December 2013, Vol 2, No 8

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Personalized Medicine and the Biopharmaceutical Industry: The Marrying of Science, Research, and Policy

An Interview With Dr William Chin of the Pharmaceutical Research and Manufacturers of America

Dr. William Chin

Interview with the Innovators

Dr Chin is an internist and endocrinologist who spent much of his early career studying the molecular mechanisms of hormonal control of gene expression. After 25 years in academia, including positions as investigator at Howard Hughes Medical Institute, Professor of Medicine at Harvard Medical School, and Chief, Division of Genetics at the Brigham & Women’s Hospital, he joined Eli Lilly and Company in 1999 as Vice President of Discovery Research and Clinical Investigation. In 2010, Dr Chin returned to Harvard Medical School as the Executive Dean for Research, Bertarelli Professor of Translational Medical Science, and Professor of Medicine. Currently, Dr Chin is Executive Vice President for Science and Regulatory Affairs for the trade group Pharmaceutical Research and Manufacturers of America. Dr Chin received his AB in chemistry from Columbia College and his medical degree from Harvard Medical School.

The Pharmaceutical Research and Manufacturers of America (PhRMA) was formed in 1958 to represent America’s biopharmaceutical research companies and to seek essential alignment between public policy and medical research to address patient needs. Its members are committed to finding treatments and cures for some of the most serious diseases such as cancer, Alzheimer’s disease, cystic fibrosis, and Parkinson’s disease.

PhRMA’s mission is to conduct effective advocacy for public policies that encourage discovery of important new medicines for patients by pharmaceutical and biotechnology research companies.

PhRMA maintains that a vibrant biopharmaceutical research industry is critical to patients and global health. Continued US leadership in biopharmaceutical research and development is foundational to American economic growth and competitiveness. This requires a business environment that inspires and rewards investment in research and development, while recognizing the unique risks and costs of the industry’s marketplace; a thriving and collaborative scientific ecosystem that advances knowledge and innovation; a modern, transparent regulatory system that evolves with the science to bring safe and effective medicines to patients quickly; and a proper valuation for innovative medicines.

PhRMA companies spent an estimated $48.5 billion in 2012 to discover and develop new medicines. More than 300 new medicines were approved by the FDA in the last decade, and roughly 2900 compounds are currently being studied in the United States alone – more than in any other region.

Headquartered in Washington, DC, with offices in leading biopharmaceutical research communities, PhRMA advocates in the United States and around the world on public policy issues critical to the discovery and development of innovative medicines.
The publisher of Personalized Medicine in Oncology (PMO) had the pleasure of interviewing Dr William Chin, Executive Vice President for Science and Regulatory Affairs for PhRMA, at the recent meeting of the Personalized Medicine Coalition where Dr Chin was a presenter. The two discussed the role of PhRMA in the healthcare system, the definition of “discovery ecosystem,” and the value of personalized medicine.

PMO Thank you for meeting with us today, Dr Chin. To begin our discussion, how do you define personalized medicine?

Dr Chin This is actually a difficult question because personalized medicine means something different to everyone. I think the best description of personalized medicine is getting the right drug to the right patient at the right dose at the right time. A key idea in personalized medicine is that in a real sense everybody is different. People with what we consider the same disease will have the disease appear differently, respond to therapy differently, and will have different complications.

Personalized medicine is a field that is based on the hope that we can utilize specific individual information to help our patients so they can truly have the best medicine for a specific disease or condition, with the appropriate efficacy and safety.

PMO Can you please describe the role of PhRMA in the healthcare system?

Dr Chin PhRMA is a major trade organization that represents the majority of large- and medium-sized pharmaceutical companies in the United States, which ultimately means many companies throughout the world because many of our companies are multinational.

A key goal of PhRMA is to advocate for policies that favor the maintenance of innovation in the system. It seeks to assure that the science voice is heard, and that science advocacy will allow personalized medicine to continue to grow and flourish.

In my talk [at the Personalized Medicine Coalition, November 2013], I referred to the number of barriers that I think we continue to face. If we don’t deal with these barriers effectively, I think it will greatly slow the growth of personalized medicine and the future of medicine.

PMO Can you talk about some of those barriers you foresee?

Dr Chin I’m happy to highlight a few of these for you. One obstacle is how our regulatory system looks at diagnostics. The FDA is making great progress here, but I think there’s still more to be done. I think the agency needs to clarify the necessary qualities of a diagnostic in order for it to be approved. The FDA talks about how biomarkers and diagnostics could be qualified relative to context of use. I think the FDA can make it even more clear in terms of how that’s done so that those who want to develop them have a better understanding of the goal line.

I think regulatory systems also need to appreciate how a potential therapeutic can be developed along with a companion diagnostic, and not allow one to slow the progress of the other. Right now they’re approved by different parts of the FDA, and while there is ample interaction, sometimes there can be better communication.

Another hurdle is the issue of how payers rely on mandated clinical effectiveness research to make decisions. If we’re not careful about how we utilize that information, payers might decide not to fund therapies for personalized medicine by saying, “You might have been convincing in a relatively small randomized controlled trial, but you need more data to prove outcomes in much larger cohorts.”

Thus, an obstacle is decision making – on what data do you base your decisions? Do they require a randomized controlled trial? What about the role of observational studies? Can studies using nontrial data such as medical records or claim reports demonstrate whether a drug works and is safe, even though they are not a gold standard approach?

PMO The term “discovery ecosystem” is used quite frequently when we talk about drug development. Can you please define this term and describe the impact of PhRMA on its maintenance?

Dr Chin The term “ecosystem” is thrown around a lot, and the “drug discovery ecosystem” is also used quite frequently. What do these terms mean? First, we understand that making medicines is a very difficult process. It is challenging for a lot of reasons, but I believe the main one is that diseases are generally complex in origin. Diversity can also affect disease expression in what we call heterogeneity of disease. Different patients with the same disease can manifest their illness in variable ways. Hence, our knowledge is incomplete, and yet we are asked to make medicines that are efficacious and safe in these uncertain settings.

The “ecosystem” refers to the many groups and institutions that are necessary in order to make a medicine. These include not only companies in the pharmaceutical industry, but very importantly, academic institutions and investigators, patient advocacy groups, and governmental agencies such as the FDA and the National Institutes of Health.

All these entities can come together to identify the important problems we need to face and to define the key unmet medical needs. They can also put their heads together to begin solving these very important problems. Cancer is one; another is Alzheimer’s disease. These vexing conditions will continue to affect our country and the world in terms of burden on health, burden on patients’ families, and governments. It will take the “ecosystem” to provide impor­tant solutions.

PMO In the advent of personalized medicine and companion diagnostics, biopharmaceutical companies face exciting and evolving scientific opportunities. Please comment on the ways in which PhRMA is working to advance the scientific processes to meet patient needs.

Dr Chin PhRMA is partnering with many groups – I’ve emphasized that we’re not alone in this – to attack the problem of defining and diagnosing disease more precisely. One way seeks to develop better biomarkers and how to qualify them. In other words, how do we make them sufficiently standardized and rigorous so they can be used in drug development for both preclinical and clinical trials by the FDA and others?

Also, PhRMA can help improve the understanding of how clinical trials can be conducted more effectively and efficiently. When you think about this in terms of personalized medicine, it’s kind of a “which came first, the chicken or the egg” situation. If you suspect a subpopulation will benefit from a certain kind of medicine, then you’d want to test it in that population. The problem is you still have to conduct a very large trial to find that subpopulation first. So until we can proactively identify subpopulations, we’re not going to be able to conduct trials as efficiently as we wish.

PhRMA is also working with the ecosystem to divine pathways for better implementation of clinical trials, improved trial design, and increased patient enrollment in studies. One of the major challenges is engaging patients from underrepresented minorities in clinical trials. There are a number of diseases such as prostate cancer that unfortunately is very prevalent in African Americans, and yet it has been difficult to have sufficient African American patients in those studies. We are also thinking about how we can better engage children in studies, but with obvious and appropriate safety considerations.

PMO As you mention, we still have to conduct the large-scale trials to identify subpopulations of patients that could benefit from a particular therapy. Can you expand on your comments about the discovery of biomarkers in oncology and the impact of the companion diagnostic?

Dr Chin Companion diagnostics and biomarkers will be critical if we’re going to make progress in finding new medicines for personalized medicine; new medicines and new diagnostics come hand in hand. A classic biomarker is a subject’s blood pressure, weight, or height. Imaging such as x-rays is also an example. We need to figure out how to bring all these signals together in order to help identify subpopulations. Now, at first, they might just represent a hypothesis, but if we think that there is a subpopulation that will respond to a certain medicine, then we could perform the experiment to determine whether that hypothesis is true.

PMO Is the Affordable Care Act (ACA) financially compatible with the growth of personalized medicine overall and specifically in oncology, or will its additional costs reduce the spread of personalized medicine?

Dr Chin I believe that the ACA will not limit the advancement of personalized medicine. It certainly doesn’t limit the hope for progress in this area. However, there are some features of the ACA to which we might pay particular attention. For instance, for our cancer patients, what effect will the role of comparative effectiveness research and health technology assessment have on determining whether a medicine will be reimbursed and hence accessible?

If you try to use the studies across the whole population, you might conclude that it really is not all that effective. On the other hand, if you focus on a subpopulation, you might conclude that it is. Comparative effectiveness research will need to work closely with the healthcare system. If not, this can limit the impact of the ACA on the future of medicine.

PMO Value is more than cost; it is the balance of quality, cost, and access. Considering the value proposition of personalizing medicine, how long will it take for personalized medicine to begin paying dividends economically and become attractive to payers by showing value? Further, how would you articulate the value proposition justifying the cost of personalized medicine in cancer and overall to the clinical business and government sectors and to patients?

Dr Chin This is a very important question because there is a current feeling that personalized medicine will end up being so costly that we won’t be able to afford it, and hence there will be limited access.

My view is that personalized medicine has already proven its value. In support of this notion, I would give you the example of Gleevec, or imatinib, for the treatment of chronic myelogenous leukemia. These patients with the Philadelphia chromosome often fare well on this medicine.

In the first couple years, we did not appreciate the full value of this cancer medicine because we didn’t know how many people would survive after treatment. A 6-year review is showing remarkable gains in patient survivor rates. And this is just 1 example.
So the point is that success with proof of value may take time to reveal itself. If you think about value in terms of paying for the medicine this year and an outcome the next year, then that’s 1 determination. But if you are able to follow the patient for a longer period of time, that positive value might reveal itself.

The other question is, what is the appropriate end point? Survival is one; there is no question of this. But how about quality of life; how about whether the individual goes back to work or lives long enough to be able to witness a granddaughter’s wedding? Sometimes we don’t account for these factors in our assessment of value, and we need to do that.

I would argue that if you can decrease the progression of diseases meaningfully or have significant prolonged survival, then you have achieved value for the individual patient and for the whole system. Ultimately, society will need to answer the question of what benefits need to be balanced by costs.

PMO Moving away from policy, I’m curious to know your opinion on immunotherapy’s place in personalized medicine. Do you view immunotherapy as a personalized approach to treating patients with cancer?

Dr Chin I don’t think we know enough about it yet. Some immunotherapies are highly personalized. So if you used a dendritic cell approach to vaccine therapy where you take the cells from the patient for his own use, I don’t see how we can get more personalized. Not everybody gets a response from a vaccine in the same way. It will vary between individuals, but also from vaccine to vaccine. What determines that? It’s likely the variation of the immune system from individual to individual.

So while I don’t have an example yet on this, I would predict that there will be many in the future where specific individual variation in immune response will require a personalized medicine approach to cancer immunotherapy.

PMO Thank you so much for your time and insights.

Dr Chin Thank you.

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