The Future of Drug Discovery and Development

The future just ain’t what it used to be.

–Attributed to Yogi Berra.

Like most people, the author always been fascinated with forecasts of life in the future. He keenly remembers as a teenager during the 1950s and as a young adult in the early 1960s reading as much as possible about the world we were going to live in during the 1970s and 1980s. Most people went to work in helicopters or drove in accident-free cars guided by electronic sensors placed in the roadbed. Africa would be relatively peaceful after the last of the colonial powers departed. Famine would be eradicated because of high-yield crops that were part of the “green revolution,” as well as because of improved distribution systems. These improvements would lead to a higher standard of living in the Third World. On the negative side, nuclear bombs would be developed by about a dozen countries in the 1960s, by about 25 in the 1970s, and by almost any country that wanted to have one in the 1980s. These and many other major predictions never came to pass. Traffic is worse than ever today, driving is not much safer, peace has not yet come to Africa, and famine still exists. On the other hand, a number of revolutionary changes barely conceived of in the 1950s are with us today, such as advanced supercomputers, a plethora of information on almost any subject available almost instantaneously, the presence of computers in daily life, and continuous high-speed communication among individuals and groups.

In the field of medicine and pharmaceuticals, many predictions from the 1950s and 1960s have also been wrong. Table 115.1 lists some of these predictions. The state of drug and pharmaceuticals in 2008 would be recognizable and comfortable to most people from 1960. The author expects that the medical world of the next ten to 30 years also will be very recognizable and comfortable to most people alive today. Most of the highly touted guesses and predictions of future revolutionary changes in medicine currently discussed in both professional and lay literature will turn out to be wrong. Those predictions that come to fruition will be scattered among many wrong guesses made by the prophets of today.

Most predictions of revolutionary change in medicine are pure “hype.” They are primarily fostered by reporters looking for stories and by scientists and clinicians seeking to promote their own work or to obtain publicity and recognition that can be turned into grants, tenure, and other career enhancements. True, there will be breakthroughs and unanticipated changes, but it is almost impossible to predict which ones will occur and when they
will occur and to distinguish them from the increasing level of hype.

Table 115.1 New drugs and techniques predicted to be “right around the corner” for over 25 years that have not yet achieved their predicted degree of success

1.	Liposomes as a common delivery vehicle for new and old drugs
2.	Nonaddictive strong analgesics
3.	Major breakthroughs in the use of drugs for treating patients with schizophrenia
4.	Cognition-enhancing drugs
5.	Drugs implanted under the skin to treat a large variety of diseases
6.	Delivery systems to bring cytotoxic chemicals to only carcinogenic cells and tissues
7.	Numerous promising drug-discovery technologies highly touted as solutions to the lack of new drugs

The following are some valid questions about the future of drug discovery:

In which therapeutic areas will new and important drugs be discovered?
Which scientific targets (both old and new) will prove to be fruitful?
Which new technologies and approaches will be found to be useful in discovery research?
How will most new drugs be administered, absorbed, and exert their pharmacologic actions? Some of the currently used technologies being studied include nanoparticles added to drugs to target specific organs, contact lenses to measure blood glucose levels, vaccine patches, and rapidly dissolving drugs placed under the tongue like some breath fresheners.

Table 115.2 Trends in the medical field that will affect pharmaceutical companies

1.	The genetic code will be mapped in greater detail, and its functions will be better understood.
2.	Genetic therapy will become a reality, with patients receiving genes that replace or supplement their deficient or defective ones (i.e., primarily in inborn errors of metabolism).
3.	Electrocardiograms and complex imaging results will be telemonitored and sent to physicians’ offices for analysis from remote locations.
4.	Patients will receive more elaborate treatment while in ambulances, including blood substitutes.
5.	Monoclonal antibodies and other targeting methods will be used more widely to treat patients; these will be targeted to reach specific sites, tissues, or organs.
6.	Improved methods of delivering drugs will become available.
7.	Improved knowledge of the chemical structure of targets for new drugs; these are primarily at the active sites or receptors on proteins.
8.	The number of targets available for drug discovery will increase greatly, but the challenge of knowing which will give feasible results will remain.
9.	Discoveries of previously unknown compounds in the body and the use of some of these as therapeutic agents will occur.
10.	There will be greater awareness and utilization of circadian and other biological rhythms.
11.	Synthetic vaccines that can control more diseases will be discovered.

The answers to these questions will affect, and be affected by, the research directions followed by large and small pharmaceutical companies. For example, it is possible that new oral drugs will be discovered to treat effectively a wide range of presently untreatable or inadequately treated viral diseases. Another possibility is that novel delivery systems will be used to direct anticancer drugs to just those organs affected by a tumor. A third possibility is that genetic experiments will result in the ability to replace defective genes in utero or shortly after birth, curing specific genetic-linked diseases.

Additional and even more revolutionary approaches to new drugs may be discovered (see Chapter 16). The first challenge to pharmaceutical companies will be, as now, to determine where to focus their research efforts. A list of some trends in medicine that are likely to be extremely important in the future is shown in Table 115.2.

The pharmaceutical industry must decide in which therapeutic areas to place resources and which specific types of targets, methods, and approaches should be used. In making these decisions and choosing a direction to pursue, scientific managers may adopt a cautious evolutionary approach or they may take the risk of applying large amounts of resources toward one or two revolutionary approaches. The author believes that an evolutionary approach leads to better planning for future drug discoveries. Some companies that invested huge amounts of money toward the end of the 1990s in genetic-based research were clearly too far ahead of their times and lost substantial amounts; whole start-up industries have arisen and essentially disappeared.

NEAR-TERM, INTERMEDIATE-TERM, AND LONG-TERM (I.E., DISTANT) FUTURES

Planning for the near-term, intermediate-term, and long-term future requires totally different approaches (Table 115.3). Planning for the near-term (i.e., up to approximately two years) involves assessing ongoing work (past and present trends) and anticipating events that may have an impact in the future. Realistically, simply projecting the present trends over the next 24 months is generally sufficient to develop appropriate plans, as long as all factors that may affect the near-term future are considered and their probable influence incorporated in the plans. But at the same time, longer term planning must not be neglected.

The two- to ten-year horizon (i.e., intermediate-term future) for commercial introductions of new drugs focuses on projects currently in the development pipeline. Most drugs that can be introduced within the next decade are either in the laboratory or advanced preclinical testing or already in the clinic. New serendipitous clinical uses of existing drugs are likely to be discovered as well. While it is impossible to predict specific new methodologies that will be used to discover drugs, many people are researching nonanimal models of testing compounds (e.g., computer modeling and simulations), genomic and proteomic techniques for diagnosing disease subtypes, and other techniques that may yield new approaches to discovering drugs. The dilemma in discovering and developing therapies for specific disease subtypes is the corresponding slicing of the market into smaller sizes, coupled with the resistance of payers to allow price increases to escalate at exponential rates.

The period beyond ten years is arbitrarily defined as the long-term or distant future. Chapter 34 describes one approach to viewing the intermediate-term and long-term future that focuses on various environments (e.g., regulatory, social, political, academic, medical and healthcare, commercial, and internal company).

This distant future is the focus of the rest of this chapter.

Table 115.3 Major influences to consider when predicting the future

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