What’s Ailing Personalized Medicine? Mark Levin Calls for Leadership at the Highest Level

1/24/08

It started out business as usual at the Personalized Medicine Coalition’s East Coast reception at The Broad Institute last week. People were touting the big steps that have been taken to advance the vision of personalized medicine, in which the best treatments are chosen for each patient based on molecular tests, imaging tools, software, and other sophisticated tools. Then, venture capitalist Mark Levin sauntered up to the podium (in his typical casual style, sporting high top sneakers and a fleece jacket) and said “I’m thrilled by the advances, but at the same time I’m frustrated and disappointed by the level of progress.”

Levin’s got a good point. While the PMC itself has been very active, amassing about 120 members—including local firms Helicos BioSciences, BG Medicine, and Boston Millennia Partners—since its formation a few years ago, there is still a lot of foot dragging going on by others, particularly in the pharmaceutical industry and in Washington, DC.

One notable sore point is GINA, the Genetic Information Nondiscrimination Act that personalized medicine proponents believe is crucial to advancing the field. That bill has still not passed despite 12 years of effort. But that’s not the only problem. Big pharma companies have been reluctant to adopt the personalized medicine model, which involves drugs aimed at smaller patient populations than the massive ones that coveted blockbuster drugs target.

Levin was himself confronting the challenge of smaller markets for personalized medicines around the time he hatched the idea of the PMC in his office at Millennium Pharmaceuticals, based on discussions with Millennium cofounders Eric Lander and Raju Kucherlapati. Now a partner at Boston’s Third Rock Ventures, Levin was Millennium’s founding CEO; that company was built around the idea of personalized medicine, but (at least so far) failed to turn the idea into suite of products. Levin argued in a 2001 interview that personalized medicine would allow companies to get more, higher-value drugs approved more quickly, offsetting the fact that the market for each one might be smaller.

“We were so excited about [personalized medicine] when we started 12 or 13 years ago,” Levin said. But since things haven’t moved fast enough, he’s now calling for leadership from the highest political level to help speed the field along, arguing that personalized medicine could even help cut the deficit because it leads to better health care at lower cost.

Speaking before Levin, Kucherlapati, the scientific director of the Harvard Medical School–Partners Healthcare Center for Genetics and Genomics, said one big thing holding back personalized medicine is that so many of the players (e.g. doctors, insurers, and biotechs) are focused on their own interests. We can’t “continue to operate in our separate worlds,” he admonished. “We need to present a common vision.”

But Levin and Kucherlapati’s frustration was balanced by Lander, the evening’s first speaker and director of the Broad, who deftly described the “miraculous” advances that have taken place over the last few years in large-scale genotyping—the process by which genetic variations are quickly detected in many parts of the genome. “This is the most remarkable period in genetics,” Lander said. Those genetic variations, most of which are so-called single nucleotide polymorphisms (SNPs), are one of the key genomic tools for sorting out individual responses to drugs.

Genotyping has truly rocketed ahead. As PMC head Edward Abrahams said, you can already “take out your iPhone, Google ‘SNPs’, and get access to databases of more than 10.5 million SNPs.” And that message is finally reverberating into the business world, leading to a small flurry of new companies using those tools to develop new diagnostics and drugs.

Levin’s call for political support for the field notwithstanding, with so much activity on the tech side, personalized medicine could end up being of those areas where the technology pulls us to our destiny, rather than our leaders pushing us there.

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  • Kellie Machlus

    The Personalized Medicine Coalition (PMC) is an organization that aspires to “educate federal and state policymakers … helping them understand the science, the issues and what is needed for the positive evolution of personalized medicine. [1]” While it is undeniable that such education is necessary, is it futile to teach others about a field that barely exists?
    Perhaps this is a question of the proverbial chicken and egg. What comes first, translational medicine or the policies and support needed to sustain it? At first, it may seem as though the logical answer would be to do the research first, and then present the successes in order to gain support. When one begins to think about the logistics of this, however, it becomes less feasible. Without the proper funding and policies in place to support a personalized medicine overhaul, this process may not be able to adequately get underway.
    The most prominent issue is one of financial funding on the national level. Both basic researchers and pharmaceutical companies need financial support to begin studying translational medicine. Current procedures are not conducive with creating personalized medicine. Bringing a new drug to the market currently costs approximately $500 million, making it economically impossible to target small patient populations. If smaller patient populations are to be served, we need to change the entire process, up to final regulatory agency approval for clinical use [2]. Without a shift in both thinking and funding, it would not be financially advantageous to develop pharmaceuticals for small, targeted populations.
    It is also important to recognize the role of the scientist in the development of new personalized medicinal technologies. While science provides us with a lot of interesting information, it is important to remember that research in the field of personalized medicine should be focused on the development of diagnostic tests for clinically important problems. Not every study leads to a potentially useful test, and financial and technical resources may be wasted if researchers don’t first focus on and test readily measurable values [3]. This shift in attitude toward clinical research is crucial because most of our knowledge about personalized medicine comes from clinical studies initiated by research institutions. The importance of adequately designed studies on associations between genetic variation and clinical drug response needs to be recognized by funding agencies, including health insurers and governmental agencies [4].
    The clinical trial process is vital to the success of personalized medicine. As with all new medical technologies, the only way that personalized medicine will gain widespread support is though clinical validation. Consistent test validation facilitates widespread clinical use. Physicians’ and patients’ needs are best met when interpretation does not differ depending on which laboratory performed the test. These kinds of large, validated multi-center trials are noticeably absent in the field of personalized medicine [5]. Without sufficient data to support the effectiveness of new drugs, they will not be adopted. On the other hand, researchers need money to perform these large trials. So, yet again, it is perhaps reasonable to say that the education of federal policy makers, etc. is needed before adequate research can be done to bolster the field of personalized medicine.
    Another concern for pioneer health care providers in personalized medicine is the fear of lawsuits. Without the necessary protections in place, doctors may be fearful of prescribing new drugs that have not been adequately validated. Fear of lawsuits may tend to promote advances in the use of safety biomarkers (predict drug toxicity) but impede application of efficacy biomarkers (predict therapeutic response to drugs) [6]. This again argues for policy preceding clinical practice. If there are sufficient laws in effect to protect doctors, researchers and pharmaceutical companies, they might be more willing to test new drugs.
    It is worthwhile to mention, however, that the aforementioned points are not without their own flaws. While it has been argued that the education of federal policy makers is needed before adequate research can be in the field of personalized medicine, it is obvious that getting funding and support would be easier with convincing preliminary data. Also, while the protection against lawsuits is undoubtedly important, we need to remember to balance this with the protection of patients and trial subjects.
    In the end, I think that one can go around in circles all day about what needs to be done to best promote personalized medicine. In reading this blog and the papers referenced, it seems as though most people are also confused on the topic. The most important thing, however, is ultimately getting people excited about personalized medicine. I think that the PMC is doing researchers a huge favor by promoting the ideas of personalized medicine and educating the people that are ultimately in charge of financing such research. Hopefully, the PMC can also begin to reach out to basic scientists and help bridge the large gap the still lingers between them, doctors and public policy makers.

    References
    1. Personalized Medicine Coalition. “About PMC.” 2 March, 2008.
    http://www.personalizedmedicinecoalition.org/about/mission-goals.php
    2. Mancinelli L, Cronin M, Sadee W. Pharmacogenomics: The Promise of Personalized Medicine. AAPS PharmSci. 2000; 2 (1)
    3. Maitland ML, DiRienzo A, Ratain MJ. Interpreting disparate responses to
    cancer therapy: The role of human population genetics. J Clin Oncol. 2006;24:2151–2157.
    4. Swen J, Huizinga T, Gelderblom H, de Vries EGE, Assendelft WJ, Kirchheiner J and Guchelaar H. Translating Pharmacogenomics: Challenges on the Road to the Clinic. PLoS Med. 2007 Aug;4(8)
    5. Katz, DA. From bench to bedside: a diagnostics framework for pharmacogenetics research. Mol Genet Metab. 2002 Sep-Oct;77(1-2):57-606. 6. Evans, BJ. Finding a liability-free space in which personalized medicine can bloom. Clin Pharmacol Ther. 2007; Oct;82(4):461-5.

  • Ken Rubenstein

    Physicians are really hard-nosed business people. If you want to sell them a new product or service, you had better show them that it provides clear medical benefits that can’t be provided already, and that it makes economic sense. Personalized medicine simply has not done this. It’s been technology-driven all the way.

  • R Guberman

    It hasn’t been technology driven. The technology is what’s holding it back, among other problems. The technology isn’t accurate and isn’t ready for the masses.