pharmaceutical biotechnology marketing strategy consulting

Around the horn in Pharma

By MaverickNY on July 28, 2009

The last week or so has brought a variety of news in the Pharma world from good, bad to just plain old ugly.

BMS's purchase of Medarex is an interesting one; time will tell what happens with the existing licensing deals and whether the pipeline, including ipilimumab pans out or not. It certainly seems like shark infested waters at the moment, with an eat or be eaten strategy evolving in Pharma and Biotech.

The other week we posted a snapshort of denosumab, a RANK-L inhibitor being tested for the treatment of breast cancer patients with bone mestastases. Yesterday, Amgen announced a deal with GSK to promote the monoclonal antibody denosumab for postmenopausal osteoporosis (PMO) in Europe, Australia, New Zealand
and Mexico once the product is approved. Amgen will
commercialize the drug for PMO and oncology in North America and for all oncology indications in Europe and specified
markets. Seems like a good deal at first sight – Amgen get increased commercialisation in areas where they are weak and GSK get to add another source of revenue in regions where they are strong.

The news that Rigel's fostamatinib has failed to meet it's primary endpoint in a rheumatoid arthritis trial is disappointing. The company announced:

"The TASKi3 Phase 2b clinical trial in rheumatoid
arthritis (RA) patients who had failed to respond to at least one
biologic treatment, the group treated with R788 (fostamatinib disodium)
did not report significantly higher ACR 20, ACR 50, ACR 70 and DAS28
response rates than the placebo group at three months, and therefore,
the trial failed to meet its efficacy endpoints."

The results for the placebo group were unusually high and so this cancelled out any possible chance of showing a statistical difference with the fostamatinib group. Very unfortunate, but it happens. It is possible that there was a carryover effect from the biologics taken as first-line therapy if the washout period was too short or the patients were poorly monitored, but who knows? My guess is that we will see further trials in this area given the promising signs, perhaps a phase III trial or testing in other imunologic indications such as lupus and B-cell lymphomas. It's unlikely to be the last of R788, but it is a major commercial setback for Rigel and significantly delays fostamatinib's time to market.

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Meanwhile in Europe, the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMEA), has adopted a negative opinion for the use of Erbitux® (cetuximab) in combination with platinum-based chemotherapy for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing, advanced or metastatic non-small cell lung cancer (NSCLC). The submission was based on the recent FLEX trial reported at ASCO last month.

Merck Serono is apparently considering an appeal, claiming that Erbitux is the first and only new targeted compound in clinical development in more than 10 years that increases overall survival in a NSCLC patient population including all histologies. Clearly they would like the CHMP to reconsider its decision.

The EMEA stated their reasons for rejecting the application as thus:

"The CHMP was concerned that the benefits of adding Erbitux to standard platinum-based
chemotherapy were modest in terms of survival times, and that the medicine did not have a convincing effect on how long patients lived without their cancer getting worse. Severe side effects were seen in some lung cancer patients who received Erbitux – these were similar to the side effects seen in patients treated with Erbitux for other types of cancer.

At that point in time, the CHMP was of the opinion that the benefits of Erbitux in the treatment of non-small cell lung cancer did not outweigh its risks. Hence, the CHMP recommended that the change the marketing authorisation be refused."

If I recall from the FLEX data presented at ASCO last month, the overall survival was something like 11.3 vs. 10.1 months, a gain of about 1 month for a very significant cost, with not insignificant side effects, including a very nasty rash in some patients. Put in this context, the CHMP clearly had doubts about the efficacy:side effect:cost benefit. No doubt there will be a lot of noise around this decision over the next few weeks, but the decision is hardly surprising given the marginal improvement in lung cancer.

A wild month so far, for sure. I wonder what next week will bring?

3 Comments

Managing the news and information in Pharma

By MaverickNY on July 27, 2009

Someone raised an interesting question at a conference hosted by the Business Development Institute (#BDI) that I went to last week. They asked how anyone could possibly keep up with all the Pharma news and information, never mind follow thousands of people and interact via social media?

The answer is I don't.

Obviously, we all dip in and snack sometimes, but for me, most of the time I aggregate my information sources and use it for intelligence purposes on demand, ie search.

It's faster, more user-friendly and ultimately, faster.

It also means I'm a lot more efficient and less overwhelmed this way. Just in the same way people find information on this blog through Google searches, I can do the same thing with my personalised Pharma database. If a drug is in the news for not being approved by the European CHMP in indication X, then I can search for relevant information in the database, as appropriate. Certainly, I don't have time (or the inclination) to read lots of news articles on the topic every day or my brain would simply fry with information overload.

What is interesting is that once you have a database then there is the ability to see and detect strategic trends more clearly, rather than isolated individual items or snippets of data. The more data you have, the more useful those pictures of the trends in real time will be.

None of us can truly predict the future, but getting some sense of change before everyone else is often very useful business intelligence that can give you or your client a competitive advantage if you can grasp the broader landscape better and faster than anyone else.

These days, I see a big craving by senior Pharma executives for better intelligence and smarter strategic decision making based on data and deeper expertise, rather than a growing shopping list of uncoordinated tactics.

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Pharma shooting for the moon?

By MaverickNY on July 25, 2009

Given the recent glut of Pharma companies snapping up baby biotechs, you could well be wondering if some of them are betting the farm on the last roll of the dice or shooting for the moon like Apollo 11.

It's a crapshoot though, as R&D offers no guarantees as the growing list of drugs failing in Phase III development over the last 12 months shows.

Is desperation starting to set in or should we be thinking that Pharma is now moving to Las Vegas from New Jersey?

Think about it, BMS already had the licensing rights to Medarex's ipilimumab, so why bother buying the company? Perhaps they thought the stock would rise or that the pipeline of autoimmune or cancer drugs in phase I was so compelling?

The Daily Finance had a useful perspective:

"On paper, Medarex is not much of a company. It had revenue of $10
million in the March quarter and lost $47 million. The firm's
attraction is in its future. Bristol is paying a remarkably high price
for that future and there is no guarantee that the risk will pay off.
But big pharma does not have much of a future without new drug
pipelines, so it will pay for what it does not have."

Indeed, but one wonders how MedImmune and AstraZeneca are feeling right now, as they have the co-promotion option on Medarex's MEDI-545 and MEDI-546, which target the anti-IFNα Pathway in lupus and other autoimmune diseases.

Ilaris, another Medarex compound, was recently approved by the FDA for cryopyrin associated periodic syndromes including Muckle-Wells syndrome. It is codeveloped and promoted by Novartis. There are several others in a similar situation including Centocor/Ortho Biotech (Stelara and Simponi), GSK/Genmab (ofatumumab), which was recently filed for FDA approval in CLL and the drug also appears to have activity in rheumatoid arthritis. There are several other deals for earlier compounds with Merck, Genmab and Pharmathene.

So if the BMS purchase of Medarex goes through, I wonder what will happen with the existing co-promotion deals? Do BMS cancel them and take them on themselves, or honour the agreements and bank the revenues?

It should be an interesting to see what evolves from the deal one way or the other as we sit by the river watching the boats and debris float by.

Photo Source: Life

The challenge of social media in Pharma

By MaverickNY on July 24, 2009

Usually, I reserve Fridays for some random musings, humour, patient stories or some out of the box observations. The end of the week needs some lighter relief as we all wind down.

During yesterday's #BDI conference on social media and Pharma, which was attended by over 350 people, someone put up this cartoon:

You can find the original link here.

It got the biggest laugh of day and resonated with any of us
who have been Pharma marketers debating issues with the
medical-regulatory-legal review team on just about any item.

That said, fortunately, I have been lucky enough in my career to work with some great review committees, staffed with excellent professionals, who were willing to work above and beyond as a team to get things done.

But what's the difference between things going well or badly? My simple answer is attitude.

Ultimately, you have to be willing to be transparent up front about those old friends: what, why, how and when. If you are clear about your strategic goals and have a willingness to be open to new ideas about how the objectives can be achieved, you may well be surprised at how a collegiate team spirit and camaraderie can evolve rather than a constant barrage of aggressive argy bargy and snark.

I'll never forget the civility, harmony and hard work that got done by a phenomenal review team (they know who they are), the agencies and the brand team while we were launching under pressure to horrendous fast track timelines. You know what? Everything got done on time with some far better pieces for the broader team perspective and input than we started with. That's a win-win surely?

It's time to salute the unsung heroes – if you are having trouble with your review committee stop and look in the mirror first: ask yourself what image and mojo are you projecting? The difference between confrontation and collaboration can sometimes be subtle.

3 Comments

Oncology R&D can be a wild ride

By MaverickNY on July 22, 2009

Earlier this year, Pfizer cancelled two major phase III trials in breast cancer involving their multi-kinase inhibitor, Sutent (sunitinib). SUN 1107 evaluated
single-agent sunitinib versus single-agent capecitabine for the treatment of a
broad range of patients with advanced breast cancer after failure of standard
treatment. In addition, SUN 1094,
a Phase 3 study, evaluated Sutent plus paclitaxel versus
bevacizumab plus paclitaxel for the first line treatment of patients with
advanced breast cancer.

In both cases, the independent Data Monitoring Committee (DMC) found
that if treatment with sunitinib continued, it would be unable to meet the
primary endpoint of superior progression-free survival (PFS).
Imagine the surprise of many then, when a Reuters press release hit the wires today stating:

"Nexavar, when combined with standard chemotherapy Xeloda, helped keep tumours in check for longer than in a control group of patients receiving Xeloda only, the drugmakers said in a joint statement on Wednesday, citing data from a Phase II study."

Wow, what a wild ride R&D is sometimes.

What's common about these two drugs? Well, they both inhibit multiple kinases, including VEGF, and both were tested in combination with capecitabine in breast cancer. It should be noted however, that Sutent showed similar promise in phase II, only for the phase III interim analysis to be resoundingly negative. It will be interesting to see how Nexavar fares, because there are no guarantees that the large scale trials will support the earlier data, as Pfizer found.

It is possible that Bayer/Onyx chose a different population of women with breast cancer. My eye was drawn to a hidden snippet in the press release that said:

"The trial involved 229 women with breast tumours that had started spreading."

This is important to note because the mechanism of action for VEGF inhibitors is via anti-angiogenesis when the tumours are sizeable enough that they need to grow by increased blood vessels and vascularisation. In the recent adjuvant colorectal trials looking at FOLFOX plus Avastin, it was clear that while Avastin (another VEGF inhibitor) worked in metastatic disease, it has significantly less value in the earlier setting before the tumour begins to vascularise.

It is therefor possible that the women in the Bayer/Onyx trial may be at a slightly later stage of tumour growth than the women in the Pfizer trials, which would likely make a better target for a VEGF inhibitor. I wonder. We shall see if this hypothesis is correct as more details emerge over the next 18 months.

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Death spiral in Pharma?

By MaverickNY on July 22, 2009

While sipping an espresso, I reading Seth Godin's blog this morning and in it he was talking about the death spiral:

"You've probably seen it. The fish monger sees a decline in business, so they have less money to spend on upkeep and inventory, so they keep the fish a bit longer and don't clean up as often, so of course, business declines and then they have even less money… Eventually, you have an empty, smelly fish store that's out of business.

The doctor has fewer patients so he doesn't invest as much in training or staff and so some other patients choose to leave which means that there are even fewer patients…"

This is never a good trend to see but it happens. Some Pharma and Biotech companies are going through it too, with diminishing pipelines, reduced budgets, layoffs and a generate climate of back stabbing and fear. It ceases to become a nice place to work anymore for many.

Not all of them are going that route though. Some are innovating their way out of the depression and focusing on how to speed up their pipelines and bring new drugs to market.

However, you don't always have to do more for less, sometimes thinking and acting smarter is a good approach.

Which Pharma companies do you see as well positioned and which ones are heading for the death spiral?

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Update on therapies for malignant melanoma

By MaverickNY on July 21, 2009

Someone asked me whether it would be possible to have an update on new therapeutics in melanoma recently and I'm pleased to say there were some interesting data in this difficult to treat cancer at the recent ASCO meeting in Orlando.

Melanona is an immune type cancer but the long held theory that various immune type therapies such as vaccines would work effectively has not yielded significant results, mainly because stimulating the body's immune response to attack the cancer cells has not led to very durable results. The bedrock of treatment has therefore remained as a stark choice between DTIC, IL-2 or interferon therapy, all of which are severely limited by side effects.

At ASCO this year, a number of new approaches were tried and tested. These included aflibercept (VEGF-Trap), an anti-angiogenic VEGF inhibitor, intetumumab (CNTO-95), an alpha integrin, ADI-PEG 20 which affects cell metabolism and arginine depletion, sagilipone (ZK-EPO), which affects microtubulin function (similar to ixabepilone), CRO11-vcMMAE, another microtubulin compound and ipilimumab, BMS's CTLA-4 antibody. This variety of new therapeutics raises a number of interesting questions, including whether the targets are clinically relevant in melanoma and were patients selected appropriately for the studies.

This blog post will focus on the data for VEGF-Trap, intetumumab and ipilumumab.

The VEGF-Trap study (Abstract #9028) looked at patients with stage III or IV melanoma with no prior chemotherapy and no brain mets. VEGF-Trap is a fusion protein combining the Fc portion of human IgG1 with the principal extracellular ligand binding domains of human VEGFR1 and 2, leading to angiogenesis inhibition. The phase II study looked at response rate and 4 month PFS. Aflibercept was given 4mg/kg iv every 2 weeks for 8 weeks. The stated goal of the trial was to improve median PFS from 2.3 months to 4 months, which corresponds to a PFS rate from 30% to 50%.

41 patients were enrolled and the therapy was shown to be well tolerated with predictable class adverse events including hypertension, GI bleeding and proteinuria. 1 response was seen and a further 20 patients had stable disease. Early results suggest that a PFS of 6 months, if so the study endpoint will be met. This is one of many trials exploring anti-angiogenesis therapy in patients with melanoma, either as a single agent or in combination with chemotherapy.

The CNTO 95 study (abstract #9029) looked at a phase II study alone or in combination with dacarbazine in patients with stage IV melanoma with two different dosage arms per treatment. 129 patients were enrolled and the main adverse events seen were cytopenias related to DTIC and uveitis related to intetumumab.

Intetumumab alone (either dose) resulted in a PFS of 1.4 months, DTIC alone was 1.8 months, while intetumumab plus DTIC was 2.5 months. Overall survival was 9.8, 7.6, 14.0 and 10.9 months respectively. This study was complicated by the sample size not based on statistical power considerations so it is difficult to draw any conclusions between the four study arms and there is little rational for the combination. Although the target may be relevant, trials to date have shown little clinical activity.

The most interesting data was on ipiliumumab (abstract #9033), which looked at the effect of the agent on 18 and 24 month survival from 3 phase II trials dosed at 10mg/kg every 3 weeks (plus maintenance therapy Q12W from week 24 in appropriate patients) in advanced melanoma, where survival outcomes are usually poor. Ipilumumab is a fully humanised monoclonal antibody that targets T-lymphocyte antigen 4 (CTLA-4). The 3 studies summarised were CA184-008, CA184-022, CA184-007.

The results clearly showed that:

– 12 month survival rates were >47%
– 18 month survival rates were >34%
– 24 month survival rates were >30%

For previously treated patients, 24 month survival rates ranged from 24% to 33%.

Long term survivors included patients with progressive disease according to WHO criteria.

These results are promising but caution must be extended because a significant number of patients were lost to follow-up, which may reduce the reliability of the results. Ongoing biomarker studies are looking at predicting which patients are most likely to benefit from ipilumumab therapy.

What did we learn from these trials? Well, there is an urgent need to define optimal endpoints for melanoma clinical trials in terms of response rate, PFS, OS and survival at 12 months. It is interesting that over the past 10 years the majority of abstracts have hyped the results in this disease as 'promising' or 'clinically active' regimens and yet very little in the way of new therapies have actually been approved by the FDA. Based on these data, I suspect it will still be a little while before we see some solid phase III data in malignant melanoma.

Social media monitoring and Pharma

By MaverickNY on July 17, 2009

For all those companies wondering whether to dip their toes in the water with social media or not, this fun presentation provides some interesting stats and snippets that illustrate some useful pointers.

Well, it is summer Friday, right?

What the F**K is Social Media: One Year Later

View more documents from Marta Kagan.

Compliance, brown bag syndrome and pharma marketing

By MaverickNY on July 16, 2009

My Mum's unexpected passing last week brought some interesting findings and revelations. For all the fancy, shiny new tools and sophisticated strategies, the one thing that often gets forgotten is that at the end of the day there are not only doctors writing scripts but patients taking drugs for various ailments. How often do patients give up treatments because the grade 1 or 2 side effects are more inconvenient than the illness they are purporting to protect against? How many elderly patients forget or become confused about why they are taking such prescriptions, especially if they have a variety of different things for different diseases? No wonder the brown bag syndrome evolves.

My mother was one of those patients.

Last Christmas, she confided in me that she couldn't remember anymore which pills she should be taking, what they were for beyond her inhalers for COPD, which she took religiously every morning with a cuppa. The rest she was dubious about and rather scathing. Guess what, seeing a variety of different doctors across two surgeries
didn't help either because none of them took a look at the bigger
picture. It's just another patient to see in the 10 min appointment
slot with complaints that could be caused by almost anything.

All she knew is that she had severe muscle aches and pains, constipation and nausea. She wasn't sure which prescriptions were affecting her negatively, nor could she remember when the symptoms started. Her practical view was to stop taking them all except the inhalers and if the original problems came back she would toodle off to the GP and sort it out afresh.

Ummmm. No amount of gentle persuading on my part would convince her otherwise, even though she was a former nurse and more aware and articulate about medical matters than most. She felt perfectly fine without them all and was at her most cheerful in years free of all the drug side effects that had plagued her.

Unfortunately, that strategy ultimately proved to be her downfall.

While sorting things out, my brother and I decided to return the unused inhalers to the doctors practice for appropriate disposal. Except that it wasn't one or two of them. There was a whole hamper box full. And then another hamper full of brown bottles. A medicine cabinet was chock full of other stuff. We looked warily at them. Half of them I had to look up myself later. Pills for hypertension, raised blood pressure, hypercholesterolemia, diuretics, congestive heart failure etc etc.

On closer inspection, the furosemide seemed to be the most likely culprit for the side effects my Mum complained about; nausea, dry mouth, muscle weakness, constipation, blurred vision and headaches.

Sometimes we need to have a greater understanding of the realities of patients. If you go to the doctor feeling unwell and walk out with a prescription, the general expectation is that you want to feel better and have those symptoms resolved, not gain a bunch of inconvenient side effects that make your daily life utterly miserable.

What we need is a real strategic understanding of compliance, it's management, drug interactions and a broader picture of how patients with multiple common problems e.g. congestive heart failure, high blood pressure, hypercholesterolaemia etc could be better managed. Pharma is renowned for giving out those naff little pill boxes for the week, but these problems go much deeper than that, a broader, more strategic approach to disease management is really needed. Such a coordinated approach to health and disease will likely lead to better patient outcomes, reduced costs and happier people all around.

Otherwise, in the end, the brown bag syndrome means that patients could well end up throwing out the baby with the bath water and that does no one any good.

1 Comment

When a month just isn't enough

By MaverickNY on July 8, 2009

Sadly my mother passed away while I was in transit back to the UK after a 2 year battle with heart disease. In the end, she went peacefully in her sleep after a sudden clot on Saturday, something we are all very thankful for. It is better to go with grace and dignity than be in pain for days and weeks or months on end. She was in very good hands and couldn't have been in better care since she was on my sister in law's critical cardiac ward and they would have done they very best to make her as comfortable as possible. My mum's worst fear was always becoming so incapacitated that she was rendered helpless, after a previous heart attack reduced her physical abilities somewhat. She was never really the same after that, but was able to function as best as she could while maintaining her independence.

My eldest niece went to visit her Grandma in hospital on Monday and was shocked at how frail and thin she looked. The youngest chose not to go, preferring to remember her as she was. I respect both of their decisions; I didn't have either choice as I was regretably late back again and she passed away in peace while I was in transit. At times like these, I am just grateful my mother didn't suffer and to be scooped up by my brother's family so my feet remain on the ground with a relatively clear head. We come from a family, my brother and I, that is relatively undemonstrative and unemotional. Excess anything would be frowned upon, no matter the circumstances.

This led to an interesting and informative discussion last night with my sister in law, a devoted and dedicated cardiac nurse. She does a phenomenal job; I don't know how she finds the strength to deal with death and dying patients every week. We talked about the differences in the US and UK healthcare systems and how NICE impacts the access to new treatments. We both agreed that a single unified national decision and formulary is much fairer than the post code lottery that exists at the moment, where someone in Cardiff can get access to newer, better, treatments than someone in say, Hull simply because their primary care trust has a different formulary. The inequities of that system seem unfair at worse and silly at best; the UK is one country not always united in consensus. Different healthcare trusts will take the NICE decision and implement them differently depending on their budget decisions and constraints.

How does this affect the US? Well, firstly this sort of healtheconomic analysis is inevitably coming across the pond, so manufacturers had better get used to the idea that different cancer drugs may be restricted in the future. After all, my mother's illness and peaceful passing made me realise that let's say she had lung cancer instead of congestive heart failure. Would an extra few weeks or a month had made any difference? No. It only prolongs the pain and agony for all around if the diagnosis is clear.

There is no cure for advanced cancer, data is measured in increments of survival, usually by a matter or a few weeks or months. But at what cost? Is spending $50,000 for an extra month of life really the best we can do?

It is my hope for the future that as we learn more about the science and biology of disease, we will develop better, more targeted combinations that shut off the critical aberrant activity that leads to cancer, thereby leading to significantly longer progression times than we have now. After all, the success of Gleevec has lead to patients life expectations improving from 3-4 years to a much more robust 10 years plus. That's a huge improvement, not a couple of weeks. We must not forget, however, that personal responsibility to one's health and fitness should play a much larger part than it does in many cases.

How should we help further better patient education and, more importantly, action for change?

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Commentary on Pharma & Biotech Oncology / Hematology New Product Development

Posts tagged ‘pharmaceutical biotechnology marketing strategy consulting’

Around the horn in Pharma

The challenge of social media in Pharma