Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

Posts tagged ‘key opinion leader market research’

BRAF mutations and response to EGFR therapy in colorectal cancer

By on October 24, 2008

This week at the EORTC-NCI-AACR meeting, it was reported that metastatic colorectal cancer patients with a mutated BRAF gene do not respond to anti-EGFR monoclonal antibody therapy with cetuximab (Erbitux) or panitumumab (Vectibix).  This means that screening patients for the mutation may determine who would benefit most from receiving the treatment.

Colorectal cancer (CRC) is one of the most common cancers globally.  Once the disease has spread, five year survival rate is less that 10%.  At present, EGFR therapies are used after several prior treatments have failed and are only effective in 10-20% of cases.  It has previously been shown that KRAS mutations account for 30-40% of non-responsive cases.  The new research suggests that BRAF mutations may acount for an additional 12% of resistant cases.

The study found that none of the tumours containing BRAF mutations responded to treatment and where it did work, none of the tumours expressed the mutation, suggesting that EGFR targets the wild-type BRAF gene. 

Interestingly, when a BRAF inhibitor, sorafenib (Nexavar) was added to the treatment regimen of patients with mutated BRAF, the sensitivity of the cells to EGFR therapy was restored, resulting in cell death (apoptosis) with the combination therapy.  This approach has yet to be validated in a broader clinical trial, but offers a promising approach in patients with mutated BRAF in colorectal cancer, if validated.

It should be noted though, that while the KRAS and BRAF mutations offer some predictive value for treatment, 52% of non-responsive patients in the study did not have mutations in either gene, so the search continues for other molecular markers.

This data, while preliminary, raises all sorts of questions.  Currently, patients are treated by diagnosis and line of therapy. 

Thus, first line treatment of metastatic colorectal cancer is usually standard chemotherapy (FOLFOX or FOLFIRI) plus or minus bevacizumab (Avastin).  Second line might typically comprise irinotecan with or without cetuximab or panitumumab and third line irinotecan with panitumumab or cetuximab.

What happens with a newly diagnosed advanced CRC patient who presents with wild type KRAS or BRAF?  Or mutated BRAF?  Should they now be treated with an EGFR inhibitor and EGFR inhibitor plus sorafenib respectively?  With or without chemotherapy?  This complicates physician decision making enormously, especially as neither EGFR inhibitor is approved for front-line use in CRC and sorafenib use would be off-label since it is approved for renal cell and hepatocellular carcinoma.

The next few years will be very interesting in this disease as key opinion leaders wrestle with the problem and decide optimal sequencing for different patient types.  What is clear though, is that a new era of personalised medicine based on particular biomarker profiles is gradually being ushered in.

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Strategically, when everybody zigs it makes sense to zag

By on October 22, 2008

"Successful companies do not abandon their marketing strategies in a recession; they adapt them."

John Quelch, Harvard Business School

Yesterday, I was scanning my Google Reader for information on 'Marketing and Recession' and came across an HBR Working Knowledge article by Prof. John Quelch entitled, "Marketing your way through a recession".  In it, he cogently argues the following:

Research the customer.  Instead of cutting the market
research budget, you need to know more than ever how consumers are
redefining value and responding to the recession. Price elasticity
curves are changing. Consumers take more time searching for durable
goods and negotiate harder at the point of sale. They are more willing
to postpone purchases, trade down, or buy less. Must-have features of
yesterday are today's can-live-withouts. Trusted brands are especially
valued and they can still launch new products successfully, but
interest in new brands and new categories fades. Conspicuous
consumption becomes less prevalent.

In other words, there are still opportunities if companies are bold enough to grab them.  Know thy customer is never a truer altruism than when times are hard.

Something else caught me eye in the same article.  Quelch went on to say (emphasis in italics mine):

Maintain marketing spending. This is not the time to
cut advertising. It is well documented that brands that increase
advertising during a recession, when competitors are cutting back, can
improve market share and return on investment at lower cost than during
good economic times.

Well, that got my attention in a month when two big pharma companies (Pfizer and Novartis) announced job losses on top of those previously announced by GSK, Merck, Schering Plough and others.  September and October are also the months when Finance Departments traditionally love to cut marketing budgets.  If the monies haven't been spent or committed, tough, never mind that there are a number of important scientific conferences coming up that offer great opportunities for announcing new data, PR activity, medical education, symposia/spin-offs and such like for the bold ones able to maximise the opportunities for growing market share into 2009.

Perhaps the Finance Directors would do well to heed the sage advice of Oliver Wendell Holmes:

“Greatness is not where we stand, but in what direction we are moving.”

In a recession, moving forward rather than cutting back may well separate the winners from the losers in the long run.

The importance of messaging in new product launches

By on October 21, 2008

What is messaging and why is it important? 

Well, in this context, it is essentially a communication about a company's product(s) or even the pharma/biotechnology company itself.  It takes the form of either the written word or verbal communications about data or a product's features.  These can be from employees of the manufacturer, the press, patients, caregivers, members of the public or doctors. 

From a company's perspective, having everyone on the same hymn sheet across promotion, PR and medical education is the desired goal, but few achieve this nirvana mainly because it is constantly like herding cats and requires an enormous amount of confidence, energy and effort, although it can be done.  The marketers nightmare is realising that there are different messages from the sales force, key opinion leaders and company press releases.  This limits the effectiveness of the overall message and ultimately will lead to confused and unsure patients and doctors.

The most successful brands are often those with a coherent, cogent and potent message that convey the essential essence of the product in a few simple words.  Rarely do you see a successful brand with poor messaging, but brands with poor messaging generally do less well.  Gleevec and Avastin are two recent blockbuster cancer drugs that spring to mind as examples of utilising effective messaging strategies to generate share of voice.  Constantly referring to new data, new clinical trials and extended survival of patients in the earlier trials adds to the body of evidence that the drugs are safe and effective.

The other side of the coin is that smart companies continually evaluate their competitors messaging and the intentions that they signal in the process.  This is competitive intelligence at its best; honing and refining your brand to best take advantage in a highly competitive market, so that you can proactively respond to your rivals rather than react six or nine months later down the line as you assess the market data.  Often by then it is too late and momentum has been lost. 

Another example would be an existing brand on the market and a new competitor is due out in the same indication; what can be done to effectively limit their market share?  Information about competitor messaging can be gleaned from press releases, conference data, online forums, key opinion leader research, third party medical education etc. 

Using these in-depth strategic analyses, brand teams can better understand the competitor positioning and message signalling in order to put in place their own effective brand strategy to defend their market.  Two recent examples of this were Gleevec (Novartis) in the CML market, which effectively limited Sprycel's (BMS) penetration while extending it's own in other indications and ImClone's Erbitux, which continued to grow it's revenues across several indications in the face of stiff competition from Amgen's Vectibix.

How companies position themselves and their portfolio is also important – Genentech's success with Herceptin, Rituxan and Avastin was no mean feat.  Each drug and new indication added not only new data, but also a clear message that monoclonal antibodies worked and were here to stay.  Contrast that with the experiences of the vaccine companies during the same period.

Messaging then, is not only important to brands already on the market but also to new products in development and company portfolios.  Getting the messages right is partly about leveraging your data, but also one of simplicity, especially if you have several drugs targeting the same tumour type, for example.  How should they be differentiated?  Is the messaging to customers clear and explicit?  It is a partly art and partly science; in oncology at least, it is important to understand the science and biology of the disease, the competitor set you are competing against and having the boldness of imagination to execute a strategy well.

At Icarus Consultants we advise companies on brand messaging, competitor messaging signals, how to work with key opinion leaders to maximise messaging and for companies with a portfolio of products, evolving a messaging strategy to take to avoid confusion between the brands.  After all, it's all about driving peak sales as fast as possible.

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Competitive update: PLK1 inhibitors for cancer

By on October 21, 2008

"You don't get to choose how you're going to die.  Or when.  You can only decide how you're going to live.  Now."

Joan Baez

The same approach could very well apply to Pharma and Biotechnology companies managing their pipelines and drug portfolios.  Everything is about what's happening right now and what can be done to move the development along to market, preferably as fast as possible.

Increasingly, the oncology market is becoming more and more complex with both chemotherapy and targeted therapies and different combinations, sequencing and mechanism of actions all playing their part.  As we learn more about the science and biology of each cancer type, so there is a proliferation of different inhibitors designed to target specific pathways.  A part of this ongoing series, today we look at PLK1 inhibitors.

According to an article in Nature, Polo-like kinase 1 (PLK1) is essential during mitosis and in the maintenance of genomic instability, as well as being overexpressed in some tumours (NSCLC, oropharyngeal, oesophogeal, melanoma, NHL), which may offer some prognostic potential.  It is yet unclear whether it is critical to tumourigenesis and hence useful as a therapeutic target, but cell cycle inhibitors are clearly worth a punt.

There are a number of PLK1 inhibitors in development.  These include  Scytonemin, a natural marine product that was originally being developed by SKB and now appears to be under the auspices of Merck KgA and EMD, ON01910 (Onconova Therapeutics), Wortmannin and BI 2536 (Boehringer Ingelheim). 

The most advanced programs at present are BI2536 and ON 01910, which are both in phase I development.  ON 01910 is being tested
in over 90 different human cancers, both as a single agent and with
other existing cancer drugs. Johns Hopkins Medicine and Mt. Sinai
Medical Center are conducting the first clinical trials of
ON01910 in patients with advanced and metastatic cancers. 

It is too soon to tell how effective these agents might be, but the class has a solid scientific rationale and some interesting data may therefore be available at the annual AACR meeting in 2009.

{Update – new data has been released on BI 2536 at the EORTC-NCI-AACR meeting at ECCO in Geneva this week – you can find out more here.}

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