How many lives could be saved if NCATS is able to pick up the slack for more common diseases currently ignored by for-profit companies? For instance, each of us has reason to be concerned about the rise of antibiotic-resistant microorganisms and the decline of effective drugs to treat them. Yet only four new classes of antibiotics have been introduced in the past 40 years.5 Most antibiotics currently under development are improvements on existing drugs. Why? Because more profits can be made developing medicines that treat chronic conditions, such as high cholesterol, where patients pay for a steady supply of medication—sometimes for the rest of their lives.
In contrast, antibiotics provide a relatively cheap one-time cure for acute conditions. The pharmaceutical industry just doesn’t have the incentive to develop high-risk/low-reward drugs such as antibiotics, even if they are desperately needed to fight life-threatening illnesses.6,7 The federal government does.
Validation of Targets
To understand how NCATS will help further catalyze drug development, consider just one of the ongoing NIH programs slated to move into this new center: the Molecular Libraries Probe Production Centers Network (MLPCN). Created as part of the 2004 NIH Roadmap for Medical Research,8 MLPCN established the first federally funded network to facilitate drug discovery by producing early-stage small molecule leads.9
These centers, most of which reside in universities and nonprofit research institutes across the U.S., provide federally funded researchers and even small biotechnology companies with access to drug discovery capabilities previously found only within large pharmaceutical companies. Those capabilities include large chemical libraries, assay development, ultra high-throughput robotic screening, cheminformatics, medicinal chemistry, project management, and several other drug discovery-related services that typically don’t exist in academic labs and departments.
The MLPCN initiative is probably too young for us to critically evaluate its impact on human health, but several unique opportunities are emanating from this federally funded enterprise. In MLPCN, academic researchers use chemical probes to explore a wide range of targets10 that are not yet validated to the satisfaction of the pharmaceutical industry.
As recently as 2006, the entire repertoire of approved drugs was determined to address only 324 targets, clearly indicating that further efforts are needed to generate chemical modulators of more targets. And there’s probably no better and more clinically relevant way to validate a target than with a chemical probe that modulates the activity of a disease-relevant protein.
Moreover, researchers interfacing with MLPCN are tackling many classes of targets largely ignored by pharmaceutical companies because they are considered technically challenging, and thus too risky for organizations that must worry about generating a return on R&D investments. The nonprofit, public-benefit research community has the flexibility to follow up on any interesting lead, no matter what the target or disease.
Not uncommonly, a MLCPN screening campaign with the objective of identifying antagonists of a particular target leads instead to the discovery of agonists—interesting compounds that can be pursued for different indications than originally envisioned. In contrast, a for-profit company screening for new drugs for a particular therapeutic area might be forced to leave findings that could cure another disease languishing on the shelf. Unfortunately, worries about the bottom line and demands from powerful marketing groups don’t always leave room for scientific curiosity.
Dr. Miller is right on one point—at the other end of the drug pipeline, the FDA approval process creates another bottleneck that keeps new medicines from reaching the market as quickly as we’d like. Here too, through NCATS, the NIH’s leadership is proposing a more robust partnership with the FDA to advance regulatory science.11 This way, FDA regulations can keep pace with the scientific innovations that are creating promising new opportunities to improve human health.
As it becomes increasingly difficult to obtain funding from any source, the infrastructure that allows nonprofit researchers to advance the next generations of innovative therapeutics and diagnostics is at risk of being lost. Without NCATS, many potential therapies will never reach the FDA in the first place, let alone the patients who need them. For this reason, I enthusiastically support the NIH’s newly proposed—and much-needed—National Center for Advancing Translational Sciences.
1. Miller, H.I. NIH Pharma Co. Is a Bad Idea. GEN. 31, no. 6 (Mar 2011).
2. Philippidis, A. Translational Research Is the NCATS’ Meow for Growing NIH’s R&D Role. GEN (April 2011).
3. Stevens, A.J. et al. The role of public-sector research in the discovery of drugs and vaccines. N Engl J Med. 364, no. 6 (Feb 2011):535-41.
4. Baunn, M.M. et al. Emergence of orphan drugs in the United States: a quantitative assessment of the first 25 years. Nat Rev Drug Discov. 9, no. 7 (Jul 2010):519-22.
5. Cooper, M.A. & Shlaes, D. Fix the antibiotics pipeline. Nature 472, no. 32 (April 2011).
6. Braine, T. Race against time to develop new antibiotics. Bulletin of the World Health Organization 89 (2011):88–89.
7. Walsh, C. Where will new antibiotics come from? Nat Rev Microbiol 1 (Oct 2003): 65-70.
8. Zerhouni, E. The NIH Roadmap. Science 302 (Oct 2003).
9. Molecular Libraries Program homepage: http://mli.nih.gov
10. Overington, J.P. et al. How many drug targets are there? Nat Rev Drug Discov 5 (Dec 2006):993-996.
11. NIH and FDA Join Forces to Advance Translational Medicine and Regulatory Science. GEN (Feb 2010).