Terra Sigillata

A paper in last month's issue of Nature Reviews Drug Discovery reported that US drug approvals during 2007 were the lowest number since 1983. (17 new molecular entities and 2 biologicals; see this figure for 1996-2007 data.) The review cites increased regulatory action as a factor in this reduction, especially following high-profile post-marketing safety issues with blockbuster drugs like Vioxx or Avandia. But other commentators have noted other problems such as the science of drug discovery in pharma being overridden by managers or the reluctance to develop agents for diseases that afflict less-than-blockbuster-sized patient populations.

I mention this in light of an article earlier this week by Sabine Vollmer of the Raleigh News & Observer on the establishment of drug discovery centers at Duke University and the University of North Carolina at Chapel Hill, each of which are led by former pharmaceutical company scientist/managers. Vollmer notes that Emory and Vanderbilt University have established similar programs. I believe that Vanderbilt has even invested in its own GMP drug manufacturing facility and was probably one of the first to have such a concerted effort.

NIH maintains intramural drug discovery and development programs and its extramural funding programs to academic drug discovery centers has expanded in the last several years. Traditionally, pharmacy schools and departments of chemistry have been the academic nuclei around which drug discovery and development was often seeded. That's where novel small molecules have traditionally come from academia and colleges of pharmacy often have the drug metabolism and preclinical/clinical pharmacokinetics expertise to get a drug to the point that might interest pharma in an outlicensing deal. As an example, the semisynthesis of the natural product antitumor drug, Taxol (paclitaxel), was licensed by Bristol-Myers Squibb from the laboratory of Robert Holton at Florida State University's Dept of Chemistry. (An engaging and detailed story can be found at FSU's Office of Research.)

But where will these new, concerted academic drug discovery programs fit in, especially if they are led by former Big Pharma scientists?

Pharmaceutical medicinal chemist and pioneering science blogger Derek Lowe at In the Pipeline discussed his own thoughts on the role of academia in drug discovery. Dr Lowe argues that while primary drug discovery requires huge, non-academic resources, university researchers can and should do what they do best to augment the process:

Another place where some academic thinking could come in very useful would be in attacking the important pharmaceutical processes that we don't understand: things like pharmacokinetics, oral availability, human versus animal toxicology, and (lots of) better disease models. The inefficiencies in these areas caused by our lack of knowledge are costing everyone billions of dollars - any improvement at all would be good news. Of course, it's not like the industry hasn't taken a crack at them, too (after all, there are those billions of dollars out there to be rescued from the bonfire). But we really need every approach we can get, and some fresh thinking would be welcome.

One thought is that, as I began this post, that academic centers may have more interest in working on therapeutics for diseases being overlooked by pharma, primarily due to economic reasons. I also think that the presence of faculty with pharmaceutical industry experience might inject some reality into the thinking of basic scientists who think they have a great compound when one need only look at the structure to realize it will be glucuronidated to hell.

Universities, in thinking more and more as revenue generating corporations, are probably looking at these drug discovery centers as cash cows. Again, there needs to be another injection of reality: the expectation should be no more than these centers will be great places for research and in training of scientists who are better equipped to enter the pharmaceutical industry than your average molecular biologist. One might hope that university leadership might have a longer view toward the time from investment to payoff (especially in investigators must obtain NIH funding for their efforts after the initial university investment has been consumed), as contrasted with pharma lead discovery efforts that last no more than 9-12 months before moving on.

So, universities must also have the appetite for investment and recognize, as pharma has learned, there are a lot of failures before there is a big hit. Only time will tell if this "new" approach will improve on traditional academic drug discovery efforts.