Fostering Pharma R&D

By Cliff Mintz Ph.D.

The economic downturn, coupled with impending patent expiry of several blockbuster drugs, has placed enormous financial pressure on many big pharmaceutical companies. One company that has managed to successfully weather the impending storm is the Swiss pharmaceutical giant Novartis.

Much of Novartis’ current success can be attributed to the creation of the Novartis Institutes for Biomedical Research (NIBR), the global pharmaceutical research organization of Novartis. Headquartered in Cambridge, MA, NIBR is a network of global R&D centers of excellence located in New Jersey, California, England, Switzerland, and China. Since its creation in 2002, NIBR has been guided and led by its president, Mark Fishman, M.D. I had an opportunity to talk with Fishman about NIBR, the institute’s current research, and its future.

Many of Novartis’ competitors are moving R&D operations to Asia and elsewhere. What were some of the factors that led to Novartis’ decision to locate NIBR’s headquarters in the United States?

> NIBR’s efforts have always been global, and our biggest research effort is in Europe, as it was when I first began working here in 2002. The main reason that we establish an R&D site in any location is the possibility of acquiring talent and stimulating our scientific programs. The various NIBR sites work synergistically not autonomously, and there is a free exchange of information. By all quantifiable measures — research output, employee morale, and talent acquisition — the investment in NIBR was a worthy and important one, and I believe we have been successful.

With regard to moving operations to China, India, Singapore, Eastern Europe, and elsewhere, I personally think it makes little sense in the long term to anticipate cost savings simply by moving to a country today that has a lower cost structure.

We have a very powerful R&D branch in Shanghai. We established it there because of the talent — not cost savings. Likewise, we established a group in Singapore because of the talent, not expenses. The issue has always been and remains what you can discover and where the science takes you. Certainly, repetitive functions can be outsourced, but the process of scientific discovery requires great talent. So, for us it has nothing to do with expenses or cost, just the science.

Many U.S. pharmaceutical companies have laid off tens of thousands of R&D scientists, and it is becoming increasingly difficult for American scientists to find jobs. Does this mean American scientists are less talented than they may have been in the past?

> I am not sure I agree that there is less scientific talent in the United States than there has been in the past. We still have the strongest system of government support for scientific and biomedical research as compared with any other country in the world. And, I think American science is still the envy of the world. There is no question that the economic downturn has affected the scientific enterprise in the United States, and I worry that this may be a problem for future generations of American scientists.

Nevertheless, what has happened in recent years is that talented young scientists from Asia and elsewhere have had the unprecedented opportunity to train in the United States — mainly because their governments have become less rigid and more open. This has allowed foreign scientists to train in the United States, pick up valuable skills, and take them back to their home countries. Because of this, we are now able to access scientific talent all over the world. While job opportunities for American scientists may be fewer than in the past, I believe that these trajectories are self-correcting, and the situation will likely be different in the not-too-distant future.

What therapeutic areas exhibit large unmet needs and represent possible new opportunities for NIBR?

> Novartis is a pharmaceutical company that is clearly driven by unmet medical needs. But, unmet medical need is only half the equation; the other is scientific tractability and the ability to compete.

Oncology and immunological diseases are two therapeutic areas that will undoubtedly grow over the next few years. However, there has been a tendency on the part of many pharmaceutical companies to emigrate from cardiovascular or neuroscience R&D because of the difficulties of developing new drugs in these areas.

At Novartis, we believe that cardiovascular and metabolic diseases still have huge impacts on society and are growing, serious problems in the developing world. Because of this, we have chosen to not exit these areas and believe there are still novel and tractable approaches to develop new medicines to treat these disorders. In general, we go where the medical need is great, and the science allows us to strategize and take some calculated risks. Along with our focus on cardiovascular and metabolic diseases, we are committed to antimicrobial drug discovery (including antiviral, antibacterial, and antiparasitic drugs) for both the developed and developing worlds. Also we have strong programs in biomarker development, regenerative medicine, and translational medicine.

Many big pharmaceutical companies are reducing their emphasis on small molecule drug discovery in favor of protein-based drugs. Do you think biotechnology will reinvigorate the pharmaceutical industry?

> No technology alone ever suffices in this industry. That said, low molecular weight drugs, protein-based therapeutics, siRNA, and other entities will play an important role as drugs in the future. I don’t see any way to determine which type of therapeutics will dominate, but I would be surprised if there were any major changes in that direction over the next few years.

At present, NIBR has invested a substantial amount of effort into biotherapeutics, and roughly 30% of the institute’s early drug portfolio is biologics. As far as the future is concerned, it is difficult to say whether or not NIBR’s commitment to biotherapeutics will increase or decrease.

The decision to pursue one type of molecule as compared with another cannot be a strategic one; it must be based on outcomes that are mainly dictated by how the science goes. To that end, I don’t like to impose artificial constraints on our R&D directions; we will go wherever the science takes us. I suspect that in the future there will be ups and downs in the types of medicines being developed and that the approach to pharmaceutical drug discovery will remain balanced.

Therapeutic monoclonal antibodies (MAbs) appear to be the molecules of choice today at many major pharmaceutical companies (there are MORE THAN 300 in various stages of development). What are your thoughts on the use of MAbs as therapeutic agents?

> There is no question that interest has been growing about the use of MAbs as potential therapeutic agents. MAbs offer greater specificity against potential targets. This specificity sometimes helps to reduce side effects commonly observed with less targeted, small molecule medicines. However, by their nature, MAbs are injectable (not orally bioavailable like small molecule drugs) and are generally more expensive to make and use. This continues to help make small molecule discovery attractive. Consequently, the cost and bioavailability issues will continue to make decisions related to MAbs and biotherapeutics, in general, something of a balancing act.

What are your thoughts on personalized medicine, and what is NIBR’s commitment in this area?

> I think personalized medicine is a fascinating term, and I also think it is misleading. This is because “all medicine” to a physician is personalized. I hope that whenever I see a patient I deliver the best possible and most appropriate care for that individual. I think that the term personalized medicine is used as “shorthand” for a method that is driving the choice of medicine based on a molecular marker, usually a genetic one. There is little doubt that these methods will play a larger role, especially in therapeutic areas like cancer and immunological diseases where we have a refined and exquisite understanding of the science.

Personalized medicine will be extremely useful to determine whether or not certain patients will benefit rather than suffer from potentially toxic treatment regimens, especially for certain oncology indications. I believe personalized medicine is clearly the wave of the future for the cancer field. But there always will be a role for medicines that can be given safely to large populations of patients for common disorders. In these instances, personalized medicine may be unwarranted. For example, I don’t believe personalized medicine will be necessary or cost-effective for certain therapeutic areas such as hypertension. The safety and expense associated with specific treatments will likely dictate whether or not a personalized medicine approach is warranted.

While personalized medicine will clearly play a role in new drug development and as therapeutic and diagnostic tools in point-of-case settings (including doctor’s offices and emergency rooms), it is mostly, in my mind, semantic to talk about personalized medicine. As far as I am concerned, it is not distinctive, and it represents the next step in the natural evolution of medicine.

Many big pharma companies are looking to emerging markets to maintain profitability because growth is slowing in developed markets. What are your thoughts on the role of emerging markets in the future of the pharmaceutical industry?

> There has been enormous growth of the middle class in emerging markets in countries such as India, China, Russia, Brazil, and elsewhere. Middle-class people in these countries are willing and able to afford important new medicines, so it makes sense to look to these markets in anticipation of future growth. However, there is a second element that is frequently overlooked when discussing emerging markets in developing nations. That is, developing new medicines for people who are likely in the near future to be too poor to afford current medications. For example, in places like South America and sub-Saharan Africa it may be necessary to develop medicines that don’t require refrigeration to maintain efficacy and potency. There are many elements that go into thinking about making those medicines. Also, there may be an opportunity and need to develop so-called “regionalized medicines” to treat diseases that are problematic and unique to various regions in the world. Again, unmet medical need and the tractability of our science will dictate our level of commitment to developing new medicines on a global scale.

Has the investment in NIBR yielded the anticipated ROI, and what may the future hold for the institute?

> NIBR works in 10 disease areas including autoimmunity, transplantation and inflammatory diseases, cardiovascular and metabolic diseases, gastrointestinal disease, oncology, neuroscience, infectious disease, musculoskeletal diseases, ophthalmology, and respiratory diseases. We have developed expertise in analytical sciences, biologics, biomarker development, developmental and molecular pathways, chemistry and imaging technologies, metabolism and pharmacokinetics, proteomics, and preclinical drug safety with the primary goal of translating biology into medicine.

While the institute is only eight years old, we are beginning to see the initial fruits of our long-term investment in fundamental science, understanding molecular pathways, and our efforts in translational medicine. It may be a little too early to comment on ROI, but I can tell you that the future for us is making important, new high-impact medicines that can change the practice of medicine.

Used with permission from Life Science Leader magazine.