Pharma Strategy Blog

Simplifying data capture and blog post workflow

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 (right photo) as an example of what I found interesting and streamed to others to read:

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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?

The Long Tail of Cancer Research

"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!

Celgene buy Abraxis Bioscience for $2.9B

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

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:

Bayer’s Nexavar fails to gain NICE approval in liver cancer

"The drug, also known as sorafenib, extended lives by an average of 2.8 months at a cost of 27,000 pounds ($38,853) for each patient, NICE said. The Leverkusen, Germany-based company had offered to pay for every fourth pack of Nexavar when used to treat hepatocellular carcinoma, a type of cancer that starts in the liver. Few patients with the disease are able to undergo the surgery that could potentially cure them, NICE said." 

Source: Bloomberg

No surprises there really and consistent with the approach the National Institute for Clinical Excellence (NICE) has taken over the last few years.  You can read what the agency had to say on the matter here. Basically, Bayer offered NICE a deal whereby every 4th pack of sorafenib (Nexavar) would be free, but that wasn't enough to sway the decision:

"Sorafenib does not provide enough benefit to patients to justify its high cost."

It's interesting that my US colleagues always point to this kind of decision as evidence of rationing but it's really an access issue based on who holds the budget strings.  

In the US, drugs might get approved at whatever cost the manufacturer chooses for now, but insurance companies and the CMS may put all sorts of strings attached such as certain conditions, formulary tiers, pre-authorisation etc and in the end the patient also has a choice whether they can and want to afford the co-pays that go with those decisions.  They may after all, still say no, that the price asked is too high a price to pay based on their means.  A drug in a tier 3 or 4 category will have a very different co-pay from a tier 2 drug, for example.

Still, in the end, who pays the Ferryman is still the moot point and sometimes Pharma forget that the days of charging exhorbitant prices that neither the healthcare systems nor the people can afford will one day come to end with excessive price charging.  

Ultimately, it's an unsustainable business model that gives Pharma a bad name synonymous with oil and tobacco companies. Perception is reality sometimes. Eventually the actions of a few will affect the sensibleness of most and in the US we will all get to deal with more systematic price controls and constraints based on the likes of health economics, comparative effectiveness and cost utilities etc whether we like it or not.

Outside of oncology, very few companies consistently engage in head to head comparative trials to prove their drug is more effective or cost effective than the standard of care.  This will ultimately change over time as the authorities get tougher.

In the long, the cost of doing business ie conducting clinical trials, will go up and the burden of proof will shift dramatically.

End of life care and treatment raises all sorts of poignant yet important questions.  Do we need a greater focus on wellness rather than palliation? What about research into better models and biomarkers so that earlier detection of cancer, where intervention can have most effect, can be initiated? Should the needs of the few (eg in the end of life situation) outweigh the needs of the many? Given the limited resources available, how best should they be allocated and invested?  

If you look at the Nexavar situation on reflection, how would that $38K be best spent for the greatest benefit given that there isn't a bottomless pit of money?

These are always tough decisions for anyone to make, especially when a relative or loved one may be involved.  Rather than the PR and media hysteria that inevitably follows these sort of rejections, hard and tough though they may be, it would be nice to see a broader public debate around some of the wider strategic healthcare issues facing us all.

Malcolm Gladwell on cancer research

I was reading an article from the New Yorker this morning by Malcolm Gladwell on the Annals of Innovation.  You can read the abstract here.  

The article centres around the story of Synta/GSK's elesclomol in melanoma in 2007.  The drug, like many others, started off promisingly but the final results showed that the patients did more poorly in the treatment arm.  What the researchers didn't know at the time was that the target in melanoma was actually different from the one they were aiming at.  The understanding of the biology had yet to evolve beyond chemotherapies at that time and our understanding of biomarkers in melanoma was sketchy at best.  

Essentially, the author concluded:

“When will we find a cure for cancer?” Gladwell writes, “implies that there is some kind of master code behind the disease waiting to be cracked. But, so far as we can see, there isn’t a master code. There is only what can be uncovered, one step at a time, through trial and error.”

In some sense Gladwell's right, the process of finding new cancer drugs based on the biology of the disease goes one step at a time, science and research is necessarily iterative, after all.  But he missed the reason why. 

It's because cancers are heterogeneous.

Photo Credit: Cnet

What makes a great Pharma marketer?

A bunch of friends and I have been debating offline about what separates a great from a good brand marketer.  In our case, we've been focusing on oncology, but really it could be any pharma category from asthma to Zellweger syndrome.

To date, the answers and ideas have been stimulating and interesting, but we all agreed that none have really captured the very essence we were seeking to describe.

Until I read Brad Feld's superb post this morning.  He was actually talking about what makes a great entrepreneur:

“A complete and total obsession with the product”

And I realised that's exactly what we were trying to describe for Pharma marketing.

If you're not absolutely obsessed with everything about your drug or brand, from scientific preclinical and clinical data to understanding market research on how your customers feel about it or indeed how anything impacts your product, then you're missing something vital.

Life is too short to just go through the motions.

Thoughts?

New Product Marketing

One of the things about oncology or any other therapeutic are new product development and marketing is that you get to spend a LOT of time at scientific congresses like AACR in DC the other week, which means early to rise and late to sleep:

Source: Personal iPhone - view of over the Potamac and Georgetown, DC from Arlington, VA. 

Anyone who thinks these meetings are junkets or jollies should join me on my schedule next trip;sometimes there isn't time to eat or by the time you do have a free slot it's too late.  Often, it means 18 hour days and a day back in the office is a relative rest.  There's always thought leaders to talk to, sessions to attend, media briefings, poster sessions (you can walk miles at those alone), plenaries etc, not to mention clients as well.  Fitting it all in makes for jam packed days.

The interesting thing about new data though, is that while trends may be obvious to those following the specific disease area, they are not to others.  I always find it amusing watching the teams of young things running around with their crib sheets frantically collecting poster handouts, rudely barging past people and trying to discreetly snap the posters without security catching them.  

In DC, I asked one what they did with all the data they amassed.  It turns out they just dump it all in a report for their client by whatever category seems apt.  No strategic analysis, what it all means or even trend spotting, just a data dump.  Ugh.

Sometimes less really is more.

Pharma Buzzword Bingo

After listening to a lot of analyst and Q1 webcasts from Pharmaland lately, I have to groan at the lack of imagination shown across the board.  Those waterfall slides, so beloved of senior management with a junior management consultant or intern on their team, drive me potty.  It's always the same story... a few upsides here, a few glitches there, oh and here's our new number.  Marketing fluff and puff, sigh.

That said, the delightful Tom Fishburne cracked me up this morning with his cartoon:

Source: Tom Fishburne 

Thus I'm glad to be heading off to DC today and relative purity of scientific cancer research at the annual American Association of Cancer Research (AACR) meeting.  Expect a deluge of posts of the next few days on hot research topics I find interesting!

Innovation, differentiation and me-toos

While everyone else is trying to spoof an April Fool post, here's some real food for thought via an awesome cartoon from Tom Fishburne:

 

What are you doing to differentiate yourself from the competition by creating something new and innovative?  Or would you rather be one of the other little piggies?

This approach works as much for people and companies as it does for brands and drugs.

It's also why we have a blog and not a static or glossy of fancy Icarus website: what you see is what you and get. You can also see what we do and how much experience we have in oncology from the daily musings and insights.

 

An overview of Roche's oncology pipeline

At last weeks investor meeting held by Roche in downtown Wall Street, the Board reviewed the pipeline opportunities in a number of areas.  Earlier this week I wrote about the non-oncology pipeline and today will form an overview of the cancer drugs in development.

One of the things that Roche is renowned for is life cycle management.  They do this better than many in the industry in my opinion and it makes an enormous difference not only to continuity, but also long term revenues and performance. Too many companies take a short term view and do not think ahead to the future. This is a big mistake. Perhaps they get bogged down in classic silos or management do not see it as a priority, but it does make a difference. 

Why?

Well, for starters, think about the basics of marketing. It is much easier to sell new products to existing customers than it is to sell existing products to new customers and even harder to sell new products to completely new customers.  

Thus life cycle management is a smart strategy and done well, enhances the experience for everyone involved whether employees or investors.  I only wish more companies paid closer attention to this important aspect of Pharma marketing.

The other thing I like about Roche's approach to R&D is rigorous and strong proof of concept studies (usually in phase II). Between Roche and Genentech, they both do this particularly well in oncology, it seems to be their signature. This partly explains why they mostly end up with a continuous wall of data across several products including trastuzumab (Herceptin), rituximab (Rituxan) and bevacizumab (Avastin). Of course, negative trials do occur but overall, they seem to have more positive trials than not. This partly explains why they have fewer phase III flops than say, Pfizer, because they spend the time in phase II working things out rather than rushing aggressively ahead on the basis of early evidence.

So what did we learn from the pipeline presentations last week?

There are late stage oncology products in development that look promising.

One example is trastuzumab-DM1, which is basically modified Herceptin with a potent cell killing agent, DM1, bolted on. The goal is to improve the action of Herceptin in metastatic breast cancer, and at the same time invetigate whether the xenograft data in a variety of cancers (breast, ovarian, lymphoma and prostate) with an armed antibody is an effective strategy in people. Recent phase II data from the San Antonio Breast Cancer Symposium in heavily treated women with metastatic breast cancer look encouraging. Phase III trials have already begun and if all goes well, filing is currently anticipated by 2012.

Also potentially strengthening the breast cancer franchise is pertuzumab, a monoclonal antibody that targets HER2. Early phase I trials in several cancer types produced so-so results, but more recent phase II data in breast (combined with Herceptin) and ovarian cancer (in combination with gemcitabine) published this month in JCO look interesting.

Perhaps the most exciting compound though, is PLX4032/RG7204, a BRAF inhibitor being evaluated in malignant melanoma. Currently available data suggests survival is improved by 6 months so the big question is what causes resistance to develop and how this can be overcome. Data on this compound is expected at ASCO, where many are keen to see how it stacks up with ipilimumab (BMS).

In hematologic malignancies, GA101 or galiximab is being evaluated in non-Hodgkin's Lymphoma (NHL) and chronic lymphocytic leukemia (CLL). It appears to target a different part of the CD20 isotope than rituximab and this may increase it's efficacy. Phase III trials began in 4Q09 thus it will be a little while before we see some results. There is clearly an unmet medical need in the 3rd line refractory disease for more tolerable agents and rituximab is very much the bedrock of treatment for both across multiple lines of therapy either alone or in combination with chemotherapy. A similar agent will likely have good take up with the right approach.

Genentech are investigating various new and improved approaches to angiogenesis, but these are in much earlier development and the bar is very high with bevacizumab (Avastin), even for the company who manufacture it. The list of anti-angiogenesis compounds that didn't make it to market is very long indeed.

I've left the best to last, as hedgehog (Hh) signalling is one of my favourite pathways - it always reminds me of the cheerful cartoon character, Sonic the Hedgehog. RG3616, licensed from Curis, is currently in phase II trials for advanced basal cell carcinoma and trials are also underway for medulloblastoma. If interested, you can find out more about the pathway and the science here.

Overall, the oncology pipeline has a nice mix of follow on compounds to strengthen life cycle management with a raft of monoclonal antibodies with different targets in new cancer types.  Such a strategy should reduce risk and drive the future bottom line if the promise delivers in phase III trials.

Baselga, J., Gelmon, K., Verma, S., Wardley, A., Conte, P., Miles, D., Bianchi, G., Cortes, J., McNally, V., Ross, G., Fumoleau, P., & Gianni, L. (2010). Phase II Trial of Pertuzumab and Trastuzumab in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer That Progressed During Prior Trastuzumab Therapy Journal of Clinical Oncology, 28 (7), 1138-1144 DOI: 10.1200/JCO.2009.24.2024

Makhija, S., Amler, L., Glenn, D., Ueland, F., Gold, M., Dizon, D., Paton, V., Lin, C., Januario, T., Ng, K., Strauss, A., Kelsey, S., Sliwkowski, M., & Matulonis, U. (2009). Clinical Activity of Gemcitabine Plus Pertuzumab in Platinum-Resistant Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer Journal of Clinical Oncology, 28 (7), 1215-1223 DOI: 10.1200/JCO.2009.22.3354

Merck KGaA reviewing cardiac data for Erbitux in lung cancer trials

"Merck KGaA is reviewing heart risks of its tumor-fighting Erbitux drug in several types of cancer after European regulators asked for more information on the treatment’s safety. 

The European Medicines Agency requested the review after rejecting Erbitux for use in lung cancer patients, according to a report published online on March 12. The drug regulator identified an “increased incidence of cardiac events” in lung cancer patients age 65 years or more, in particular high-risk patients with a history of heart problems."

Source: Bloomberg

This was an interesting snippet of news that I saw in the mass of alerts this morning, and no obvious press release from any of the companies involved with the drug, Merck KGaA (in Europe), BMS or Imclone (US partners).  

Part of the problem here is that many people with lung cancer also tend to have cardiac co-morbidities and thus the two may go hand in hand. To be fair, similar side effects have not apparently been reported in other cancers, such as colon cancer.

If the analysis reveals negative findings, then it may lead to changes in the prescribing information, which will not be good news.  Of course, the company are hopeful that will not happen, because changes in the EU labelling for Erbitux (cetuximab) may subsequently impact the US one too.  

Merck are already having a rough week on the issues management and communications front with the suspension of the Stimuvax trials after a patient being treated with the vaccine developed encephalitis. At least the current issue didn't get reported on a Friday!

Thoughts on the Roche non-oncology pipeline

Last Thursday, I attended the Roche Investor meeting in Wall Street, live-tweeted it using the hashtag #RocheIR and enjoyed an interesting event packed full with lots of information to digest.  

Luckily, I bumped into an old colleague from Sandoz UK days and was delighted to learn that he is now Global Head of Regulatory at Roche.  Of course, if you spend a day out of the office, you pay for it severely the next day with an even bigger pile of emails, client requests, RFPs and telecons to catch up on >.<

In fact, I was so busy, I didn't have time to post a blog about Thursdays event on Friday, but I did manage to interview Dr. Laura Esserman, the breast cancer surgeon at UCSF behind the fascinating I-SPY2 project that we discussed last week. More on that tomorrow.

The next two days of blogs will cover two reports on the Roche pipeline (non-oncology and oncology) and Dr. Esserman's unique perspective on getting the I-SPY2 project up and running, she has certainly made a difference shaking things up and challenging people's approach to drug development in a short space of time. 

Let's begin with the non-oncology agents in Roche's pipeline.

Granted I normally write more about oncology, hematology and immunology here, but my background in Pharma started in more humble beginnings as a sales rep in the statin market, where we were also looking to differentiate ourselves by being an attractive option for people with diabetes, who have a much higher risk from long term CV mortality.  

I was therefore very interested to see where Roche were going with this approach fifteen years later because we never had much success with it, despite Marketing thinking it looked to be an attractive opportunity no one was exploring.  However, the undoubted long risk of earlier mortality and morbidity is subsumed to more urgent and immediate needs such as getting sugar levels under control and insulin levels regulated.  Adding yet another drug into the mix complicates things for physicians considerably. Plus taking oral drugs over time also results in long term compliance issues, which may impact outcomes negatively.

Dalcetrapib is being developed for dyslipidemia and cardiovascular high risk patients. The first trial looks at artherosclerotic disease progression, lipid profile and biomarker profile and long-term safety profile of dalcetrapib in people with established coronary artery disease compared to placebo. 

The primary endpoints include:

• Nominal change from baseline to study end in coronary percent atheroma volume (PAV) of the target coronary artery assessed by IVUS.
• Rate of change from baseline to study end in carotid intima-media thickness (CIMT) using B-mode ultrasound

The second trial is looking at the potential of dalcetrapib to reduce cardiovascular morbidity and mortality in stable coronary heart disease patients with recent Acute Coronary Syndrome (ACS) and evaluate the long term safety profile of the drug, again, compared to placebo. 

The primary endpoint is defined as:

• Time to first occurrence of any component of the composite cardiovascular event (cardiovascular mortality and morbidity)

These two phase III trials are currently recruiting people with coronary artery disease, so we won't know the results for quite a while, probably over the next 2-3 years.  Such large scale trials are very expensive and time consuming to conduct.  For all the the noise about statins reducing cholesterol, I sometimes wonder what impact they actually have on long term mortality and morbidity. Do they lead to any meaningful clinical change in outcomes, ie improved survival, rather than just lowering cholesterol per se?

Roche also have two drugs in development for type II diabetes, both of which are tongue twisters: taspoglutide, a new GLP-1 drug for Type 2 diabetes, and aleglitazar, for cardiovascular high risk in diabetes. The diabetes market is suddenly getting very crowded with numerous insulin, syringes, pens, pumps, and oral therapies all available. 

Thus as a marketer, I'm wondering how new products into these segments differentiate themselves from existing therapies in this competitive disease?  It's one thing to claim blockbuster potential, but quite another to capture the heart and minds of the physicians prescribing yet another me-too in a crowded existing market segment.  

The $64M blockbuster question in diabetes for BMS's Onglyza, in the DPP-4 segment, rapidly turned into a spectacular $4M flop in the launch year. The inhaled insulins such as those from Pfizer and Mannkind were either withdrawn or struggle to make it to market. Two precautionary tales of humility in the diabetes market if there ever were some.

How Roche develop and differentiate taspoglutide and aleglitazar from existing segment leaders will therefore be an interesting process to watch.  For now, we can sit back and wait for the various clinical trials to complete and see how the agents stack up.  The phase III trials were initiated for aleglitazar were initiated in 1Q10, taspoglutide initial phase III results were released in 4Q09 and further results are expected in 2010. The results for dalcetrapib will not be available for a few years given the enrollment is just starting.

Two other non-oncology drugs in development include RG1678, a GLY-T1 inhibitor, for treatment of the negative symptoms of schizophrenia. The initial phase II results were positive last year and phase III trials are planned for 2010.  

Ocrelizumab is a humanised CD20 monoclonal antibody similar to rituximab. The phase III trials were negative in rheumatoid arthritis and lupus, despite the agent being developed to reduce the development of drug neutralizing antibodies and infusion reactions. Recent studies, however, established that the safety risk associated with ocrelizumab outweighed the benefits and Roche disclosed that several patients died from infections so the development in RA and lupus was promptly suspended. Meanwhile, ocrelizumab is also being developed for the treatment of people with multiple sclerosis and a Go/No Go decision for the phase III development is expected this year.

Given the focus on five main disease areas including oncology, virology, immunology, metabolism and CNS, it is good to see new agents being developed in the metabolism and CNS areas after the long term focus on oncology with Genentech lately.  How well they will do in the long run compared to the oncology pipeline, only time will tell.

Thoughts on the pixantrone FDA ODAC meeting

Yesterday was quite day, with one thing and another.  For starters, the FDA ODAC committee finally held a session for Cell Therapeutics pixantrone in 3rd line NHL and ChemGenenex's omacetaxine, for people with the T315i mutation in CML.  The previously scheduled meeting was cancelled due to the Snowpocalyse that hit DC last month. 

I had to dash off to a doctor's appointment myself so missed most of the action on Twitter and rushed back to catch up at lunchtime by checking Twitter buddies such as Kerri Wachter who was live tweeting from the meeting and Adam Feuerstein of The Street's excellent live blog.

Image via Wikipedia

You can see my original review of the February FDA documents here.  Sadly, the analysis turned out to be accurate and Adam had noted:

"That was brutal."

Approximately 20 minutes into Richard Pazdur's opening introduction. 

In particular, the FDA felt that:

"Pixantrone has demonstrated evidence of biologic activity, but the mere demonstration of biologic activity is not sufficient for approval."

Ouch!  At that point it becomes incumbent upon the company presenters to argue persuasively to the nine panel members to convince them otherwise.  However, that was going to be a tall order given the FDA concerns regarding:

1. Neutropenia and infections were higher in pixantrone than the control
2. Cardiac toxicity was higher in pixantrone than control, including heart failure and ejection fraction

As highlighted in the original analysis of the pixantrone filing, the FDA were also unhappy about the shortened study given only 140 people were enrolled out of the planned 320, leading them to conclude:

1. Study was not well executed or complete.
2. Study was inconsistent (only 8 people enrolled in the US and none had a complete response).
3. Trial did not demonstrate statistical significance or robust findings.

What was weird about the proceedings though, was a clear disconnect between the two parties, as Adam Feuerstein reported live via the webcast:

"Pazdur: FDA not consulted about halting enrollment in trial, not pre-specified in study's statistical plan."

"Bianco: In March 2008 after 140th patient was enrolled, study was closed to enrollment. We consulted with FDA about this."

Checking my Twitter stream, Kerri reported:

Personally, I was surprised that CTI thought that the statistical parameters would not change if they only recruited 140 of the 320 people expected and could proceed on that basis.  This is basic college level statistics - if you majorly change one input, the outliers must also be adjusted.  For this reason, the FDA's decision to treat the data as if an interim analysis had been done is fair and reasonable.

Going forward, it is likely that either all 320 patients would need to be enrolled in a study to meet the minimum FDA requirements or new studies in combination with other agents would be needed.  This latter approach is probably more likely, because the US sites (28 of them) only enrolled 8 people because the preferred treatment in the 3rd line refractory setting is combination chemotherapy, not single agent therapy. 

Perhaps the snowpocalypse last month was a portend of what was to happen.  Either way, yesterday was a bad day in DC for CTIC.

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Abbott makes some waves in Pharma

While listening to last week's presentation by BMS on their pipeline, one slide in particular caught my attention:

Source: BMS

Now, it wasn't the fact that BMS were second in their table of Total Shareholder Return (TSR) that was interesting to me, but that Abbott were first, and by a long way, according to the chart above.  Of course, shareholder return is only one measure of performance and says nothing at all about putting customers and patients first, but that is another story/blog.

Recently, Abbott has been in the news with the acquisition of Solvay, a generics company, which added $3B to their revenues and last night it was announced that the company are also acquiring Facet Biotech, which was being pursued by Biogen Idec.  The Biogen deal clearly fell apart after the company declined to raise their offer beyond $17.50/share.  Abbott offered $27/share and thus a white knight was found.  Interestingly, the Facet CEO, Faheem Hasnain, is a former employee of Biogen Idec.  

The acquisition is a hot one, so to speak, and many of us in the industry have been speculating in vain on who the partner might be, so you would think that going on CNBC's Pharma's Market with Mike Huckman would be a nice coup for a small company.  I thought it was odd though, to see that they seem a little publicity shy, as this tweet shows the company's rather gauche immaturity:

 

What do Abbott get from acquiring Facet?

Well, first we need to think about where Abbott is coming from.  Most companies with either build on existing platforms and franchises or add new products in areas where they want to expand.  Abbott is probably best known for it's immunology franchise, with adalimumab (Humira), its TNF inhibitor for rheumatoid arthritis and psoriasis. 

Several companies, including Abbott and BMS, have embarked on a race to develop the next generation of Hepatitic C drugs and vaccines.  Infectious diseases are not something that are going away fast, so this is seen as an attractive market segment by many.

Looking at the Facet acquisition, the pipeline is thus interesting because they have also been developing monoclonal antibodies but in different diseases including immunology and cancer. The lead compound is daclizumab, which is in phase II development for multiple sclerosis in partnership with... Biogen Idec. Facet own the exclusive rights to the asthma indication though.

There are also several anticancer antibodies such as volocizumab (solid tumours) and elotuzumab (multiple myeloma) in Facet's R&D.  Oncology is an area where Abbott has been relatively weak, although they have some interesting compounds in development for liquid and solid malignancies. In 2009, a joint venture with TAP was concluded, adding Lupron, one of the best selling drugs for hormone-sensitive prostate cancer to the portfolio of currently marketed products.  

Abbott may well see topline growth from it's cancer franchise in the future... if the pipeline products from their own labs or Facet's deliver.  If those from Facet fail, Biogen Idec will be breathing a sigh of relief that their offer was turned down.  

Such is life on the Pharma roller coaster.