Thursday, March 28, 2013

Drug Discovery- a Fair Share for Academia and the Feds?

An interesting letter from Senator Ron Wyden to Francis Collins, the NIH director, brings up the issue of public contributions to private drug discovery research (1). Specifically at issue is Tofacitinib a new anti-arthritis drug that grew out of a collaboration between Pfizer and an NIH funded academic investigator. Senator Wyden asks why isn’t some of the expected $2.5B in revenue from Tofacitinib being funneled back to the NIH. However, this letter underscores a much larger set of issues regarding the evolution of the partnership between academia, the pharmaceutical industry and federal funding agencies.

Currently much of the basic research that leads to new drugs is conducted in academia and is funded by the NIH or charitable foundations (2). Because of the Bayh-Dole act universities can glean some financial benefit by licensing intellectual property rights to companies that want to further develop the research. However, the feds are pretty much frozen out. Further, since much of the academic work deals with early stage research, usually the return on academic IP is small. 

While it is clear that the pharmaceutical industry must make major investments to convert early stage academic research to a drug, one wonders if the initial academic/federal component is being properly valued and rewarded. Rather than the haphazard system of shopping university IP around to various companies, a better approach might be to develop collaborative agreements that share both the risk and the reward of drug development. This would allow both academia and federal funding agencies to glean part of the enormous profits associated with successful drug development. Putting these funds back into fundamental research would create a sort of virtuous circle leading to increased numbers of promising drug candidates. An analysis of this type of activity has recently been published (3).

Interestingly the Wyden letter was recently discussed on the popular blog ‘In the Pipeline’.  Most of the commentary there stated that Sen. Wyden was wrong and the NIH had no business being compensated for its contributions. I think this is a very shortsighted viewpoint. We clearly need major changes in the drug development process to make it more efficient and less costly. A smoother integration of federal, academic and commercial research, with appropriate rewards to the parties, would go a long way toward that end.

(2) Stevens, A. J. et al. The role of public-sector research in the discovery of drugs and vaccines. N. Engl. J. Med. 364, 535–541 (2011).

(3) R.L. Juliano Pharmaceutical innovation and public policy: The case for a new strategy for drug discovery and development. Science and Public Policy (2013) pp. 1–13 (

Friday, March 22, 2013

Open Access to Clinical Trials Data?

In a potentially revolutionary development the European Medicines Agency (EMA) plans to begin broad public access to clinical trials data, including company reports. The exact format remains under discussion, but clearly this new approach will be radically different from former practices at the EMA and current practice at the FDA wherein commercially generated data is available only to the regulators but not the public.

There are clearly many positive aspects of the EMA’s plan. Thus it will allow unbiased academic investigators and other knowledgeable individuals to evaluate the entire clinical data set and not just limited material selected for publication or for posting on the US site. It also seems likely that early availability of clinical data will reduce the number (and immense cost) of essentially redundant trials of similar drugs done by different companies.

Some in the pharmaceutical industry have expressed strong concerns about the EMA plan. One potential problem involves intellectual property; open access to clinical data may prematurely reveal key IP and provide advantages to competitors. Another issue is that full access by the general public may result in health scares as data is misinterpreted by laymen. Perhaps the greatest concern regards patient privacy. Although the data would be anonymized, it is possible that security could be penetrated.

Likely the optimum resolution of these issues will involve some sort of ‘gatekeeper’ that will allow parties with legitimate interests to view the full data while screening out more frivolous requests. However, setting up a fair gatekeeping process will no doubt be challenging.

Despite some problematic issues, the EMA thrust is clearly a step forward in providing greater openness, rationality and productivity in the drug development process. 

Monday, March 11, 2013

Salute! Resveratrol does activate sirtuins!

There is a long and complicated story about the role of a class of enzymes termed sirtuins in ageing. Substantial evidence indicates that activation of these enzymes can have many positive health benefits and (at least in simple organisms) can extend the lifespan. This really got interesting a few years ago when it was discovered that resveratrol, a small molecule found in red wine, could activate SIRT1, one of the key sirtuins. Obviously this conjures up images of spry nonagenarians quaffing huge glasses of vino! However, the linkage between resveratrol and sirtuin activation has remained controversial. Now, however, a solid publication in SCIENCE has confirmed the link. This sets the stage for the pharmaceutical industry to pursue novel molecules that will act like resveratrol but be much more selective and powerful. Whether this will be of benefit to human health and longevity remains to be seen, but you can bet the race for anti-ageing drugs is on! 

Friday, March 1, 2013

Is the nanomedicine wave cresting?

The interdisciplinary field of nanomedicine has experienced a tremendous surge over the last decade. The potential implicit in applying the unique physical properties of nanomaterials to challenging problems in medical diagnosis and therapy has evoked great enthusiasm in the scientific community, the corporate world, and among the public. Many quantitative parameters indicate continuing rapid expansion of this field. Amidst this efflorescence of enthusiasm, however, there are a few voices of concern. 

For example, an article provocatively entitled “Cancer nanomedicines: So many papers and so few drugs! “ describes the difficult path for clinical development of nanoparticle-based drugs (1). Additionally a recent commentary in Nature Reviews Drug Discovery asks if the surging wave of nanomedicine is cresting. It mentions changes in funding prospects, growing realization about the limits of the technology, and problems inherent is the complexity and cost of nanomedicines.

Clearly nanomedicine remains an exciting and rapidly evolving field. However, it seems prudent to have a balanced view of its limitations as well as its potential, and not to oversell its benefits to the public.

Venditto, V. J. & Szoka, F. C. Jr. Cancer nanomedicines: So many papers so few drugs! Adv. Drug Deliv. Rev. 2013 Jan;65(1):80-8. doi: 10.1016/j.addr.2012.09.038. Epub 2012 Oct 1

More money, fewer PhDs

At the recent annual meeting of the AAAS a panel of experts on the scientific workforce severely criticized NIH’s wimpy reforms on graduate and postdoctoral training in biomedical fields. Several prior studies including a recent report to the NIH Director from a panel led by Shirley Tilghman ( have advocated reducing the number of graduate students supported on research grants and increasing the number supported on competitive training grants. The net impact of this would likely be to reduce the total pool of biomedical graduate students but increase the quality. No doubt this would be beneficial to PhD career opportunities, especially given the current scaling down of research in pharmaceutical and biotech companies. However, the NIH failed to take this step and only provided some cosmetic changes to its policies on funding of graduate students and postdocs, as discussed previously on this Blog (NIH’s Feeble Response to Problems in Biomedical PhD Training. Jan 11, 2013).


At the AAAS panel additional measures were discussed including drastic increases in salaries for students and postdocs. This would serve to make scientific career paths more attractive and would also force senior investigators to use their resources wisely, rather than ‘burning’ students or postdocs on impossible projects as is now sometimes done. Gregory Pestko, one of the AAAS panelists, stated "I would ratchet up the salaries for postdocs and for graduate students by a lot, and I would do it as a cold-blooded, deliberate way of shrinking the pool of manpower." Good for you Dr. Pestko. It’s about time that somebody was brave enough to really get to the nitty-gritty on this issue! Given the current status of the job market, as well as any reasonable future projections, it is clear that academia needs to engage in some scientific birth control.


Interestingly, a number of my local colleagues read the account of the AAAS discussions. While some were sympathetic, many were outraged, being concerned about how they were going to support enough students to keep their labs running smoothly. Once again this shows that some professors are more concerned with cheap labor than with training.