Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

Posts by MaverickNY

This week I attended the ePharma conference in Philadelphia and thoroughly enjoyed the opportunity to catch up with Twitter buddies for some extended conversation and sharing of news and views. 

One of the challenges of Twitter is that it is hard to have extended discussions around topics of interest, which Friendfeed does very well, except that hardly anyone outside of tech or science geeks is on Friendfeed.  It was therefore really delightful to meet the regulars in the digital pharma space in person at the intimate gathering on Moshulu, kindly hosted by Pixels and Pills.  Lot's of interesting conversations evolved and set the tone for a productive conference.

Having heard from several folks that 2009 was a quiet one for pharma digital conferences, it was a big surprise to see this one packed to the gills.  Many of the attendees were from eMarketing departments, digital agencies or specialist groups. 

Clearly the buzz about social media is beginning to gain momentum in Pharmaland, but there is also a sense of frustration with lack of guidelines and the conservatism of internal review committees.  I couldn't help wondering if they were preaching to the converted; what would be nice is to see more brand marketers, legal and reulatory folks attend to learn more and gain comfort around what others are doing in the space.

Rather than do a review of all the sessions, as I'm sure others will do that most admirably, I going to look at a couple of concepts and trends that appealed to me.

Over the last couple of years, video has become a firm mainstay in the general public's imagination, largely as prices have come down for things like Flip cameras and with the ease of posting and sharing videos via platforms such as YouTube, Vimeo, Viddler etc virally through social media.  In the opening session, Paul Ivans from the organisers, IIR, pointed out that:

"Video accounts 34% of time people are online. But for health information, people want to read it."

Do they?  Or is it that the videos on health and medical information aren't yet in a digestible, easily understood level? Videos on Pharma channels get very low views, so this could be a reflection of general distrust about corporate Pharma, lack of viral marketing or disinterest in the information.  Ultimately, more granular research is needed to understand patient and consumer needs before things improve. 

The neat thing about video such as YouTube though, is that it is seamless on smart phones such as the iPhone or Droid.  If you have a YouTube video on your site or someone shares a link to a YouTube with you on Twitter or via email, clicking the play button or link takes you straight into YouTube to see it on your screen and allow you to share it with others if you like it.  More and more people are surfing the web on their smartphones, making mobile an important and rapidly growing aspect of marketing.  People are social creatures, they want to share something easily with their friends or relatives.

Recently, I've noticed how many brand or comporate sites are not optimised for mobile.  There's a great opportunity to improve your image right there.  It's relatively easy to do and yet has a huge impact.  Imagine how many doctors are searching for medical information daily on their smartphones while in a hospital?  Or a patient and friend are in the hospital waiting for tests having just been told by the doctor he/she has X.  One is in shock, the other starts to Google on their iPhone for basic information.  We've all been there.  Ivans went on to say:

"Digital marketing provides health information and support to consumers and HCPs, but Mobile unlocks the opportunity for improving outcomes."

Of course, the wags will chirp, "there's an app for that!" but after the diagnosis, researching the disease, treatments, side effect management etc, improved patient outcomes are indeed what the ultimate goal is for everyone.  The brands and companies that really start to understand and focus on this aspect of education are the ones that will do well in the long term.  It won't be easy though, because it takes a) deep understanding of the disease and patient needs and b) focused strategies rather than random and haphazard tactics.

Another theme I liked at this meeting was innovation.  Dennis Urbaniak from sanofi-aventis (a client company) emphasised strongly that innovation is not creativity or shiny object syndrome.  That was music to my ears – how many of us have sat through agency meetings hearing about about some new idea or tactic that they thought 'very creative/innovative/cool (substitute words of your choice)' and you're deep down you're really wondering,

"Hmmm yes, but what impact will it have, how will it help doctors/patients/advocacy groups (or whatever is the target audience), how will it change outcomes?  How does it fit in with our overall strategy and goals?  Does it integrate well and can it scale?  It might be pretty and win an award, but what if the target group doesn't find it useful? Then it's money down the drain."

Therein is the rub that Dennis was alluding to that marketers constantly wonder about: "is it relevant?" and offered 5 smart rules to live by:

  1. Understand no matter how hard you try, you canʼt read your customerʼs minds. Donʼt pretend to.
  2. Optimise your mix at the customer level not the brand level.
  3. Respect channel preference and channel response, equally.
  4. Apply predictive analytics as the foundation of your approach.
  5. Content remains king. Channel optimization gets you in the game. Content optimization drives sustainable performance.

These ideas tally well with my own experience – broad ideas and tailored messages based on customer needs across multiple platforms always work better than isolated tactics with one set of messages on one channel, yet many marketers spend a lot of time and money trying to read customer's minds instead of gathering insights and using more intuition to make a bigger impact.  They forget that what people think they want today may be very different tomorrow.

In the end, great content is king, not tools and channels.  Relevance is ultimately about finding the tricky balance between expressed customer preferences and what people respond to.  How does this all fit together?  Urbaniak nailed it when he finished with:

"Let customers pick what they want and measure outcomes, then optimise progams accordingly." 

In other words, be clear on your true intent but let the customer drive the direction.  Predict, Project and Validate.

For many in Pharmaland senior management though, if they are insecure or unenlightened control freaks that might well be a very scary thought but new technologies are rapidly changing the landscape about how we communicate and interact.  We can adapt and change with them or die of ignorance.

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"When you do smaller to mid-sized deals, it is easier to search, complete a deal, and then hand it over to your line management and move on to the next deal.  It’s when you do a big deal that the whole company gets bogged down in deciding whose e-mail system you’re going to use or where headquarters are going to be."

Chris Viehbacher, sanofi-aventis

Source: Bloomberg

This afternoon I was catching up on the Pharma news after driving back from the ePharma conference in Philadelphia and racing the snowstorm home and the quote caught my eye.

Viehbacher is right. 

While sanofi-aventis (a client company) have been quietly focused on small to medium deals to offset the patent cliff and evaluating their pipeline, Pfizer and Merck have been more inwardly focused and seemingly bogged down in decisions at all levels of the organisation that inevitably descends on companies going through mega mergers.

Sometimes bigger isn't always better.

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The ePharma summit is taking place this week in Philadelphia.

Today is the social media boot camp for newbies interested in getting started with social media and tomorrow the main meeting starts with some interesting speakers lined up, including sanofi-aventis’s Dennis Urbaniak and Mike Fowler from Eli Lilly.

You can follow the tweets using the #epharma hashtag on Twitter or for ease of use you can click the widget below to see the aggregated tweets in one stream. You can also catch it live or even later, if you want to get a summary and scan after the event or at the end of the day.

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This week, (10th February) the FDA's Oncologic Drugs Advisory Committee will be meeting to review the filings from Cell Therapeutics ($CTIC) and ChemGenix ($CXSPY) for pixantrone and omacetaxine, in relapsed refractory NHL and CML, respectively.

I've just taken a few minutes to read the briefing documents and here are my initial thoughts.

Cell Therapeutics, a Seattle based biotech company, are going to have a very tough morning on Wednesday in DC for the following reasons: 

  1. The pivotal study had a very poor accrual with only 140 out of 320 patients enrolled.
  2. Substantial cardiac and hematologic toxicities.

Risk:benefit trade-offs are always going to be a question for debate in the third-line setting, but CTI may well have shot themselves in the foot by closing enrollment early.  This led the FDA to raise an important question about the study and whether there was sufficient information:

"the level of evidence necessary to draw conclusions from this Phase 3 study and the reliability of these conclusions."

Ouch.

After recent trials and tribulations over studies in elderly patients with AML had problems with a placebo comparator, it was good to see that in PIX301, patients were randomized 1:1 to single agent pixantrone or the following choice of comparators:

  • Oxaliplatin
  • Ifosfamide
  • Vinorelbine
  • Etoposide (PO/IV)
  • Mitoxantrone
  • Gemcitabine (only at U.S. sites)
  • Rituximab (only at U.S. sites)

Patients were treated for up to 6 cycles.

However, perhaps the most damning part of the FDA briefing document is the impact of halting enrollment early:

"The pivotal trial, PIX301, was discussed at an End of Phase 2 meeting on October 8, 2003. At this meeting, FDA stated, “Accelerated approval could be based on an interim analysis of a surrogate endpoint with completion of the trial demonstrating an improvement on a clinical benefit endpoint (survival or symptom benefit).”

FDA recommended that the trial assess complete response and the duration of complete response. Subsequently, agreement was reached concerning a Special Protocol Assessment for PIX301.

On March 28, 2008, CTI notified the FDA of an early halt to enrollment for PIX301. The study was not stopped at a planned interim analysis and early study stopping invalidated the applicant’s Special Protocol Assessment."

Based on this history, I think CTI will have a tough time arguing for approval on the basis of a shortened 140 patient study.  It is clear in the FDA's analysis that they do not believe statistical significance was reached for the key efficacy measures.

Meanwhile, ChemGenex, a biotech company based in Australia with an office in San Francisco, are applying for approval of omacetaxine (Omapro) as treatment of adults with chronic myeloid leukemia (CML) who have failed prior therapy with imatinib and have the Bcr-Abl T315I mutation.

Interestingly, the FDA had completely different concerns with this filing. 

The main issue with omacetaxine was that a commercially available assay does not exist for the T315i mutation and the company apparently didn't submit any information on how they were going to address this going forward.  It's one thing to have central labs and academic labs do testing for trials, but given the majority of CML patients are seen by community oncologists in the US, a commercial assay is crucial for enabling decisions to be made on when to start therapy if the T315i mutation appears.

I would be surprised if a such a test hasn't been considered, but we will see what happens at ODAC on Wednesday.  Approval may possibly be delayed until one is made available.

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Recently, I noticed that oncology companies are in the news for raising new financing or even announcing IPO's, and wondered if that was an anomaly after the credit shutdown following the Wall St crisis.  In general, my perception was that they seemed to be down overall.  To find out more, I checked out the VC funding statistics at OnBioVC:

Picture 12
Surprisingly, oncology dominates the market at the moment, with the latest data being available from 3Q09: nearly one-third were from oncology alone during that period.  According to the report, they represented:

"… a diverse therapeutic approach; from small molecules targeting the inhibition of receptor tyrosine kinase to HDAC to metallo-enzymes to PI3K and mTOR, as well as a variety of mAb’s and therapeutic vaccines."

In more terms, though, the aggregated dollars raised per sector is significantly down over the same period in 2008:

Picture 10
But overall, the total number of financings for Biotech are up, thanks to a strong growth in the medical device sector, although the biopharma sector is down slightly:

Picture 11

Last October, Auxilium received proceeds, net of offering expenses and underwriting discounts and commissions, of approximately $115.7 million.  The company closed its previously announced public offering of 3,000,000 shares of common stock at a price of $34.50 per share.

Meanwhile, last week was a busy one. 

Firstly, Ironwood raised $188M from their IPO in one of the biggest deals of the decade (more than Eyetech's $150M in 2004) by selling over 16M of shares at a price of $11.25.  It was, however, perceived to be a discount price, because their SEC filings in November hoped for a higher target of $14-16/share.  As a friend commented last week, "Well, $188M isn't chump change!"

Secondly, Reuters reported that the private French Biotech company, AB Science,

"is preparing for a 50 million euro ($70 million) initial public offering next month in a move that could make it France's first biotech stock exchange listing since mid-2008."

What's interesting about AB Science is that the company have yet to officially announce or confirm the date of the IPO, although they made clear their intent to pursue one in 1Q10 when we interviewed Alain Moussy, the CEO, in October. 

The company has an interesting KIT inhibitor on the market in Europe, masitinib, for mastocytosis in dogs and is now developing the drug in pancreatic cancer for humans.  In order to fund the phase III trials, more financing is needed so the IPO is clearly a sign that the company is going places.

This week heralds the annual BIO CEO meeting in New York, where there will doubt be a lot of interesting discussions and presentations going on.  The schedule is packed with a quite a few oncology focused companies, so more news will be covered on this blog later this week as details emerge.  Sadly, I will miss the event, as I'll be at the ePharma meeting in Philadelphia.  More on that tomorrow!

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This snippet from Reuters posted earlier this week while I was listening to the Roche earnings call in Basle, which was a nicely put together presentation:

"Roche Holding AG overhauled the sales efforts for its best-selling drug, the Avastin cancer treatment, after the company “lost steam” during the fourth quarter.  

Sales of the medicine were hurt by a focus on selling it as a treatment for breast tumors, Pascal Soriot, the head of the pharmaceuticals division, said in an interview today.  The company beefed up marketing by assigning the sales team responsible for the Herceptin breast cancer drug to also promote Avastin, while the group that sells the Xeloda therapy will promote it for use against colorectal cancer, he said. 

“We focused on breast and then kind of lost steam on lung cancer a little bit,” Soriot said at Roche headquarters in Basel, Switzerland. “We’ll increase the promotional effort and I think we’re going to turn this around.”"

Sadly, though, this is not something that was unexpected, as many of us industry observers were secretly wondering how Genentech would fare once absorbed in the more conservative Roche system.  One is very science based and the other is more corporate.  

Just take a look at the two management teams and you get the big picture:

Roche
Genentech
In the top picture, you see the Roche management team individually taken and in suits, but look like they have taken their ties off just for the photoshoot to make them a little less stiff and formal, perhaps. 

In the bottom picture, the Genentech management team, taken as a team in fairly casual attire, with the CEO, Ian Clark, even wearing a fleece!

A tale of two very different cultures in one quick glance.

What impact does this have on the physicians?  I asked around.  Now, lung cancer doctors are fairly academic and science based, many also do translational research, for example.  Underneath they are generally approachable, fun and always willing to answer questions or help people understand a complex topic. They're much more easy going than some of the other cancer specialties.

Which group do you think they would most likely mix with?

Therein lies the rub.  

Corporate suits may look sharp, but do they engage and have fun with the scientists, or even understand their world?  How much of a subtle impact might that have in the long run?  While it is true that in the end, all marketing is ultimately about sales, the intangibles such as how you approach it and engage with customers along the way is often crucial to success.

Time to stop drinking the corporate Kool Aid and focus on the science, methinks.

   

As you may already be aware, one of the primary reasons the National Cancer Institute is building the new Riverside Research Park is to provide space for “synergistic partners” from academia and Industry to work together to cure cancer.  I was just alerted to several new opportunities by my friends at FITCI

A new collaboration opportunity, “Gene Expression Signature Predictive of Response to Chemotherapy” has been added to the NCI Technology Transfer Center web site. Please go to: http://ttc.nci.nih.gov/opportunities/opportunity.php?opp_id=1881

A new collaboration opportunity, “Antibody and Immunotoxin Treatments for Mesothelin-Expressing Cancers” has been added to the NCI Technology Transfer Center web site. Please go to: http://ttc.nci.nih.gov/opportunities/opportunity.php?opp_id=1883

A new collaboration opportunity, “Knockdown and Enhanced Expression of P53 Isoforms to Treat Age-Related Disorders and Cancer” has been added to the NCI Technology Transfer Center web site. Please go to: http://ttc.nci.nih.gov/opportunities/opportunity.php?opp_id=1885

A new collaboration opportunity, “Engineered Biological Pacemakers” has been added to the NCI Technology Transfer Center web site. Please go to: http://ttc.nci.nih.gov/opportunities/opportunity.php?opp_id=1884

A new collaboration opportunity, “Novel Kinase Inhibitors Targeting the PH Domain of AKT for Preventing and Treating Cancer” has been added to the NCI Technology Transfer Center web site. Please go to: http://ttc.nci.nih.gov/opportunities/opportunity.php?opp_id=1882

Interested? Or know someone who might be?

Click on the links to see more details. Spread the word!

(HT Jim Hardy @fredcobio)

Posted via web from sally church’s posterous

"The beauty and mystery of life
extends down to the molecular level. 

The more we see, the more we can appreciate
the wonder of our own nature."

Prof Arthur Olson, Scripps Institute



Every now and then, something lands in my Google Reader that makes me stop and gasp, or at least eagerly look a little more closely. Today's head turner was:

"Scripps Research scientists find two compounds that lay the foundation for a new class of AIDS drug"


Whoa!
On more
careful examination, it seems that a team of scientists at The Scripps Research Institute really has identified two compounds that act on novel binding sites for an enzyme used by the human immunodeficiency virus (HIV), the virus that causes AIDS. The discovery apparently lays the foundation for the development of a new class of anti-HIV drugs to enhance existing therapies, treat drug-resistant strains of the disease, and slow the evolution of drug resistance in the virus.

I've written about AIDS and HIV previously and how the disease evades treatment in the past, but if this new finding holds true, we could potentially have a new approach that will add to the current pool of treatment regimens that slow down the path to drug resistance and improve patient outcomes.

Current HIV-protease drugs mimic the shape of certain regions of the HIV protein chain, known as the "cleavage sites" and bind to the active site in the hollow center of protease.  Once this site is blocked by the drug, the protease is disabled, and HIV cannot make new infectious particles.  Protease drugs therefore impede the spread of the HIV infection to other cells within a patient.

The researchers decided to look at drug-resistant strains of the virus.  They then conducted computer simulations of the movement of a particularly nasty multi-drug-resistant mutant strain of HIV (V82F/I84V) to see what happened and if they could learn from it.

The results showed that the flaps of the drug-resistant protease molecule tended to be open more often than their counterparts and they were also more flexible. While the anti-HIV drugs still fit into the active site binding pocket, more energy was needed to close the flaps than the drugs could muster.  The drugs wouldn't stay in the binding site and the pocket remained available for the HIV protein chain, which was still able to close the flaps and go on to create new infectious particles.

We can now see that a new type of drug might be able to bind to alternate sites on the sides of the protease, restraining the flaps from their ends and providing the current anti-HIV drugs enough help to close the flaps and disable the protease. Instead of blocking the protease's active site, these compounds would be "allosteric fragments" ie small molecule building blocks that shift the dynamics of the molecule, allowing a different conformation or shape.

How are these two compounds different from currently approved drugs for HIV?

Well, in plain English, current treatments target HIV protease, however, the two new agents in development are small chemical units or "fragments," which bind with the two specific parts of the molecule where they identified resistance occurring.

Essentially, this approach is an important proof-of-concept that the protease molecule has two non-active site binding pockets or 'allosteric sites', which can be exploited as a powerful new strategy to combat drug-resistance in HIV.

Overall, there is a long way to go yet, including extensive clinical trials to determine the safety and efficacy of the compounds, but in theory, with this approach, future drugs incorporating the fragments' novel structural elements may offer new angles that can be exploited biochemically.

Take a look at a beautiful picture of the HIV complex, courtesy of the Scripps Institute, which was created by Dr Stefano Forli, Ph.D:

Forli_HIVreflection
Once you have finished comtemplating, please re-read the quote at the top of the post. The more we understand about the science and biology of disease, the more awed I feel.

You can also check out the Scripps Fight AIDS at Home page if you want to learn more.


ResearchBlogging.org
Perryman, A., Zhang, Q., Soutter, H., Rosenfeld, R., McRee, D., Olson, A., Elder, J., & David Stout, C. (2010). Fragment-Based Screen against HIV Protease Chemical Biology & Drug Design, 75 (3), 257-268 DOI: 10.1111/j.1747-0285.2009.00943.x

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