CNS Drug Discovery & Development 2012: Problems, Promises and Solutions
President, RHL Consulting, LLC
BioPharmaceutical CNS Drug Discovery and Development
Professor of Pharmacology and Clinical Neurosciences
University of New England, College of Medicine
Q: Over the last 30 years how have you seen drug development evolve?
A: Over the past 30 years, the discovery of new chemical entities and bringing them to the market place has significantly decreased. In fact, if you look over the past 50 years, the number of new chemical entities that have come to the market versus the dollars spent has halved every nine years over that period. So there really is a crisis occurring in the pharmaceutical industry, in terms of our ability to develop new drugs and in particular, within the central nervous system and in psychiatry. However, there are ways that are going to be developing over the next several years that should try to stem this process.
Q: What do you see in the near future, for better or worse, in drug development and research?
A: Well, I think that several things have occurred. The most difficult part of the process has been the inordinate amount of time it takes to do the preclinical discovery. In many cases the preclinical discovery, while it gets done, does not produce compounds and drugs that are eventually validated within the clinic, for the clinical indication. So much of the industry, right now, is beginning to focus on the short-term strategy of repurposing old drugs for new indications, and the assessment of compounds that have been tested for one reason or another, within the clinic and found to be either not efficacious, or the program has been stopped, or not able to get safely into the human. So there are potentially ways for us to begin to have the drug tested in humans where many of the diseases, particularly in psychiatry, are really fully phenotypically expressed. This would avoid the deficits within the current models that are being used. So, I would say, there is promise in our ability to alter the regulatory process that may make this a bit easier.
Q: What specific role(s) does industry, the NIH, Private Philanthropy, FDA play in the future of drug development?
A: The fact of the matter is drug discovery is best done by people that are focused in the area of drug discovery. It really needs the support of a team of investigators ranging from medicinal chemists to pharmacokineticists, looking at PKPD relationships, looking at metabolism, and ultimately looking at safety and toxicity, so there is a rationale for the pharmaceutical industry. The issue is, at what point are they most effective? I would say they are most effective in diseases in which we can identify a clear target, and I would have the industry put the full brunt of force that they have in medicinal chemistry, virtual screening, high-throughput screening, and com matura chemistry; bringing that to bear on targets that have shown some validation.
This will be particularly evident over the next several years, as it is this year, particularly in oncology where we can do that kind of thing. To what extent we will be able to do this in the future, in neurobehavioral disorders, will really depend upon the basic science that is expended within academia to better understand the pathophysiology, systems and circuits that are involved with these particular diseases.
Finally, I think it’s also important to recognize that the FDA needs to understand that many of the drugs that are coming out will need exposure to a greater population of patients, to begin to understand more fully their impact both in terms of efficacy and safety. While we can certainly demand that prior to a drug being marketed, the drug have significant efficacy for the disease indication, it seems unattainable to guarantee that a drug is 100 percent safe. The FDA really needs to move from a cross-sectional approval to a longitudinal approval, and look at it as an approval process that basically looks first at initial approval and phase 4 studies and then looks over time at patient safety data while monitoring closely the exposure of the drug to the populations we are treating. This will then assure that we optimize our ability to get drugs to the patients that need them rapidly, while also assuring the best safety measures we can.