cases a year in the US with 3,800 deaths.  In the UK, over 700 women a year die from cervical cancer.  The condition can be picked up early by PAP smears.

What was fascinating about the Jade story was that she got the conservative and shy Brits talking about death and dying in an open way that has rarely been seen in the country before.  Even my mother discussed it despite not being able to talk about my father's death from prostate cancer a few years ago.  Some cancers are slow growing, some recur, Jade Goody's battle was a short and very brutal one.

Cancer is devastating. It's not just a life-threatening illness. It can make you poor, it can collapse your family life and it can have huge emotional consequences.  But most of all, it can leave you isolated and alone. 

In the end, perhaps we should think more holistically about about the patient as a whole and not just treat the tumour.  If more young (sexually active) women consider getting annual PAP smears and parents vaccinate their under 21 yo's, we may well see a decline in the death rate for cervical cancer in the future.  If that happens, it may not bring the Jade Goody's of this world back, but at least the publicity and raised awareness will have achieved something lasting and impactful.

#EyeforPharma Live coverage of the Business Intelligence Summit

Today we will be covering the above meeting via live microblogging from Princeton, New Jersey.  It's an interesting lineup of some of the top business and competitive intelligence professionals in pharma and biotechnology.

You can follow the meeting via the widget below or join us on Twitter and contribute to the discussion remotely by ending your tweets with #eyeforpharma so we can pick up any comments and questions you may have.

Eye for Pharma, the excellent organisers of the meeting are also on Twitter as @eyeforpharma, while this contributor is @MaverickNY.

We hope to see you at the meeting or on Twitter - do join us!

Eye For Pharma BI Summit starts tomorrow

I'm looking forward to the Eye For Pharma Business Intelligence Summit tomorrow in Princeton, NJ.

We'll be live tweeting and blogging the conference so anyone can follow in Twitter using the #eyeforpharma hashtag in Twitter search, via Cover It Live on this blog or on the Eye For Pharma blog.

Hopefully, the speakers will have some new and interesting trends to talk about!

Innovate or die

I was reading Clay Shirky's rather long yet illuminating article on the rise and fall of newspapers as a modern viable business.  In it he says:

"When reality is labeled unthinkable, it creates a kind of sickness in an industry. Leadership becomes faith-based, while employees who have the temerity to suggest that what seems to be happening is in fact happening are herded into Innovation Departments, where they can be ignored en masse. This shunting aside of the realists in favor of the fabulists has different effects on different industries at different times."

In different ways, the same revolution is happening in Pharma and Biotechnology.  Many saw the lack of pipelines eons ago and investigated ways of addressing it, but of course, like newspapers, the unthinkable worse case scenario happened.  The drugs failed before they made it market and many were slow to catch onto innovations such as targeted therapies, focusing instead on me-too chemotherapies, for example.  Now, just about every major oncology company has targeted therapies in their R&D and the market is suddenly becoming very competitive and crowded. 

It does beg the big question though; which targets are absolutely critical to the tumour and will different approaches in how they might be used make a difference in long term survival to patients?

Darwin's survival of the fittest is also at play in the background here.  Those that fail to adapt, adopt and modify will be left behind as dinosaurs, just like the newspapers.  In times like these, it's new innovations and game changing approaches that will win out rather than following the herd and making yet more me-too copies.  The next 18 months may well see a bloodbath in the industry with patent expiries, desperate corporations and a lengthy credit crunch strangling access to cash flow.

Innovate or die.

What will happen to baby Biotech?

The WSJ Health blog has an interesting post this morning on "The Great Biotech Shakeout is Near".  Now, that may sound a little alarmist, but since November, 15 have already gone to the wall and the suspicion of a VC firm is that:

"120 out of 360 publicly traded biotechs have less than six months of cash left. A year ago, only 12 companies were in that position."

Burrill & Co.

In theory, this should be a good time for cash rich pharma and biotech to be shopping for good deals to replenish their pipelines.  In reality, our experience is that many are looking keenly, but hoping for a better deal by waiting.  Who knows where the bottom of the market might be?

For some baby biotechs, help in the form of licensing deals or buyouts may not come soon enough as their cash dwindles fast and the credit crunch continues to impact business.

Why do some smokers get COPD and others do not?

The answer is in their genes.

Chronic obstructive pulmonary disease (COPD) is characterised by progressive decline in lung function, and encompasses both chronic bronchitis and emphysema. Almost 90% of COPD is caused by chronic cigarette smoking, but only 25% of long-term tobacco smokers will go on to develop COPD.

New research published yesterday in Respiratory Research from the Wake Forest School of Medicine and Saint Louis University, may shed some light on why.

The researchers looked at a disintegrin and metalloprotease (ADAM) gene known as ADAM33 in 880 long-term heavy smokers. ADAM33 is located on chromosome 20 and has been linked with asthma in previous research. This study is unique in comparing long-term smokers with COPD versus a control group of long-term smokers without COPD.

Five single nucleotide polymorphisms (SNPs), which are human DNA sequence variations, were found in ADAM33 that were more frequent in the COPD group than in the group of smokers without COPD. One particular SNP, known as S1, had a particularly strong link to lung abnormalities.

Functional studies will now be needed to evaluate the biologic significance of these polymorphisms in the pathogenesis of COPD, but the early results suggest that the abnormalities may affect the chances of developing chronic obstructive pulmonary disease (COPD) in later life.

Sadeghnejad, A., Ohar, J., Zheng, S., Sterling, D., Hawkins, G., Meyers, D., & Bleecker, E. (2009). ADAM33 polymorphisms are associated with COPD and lung function in long-term tobacco smokers Respiratory Research, 10 (1) DOI: 10.1186/1465-9921-10-21

Herceptin proven to benefit women with HER2 positive early breast cancer

Roche and Genentech have announced the latest results from the HERA study performed by the Breast International Group (BIG).

Historically, HER2 positive breast cancer has been associated with a poor prognosis, but the first analysis of the HERA trial, released in 2005, established unprecedented benefits in terms of lowering the risk of cancer returning (disease-free survival).

The latest HERA (HERceptin Adjuvant) study analysis showed that women treated with Herceptin (trastuzumab) had a 25% reduction in the risk of their cancer coming back compared to women who did not receive Herceptin, and after an average of four years, almost 90% of the Herceptin-treated women were still alive.  In addition to the significant treatment benefit, the analysis confirmed the long-term safety profile of Herceptin, with good cardiac safety and tolerability maintained throughout the four-year follow-up period.

There are now data from four large studies – HERA, NSABP B-31, NCCTG N9831 and BCIRG 006 that have consistently demonstrated that Herceptin prolongs survival in women with HER2 positive early breast cancer.

Herceptin is approved for the adjuvant treatment of HER2-overexpressing, node-positive or node-negative (ER/PR-negative or with one high-risk feature) breast cancer.  These results are reassuring to HER2-positive women that their lives are significantly prolonged on treatment with the therapy.

Yesterday, I met the lovely Joanne Gere from the Bioanalytics Group, who pointed me in the direction of an interesting abstract on Herceptin from 2005 at the San Antonio Breast Cancer Symposium, which demonstrated the effective combination of computer modeling and immunohistochemistry to predict the most likely patient outcomes after treatment with Herceptin.  The data suggested that efficacy could be drastically improved from 41.67% to 74.07% by selecting patients most likely to respond using a panel of biomarkers.  This would add to the weight of evidence for personalised medicine and appropriate therapy by pre-selecting women most like to respond to Herceptin.

Cell pathway on overdrive prevents normal cancer response to dietary restriction

An interesting paper in Nature revealed why some some tumours are resistant to dietary restriction. Normally, restricting food intake will lead to tumour shrinkage but some tumours grow despite limiting calorific intake.  The answer?  PI3K activation is permanently turned "on" via a mutation, so the tumours grow and proliferate independent of the amount of food consumed:

"Substitution of an activated mutant allele of PI3K with wild-type PI3K in otherwise isogenic cancer cells, or the restoration of PTEN expression in a PTEN-null cancer cell line, is sufficient to convert a dietary-restriction-resistant tumour into one that is dietary-restriction-sensitive."

Further information can be found on the institution's website at MIT:

Meanwhile, there are a number of PI3K and PTEN inhibitors in development, but if these only affect the wild-type, not mutant, mutation, then they may only have a limited effect in overcoming the proliferation.  This blog has covered PI3 Kinase and PTEN in tumourigenesis in the past.   Companies with active research in PI3 kinase pr PTEN inhibitors include Genentech, Exelixis, Calistoga, Semafore, EMD and others.  It will be interesting to see how the research pans out. 

Finally, some thoughts from the researchers on what they found from their studies:

“We already know that the United States has an epidemic of obesity and that obesity is probably the biggest contributor to cancer in the U.S., even more so than smoking. Does this research have anything to do with that correlation between obesity and cancer, that if we make animals really obese, that this pathway is also involved in determining their sensitivity to cancer?  Answering that question is the next step.”

Kalaany, N., & Sabatini, D. (2009). Tumours with PI3K activation are resistant to dietary restriction Nature DOI: 10.1038/nature07782

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MicroRNA-based Diagnostic Identifies Squamous Lung Cancer With 96% Sensitivity

Approximately 80% of lung cancers are of the non-small cell (NSCLC) type and these can be differentiated further, i.e. squamous or non-squamous histology.  One of the challenges facing oncologists is that up to a third of squamous cell carcinomas are misclassified, which is important because increasingly, different treatments may be selected depending upon the histology.

An interesting study that may address this issue has just been e-published in the Journal of Clinical Oncology by researchers from NYU Langone Medical Center at New York University School of Medicine.  In it, they reported that a microRNA-based diagnostic test can objectively identify squamous lung cancer with 96% sensitivity. 

Squamous lung cancer carries increased risk of severe or fatal bleeding from vascular endothelial growth factor receptor (VEGF) inhibitors such as bevacizumab (Avastin) and other similar drugs in development. In addition, other approved therapies such as pemetrexed (Alimta) are indicated for non-squamous lung cancer only, so accurately defining a patient's histology is crucial.

According to the Institution press release, Dr Harvey Pass, one of the lead investigators reported that:

"The study has demonstrated that a microRNA biomarker successfully identifies squamous lung cancer with high reproducibility, sensitivity and specificity. The study certainly demonstrates the power of microRNAs in correctly classifying lung cancer and hopefully can immediately translate into more accurate choices of targeted therapies as well as cytotoxics for the disease."

The test involves use of qRT-PCR assays, a standard process in testing for various cancer markers.  While is it likely that most academic institutions will be able to perform the test quickly and easily, use of the assay may take a little while to filter out to the network of community oncologists who treat the vast majority of lung cancer patients in the US and order tests from commercial diagnostic companies. 

 
Lebanony, D., Benjamin, H., Gilad, S., Ezagouri, M., Dov, A., Ashkenazi, K., Gefen, N., Izraeli, S., Rechavi, G., Pass, H., Nonaka, D., Li, J., Spector, Y., Rosenfeld, N., Chajut, A., Cohen, D., Aharonov, R., & Mansukhani, M. (2009). Diagnostic Assay Based on hsa-miR-205 Expression Distinguishes Squamous From Non-Squamous Non-Small-Cell Lung Carcinoma Journal of Clinical Oncology DOI: 10.1200/JCO.2008.19.4134

Eye for Pharma - some interesting meetings this month

It is a bit of a shock to realise that this is my 200th blog post and 25,000 views since the first one, how time flies!

This month sees a couple of really interesting conferences that I'll be attending, Twittering and live blogging.  Both are from Eye for Pharma.  The first one is on March 18-19th in Princeton and will cover the 2nd Global Business Intelligence Summit meeting, including areas such as drug pipelines, emerging markets and the global economic downturn.

A number of industry speakers in the competitive intelligence field will be speaking on key topics including representatives from Merck, sanofi-aventis, Amgen, Wyeth, Bayer, Genzyme and Shire among others.  It looks to be a very topical and interesting conference overall.

The second meeting I'm looking forward to covering live is also from Eye for Pharma, this time the first Oncology Summit from Boston on March 30-31.  Topics covered include a range of subjects from product commercialisation strategies, regulatory environment, reimbursement, pricing and market access.

I've already interviewed Steve Heller from Johnson & Johnson on how biomarkers can influence and add value to the new product commercialisation of cancer drugs and will be posting the interview here on the blog this week, so watch this space.

NIH and science: stimulus or porkulus?

Two things crossed my thoughts this week.  One was chancing upon Senator John McCain's Twitter account and finding a series of tweets ranting about earmarks, presumably in the new stimulus bill.  One the tweets amused me:

Now, I'm no expert on catfish or genetics, but I do know that in science and medical research you can never predict where and how discoveries will be made or in what form the research may benefit people. 

Image via Wikipedia

Harold Varmus, the former head of the NIH, illustrated some great examples of serendipity in his book, The art and politics of Science. 

For example, the studies of retrovirus-induced breast cancer in mice lead to the discovery of the wnt genes.  Now, while these have no role in breast cancer, abnormalities in the wnt signalling pathway were found to exist in virtually every case of colon cancer.  In another example, Bob Weinstein's laboratory discovered the HER2 gene while researching rat neuroblastoma.  The gene plays no role in brain cancer, but is critically aberrant in about 30% of breast cancers, causing poorer prognosis.  This lead to the development of Herceptin, a monoclonal antibody that targets the HER2 gene and the rest is history.

Of course, Varmus made no mention of earmarks in his book other than repudiating Nancy Pelosi, while head of the NIH, for an increase in the HIV/AIDS budget because the funding would have to come from other projects.  After all, scientists grab what budget they can because not every Administration sees science and research as an important priority, especially if they are military-minded.

Which brings me onto the second thought this week.  What's happening to the $10B windfall being doled out to the NIH from the stimulus bill?  Mostly, it seems that it's being allocated back to projects that were put on hold from previous budget cuts.  There was a heartening story in the The Scientist though (free registration is required to access it):

"The National Institutes of Health is inviting researchers to apply for newly created grants, funded by the $10 billion that the agency netted in the recently-signed economic stimulus legislation.

The new initiative, called the NIH Challenge Grants in Health and Science Research, will make a pot of $200 million of that stimulus cash available for projects focusing on a broad array of more than one hundred topics, from behavioral sciences and genomics to stem cells and translational science. These areas, according to the NIH, reflect a 'focus on specific knowledge gaps, scientific opportunities, new technologies, data generation, or research methods that would benefit from an influx of funds to quickly advance the area in significant ways.'  The agency said on its website that it expects to fund 200 or more projects over the next two years."

Wow, well that is something - at least it's focused towards areas of need, even if some of the best medical research has come from serendipity.  Submissions for grants from the American Recovery and Reinvestment Act of 2009 are due by April 27 and any scientists interested can find the application information here.  Some of the key topics include stem cell research, genomics, regenerative medicine, translational research, biomarkers and biomaterials etc. 

So, going back to McCain's rant against pork, is the NIH funding necessary?  I don't know, but like all scientists I would rather see more funding in science than less, so up to $200M on new grants for science can't be all a bad thing and it's hardly a huge pot but 200 new research projects in one go is a rare and beautiful thing and I applaud the Obama Administration for including the NIH in the bill.

If you're a scientist or medical researcher, better get going on those grant applications - who knows what great new discoveries will come out of this important legislation?