How much does the man or woman in the street know about pharmaceutical companies?
Certainly, those people know something. They know that drugs cost an awful lot, and suspect that pharmaceutical companies are profit engines that sit around waiting uneasily and charging high prices until their products become generic.
Dr. Palkowitz pulls back the curtain to examine other, potentially better, ways that pharmaceutical companies are expanding their world beyond drugs with information technology.
But many consumers, if they have had the wonderful experience of being cured by a drug, might feel somewhat differently about pharmaceutical companies. If they have a family member or friend whose health has been restored thanks to a wonderful new drug, they have a more positive attitude toward the companies that make drugs.
Few people, however, seem to realize that there is a deeply moral aspect to what pharmaceutical companies are doing. Some of their scientists have devoted their lives and remarkable intelligence to saving lives, restoring health, and defeating disease.
Dr. Alan Palkowitz recently retired from Eli Lilly and Company, where he served for 28 years. His most recent leadership role was Vice President of Discovery Chemistry and Research and Technologies. At Lilly, he supervised the work of more than 500 scientists and was responsible for small molecule (oral medicines) drug discovery for diseases that include cancer, diabetes, immunology, pain and neurodegenerative disorders.
Dr. Palkowitz’s love of chemistry and biomedical research began early in his life and his career has kept him at the leading edge of pharmaceutical research. As he enters a new phase of his career, he stands among the most knowledgeable medical researchers in the world.
Kevin Pereau: Medicinal chemistry and drug discovery is a highly specialized field of research that requires remarkable ability, experience and skill. How did you decide to dedicate your life to it?
Alan Palkowitz: My entry into research and the pharmaceutical industry was shaped by my undergraduate education at U.C. Berkeley. I was very interested in chemistry and in my second year, I started studying organic chemistry. And I really enjoyed it – organic chemistry could be called the chemistry of life, because it is fundamental to all living beings. I was inspired by a professor I had at Berkeley, Henry Rappaport. In the year when I started in his lab, he was focusing on structural modification of opioids, like morphine. Part of his research was trying to modulate their biological activity, with the goal of making painkillers non-addictive. It is an issue that is still important today.
I was working with graduate students in his lab, many of whom were thinking about their career direction. Several were going into the pharmaceutical industry, because that was where many job opportunities existed for scientists who could design and make molecules, which is a central aspect of drug discovery. In other words, scientists who wanted to find ways to create molecules that function as medicines. The idea of using the fundamental rules of chemistry to help people really excited me.
So that pretty much set me on my course. I wanted to further develop my skill as a chemist to prepare for a career in pharmaceutical research and so after Berkeley, I went to MIT for my doctorate. And after that, in early 1989, I began to look for job opportunities in the pharmaceutical industry. I accepted a job at Eli Lilly and that began my career. I entered as a bench-level chemist, working on therapies for cardiovascular diseases.
Kevin Pereau: How did you make the transition from chemist to a leader in Lilly’s enterprise and business activities?
Alan Palkowitz: Early in my career, I had a fairly rich experience as a laboratory scientist that was excellent grounding in the challenges and opportunities in drug discovery. I then gradually moved into managerial positions and began to take a larger interest in the broader dimension of the company, thinking about research in the context of business and the enterprise. During my time at the company, I saw a tremendous transformation from the early 1990s until today. Eventually, during my last 11 years at Lilly, I took on the position as Vice President of Discovery Chemistry and Research and Technologies, and I was responsible for small-molecule drug discovery.
I became very involved in building our pipeline of innovative medicines. And with that came a larger responsibility for the process of taking a therapeutic concept and converting it into a molecule that could be tested and developed for use in humans. And hopefully, one that could become a drug. That involved managing a large portfolio of projects, dealing with scientific complexity, differentiating our work from competitors, creating intellectual property, as well as making sure we were continually investing in promising science and technology that would keep us on the cutting edge of creating novel medicines.
Being with a company that is at the forefront of the race to find medicines has been tremendously fulfilling. I recently retired, at the end of last year. I am now planning to explore new types of opportunities in biomedical research.
Kevin Pereau: This is maybe too big a question, but what major trends have you seen during your years in the pharmaceutical industry?
Alan Palkowitz: Let me generalize first. Certainly, when I entered the industry, there had been a tremendous amount of progress in the previous decades in many disease areas. For example, in cardiovascular, statins and blood pressure medicines were dramatically changing the management of heart related disease. Additionally, many versatile options existed for the treatment of infectious diseases and was an area of major emphasis among many pharmaceutical companies. The control of diabetes, while still a growing problem today, had been advanced due to the availability of biosynthetic insulins. So that era was a time of tremendous growth and many companies began to venture into new areas of further unmet medical need. But during my time at Lilly, I think the trends have been marked by tremendous advancement in our understanding of disease and medicines at a more molecular level. And there have been more and more insights in developing new types of therapies and interventions—getting beyond the symptoms and focusing on the underlying causes of certain diseases that may someday lead to cures.
When I think about the past 30 years or so, we have gone from a reductionist approach to more of a knowledge-based approach, one that is now being informed by tremendous clinical learning and an increasingly large and accessible volume of data from patients. We are developing a deeper understanding of why some patients respond, and others don’t respond, to certain types of therapies, and why some therapies can be safer for subsets of patients in a given population. So we are peeling away layers to get a more fundamental understanding of diseases and how to address them. That has accelerated innovation, driven by novel insights and informed experimentation. And also, we are arriving at more sophisticated methods to visualize the potential interactions of molecules with target proteins, which gives us insight into how to attack disease and design better medicines at the molecular level.
Biotechnology is also now playing a bigger role in expanding the breadth of medicines that are available for many diseases. Several years ago, we had only a handful of biomolecular therapies like insulin or growth hormone, that mimicked natural proteins in the body. Today, thanks to the advancements in biotechnology research and development, the industry has created therapeutic antibodies and other complex proteins that have transformed the treatment of disease. In oncology, for example, we now have immune checkpoint antibody drugs that have dramatically changed the treatment paradigm of many tumor types.
For patients with rare single point genetic abnormalities, like hemophilia, we are seeing innovative gene therapy approaches progressing in development. These trends are exciting and could lead to curative paradigms for some rare diseases.
But even so, there is still a long way to go – a lot of opportunity ahead of us. We have made great progress in oncology and the ability to prolong life expectancy for some cancers has been great, but there are many tumor types where solutions are still years away. We still don’t have effective treatments for Alzheimer’s disease and few viable pain medication options. So the future will be informed by a greater basic understanding of disease and dependent on the collective work of academic and industry researchers around the globe to create new avenues of productive discovery.
Kevin Pereau: And looking ahead?
Alan Palkowitz: When I look a little bit forward, I think that the intersection of drug discovery and digital information will become much more important to improve overall patient outcomes. You can go all the way from discovery to a phase-three trial and find out the drug you are testing didn’t work, or wasn’t safe, or wasn’t better than standard of care. This is extremely costly both in terms of dollars and opportunity. So that creates a challenge, but also a great opportunity. One of the burdens we have in our industry is that we must continuously force the innovation frontier, the innovation curve. We need to focus on the best possible disease hypotheses, accelerate potential medicines in research and development that will have a large impact, minimize clinical failures, and find ways to improve drug access and compliance for patients. Continually harvesting knowledge and critical information from many sources of data along the value chain will be a key variable to addressing these challenges.
We must consider how we use patient data, clinical data, and research data to better understand the drugs that we are developing, whether they will have the impact we envision, and whether they will be safe. We need to think about how the drugs we develop will reach the patients who will derive the most benefit from them. For example, there are genetic fingerprints that suggest how certain patients are going to respond to certain drugs and how to administer those drugs more precisely. The ability to do that is central to precision medicine initiatives that maximize the impact of medicines and avoid treating patients that we know will not benefit. This is already happening in diseases such as cancer.
So, precision health is a very important trend and value proposition. One of the things that is going to drive it will be the ability to harvest learning and data that is associated with individual patients, along with the data from the many clinical trials that are ongoing today. That will yield insights into how some patients respond and some do not, and to help insure that the investments that drug companies are making will actually result in better outcomes.
In effect, that means trying to insure that better ideas will result in better drugs that will be valued by payers and providers, and which will ultimately have a profound impact on improving patient’s lives.
Kevin Pereau: You mentioned data. And since that is the subject of this book, can we talk about that again?
Alan Palkowitz: So that is where convergence is taking place, the place where the progress that has been made can now be amplified. Suppose we are able to use data to simulate clinical trials, or a trial for one individual, and understand whether he or she will respond or not respond to a particular treatment.
With data and modeling, we should be better able to understand what the transformative effects of a drug will be over a span of years. We should move toward developing predictive models and use them in the early research and development space before we ever study drugs in humans, so we better understand the potential outcomes. While likely to not be definitive, this approach may better inform the design of actual clinical trials as well as reduce costs of development. Again, I think the collective body of data being generated from so many places – from treatment, clinical trials, understanding the genetic basis of disease – is going to converge in some pretty special ways. Today, we are only beginning to scratch the surface.
Kevin Pereau: Does government regulation impede or help the adoption of new technologies?
Alan Palkowitz: I think everyone involved in the ecosystem has a vested interest in advancing health care. I think we all do, and I don’t think government has been an impediment. The FDA has been more proactive in its initiatives to speed up the approval of drugs that will have a positive impact on patients. The FDA also has a very important role, which is to ensure that we’re addressing patient safety. So, I think that is a very good relationship that will continue to evolve.
I think there is greater and greater sophistication in the FDA, for example, in understanding how to partner with the innovators in the medical space. It has been very exciting in the last year, really a breakout year in the development of new drugs. Forty-six new drugs have been approved. So that is a sign that there is a tremendous amount of progress being made, both in the industry and with regulators, to bring high-potential therapies to market as quickly as possible.
To get back to digital health, the pharmaceutical industry is increasingly interested in utilizing data to optimize the care of patients. And I think that making patients better informed and more in touch with their health care will ultimately improve their compliance, which is necessary to maximize the effectiveness of medications. Coming from pharma, I believe that medicines are only going to be effective if they are properly and consistently used . . . if they are matched to the individual patient for maximum benefit. And some of the digital health tools that are coming will specifically address compliance. We know, for example, that certain therapies can reduce the incidence of cardiovascular disease, but only if they are properly utilized every day. That would be a very valuable outcome when you think of the overall health care problem.
That is why at Lilly and many other companies, there is emphasis on approaches to connected care in applicable settings for disease management. For example, there are devices that continuously monitor blood glucose, and can administer insulin on demand, based on what is happening with the patient. And then you have information that is being collected and delivered to health care providers, so that medication can be adjusted when need be. Integrated approaches like those will be transformative.
I also think that there are now some big opportunities in chronic diseases, where there aren’t obvious signals when treatment is not effective. If you have diabetes and your blood sugar becomes too high or too low, you will know because of obvious symptoms. But if you have high blood pressure, unless you check your blood pressure, you might not even know that it is elevated. But if temporal data can be collected and shared by a device that assures that patients are aware of the need to take medicine, that can be very powerful.
I do think though, that there is oftentimes a tendency to overhype, to begin to extrapolate too far about what might be possible with information and associated technology. Of course, many things can be done with information. We will soon have more phone applications that will utilize artificial intelligence to gather and contextualize information as well as suggest action. You already have people wearing Apple watches that are reporting back to their physicians, but I think the key thing is that it must somehow lead to a meaningful action and outcome, and not just an information exchange or collection. And so, I think that as digital health evolves and many more ideas surface, some will emerge as important and impactful, while others will not be scalable in a meaningful way.
Overall, we are looking at ways to improve results and reduce the burden on health care systems. It is an exciting time ahead to see how data can be used in the most productive ways to make this possible.
Kevin Pereau: Let’s talk, if you don’t mind, about a story that has been making the news only recently – the merger between Aetna and CVS. Do you think that their merger serves as a predictor of other events to come?
Alan Palkowitz: In a sense, I think that the merger gives us a small glimpse of how different entities on the health care landscape will begin to cooperate in some very interesting ways.
We begin to see ways that different systems can work together. CVS is normally a place where people go to pick up their prescriptions. CVS stores also now have clinics where customers, in cooperation with their insurance providers, can enter into more of a partnership with CVS.
We are already noting that instead of going to emergency rooms when they have colds, for example, customers will visit CVS in-store clinics. That offers a way for individuals to go where they will find the most effective treatment option, in real time and at the lowest cost. That will be tremendously powerful. It will allow insurers to provide the most effective coverage for their customers, as well as for different providers within the health care community. It will eliminate waste. If you are a physician for example, you’ll be better able to focus your high-end skills on the patients who need them the most, not spending your time treating patients whose minor ailments can be dealt with by a nurse practitioner or at a walk-in CVS clinic, for example.
I think all the things we have been discussing have the potential to work together very proactively and have an impact. All the information that is being gathered will begin to serve customers more effectively with their medications, with their health care providers, with their insurers, and more.
Ultimately, progress will depend on new ways we find to contextualize information, integrate technology with devices, and maximize the impact of diverse contributions made by pharma, insurance companies, care providers, and others to improve health. It’s a broad, broad spectrum, and we are entering a very exciting time.
Dr. Alan Palkowitz is a drug discovery scientist who recently retired from Eli Lilly and Company, where he served for 28 years. His most recent leadership role was Vice President of Discovery Chemistry Research and Technologies. At Lilly, he supervised the work of more than 500 scientists and was responsible for small molecule (oral medicines) drug discovery for diseases that include cancer, diabetes, immunology, pain and neurodegenerative disorders.
Thank you, Thomas, for recognizing and tracking the trends on patient data and contributing to ‘The Digital Health Revolution’. – Kevin Pereau, The Digital Health Guy
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