Personalized Medicines: Implications for Pharma

The President's Council of Advisors on Science and Technology defines personalized medicine as "tailoring medical treatment to the individual characteristics of each patient by classifying individuals into subpopulations that differ in their susceptibility to a particular disease or their response to a specific treatment." To this end, FDA is now developing guidelines that address the co-development of a drug and the companion diagnostic test (or diagnostic test and companion therapeutic) that will allow these subpopulations to be identified and treated accordingly.

Kathleen Dunn

Pharmaceuticals, in vitro diagnostics, and medical devices have historically used different marketing techniques. For the most part, pharmaceutical marketers have targeted office-based physicians, both primary care and specialty; pharmacists, both retail and hospital-based; and hospital and managed care formulary committees. Diagnostic marketers have targeted hospital-based physicians—particularly pathologists, laboratory managers, laboratory department supervisors, and point-of-care coordinators. Device marketing has an extremely broad range of targets, from physician specialties such as radiologists, cardiologists, orthopedic surgeons, and other surgical disciplines to nursing and materials management representatives.

One of the major differences between marketing in these three segments has been the size of the promotional budget: large for pharmaceuticals, small for diagnostics, and somewhere in between for devices, depending on the type. Personalized medicine blurs those boundaries, and will require interdisciplinary marketing of drugs and diagnostics by marketers that historically have been siloed. Except in those situations where therapeutic drug monitoring is necessary, drugs and diagnostics have been historically separated. Now, however, drugs and diagnostics will not only be co-developed, but also co-marketed, requiring marketers to possess both pharmaceutical and diagnostic expertise.

A Glimpse into the Future

What do marketers consider when trying to sell a diagnostic test? Sample type and ease of sample preparation, specificity, sensitivity, reproducibility, accuracy, precision, false positives and false negatives, turnaround time, hands-on time, compatibility with automated platforms, and cost/test. When personalized medicine arrives (as it has in the case of breast cancer and Herceptin, leukemia (CML) and Gleevec, metastatic colorectal cancer and Erbitux), the key attribute for a genetic-based diagnostic test will be all of the above plus its clinical utility.

Within the proposed FDA drug and diagnostic co-development guidelines will be a definition of clinical utility. The definition previously developed by the National Institutes of Health Secretary's Advisory Committee on Genetics, Health, and Society (SACGHS), reads as follows: "Clinical utility refers to the usefulness of the test and the value of information to the person being tested. If a test has utility, it means that the results—positive or negative—provide information that is of value to the person being tested because he or she can use that information to seek an effective treatment or preventative strategy. Even if no interventions are available to treat or prevent disease, there may be benefits associated with knowledge of a result."

One of the first examples of clinical utility in a molecular diagnostic test was Roche Molecular Systems' quantitative PCR assay (Amplicor HIV Monitor), which allowed clinicians to measure extremely low levels of HIV viral load in order to monitor a patient's response to a Roche antiretroviral drug. While not an example of a genetic-based companion diagnostic, this serves as a good example of using a diagnostic assay based in molecular medicine to demonstrate clinical utility.

When marketing diagnostic products, it is very tempting to sell the technology rather than the result, particularly when the input is coming from the point of view of the assay designer. That may be fine for the laboratory performing the test—they'll want to know how the assay is performed to help determine if they have confidence in the test platform. The same will not be true, however, for physicians.

When discussing a diagnostic test, a physician will invariably ask, "If I know the result, will it change the way I treat the patient?" In the case of many personalized medicine examples, the answer is a resounding "yes."

The basic strength of any diagnostic test is the assay's ability to get the same result on the same sample day after day (reproducibility); the ability to detect the target even when it is present in extremely low quantities (sensitivity); and the ability to measure the correct concentration (accuracy) on a single sample every time it is tested (precision). If the assay is robust, its reproducibility, precision, sensitivity, and specificity will result in few, if any, false readings so that physicians can rely on the results to help direct treatment.

Emergence of Companion Diagnostics

As personalized medicine becomes a reality, more drugs will be marketed with a diagnostic test (companion diagnostics), which means a patient's treatment will be guided by his or her own genetic information. Currently, there are approximately 37 products that facilitate personalized treatment, mostly in cancer, and approximately 10 percent of labels approved by the FDA now contain pharmacogenomic information. In fact, studies of a gene called KRAS have recently resulted in the makers of Erbitux (Lilly/Imclone) and Vectibix (Amgen) requesting that the FDA limit the use of these drugs in colorectal cancer patients with a mutation of the KRAS gene because the drugs do not work for this population.

The emergence of companion diagnostics has opened the door to new marketing channels. One example of pharmaceutical marketing in the diagnostic space is the appearance of print advertising for therapeutic agents in the College of American Pathologists' official publication. Pathologists, molecular pathologists, and heads of molecular diagnostic laboratories will be new marketing targets for gene-based therapies. It is important that you familiarize yourselves with the media that can be used to reach companion diagnostics decision-making audiences.

What's Next?

Personalized medicine has the potential to replace traditional trial-and-error medicine. Marketers will need to be fluent in marketing companion drugs and diagnostic tests, including laboratory-developed tests, analyte-specific reagents (ASRs), and IVDMIAs (in vitro diagnostic multivariate index assays) such as the multi-gene, multi-pathway gene expression test (XDx AlloMap), which can be used to assist physicians in managing heart transplant patients for potential organ rejection. Clinical laboratory diagnostic testing will become as important as the drug entity as it identifies suitable patients for treatment. Will we soon hear the phrase "blockbuster diagnostic"?

Comparative effectiveness research, recently funded at $1.1 billion under the US government stimulus bill, will seek to identify which treatment protocols provide the best patient outcomes. Based on the role some diagnostic tests have played in identifying populations that would benefit from a particular drug, we may see diagnostic medicine—both laboratory- and imaging-based—gain as much importance as the drug itself, especially if the tenets of personalized medicine can be incorporated into this legislation.

What does this all mean for marketers? Just as new therapeutics will be much more specific in terms of intended patient subpopulations, equally targeted will be communications that speak to the therapeutic/diagnostic decision maker. Pharmaceutical and diagnostic companies will be able to contribute even more fully to informed decision-making, and not simply interact with physicians. Third party payers will need to be educated on new—and potentially more costly—treatments. Quality rather than quantity will be rewarded.

Simply put, medical marketers, regardless of past experience, will need to break out of their silos and greet the bright new day of personalized medicine.

Frequently Asked Questions

Who are the in vitro diagnostic test leaders today?

Roche, Siemens, Johnson & Johnson. Bayer has dropped from fourth to seventh.

Where will the next diagnostic breakthroughs originate?

Probably not from the large IVD players who are accustomed to developing assays for high throughput of high volumes of tests.

Where do I look for a companion diagnostic partner?

Look for companies with proprietary technologies; for example, Asuragen and its expertise in miRNA; or OncotypeDX testing from Genomic Health, whose IVDMIA test predicts recurrence of breast cancer.

What's the profile of the ideal companion diagnostic?

It is a molecular diagnostics test performed at the point-of-care, using a buccal swab, immersed in a room-temperature, ready-to-use amplification reagent that provides a definitive colorimetric endpoint, read by any operator as "yes" or "no," with sensitivity and precision at 100 percent and unquestioned clinical utility. This immediately triages the patient, who is protected by GIST legislation, to a dispensing unit for a one-time treatment.

Kathleen Dunn is president of KFDunn Life Sciences, a division of Aloysius Butler & Clark, and a member of the Personalized Medicine Coalition. She can be reached at kdunn@a-b-c.com