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Tag Archives: Personalized Medicine

Biotech Trends in 2011: Comparative Effectiveness and Personalized Medicine

When this blog was launched in 2009, comparative effectiveness and personalized medicine were fairly new features in the North American landscape. Our initial argument that they were related topics — determining which treatment is best depends on which patient is being treated — was soon bolstered by the comparative effectiveness provisions in the U.S. stimulus bill and new personalized medicine data via the FDA.

The proposition has since become common knowledge, culminating in statements by Francis Collins and at BIO 2010 and discussed in the New York Times. Personalized medicine is now a key strategy for 12-50% of current drug pipelines, according to a recent Tufts study, and is a significant driver for DNA sequencing technology companies. If anything, the pendulum has swung a bit too far towards ‘hype,’ and as Matthew Herper reminds us, there are still non-personalized potential blockbusters in the pipeline.

The two concepts have even merged in a motto:

“the right drug to the right patient at the right time,”

which I still don’t like as much as “Personalized Effectiveness” (my neologized mash-up), but seems to be sticking. We’re just going to call it “Personalized Medicine” for now and will continue to follow major developments. You can too, on this page.

This post is the second in a series briefly outlining the biotech industry trends we’ve been following on the blog and noting some recent developments, plus directions for 2011.

Biotech Trends Update — Personalized Medicine: Duncan’s Personalized Health Manifesto is Primarily Preventative

Image from flickr user Steve Rhodes. Some rights reserved.Journalist David Ewing Duncan’sPersonalized Health Manifesto” was published this week by the Ewing Marion Kauffman Foundation. The most interesting thing about the manifesto* is that it assumes that the technical hurdles to generating and understading a full set of personalized health data have been overcome, and focuses on how that information can be deployed most effectively.  Duncan says that “a widening gap exists in integrating and implementing this promising new epoch of personalized health.” There are two main themes in the manifesto: integration and prevention.

Integration comes from Duncan’s view about how the flood of personalized data should be analyzed by researchers and physicians:

“A balance between specialization and integration needs to be restored,with an emphasis on the whole human organism as much as its parts…”

Prevention is, for Duncan, the natural best use of personalized data:

“Shifting to a health care system based as much on healthy wellness as illness is achievable…”

Both are laudable long-term goals, but I am not convinced of the need for urgent action on either point.

Specialization is (as Duncan acknowledges) what has enabled us to discover personalized markers and to analyze them on a allele-by-allele basis. We are a long way from making meaningful predictions about systemic effects on complex traits based on the available information. A shift too early away from specialization could prevent us from ever developing the underlying science sufficiently to make reliable predictions.

And shifting to a preventative healthcare system is not a goal I view as being unique to personalized medicine. As genomic testing becomes widely available, and patients begin to process their data, complex traits continue to present a challenge for them and their doctors — now that I know I have an increased risk of heart disease, I should shift my diet and increase my exercise. But these are things preventative healthcare advocates have been recommending for decades; and there is no evidence that I’ve seen that suggests the genetic information about increased risk is more motivational than family history, or peer behaviour, or any other non-personalized factor.

Bottom line: I’m no expert on manifestos, but while there’s nothing in this one I feel strongly opposed to, it doesn’t move me to action either. Read the whole thing (it’s not very long) and form your own (personalized) view.

* Other than his decision to call it a manifesto.
Image from flickr user  Steve RhodesSome rights reserved.

Friday Science Review: June 11, 2010

Catch up on these genetics stories between World Cup soccer games…

Genetic Links to Autism: Phase 2 results of the Autism Genome Project mapping the genetics of autism is reported this week in Nature. Researchers used the latest microarray technology to identify a trend that autism patients carry more insertion and deletion mutations affecting their genes.  Several genes were also labelled as potential autism risk factor genes and could be very useful for diagnostic purposes. “Guided by these massive genomic data sets, we can start to see the forest through the trees, offering answers and hope for families with autism,” says Dr. Stephen Scherer at The Hospital for Sick Children who led the consortium along with Dr. Peter Szatmari at McMaster University.  You can read about it here or sit back and watch this interview with Dr. Scherer.

Note that this study contrasts the controversial 1998 Lancet paper by Dr. Andrew Wakefield who suggested a strong link between the MMR (measles, mumps, rubella) vaccine and autism, leading to many parents withdrawing their children from the effective vaccine program.  The Lancet journal retracted the paper in February 2010.

Nature versus Nurture: Epigenetics is at the crossroads of genetics and environmental factors – the science of how the environment affects gene regulation at the molecular level that leads to a disease pathway.  “With the concepts of epigenetics we can start to understand how a disease risk factor is alternately switched on and off,” Dr. Arturas Petronis at the Centre for Addiction and Mental Health (CAMH) explains in this new perspective article published in Nature.

Epigenetics provides a new theoretical framework that addresses the vast complexities, irregularities, and controversies detected in common human diseases. For instance, epigenetics explains why one identical twin may be affected with cancer or diabetes although the co-twin is perfectly healthy. “In a case like this, the inherited genes are identical and the environment is similar. But one twin’s risk factor has been triggered, while the other twin’s risk factor has not been triggered,” says Dr. Petronis.

For personalized medicine to move forward, it is imperative to understand the mechanism of how environmental cues lead to genetic changes and how this process can be controlled.

BIO Panel on Comparative Effectiveness Research Notes “Silver Lining” of Personalized Medicine

Speakers Daniel Todd, from EMD Serono, and Steve LaPierre, from Boston Scientific, were led by Foley Hoag lawyer Jayson Slotnik in a discussion of the final CER legislation and predictions about implementation. The overall tone was skeptical — the panel noted the potential for CER data to ultimately contribute to CMS coverage decisions, and worried about the cost of prospective randomized trials and about potential impacts on the FDA approval process.

They were, however, optimistic about the role of personalized medicine in the CER implementation. Steve LaPierre expects it to be helpful, and Daniel Todd advocates using the reference to molecular and genetic subtypes in the legislation to push for personalized analysis if a product is selected for a CER study. He calls personalized medicine a silver lining.

The panel also noted positive structural aspects, including helpful governance provisions in the CER legislation. Specifically, they were impressed with the public reporting and audit provisions and the availability of comment periods to allow private sector input.

In looking at how CER will shake out, the panel expected progressive adaptation of the program over the next 3-7 years.

Daniel Todd emphasized the importance of picking a first recommendation to establish credibility. The controversy this year about breast cancer screening recommendations shows the loss of credibility that can come from a debatable result, so they expect CER to ramp up over time.

He also predicted that dissemination of CER results through social media may drive bottom-up adoption of findings, and that defensive medicine may also contribute to adoption.

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Biotech Trends at BIO 2010

As I’m preparing for the BIO conference in Chicago next week, I’m excited to see that several of the biotech trends we’ve been following on the blog are showing up as conference sessions.

  • Interested in “A New Kind of Non-Dilutive Financing and Fundraising: Partnering With Not-for-Profits”? Get an early start at our trends page on Commercialization by non-profit foundations!
  • Does “Comparative Effectiveness Research and the Government Role” or “Transforming Health Care Through Personalized Medicine” catch your eye? Check out the stories we’ve highlighted on Comparative Effectiveness and Personalized Medicine!
  • Of course, with the new regulatory pathway created by Health Reform legislation in the U.S., Follow-on Biologics (aka Biosimilars) are all the rage at BIO this year.
  • and the whole thing kicks off with Lilly’s General Counsel speaking on “Leveraging IP to Spur Global Biotechnology Innovation, Investment and Jobs” – emphsizing the link between IP Constituencies and Global Innovation that we have been following for some time.

Stay tuned for news from these and other sessions as we hit the conference next week!

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Comparative Effectiveness and Personalized Medicine are “Part of the Same Question” Collins Confirms

In a very informative Kaiser Health News interview (via GenomeWeb), Francis Collins says that

“personalized medicine strategy and CER strategy are part of the same question. … There will often be more than one therapeutic intervention, so you have to compare them. But you also want to know what’s different about the individual that might have an influence on that answer.”

Couldn’t have said it better myself.

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Biotech Trends Update: ChemGenex and the Importance of Companion Diagnostic Development

Australian cancer drug developer ChemGenex was scolded by the FDA’s oncology panel for “fairly sloppy drug development.” The company’s mistake? It presented its leukemia drug, designed for patients with a particular genetic mutation, without a validated diagnostic test for the mutation.

ChemGenex says it’s a matter of months, not years, before it gets a test validated for Omapro; but the company’s stock took a beating on news of the FDA’s decision, losing 37% of its value on record volume.

Many companies, unwilling to risk such delays, have already shifted to a joint Dx/Rx co-development model.  Until it was bought by Qiagen, DxS was making an entire business out of developing companion diagnostics in partnership with pharmaceutical companies.  Similarly, Dako Denmark is developing companion diagnostics for AstraZeneca’s oncology pipeline.

The FDA’s message here is pretty clear: the quality of companion diagnostics matters.  One day, when everyone’s genome is fully sequenced, many personalized products won’t even need diagnostics.  Until that day, when you’re developing a personalized product, don’t give the diagnostic short shrift.

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Biotech Trends Update: A Personalized Critique of Comparative Effectiveness Misses the Mark

As the U.S. and Canada move to invest and rely more on comparative effectiveness research (CER), lack of personalization has been the loudest and most frequent objection.  That is why we have been following the interaction between comparative effectiveness and personalized medicine as a key industry trend.

Yesterday, an opinion piece in the WSJ by Leonard Zwelling, a professor of medicine and pharmacology at M.D. Anderson, came out strongly in opposition to CER.  Zwelling takes a number of swipes at CER, but most of the time he is focused on the inability of CER to personalize treatment — for a patient’s genes, age or preferences — in identifying a “best” treatment.  For example:

“If decisions based on CER inhibit the progress of personalized medicine—or in any way interfere with a meaningful interaction between doctor and patient to individually tailor the most appropriate therapy—no one is helped.”

Zwelling’s argument sets up more than a few straw men — that CER uses only retrospective data, that it will ignore qualify of life, and that treatment options change too quickly for CER to provide timely advice — but the main problem is that he assumes that CER and personalization are incompatible.

As this blog has noted on many occasions, CER is at its best when coupled with personalized medicine.  This post about KRAS genotyping is a great example.  This point is not lost on the Obama administration, which is aware of and sensitive to the need to account for personalized treatment in CER.  Zwelling himself opens with a quote from relevant legislation that says the current CER funding is supposed to find out

“what works best for which patient under what circumstances.”

The clause “for which patient” is a built-in acknowledgement of the importance of personalized approaches to CER. 

My bottom line: Both comparative effectiveness and personalized medicine are critical to medically effective and financially sustainable medical care and drug development.

Friday Science Review: February 26, 2010

A few medical research applications this week…

Personalized Medicine – for Lung Cancer: To develop a personalized medicine approach to treating non-small cell lung cancer (NSCLC), researchers generated a xenograft model where they implant human tumour tissue into the renal capsule of a host mouse.  As the tumour establishes itself, the mouse then becomes the platform for testing various chemotherapy regimes (cisplatin+vinorelbine; cisplatin+docetaxel; cisplatin+gemcitabine) to determine which one or combination therapy is the most effective against each of the different tumours.  They compared the results of the treatments in mice to retrospective patient outcomes and found significant correlation to consider the xenograft model a success.  Although it takes about 6-8 weeks for the results, they believe that it is quick enough to gain an insightful preliminary assessment of the potential therapeutic outcome.  Dr. Yuzhuo Wang led his team at the BC Cancer Agency and reports their work in Clinical Cancer Research.

HIV-1 Molecular Manipulations: HIV-1 infected patients exhibit a loss of CD4+ T cells, which are essential players in the defense against viral infections.  A new study reveals how the HIV-1 protein, Vpr, activates the Natural Killer (NK) cells by inducing the expression of stress-related proteins at the cell surface of CD4+ T cells.  The NK cells recognize the stress signals on CD4+ T cells and attacks and destroy these cells, leaving the patient with severely reduced CD4+ T cells.  Researchers also noticed that the continuous activation of NK cells eventually desensitizes them and they eventually lose their ability to perform their normal duties in attacking infected cells.  The molecular mechanisms of Vpr discovered in this study should help in future research leading to new therapeutic strategies.  Dr. Éric Cohen and his team at the Institut de recherches cliniques de Montréal describe their research in last week’s issue of Blood.

Protecting Your Heart: The blood pressure cuff you see in every doctor’s office can be used to limit the severity of heart attacks by triggering a molecular response in the body that protects the heart during an attack.  It is called remote ischemic preconditioning where the blood pressure cuff is used to intermittently cut off blood flow to the arm during an attack.  This triggers an innate response warning message throughout the body to release molecules to protect itself from the lack of blood flow.  In this particular study, the size of the heart attacks were reduced by 30-50% compared to control groups.  It is one of the most effective treatments and is relatively simple to administer.  Dr. Andrew Redington at The Hospital for Sick Children led the international study and is published in the The Lancet.

Biotech Trends Update: Costs Savings from Personalized Medicine Sought by PBMs, Employers, Pharma Face Legal and Privacy Hurdles

When AstraZeneca announced a companion diagnostics collaboration recently, their head of oncology development said the goal was to get “the right treatment, to the right patient, the first time,” a nice turn of phrase* that is becoming a chorus in the healthcare industry.

This week, giant PBM Medco purchased DNA Direct, saying “[o]ur whole thing at Medco is to get people on the right drug the first time.”  DNA Direct uses its research on 2,000 available tests to help physicians, health insurance companies and patients understand how to use personalized medicine.  This is a good move — we said last month that education is key to expanding the personalized medicine market

AstraZeneca, Medco and other providers, employers and insurers would all like to use information on individuals’ health risks in order to reduce their costs, and as the Wall Street Journal reports, they are willing to provide incentives to their employees to mitigate those risks.  However, some of these efforts conflict with barriers put in place by the Genetic Information Nondiscrimination Act (GINA), which prohibits the intentional acquisition of genetic information about applicants and employees, and imposes strict confidentiality requirements on data that is acquired. (H/T @genomicslawyer)

In addition to legal barriers (some still being erected), AMA and other advocacy groups have also reportedly expressed concern.  I agree there is risk inherent in putting the decision of what the “right drug” is in the hands of manufacturers or payors, neither of whom is neutral in the outcome.  Medco, in particular, does not seem a neutral player here (at least based on their approach to Plavix and Effient, though I invite comments if I’m misinterpreting that study).

Still, a solution is required.  As I have been saying for over a year, personalized approaches to treatment have the potential to benefit all participants in the healthcare system, as the KRAS-Erbitux story has proven.  As Procter & Gamble said when investing in Navigenics’ funding round this week, “Personalized genetic testing can have significant meaning in helping consumers focused on prevention and wellness live better, healthier lives.” 

My bottom line:  A large part of the problem here is the low level of trust from the public, which even limits governments’ ability to act.  That’s particularly unfortunate, because government is the closest thing we have to a neutral funding source for comparative effectiveness and personalized medicine research (despite also being a payor). This is a problem much bigger than just personalized medicine, but until trust is restored, valuable cost savings and health benefits will go unrealized.

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* A concept I’ve been trying to call “personalized effectiveness” — tell your friends.

Biotech Trends Update — Personalized Medicine: The Case for Diagnostics Focuses on Cost and Effectiveness

A report in FierceBiotech today distilled the views of three life science VCs on trends to watch in 2010.  Along with other worthwhile observations (and I’d encourage you to read the whole thing) was this bullet pointing out the value of personalized medicine in addressing comparative effectiveness concerns:

“Interest in molecular diagnostics is heating up. It’s one of the most attractive areas because physicians are increasingly demanding test that can tell them which treatments have the best chance of working before expensive medicines are issued. And diagnostics fit well with the healthcare reform efforts. Bloch adds that any technology that improves the efficacy of how care is delivered will be attractive to investors.”

The business case is eminently obvious.  Earlier this week AstraZeneca announced a collaboration with Dako Denmark A/S that will see Dako developing companion diagnostics for products in AstraZeneca’s oncology pipeline.  Key quotes from the announcement highlight the companies’ focus on “health care costs” and “reimbursable products”:

“Targeted treatment with personalized medicine is the future, and … is also a significant contributive factor in cutting health care costs” (Dako CEO)

“This agreement … will enable us to develop novel, reimbursable products that … predict which patients are most likely to respond to treatment, ensuring that we are giving the right treatment, to the right patient, the first time.” (AZ Head of Oncology Development)

The economic case for personalized medicine was one of this blog’s top biotech trends in 2009 and looks to continue at a strong pace through 2010.  To reach its full potential, though, the industry will have to convince policy makers and clinicians that personalized medicine can live up to its promise.

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Biotech Trends Update — Personalized Medicine: A Big Market, If We Can Just Figure Out How to Get People to Use It

Late last year, a PwC report made the rounds with a big headline number — $232 billion — as the size of the personalized medicine market.  FierceBiotech called it a “tipping point,” for personalized medicine.  George Church called us “the first genomic generation” in Newsweek, and Francis Collins’ new book “offers practical advice on how to utilize these discoveries for you and your family’s current and future health and well-being” (at least according to its publisher).

And this isn’t just idle speculation, it’s being reflected in real investments. Cancer Research UK, the Medical Research Council, University College London, and the Wellcome Trust are developing a £500 million new home for their partnership, called the UK Centre for Medical Research and Innovation (UKCMRI), where “genomic technologies will play a key role in the array of research its partners plan to pursue there.”

However, there are real challenges to realizing the 11% annual growth rate PwC predicts.

  1. Health care providers need to learn a whole new language and a whole new set of tools and approaches.  A new year-long project at Valparaiso University aims to meet the new criteria of the nursing curriculum essentials in genetics that are set by the American Association of Colleges of Nursing (AACN), but this is just the tip of the iceberg. (h/t @mikesgene)
  2. Even when health care providers are educated, it doesn’t mean that the market will grow.  For example, there is high awareness (80-90%) of a new genetic test designed to reveal a breast cancer patient’s sensitivity to tamoxifen.  However, according to research from Duke University Medical Center, “[a] greater awareness of the emerging data for this new test corresponded to less likelihood of ordering the test and lower likelihood of changing practice based on test results.” (emphasis added) (h/t @DukeIGSP)
  3. The Genetic Information Nondiscrimiation Act loopholes are still intimidating.  GINA does not expressly cover long-term care and other types of insurance and is focused to some extent on prohibitions on requiring genetic tests (which will be moot when everyone’s full genome is sequenced).  Some efforts to remedy or mitigate GINA loopholes are underway, including:

    However, many patients (and, anecdotally, everyone in the insurance industry) are vociferously refusing genetic testing and sequencing.

  4. FierceBiotech notes that the PwC report itself identifies another caveat: “Big Pharma will have to bury its blockbuster business model in favor of a more “collaborative model.”

My bottom line:  Those who are counting on seeing the growth predicted by PwC will have to make an unprecedented investment in educational and regulatory changes to sychronize with the unquestionably giant strides in product innovation that are occuring daily.

For more on personalized medicine, check out the Biotech Trends in 2010 page.

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Top Four Biotech Trends of 2009

These may not all be consensus picks (and don’t miss the IVB’s year-end deal-centric fun) but I’m sticking with these four trends as the ones that have really shaped the year that was:

  1. Follow-on Biologics. Call them what you want (we like “biosimilars”, but we’re internationalist like that), there’s no denying that biosimilars were a major force in the industry and in politics this year.  Some in the press are calling the 12-year exclusivity period a done deal, but I say don’t count your chickens ’til the fat lady sings.
  2. Comparative Effectiveness and Personalized Medicine (not a two-fer, a trend of convergence). How much of comparative effectiveness variation will turn out to be an artifact of genetic sub-populations (each with binary responses to the drugs in question)?  Nobody knows, but as money pours into both fields, the truth will set us (and drug pricing) free.
  3. Shifting IP Constituencies. What do you get when you cross generics-hungry pharma companies with innovation-hungry Asian countries?  A whole new world of collaboration that will ultimately change the face of TRIPS and pharma R&D.
  4. Electronic Medical Records. Not really biotech (if you want to be picky), but it will have a massive impact on the way physicians, patients and payors interact with each other and with drug companies over the coming years.  Plus, with billions allocated to electronic medical records in Canada and the U.S., the pace of innovation and implementation really took off.

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Preventing Bias in Comparative Effectiveness Research

Comparative effectiveness research has the potential to avoid wasteful spending and create net benefits for patients if approached properly, but it’s expensive.  Many of the large-scale comparative effectiveness studies include industry funding, and benefits managers are no strangers to the game, but giving those partners a say in study design risks introducing bias. 

An interesting example comes from today’s report that pharmacy benefits giant Medco is planning a head-to-head study of nearly-off-patent Plavix versus brand-new Effient.  The interesting tweak here is that the study will exclude people with a genetic variant (of the CYP2C19 polymorphism) who can’t metabolize Plavix.

This seems like another great example of personalized medicine informing a comparative effectiveness decision.  But, as the In Vivo Blog pointed out in an August post about Plavix and Effient, the effect of the CYP2C19 polymorphism on Effient efficacy is unknown.

So the PBM, with cost-saving incentives, is setting up a study to make payment decisions in which the efficacy of the (cheap) generic is boosted by excluding patients with the CYP2C19 polymorphism, with the validity of the comparison based on the untested assumption that there is no systematic bias to the branded product’s efficacy in the excluded population.  Am I missing something here?

The moral of the story: fund comparative effectiveness research through neutral parties and keep a careful eye on genetic and phenotypic subgroups to maximize the value of these important studies.

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In Praise of Universal Coverage From a Genomics Perspective

This could be the last chance in the U.S. to make good decisions about health care.  Why? Because now, before genome sequencing is fast and cheap and universal, we are in a political position rarely experienced outside philosophy books: we are still in the “original position,” behind the “veil of ignorance.”  I’ll try to make this quick, so forgive my mangling of Rawls.

Making “Just” Decisions

Rawls says that in order to make “just” decisions, you need decision-makers who do not know their “fortune in the distribution of natural assets and abilities, [their] intelligence, strength and the like.” 

That’s very close to the situation we have now — politicians don’t know much (beyond family history) about their own genomes or about their constituents’.  It has led to some good decisions, like the passage of the Genetic Information Nondiscrimination Act, but it’s temporary. 

Lifting the Veil with Genomics

Soon, genome sequencing will be fast and cheap and universal and there will be no more veil of ignorance.  Absent that, “[m]ore powerful parties rely on knowledge of their ‘threat advantage’ to extract favorable terms from those in less advantaged positions.”

For Example

A good example comes from the UK this week (via @jensmccabe).  According to The Times, new guidance from the General Medical Council (GMC) says that when a patient is found to have certain genetic diseases, doctors will be obliged to inform relatives about potential risks to their health.  As with any public health notification, there is a need to balance privacy concerns against public health concerns, but when you’ve struck that balance, should you have to re-visit the decision because of coverage gaps? 

Universal Coverage is the Cure

Universal coverage makes a just decision possible.  People with genetic diseases can be informed of their risk because they won’t lose their insurance or be forced into a high-risk high-cost pool as a result.  If there is no adverse coverage consequence — not availability and not cost — then there is very little “threat advantage” and people remain (functionally) genomic equals when deciding on healthcare policy.

My bottom line: If the U.S. moves into the genomic era without universal coverage, it will exacerbate existing inequalities and create new ones we haven’t even imagined.

First time here? Welcome! The Trends in 2009 page is a great place to start. Also check out the Twitter stream @crossborderbio.

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Trends Update — Personalized Medicine: Montreal CRO ethica Licenses Artificial Intelligence Data Analysis Product for Stratification

B&W_DNA_sequenceethica Clinical Research acquired a worldwide exclusive license to Matrix Pharma’s  artificial intelligence (AI) data analysis platform.  Neither the form of consideration nor payment structure (up-front vs royalty etc.) was disclosed, but the deal is “valued at CAD1.25 Million.”  The companies say the AI can:

“extract interdependencies, correlations, and predictive models from complex data sets that conventional statistical tools are unable to detect.”

In other words, it’s an approach designed for stratification of clinical trial data to identify personalized subgroups for whom a drug may be particularly effective.

ethica says the product, which will be marketed as “eidyia™” (pronounced “idea”)

“has already yielded successful results in a series of clinical applications such as identifying biomarkers, optimizing the predictive power of biomarkers, identifying responder/non-responder indices, genotype-phenotype linkages, elaborating models for early diagnosis, and for classifying participants in Phase II clinical trials for the optimization of Phase III clinical trials.”

I don’t know if  “eidyia” is (or isn’t) the best platform for these tasks; but I am convinced that in many cases, the ability to stratify patient populations will be key to demonstrating the effectiveness of new drugs and winning approval and reimbursement.

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Trends Update — Personalized Medicine: Merck Strategy Head Skeptical

As I’ve been following personalized medicine on this blog, I have become almost convinced that recent advances in genomics technology put us at the brink of an era of personalized diagnosis and treatment.  Not everyone agrees.

Chris Morrison, reporting from the Pharmaceutical Strategic Alliances meeting, quotes Merv Turner (the head of strategy at Merck) as follows:

“‘You can reduce cardiovascular mortality by 50%’ by using statins, he said. ‘That means 50% cardiovascular disease is unsatisfied. Is that 50 different small diseases or one large one? Personalized medicine is like soccer in the US: it’s the game of the future and always will be.'” (emphasis added)

Maybe I’m missing some context here, but I think the answer to Turner’s question (50 different small diseases or one large one) is “we don’t know.”  It is an interesting question and I think it would be prudent to find out the answer.  Preferably before we try treating the 48th disease with a drug developed for the 35th.

Trends Update — Comparative Effectiveness and Personalized Medicine: Is Canada Ahead of the U.S. In the Use of HER2 Testing for Personalized Breast Cancer Treatment?

B&W_DNA_sequenceFor the 20%-30% of breast cancer patients with tumors that overexpress HER2, treatment with Herceptin (an antibody drug from GenetechRoche) is highly effective.  That’s why this article in the journal Cancer is so shocking.  The authors gathered data from a variety of published sources and estimate that:

“up to 66% of eligible patients had no documentation of testing in claims records, up to 20% of patients receiving trastuzumab were not tested or had no documentation of a positive test, and 20% of HER2 results may be incorrect.”

I asked a friend, who is a genetic counsellor in Toronto, if she thought the gaps here were as bad.  She said no, and that she would be extremely surprised not to see a HER2 result in a patient’s file.

Of course it’s not valid to draw conclusions about national health care from a comparison of the Cancer study to my anecdote.  Among other reasons, the authors admit their data is flawed and dated, and my friend works at one of Canada’s top teaching hospitals.  Nevertheless, the possibility that many U.S. patients could be falling through the cracks is extremely disturbing.

If clinicians can’t adopt and maintain near-universal use of a personalized medicine approach like HER2-Herceptin with recognized and measurable benefits, the future of pharmacogenomics is in some big trouble and we will never generate truly useful comparative effectiveness data.

H/T @FiercePharma.

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Trends Update — Comparative Effectiveness: Where Data Shows No Difference, Tie Should Go To the Patient

A post by Scott Hensley on the NPR Health Blog yesterday has some good food for thought in the comparative effectiveness debate: what to do when comparative effectiveness studies show no statistically significant difference between treatments.

The post notes that insurance coverage will be a factor in these decisions, but that:

“in the end, it might be you and your gut feeling.”

In one of this blog’s prior posts, I noted that it will be hard to distinguish between treatments that show different effectiveness because of personal differences between patients and those that would show different results even if the patients were identical. 

Hensley’s post illustrates that no matter how much data we gather, there will be gray areas where doctors and patients have to make subjective calls.  I hope payors will be extremely cautious about second-guessing these decisions.  Tie goes to the patient.

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Q3 Is Looking Up for Biotech: Emdeon, Cumberland, Domain, LOM BioQuest, OETF

light at the end of the tunnel smallThis week has seen a continued upswing for biotech and other health industry companies in the U.S. (with two IPOs) and in Canada (with great VC news and the pending appointment of an administrator for the Ontario Emerging Technologies Fund):

In the U.S.

Here in Canada

In the pipeline

With personalized medicine seeing increasing validation as a clinical strategy, genomics technology will be key.  News this week from Helicos Biosciences that an individual’s complete genome was sequenced in one month for just $50k in consumables is an important marker (har) on the road to regular full-genome scans as part of our medical toolkit.

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Trends Update — “Personalized Effectiveness”: Amgen Gets Prospective Data to Back KRAS-Vectibix Plan

B&W_DNA_sequenceA few weeks ago, when the FDA changed the labeling on anti-EGFR drugs, Amgen was pretty enthusiastic about “avoiding unnecessary treatments in patients [with a specific genetic marker] who are unlikely to benefit” from Vectibix.  Avoiding these patients leaves more reimbursement available for patients who would benefit from Amgen’s product.

Now Amgen has even better data to support its personalized approach to colorectal cancer treatment: their study of Vectibix as a first-line treatment tracked the KRAS genetic status of participants and showed “significantly prolonged progression-free survival” for the wt-KRAS group.

In patients with mutated KRAS, Vectibix wasn’t just “unnecessary,” it actually showed worse outcomes than the control group, meaning genetic testing of all colorectal cancer patients will be a top priority.

A second important note for companies thinking about companion diagnostics and personalized effectiveness is that the Amgen study was a prospective study that will support much more robust conclusions.  H/T @ldtimmerman.

In contrast, recall that the CMS decision not to reimburse genetic testing for Warfarin dosing specifically cited the lack of prospective data on which to base a decision.

This new data from Amgen will:

  1. Drive tumor genotyping as a standard of care; and
  2. Help make the economic case for companion diagnostics.

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Trends Update — Comparative Effectiveness and Personalized Medicine: Genetic Test Identifies Patient Subpopulation for Benefit, Avoids Wasted Money and Time for Others on Erbitux, Vectibix

B&W_DNA_sequenceThis is exactly how personalized medicine and comparative effectiveness can interact to benefit patients, pharma companies and payors:

  • data shows that patients with KRAS mutations don’t benefit from anti-EGFR antibody meds Erbitux or Vectibix;
  • the FDA approves a labeling change identifying the patients who won’t benefit;
  • payors see costs savings from eliminating pointless prescriptions;
  • patients without the KRAS mutations have added incentive to take the drugs, benefiting themselves and the pharma companies who make the drugs.

As the WSJ Health Blog says:

“Erbitux and other expensive cancer medicines have faced repeated questions about whether drugs that prolong life for short periods of time are worth the high costs… Not using Erbitux as a first-line treatment for [KRAS-variant] patients could save about $600 million a year.”

The manufacturers Bloomberg’s reporter spoke to are fully supportive:

“‘The inclusion of KRAS as a biomarker in the Erbitux labeling helps physicians to better understand the most appropriate use of the drug in the management of patients with metastatic colorectal cancer,’ said Fouad Namouni, an oncology executive for Bristol-Myers …

Physicians can eliminate Vectibix and Erbitux for colon cancer patients with the KRAS mutation and ‘redirect those patients to alternative therapies, avoiding unnecessary treatments in patients who are unlikely to benefit,’ said Sean Harper, Amgen’s chief medical officer.”

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No Company is an Island: More Pharma and Biotech Collaboration

Island Nihoa_aerialTwo deals this week showcase collaborative efforts between major pharma players:

 

 

These follow last month’s earlier-stage collaborations between GSK and Pfizer for HIV treatments and betwen AstraZeneca and Merck for cancer treatments.

Why are we seeing these collaborations?  I have a couple of thoughts:

  1. This is a tough regulatory environment and companies are going to reach for every advantage they can get … maybe putting more effort into initial approvals that they might otherwise dole out over time.
  2. I think it’s notable that these projects are all aimed at HIV and cancer, two complex and incredibly tenacious diseases.  The low hanging fruit is (a) gone, and (b) not finishing the jobs. 

Is this the end of magic bullets and the beginning of biotech patent pools?  Too soon to say.

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Pfizer and Ontario BIP Program Funding New $6.9 million “POP-CURE” Project for Colorectal Cancer Genomics

B&W_DNA_sequence Pfizer Global Research and Development is contributing $6 million and the Ontario government is contributing $900,000, through the Biopharmaceutical Investment Program (BIP), for a new project “to discover and validate new targets for the diagnosis, prognosis and treatment of colorectal cancer.”  Brad Wouters, a Senior Scientist with the Ontario Cancer Institute (OCI) and a Senior Investigator at the Ontario Institute for Cancer Research (OICR), will lead the project.

Here’s the scoop from the OICR press release:

“Dr. Wouters and a team of scientists at OCI and OICR will use genomic and molecular pathology approaches and develop a large clinical biobank to identify molecular signatures in colorectal cancer. These molecular signatures will be used to accelerate the development of biomarkers for early detection, monitoring and treatment of cancer.”

The Canadian Press article includes some additional background info on the project, which Paul Lévesque, president of Pfizer Canada, says began with a trip by Ontario researchers to meet Pfizer scientists in San Diego almost two years ago.

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Bailout Update: New UK Life Sciences Blueprint Aims to Promote Innovation

world_map_2002The UK has a new Life Sciences Blueprint that sets as a goal the creation of an internationally-recognized life sciences cluster.  Here’s the press release and here’s the full report (pdf). 

Innovation Pass and Changes at NICE:

The Blueprint kicks off an “Innovation Pass” program under which certain novel medicines (criteria TBD) will be available for a 3-year period without the otherwise mandatory predicate of review by the National Institute for Health and Clinical Excellence (NICE).  A further report is due from Sir Ian Kennedy next week (July 22) that aims “to identify the aspects of value and innovation which NICE should take into account in its work.”  If innovation stimulus is considered a part of the comparative effectiveness analysis, who knows how widely the door may open even after the Innovation Pass. 

Between these changes and the recent report on genomic medicine from the House of Lords Science and Technology Committee, which recommends that the purview of NICE be extended to “include a programme for evaluating the validity, utility and cost-benefits of all new genomic tests for common diseases, including pharmacogenetic tests,” big changes may be heading NICE’s way.

Also notable:

  • The Government will invest £150 million alongside private sector investment, with the aim of leveraging enough private investment to build a £1bn, 10-year Venture Capital Fund.  This is Lord Drayson’s idea that we held up at the time as a model for technology-agnostic lobbying;
  • Along with a variety of educational initiatives and programs, the Society of Biology will begin to accredit undergraduate bioscience degrees to help ensure that graduates leave with the core skills and competencies required by employers;
  • A reassessment of the UK’s various R&D tax incentive programs (A little tax joke for you there as a prize for making it this far down the post.);
  • An £18 million program for regenerative medicine R&D; and of course
  • A marketing initiative to make sure everyone knows all the great stuff they’re doing.

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Trends Update — Comparative Effectiveness and Personalized Medicine: Study by CAMH in Toronto will Integrate Genetics, PET Brain Imaging and Pharmacology

CAMH logoToronto’s Centre for Addiction and Mental Health (CAMH) will use a $2.8 million grant from the Canada Foundation for Innovation, along with expected Ontario matching funds, for their ambitious neuroIMAGENE initiative.  The neuroIMAGENE program aims

“to combine the power of genetics and sophisticated brain imaging to personalize treatment … for common psychiatric conditions like major depression, bipolar disorder, schizophrenia, as well as addictions.”

Specifically, CAMH will compare DNA characteristics across 18 different psychiatric conditions and integrate that data with PET scans showing individuals’ neurochemical changes induced by drug therapies. The idea is to create tools to identify the medication that will work best for each individual’s brain chemistry and genotype,

“helping to avoid trial-and-error prescribing, treatment failure, relapse, and serious side effects.”

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Trends Update — Comparative Effectiveness and Personalized Medicine: Patient-Centered Outcomes Research Act of 2009 Increases Personalized Medicine Focus

story on GenomeWeb yesterday takes a close look at the Baucus-Conrad Comparative Effectiveness Bill and notes that the influence of personalized medicine that we’ve flagged as a trend in 2009 has shown up in this year’s verison of the bill as

language specifying research approaches such as “molecularly informed trials” and “genetic and molecular sub-typing.”

This year’s version of the bill also

includes more emphasis on involvement with the diagnostics community and calls for an expert in genomics to serve on a methodology committee.

In addition to a focus on personalized medicine, the changes to Baucus’ bill incorporate another idea from Sen. Kyl’s amendment in April — adding some hurdles before CER results could be used (by CMS) for coverage decisions. 

Even so, the bill continues to meet procedural impediments and substantive objections, resisting Baucus’ efforts to re-brand the concept.

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Trends Update — Personalized Medicine: DxS’ Latest Companion Diagnostics Deal

B&W_DNA_sequenceAs personalized medicine inches toward becoming the standard of care for cancer, the question of who pays for the genotyping becomes more important.  A deal announced Friday between DxS, a molecular diagnostics company, and Boehringer Ingelheim suggests that pharma companies will end up footing at least part of the bill by paying for the development (and marketing?) of companion diagnostics.

As noted by IVB in their Deals of the Week this week, the Boehringer Ingelheim deal is only one of several that DxS has done recently:

Last December, DxS signed a US-centered deal with Amgen to provide a companion diagnostic for the Big Biotech’s colorectal therapeutic Vectibix. The test maker’s so-called TheraScreen K-RAS test is already on the market in the EU and is used to help doctors determine which patients are unlikely to respond well to anti-EGFR therapies such as Bristol-Myers Squibb/ImClone’s Erbitux (cetuximab) and Amgen’s Vectibix. Moreover, DxS and Amgen have collaborated since last year on selling TheraScreen K-RAS alongside Vectibix in Europe, where the drug is cleared for patients with refractory metastatic colorectal cancer in which there is no K-RAS mutation.

Also notable: this statement in the press release attributed to Dr. Manfred Haehl, Corporate Senior Vice President Medicine of Boehringer Ingelheim…

As this year’s theme at ASCO highlights, it is very likely that personalised medicine will play an important role in selecting the most effective treatment for patients with cancer.

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