Advancing personalized medicine through molecular diagnostics

With the mapping of the human genome and the revolution in molecular biology technologies, we are increasingly capable of monitoring human biology and disease in very sophisticated ways. Our ability to measure biological processes and indicators is now essentially "turning on the lights" on our ability to understand how life works. But tests using molecular methods, including molecular diagnostics, are the rate-limiting step for the full promise of personalized medicine to be realized. Challenges include the development of viable business models and the lack of reimbursement policies that recognize the value of companion diagnostics. In addition, laboratory-developed tests are being used extensively, but not always with proper validation, and the Food and Drug Administration (FDA) is struggling to provide regulatory guidelines that address this issue without stifling innovation.

A panel of diverse experts, moderated by Wendy Selig of the Melanoma Research Alliance, came together at Partnering for Cures to discuss the realities and opportunities in the world of molecular diagnostics. Several themes emerged during the discussion, including:

• Regulatory gaps – for example, laboratory developed tests – are creating uncertainty, particularly when it comes to reimbursement.
• Managing next-generation data in a productive way will be key to optimizing the potential of molecular diagnostics.
• Payers are fundamentally optimistic about personalized medicine but cynical because of experience.
• Though we have a lot of information, we don’t always know what it means.

David Parkinson of New Enterprise Associates, who spoke from the perspective of a clinician turned drug developer turned investor, pointed out that there are major disconnects in the world of molecular diagnostics – from regulatory expectations to payment incentives – that impede our ability to take advantage of the technology. “Until these disconnects are brought into equipoise, the question remains: who is going to develop these highly predictive tests, these biological characterizations of patients that allow clinicians to make personalized treatment decisions based on an individual patient’s tumor?”

Michael Pellini of Foundation Medicine underscored this point by highlighting the practical challenges that need to be addressed. “If we continue to think about each molecular test for a targeted therapy as a single test in which the clinician needs to be brilliant enough to single out the markers that he or she will test for in that patient and be right, that is challenge number one,” he explained. Pellini also pointed to other practical challenges, including the question of whether there will be enough tissue from a biopsy to conduct each test and how push-back from payers on reimbursement could impact use.

Jeffrey Trent of The Translational Genomics Research Institute (TGen) added that although technology has led us to a place where we can make informed treatment decisions based on molecular genetics, it is important that we do not overlook patients who do not have genetic alterations that can be specifically targeted by drugs. This is a challenge that TGen is addressing by conducting clinical trials in patient populations who cannot be stratified and treated based on genetic lesions.

Alberto Gutierrez of the FDA discussed some of the challenges with respect to the regulatory environment. He explained that the regulatory environment in this area is not clear and that a lot of the molecular testing that goes into diagnostics are laboratory-developed tests, which are not regulated by the FDA. Despite this gap, Gutierrez said that the FDA is more interested in clinical validity than clinical utility when it comes to molecular diagnostics. He explained the importance of ensuring that these tests provide physicians with meaningful data that they can understand and use confidently when making treatment decisions.

Sean Tunis of the Center for Medical Technology Policy provided the payer perspective. “Payers are fundamentally optimistic about personalized medicine, but cynical by experience because they know that they aren’t going to get exactly what they were promised in terms of savings,” he said. Tunis explained that payers are most concerned that the smaller populations of patients as a result of stratification by genetic subtype will lead to higher cost due to low demand for each individual test. He also said that payers are worried that in cases where risk outcome is low, clinicians may decide to continue with a more aggressive treatment path. In these cases, not only is the test reimbursed, but payers are also paying for a therapy that may not be necessary for the patient.

In conclusion, Selig asked the panelists what they think is the most important change that we need to pursue right away. Everyone agreed that first and foremost, we need not become overly engulfed in exploratory technology, and instead continue to make sure that we can treat the patients that need treatment today. Parkinson and Tunis highlighted that important changes need to be made with respect to reimbursement for diagnostic tests. As Tunis put it, “Whenever we get the regulatory framework figured out, we then need to tie it to reimbursement.”

A Great Opportunity for Medical Research Philanthropy: Fund Team Science

by LaTese Briggs, Philanthropy Advisory Service Program Analyst, FasterCures

As seen in Philanthropy News Digest:

Today we are plagued by a variety of vexing and complex diseases. Many of us are affected, directly or indirectly, by cancer, HIV/AIDS, diabetes, and heart disease. While there is indeed an army of researchers working persistently to find cures and lifesaving treatments to these and other diseases, the rate at which they are making discoveries is impeded by limited resources and a reward system that discourages collaboration.

While there is a common misconception that most biomedical discoveries that lead to new treatments originate in the laboratories of major pharmaceutical companies, many groundbreaking discoveries are actually made in the labs of academic researchers. These labs are usually severely underfunded, and the intrinsic reward system and career growth opportunities for researchers almost exclusively hinges on the amount of grant funding they are able to secure. In a constrained and highly competitive funding environment, this often indirectly discourages collaboration among researchers, thus slowing progress on finding answers to complex questions in medical research.

Unfortunately, the development of new technologies such as genome sequencing has led the academic research community to realize that many diseases are more complex than originally thought. To tackle the biological complexity of these diseases, researchers across different disciplines need to work together. But to enable this type of "team science," we need to reconsider how the structure of philanthropic research funding affects the research itself and acknowledge that in order to improve the current research paradigm, we need to change the way academic research is funded.

Recognizing this, a new model for medical research philanthropy with an emphasis on scientific collaboration is being brought to fruition at institutions such as the Howard Hughes Medical Institute, the Scripps Research Institute, and the Broad Institute of Harvard and MIT. Each of these institutes initially was funded by seed money from private donors, and each has gone on to become a dramatically successful nonprofit research organization at the forefront of biomedical science. And because they unite multiple academic institutions and bring together experts from various disciplines to work on high-risk, high-impact projects in the absence of traditional funding barriers, they promote collaboration by their very design. The results speak for themselves. Some of their contributions to biomedicine to date include identifying new genetic risk factors for diseases such as schizophrenia, bipolar disorder, and autism; the classification of human cancers by their genomic alterations rather than by their location in the body; and the identification of key genes that regulate stem-cell development. These initial successes have attracted more traditional capital (including public-sector investments) to the field and promoted additional giving by other philanthropic organizations, further expanding the pool of capital available for high-impact research.

But you don't need tens of millions to found a new institute to make an impact in the team science arena. Donors and foundations can choose instead to fund interdisciplinary teams or multi-center collaborations focused on biomedical discoveries with the potential to lead to new treatment options and cures. Philanthropic gifts can also be directed to organizations like the Melanoma Research Alliance, the Michael J. Fox Foundation, and the Burroughs Wellcome Fund that already fund team science.

Philanthropic opportunities in medical research — funding team science among them — will be a hot topic at our annual Partnering for Cures meeting, November 28-30, in New York City. At this year's meeting, more than seven hundred venture capitalists, philanthropists, policy makers, biotechnology and pharmaceutical company executives, patient advocates, and medical researchers will gather for a series of engaging panels and one-on-one meetings, with the ultimate goal of advancing the field of biomedical research and finding cures to a range of diseases. Partnering for Cures is uniquely positioned to introduce new and emerging foundations and philanthropists to the fundamentals of medical philanthropy and to provide more seasoned givers with a range of due-diligence opportunities. We hope you'll join us in further exploring how we can all work together to facilitate the flow of philanthropic capital into medical research in the most impactful ways possible.

About FasterCures and the Philanthropy Advisory Service

The FasterCures Philanthropy Advisory Service (PAS) was specifically created to help philanthropists make informed investment decisions on giving to biomedical research. Since its inception, PAS has successfully channeled funding to a number of high-impact collaborative biomedical research projects and has created a pair of giving guides: Getting Started: The Medical Research and Development Primer and Giving Smarter: Building a High-Impact Medical Philanthropy Portfolio.

About LaTese Briggs

LaTese Briggs is the Philanthropy Advisory Service (PAS) program analyst at FasterCures. Briggs previously served as a pharmaceutical market analyst for Decision Resources, a Boston-based research and consulting firm serving the biopharmaceutical industry. In that capacity, she provided expert analytics on the state of research and clinical development, including research challenges, market drivers, and unmet patient needs in the infectious disease space. She is trained as a biochemist and completed her doctoral studies at the University of Maryland Baltimore County and her postdoctoral training at Harvard University/Broad Institute, where she focused on chemical biology and early drug discovery. In addition, she has received a number of honors, including being named a Gates Millennium Scholar, and has authored several scientific articles.

Public Service Announcement Inspired by Danny Federici

The Melanoma Research Alliance has partnered with Bruce Springsteen, the E Street Band, and the Federici family to alleviate suffering and death from melanoma. Please view Bruce Springsteen’s public service announcement inspired by Danny Federici. Danny was the E Street Band’s organist and keyboard player. He died on April 17, 2008 at Memorial Sloan-Kettering Cancer Center in New York City after a three year battle with melanoma.

Glass Half Full

FasterCures has been helping to incubate a new disease research entity – the Melanoma Research Alliance. The Web site went up recently (www.melanomaresearchalliance.org) and the first funding RFP is out (details can be found on the Web site). We took lessons learned from the experience of the Prostate Cancer Foundation and other disease research groups, and shortened the number of pages for the funding proposal, condensed the review turnaround time, and we will send grant award notifications out in spring.

By coincidence, I had a routine appointment with my dermatologist right after our State of Melanoma Research Call to Action meeting in November. When I mentioned to my dermatologist that I’d been part of the process to create this new melanoma entity, he replied that we already know all about melanoma but of course new funds for research were always a good thing.

More money can help, but that being said, this non-scientist would posit that we don’t have all of the answers. The American Cancer Society estimates almost 60,000 people in the United States were diagnosed in 2007. Additionally, 15 percent of those with metastatic melanoma will live for five years. It got better, or worse. When I asked if I should be getting a full body check since I’d been a lifeguard through my teenage years and spent most waking moments poolside, the reply was “sure, that is a good idea.” Hmm, I thought it would be a good thing if it hadn’t been my idea, but at any rate, I made an appointment. However, even if it is a good idea, detection methods still need to be improved and are currently imprecise.

Certainly knowing one or two more cures than we know now would be a major improvement and would save thousands of lives. It is certainly of concern when the medical profession’s knowledge of what is known and not known is lagging. Much to do. While this story might end on a negative note, I’ll go with the glass half full approach, since I am invigorated by the prospect of what the newly formed Melanoma Research Alliance will be getting done in 2008 for those currently diagnosed with melanoma and those at risk. Here's to getting the research done in a streamlined way, getting results translated into therapies as fast as possible, and getting up-to-date information to clinicians who are on the front lines.

Margaret Anderson, COO, FasterCures