Wednesday, March 24, 2010

The Wrong Medicine – Getting Personal

“I ain’t got a fever, got a permanent disease; It’ll take more than a doctor to prescribe a remedy; I got lots of money but it isn’t what I need; Gonna take more than a shot to get this poison out of me.” These are the opening lyrics to “Bad Medicine” from the rock group Bon Jovi. While the song concerns an addictive love affair, the words and the title bring to mind important issues concerning major challenges for the pharmaceutical industry. Google the term “bad or wrong medicine” and you will get results ranging from political views on healthcare reform to stories about patients exhibiting adverse drug reactions or being prescribed the wrong medication. If you dig hard enough, you will find news articles and commentaries based upon patients being treated with a drug that simply does not work. Within the context of patient efficacy and safety as well as the cost of some drugs, the wrong medicine has profound implications for the future of the pharmaceutical industry. These clinical and commercial aspects call into question issues concerning how patients and physicians will be able to avoid the wrong medications and realize the full benefits of an optimal therapy. Personalized medicine, the use of diagnostic testing to identify those patients most likely to benefit from a particular treatment, may be an answer. However, pharmaceutical companies will have to resolve whether personalized medicine is something of value or a necessary evil to be avoided when possible. If you ask Steve Burrill, CEO of the life sciences merchant bank Burrill & Company, personalized medicine and associated diagnostics will become more valuable than prescription drugs in the future. Mr. Burrill may be right. Pharmaceutical companies have traditionally shied away from targeted patient population markets due to concerns of perceived lower revenue and higher marketing costs. Now, as the prospects from pipelines have dwindled and major drugs face patent expiration, some companies are beginning to realize the potential benefits of targeting certain treatments to smaller patient populations. If the benefits of increased safety and/or efficacy are realized, as well as the higher probability that drugs will make it through development, marketing and R&D experts believe that personalized medicine may the right therapy for an ailing industry. An additional factor involves the recent passing of healthcare reform legislation in the US. The new law is projected to provide significant dividends to drug companies who will gain access to millions of more customers with the ability to pay for high cost treatments. However the situation is not so good for insurers who will have to pay for the expensive treatments. Why pay for a treatment that does not work, or worse, may result in harm to the patient and thus additional payments by the insurer? Such a scenario should bode well for broader development and commercialization of personalized medicines. However, who will lead the way? Will it be the insurers / payers, the drug companies or the test providers? Will all three entities work together or will two defer to the one with the most to gain to lead the way in terms of adoption? The answer may lie in a better understanding of who has the most to gain and what they do to capitalize on the opportunities and challenges associated with this intriguing area of healthcare. So, who has the most to gain?

The basis for personalized medicine lies in the fact that genetic variation within human populations results in patient-to-patient differences in drug response. The response may involve efficacy at the target site or metabolism of the drug to an inactive or active metabolite. There may also be variability for safety where some individuals metabolize the drug into a toxic metabolite. In addition to extensive research studies for drugs and genetic-based response, validity can be found in the recent actions of the US Food and Drug Administration (FDA) in modifying labels for drugs such as warfarin and clopidogrel to advise patients and practitioners that genetic variants warrant consideration of whether to use the drug and, if prescribed, carefully decide on the optimal dosage. There are several additional examples of drugs with available companion diagnostic tests to aid physicians in deciding whether to prescribe the corresponding drug.

Source: Personalized Medicine Coalition; The Case For Personalized Medicine 2009.

The FDA has required that test information be on the labels of several drugs such as tratzumab and the EGFR inhibitors cetuximab and panitumab (highlighted in blue) while for others (e.g. warfarin and clopidogrel) it is only recommended. But testing information on the label is just the beginning and may result in more questions than answers for patients and the medical community. Furthermore, the companion diagnostic test will present unique marketing challenges as well as opportunities for the commercial arms of drug and diagnostic companies. The opportunities and challenges may well revolve around the genetics education of physicians, many of whom may be ill-suited for practicing personalized medicine due to poor training. Of critical importance will be the assurance that physicians understand genetic variation principles in the human population and within the context of complex diseases. While a long term remedy would be for medical schools to improve their curricula relevant to basic concepts in genetics and genomics as well as practical applications in clinical medicine, over the next few years, medical affairs resources from the drug and testing companies will be required to effectively translate the science and the benefits of the tests to determine the optimal therapy. This will require either a divide and conquer strategy between the drug company and test provider or by consolidating the activity within a single organization. Unique skill sets will be needed by these organizations to effectively advise on the requirement for or promote the benefits of testing, depending on the specific circumstances of the drug-test combination. The challenges associated with this activity can be turned into opportunities for communicating the need to test patient populations to ensure that patients receive the optimal therapy. Such marketing activity can be coupled with a specific drug to drive script writing by a target physician audience.
The second component of the question, “who has the most to gain?” in the world of personalized medicine concerns the ratio of value between the drug and the test. This factor is of considerable interest from a licensing perspective relative to deal negotiation including milestone and royalty payments not to mention responsibilities during development of the drug and test. Traditionally, drugs have had much higher financial values compared to diagnostic tests. In fact, during the early days of personalized medicine, many industry experts questioned the viability of the concept given the substantial disparity between drug and test valuation. Unless the commercial rights for the test resided with the drug developer, why would a separate entity invest in development of a test if the bulk of the rewards go to the drug developer? This maxim may change, especially in situations where the test determines whether a patient will or will not receive the drug treatment. If the commercial rights to the diagnostic test belong to a separate test developer / provider, this entity will have considerable leverage with the drug developer in negotiating the terms of a license or collaborative agreement. Also, there now appears to be sufficient incentive for diagnostic companies to invest in the discovery and validation of relevant biomarkers and / or proprietary assay platforms that will enable efficient testing and provision of results during drug development and by physicians in clinical practice.
And what about the payers, what will they do or say regarding the adoption of personalized medicine? If you consider the health insurers that utilize Medco for prescription benefits, they may have already spoken in the positive. Medco Pharmacy claims to be on the cutting edge of personalized medicine via the Medco Research Institute. This institution is dedicated to translating science into clinical practice through research initiatives with an emphasis on comparative effectiveness research that includes personalized medicine. Much of the research is based upon the company’s extensive medical and pharmacy claims database and led by researchers from a personalized medicine division. Other insurers may partner with Medco or duplicate the company’s efforts to adopt a personalized medicine program.
While it appears that everyone has the potential for gain in the application of personalized medicine, the one who gains the most may be the patient. Many physicians, most notably oncologists, have been frustrated by relying on therapeutic regimens that they know will not cure their patients and in many cases have little or no benefit while causing severe side effects. Many of these treatments are very expensive and thus under the watchful eye of the payers. “Whooah, we’re half way there; Whooah, Livin on a prayer; Take my hand and we’ll make it, I swear; Whooah, Livin on a prayer.” These words form the chorus of another Bon Jovi song entitled “Living On A Prayer.” Perhaps personalized medicine will answer the prayers of patients as well as the healthcare industry that collectively must lead the way in avoiding the wrong medicines because of their profound financial as well as physical and emotional costs.

Robert Morrison, Ph.D. is Director, The Invotex Group, a specialty consulting firm that provides a range of financial and technical services to companies and academic institutions. Dr. Morrison’s practice focuses on issues associated with clinical development and intellectual property of pharmaceuticals and medical diagnostic applications.


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