Posts Tagged ‘companion diagnostics’
When is $100,000 a year more expensive than $500,000 a year? The answer: when developing drugs to treat common diseases (e.g., cancer) rather than rare diseases. According to a new article in Forbes magazine, governments and insurers are willing to pay upwards of $200,000 and as much as $500,000 for new orphan drug treatments that attack rare diseases (usually caused by a single gene). Since people suffering from these diseases have a known genetic profile, these targeted treatments are far more effective than most cancer drugs, for which insurers will usually cover up to $100,000 per patient per year.
National Institutes of Health (NIH) Director Francis Collins is urging companies to find more treatments for rare diseases. Of the 7,000 diseases that affect humans worldwide, 6,000 are rare. Traditional drug discovery and development methods for mass populations won’t be effective against these diseases. But more targeted approaches, with specific biologics and companion diagnostics, could be.
What do you think? Are companies like Agios a flash in the pan? Does $500,000 a year per patient sound like a viable pricing strategy? Are orphan diseases and drugs to treat them the future of medicine? Share your thoughts with us.
Tags: cancer drugs, companion diagnostics, genetic profiles, orphan drugs, targeted treatments, treating rare diseases
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Last week, we discussed new drug approvals that reflected a paradigm shift for cancer drug development and for treatment of people living with cancer. Finally, we are starting to see a matchup of specific diagnostics with targeted biotherapeutics to address (effectively, we hope) targeted treatments for smaller groups of cancer patients.
Just recently, the American Society for Clinical Oncology (ASCO) urged the use of new biological knowledge to develop treatments faster, design more targeted clinical trials, and use information technology to integrate once-separate translational and clinical research. ASCO even says that targeted therapies can improve clinical trial responses from 8 to 30 percent. Also, just recently, the FDA gave itself a pat on the back as it highlighted its recent innovative drug approvals, with targeted cancer therapies included among those on the list.
What both of these events underscore is that we’re now finally seeing real co-development of drugs and companion diagnostics. This is a refreshing departure from the old system in which tests were developed after the drug was approved, often to rescue certain drugs that were facing rejection or had been pulled from the market.
We expect this trend to continue and will probably start to see new tests in two categories—
- Tests designed to include or to qualify patients. For example, if the specific drug target is present or activated, say, by a genetic alignment that creates the target (like Bcr-Abl fusion for leukemia), or mutations activate the target (like V600E in BRAF for melanoma), it will be sensitive to inhibitors.
- Tests designed to exclude or to disqualify patients. An example would be tests that determine the vicinity of the target pathway to determine if pre-existing mutations would enable the cancer to bypass drug activity (like KRAS mutations that circumvent EGFR inhibition).
While this may bring optimism to patients and investors alike, Ken Walz, my colleague at Popper and Co., has a warning:
“Don’t discount the economic impact of this new world of cancer therapies. Pharmaceutical companies will at first be hesitant to abandon their blockbuster strategy. Niche drugs would not be sustainable under their cost structure. If discovery and development costs stay the same, the price of niche drugs would have to be very, very high. But if ASCO’s goals come true, R&D costs could realistically come down. And a portfolio of niche drugs could work very well, indeed.”
Good food for thought, considering how many times that light at the end of the cancer therapy tunnel was just a reflection off more muck. What do you think? What does the future of cancer therapy look like? Or the future of pharmaceutical development and R&D investment, for that matter? Share your thoughts with us.
Tags: cancer, cancer drugs, cancer therapies, cancer treatment, companion diagnostics, drug discovery
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It’s increasingly clear to anyone who deals with human health – from the bench biologist to the clinical oncologist – that humans are a heterogeneous species. As a result, a drug that works well in one individual may not work at all in another. Thus, the field of targeted (or personalized) medicine came about so doctors could optimize patient care through the use of genetic and biomarker testing. Such tests help identify patients who are (or who are not) most likely to respond to a given therapy. The field is often promoted as a way to get the “right drug to the right patient at the right dose.”
Correct dosing is critical because about 25 percent of all outpatient prescription drugs in the U.S. are taken by patients with genetic variations (specifically, polymorphisms) that affect absorption, metabolism or excretion of those drugs. Again, at risk of stating the obvious, human beings are heterogeneous.
Today, genetic tests are widely used to identify so-called “fast” and “slow” metabolizers of specific drugs and to adjust the dosage according to how long the drug may persist in an individual’s body. Other tests are used to determine whether patients carry drug targets that are sensitive to drugs (like Herceptin), or whether they harbor mutations that will render drugs inactive, either through resistance (from conditions like HIV) or via the presence of alternate pathways that can circumvent—or short circuit—the effects of a drug.
These current tests can therefore reveal whether mutations have either a pharmacokinetic (i.e., drug metabolism) effect or a pharmacodynamic (i.e., drug target) effect. Genetic and biomarker tests are also proving to be important in the management of many diseases, particularly those for which there are multiple therapeutic options and in those cases where the underlying pathology is caused by one of several possible mutations or other risk factors (e.g., breast cancer and diabetes).
While the U.S. Food & Drug Administration website lists approximately 115 biomarker tests associated with just over 100 approved drugs, researchers are moving quickly to add additional tools to the personalized medicine toolbox. One exciting new advance is the use of induced pluripotent stems cells (iPSC) to test drug response directly in cells isolated from individual patients. The idea is that skin cells, or blood cells, can be isolated from individual patients and used to generate iPSC, which are then induced to differentiate into multiple cell types such as neurons, cardiomyocytes, and hepatocytes. Such cells harbor the genetic legacy of the patient from whom they were derived, and therefore a response (or non-response) of those cells to various drugs can be used to predict how a patient will respond.
The biotech firm, Cellular Dynamics International, which was co-founded by stem cell pioneer James Thomson, is now trying to undertake this approach. The firm is currently focused on the creation of iPSC-derived cardiomyocytes. However, it soon plans to add other cell types, including those from liver, brain and blood to the list.
So how “futuristic” is all of this? The good news is that many of the tools needed to realize the vision of personalized medicine are rapidly coming together. The combination of genomics, proteomics, stem cell biology, and other technologies are providing the information that is needed to drive the process. The challenge lies with the drugs themselves—the industry needs to apply the same tools more efficiently to guide the drug discovery process. Research, testing, approval, and application should work in tangent because the faster the next generation of drugs come into play and are FDA approved, the faster these new protocols of personalized medicine can be applied to save lives.
We also need to organize and apply the knowledge we’ve gained in genetic studies over the past ten years and apply this knowledge to evolving research. Effectively communicating the on-going research and applications of personalized medicine to the medical community will mean we’ll see designer drugs that are targeted to ever more specialized groups of patients. That day is on the near horizon, something that is of benefit to all of us, doctor and patient—the emergence of truly personalized medicine.
Are you involved in the discovery and/or development of companion diagnostics and/or drugs designed specifically for particular patient subsets? What do you see as the critical next steps to continue moving towards matching drugs with patients who will benefit most? Please share your thoughts with us here.
Tags: biomarker testing, companion diagnostics, drugs, genetic testing, personalized medicine, Popper and company, targeted medicine
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This week, the FDA issued draft guidance for in vitro companion diagnostics. After a day or so of reflecting about it, here’s what I think it may mean for you:
Overall, while the guidance itself may not be BIG news, it does seem to make good sense for business and to offer life science companies some flexibility. Whether you are a therapeutics company or a diagnostics company, you should see new opportunities as a result.
Following are the key points I took away from my review of the guidance:
- The FDA acknowledges that not all co-development of diagnostic tests and therapeutic drugs can occur simultaneously. Thus, there is room for you to secure approval of a drug before the test is available and also to seek to modify the drug’s label as new diagnostics information emerges. There is also room for you to potentially market an as yet uncleared or unapproved test, if the marketing of the test is critical in the context of a drug.
- Every test that provides guidance about a treatment is NOT a “companion” diagnostic. For example, tests that predict a patient’s risk for adverse reactions to Warfarin are not companion tests. Instead, they are adjunct tests in clinical decision-making. This is an important distinction.
- Put another way: Labeling really matters! A companion diagnostic would be labeled to indicate it is the determining factor in the safe and effective use of a drug. Keep this in mind as you plan your regulatory strategy.
- Furthermore, drug labeling is likely to refer to a category of tests rather than to a specific branded test. Test labeling may reference a specific drug or drug class. Here again, this has implications for how you intend to market your companion diagnostic or targeted therapy.
- FDA will allow submission of a test’s clinical validity data from the drug trial as the agency is keen to make the approval process efficient rather than requiring a separate study. This would obviously play into your clinical strategy in conjunction with your regulatory strategy.
So I see this approach as good news for my friends, colleagues and clients in the diagnostics and therapeutics industries. Clearly, the guidance shows a strong acknowledgement by the FDA of the growing role of diagnostic tests in targeted therapy. The agency appears to recognize that its facilitation of a smooth approval process is in the public’s best interest.
What are your thoughts about the guidance? Do you plan to submit comments? Are you willing to give us a sneak preview of your thoughts? We’d love to see them included below.
Tags: companion diagnostics, diagnostics, drug testing guidelines, fda drug testing, life sciences
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In late 2008, Novartis established its molecular diagnostics unit, to be known as Novartis Molecular Diagnostics (MDx) and to function as an integrated unit within the Novartis Pharmaceuticals Division. Led by Michael J. Nohaile, Ph.D., Global Head of MDx, the unit is designed to leverage the global pharmaceutical company’s strengths and capabilities in research, development and commercialization to translate identified biomarkers into high-quality diagnostic tests. As Novartis explains via its global website: Novartis MDx strives to become a world leader in developing and commercializing diagnostic tests to optimize patient outcomes and to transform the practice of medicine.
Recently, I spoke to Novartis MDx Global Head of Diagnostics Development Michael C. Little, Ph.D., an old colleague of mine from Becton Dickinson and Company, and to Director of Business Development and Licensing Yves Dubaquie, Ph.D., who presented on behalf of Novartis MDx at the Personalized Medicines Partnerships Conference last month. Both gentleman arrived in their current Novartis MDx roles about two years ago and both have impressive industry experience.
While many of the leading international pharmaceutical companies have embarked upon research and business strategies to bring companion diagnostics to market alongside targeted drug therapies, Novartis has created a unit dedicated to the development of molecular diagnostics within its pharma division. Below, Michael and Yves share some of their insights into this unique model and its promise.
CP: Explain the Novartis MDx model and how it differs from other big pharma approaches?
ML: To date, big pharma has taken three general approaches to the development of personalized medicines alongside companion diagnostics. First, companies like Abbott and Roche have set up internal diagnostics R&D (based on legacy diagnostics businesses), but in separate business units from their pharmaceutical research. Separate diagnostics and pharma businesses must compete in their legacy businesses, which may reduce their opportunity for collaboration and integration.
In the second approach, some large pharma companies have created arm’s length arrangements with diagnostic companies (e.g., Amgen and DxS). This model may be convenient for each entity, but arm’s-length relationships prevent true integration and may inhibit upstream opportunities for the two companies to work together.
Third, there’s our model. Novartis began with a fresh piece of paper. The company placed the molecular diagnostics unit within our pharmaceutical division to do what is best for the business. We work to integrate the efforts of our Biomarker Development unit in the Novartis Institutes for Biomedical Research with our clinical drug development while ensuring regulatory alignment on both the diagnostic and drug development sides of the equation. Our process is cohesive and internally integrated. This is an innovative approach, and many in the industry seem to be watching us closely.
CP: During his presentation at the Personalized Medicines Partnerships Conference, Yves spoke about companion diagnostics becoming a NEED to have, rather than just a NICE to have. Please explain.
YD: In the future, more payors and regulators are likely to require companion diagnostics to accompany some new targeted therapies. At Novartis MDx, we recognize this fact and that we need to develop more precise medicines to improve patient outcomes. Once we have proven that a targeted drug works for a select patient subset, there’s no stepping back when FDA requires concurrent filing of a companion test. We will aim to move the therapy and the diagnostic down the regulatory path together so that the companion diagnostic doesn’t hold the drug hostage, which could cause delays in drug approval that could be costly.
CP: Is there a disease area that you are most optimistic about in terms of where your company can make a difference in healthcare?
YD: In the near term, Novartis is a big player in oncology and this is one therapeutic area where there is a big push to create targeted therapies because of the potential to improve outcomes for sub-groups of patients facing life-threatening diseases. About 50 percent of our MDx portfolio is in oncology. But, MDx supports all our General Medicines efforts and infectious disease and transplant are two particularly important areas for targeted therapies. In the long term, we may have collaborations with our newer Novartis divisions, such as through the company’s acquisition of Alcon, a global leader in eye care.
CP: What are some of the biggest challenges to bringing the promise of personalized medicine to the next level?
ML: First, I’ll address the U.S. regulatory process and the product development processes. It’s complicated to bring a diagnostic to market. It’s complicated to bring a drug to market. You need to manage both pieces effectively and in an integrated fashion (our model recognizes this, hence our structure) if you aim to co-file the diagnostic and the drug together for a targeted therapy review process. The stakes are high to do it well.
Another challenge is intellectual property (IP). If the U.S. higher courts uphold a recent decision that says that certain biomarkers are no longer “patentable,” then this will change the way companies think about IP. There will need to be a new model for funding innovation if you can’t protect biomarkers.
I’d add that the identification of potential biomarkers is only the beginning of the process. Once research with the biomarker can be reproduced, formatting and creating FDA-acceptable tests is a lot of hard work. For example, you need to develop analytically validated tests before you assess the biomarker performance. This is to ensure that the apparent change in the biomarker in the clinical realm is not change that is due to your measurement system or assay. You also need enough clinical samples for the development work, but these samples don’t always exist in abundance. The hurdles that exist – plus the work that needs to be done to surmount them – make it challenging to “deliver” a real biomarker baby.
CP: What keeps you optimistic and focused?
YD: For me, it’s the prospect of breaking new ground. There aren’t many successful examples in the marketplace today of companion diagnostics and targeted therapies. We are at the beginning of a new revolution in the drug industry, and I’m excited about the prospect of delivering improvements in patient outcomes.
ML: I think about two things: past successes and living into the future. As far as the past: Ten years ago CML, a rare form of leukemia, was a fatal diagnosis. With medical developments, including by Novartis, we have been able to drastically improve the overall survival rate. Today, we are improving upon the tests that manage these CML patients. It is a very powerful success story. Looking forward, the people in Novartis Pharma and MDx are ultra-dedicated to patients. They know we are making a difference for real patients with real names.
As a life science professional who has been involved in the diagnostics industry for many years, I’m closely watching the model of Novartis MDx and the other approaches our industry is taking to develop companion diagnostics. Are you a fan of one development model versus another? Where will the next drug/diagnostic companion pairings make the biggest impact in healthcare? Please share your thoughts and experiences with us here.
Tags: biomarkers, companion diagnostics, diagnostic tests, mdx, molecular diagnostics, novartis, Pharmaceuticals, targeted therapies
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