The tuberculosis genome has been known since 1988, but so far that hasn't translated into a library of targets. And researchers
have only recently begun to look for biomarkers or other key diagnostics. "In the case of HIV/AIDS, you have viral load as
a surrogate marker, or CD4 counts as a biomarker," says Freire. "We don't have that. We have to wait 18 months for people
not to get sick [to know if the drug works]."
As these tools come together, it becomes far more practical for the industry to be involved in TB research. "The pharma industry
can come in and bring along that knowledge and experience of what targets are potentially 'druggable,'" says Duncan. "Then
we have a realistic potential of actually making a drug, rather than just doing academic research."
A New Framework for Research
The world needs new, more powerful TB drugs. In the short run, that probably means repurposing existing compounds. For example,
studies show the fluoroquinolones gatifloxacin (better know as Tequin), and moxifloxacin, (the brand Avelox), can help reduce
TB treatment to four months from the current six or eight months when substituted for ethambutol.
But in the long run, the real progress should come as new drugs emerge from the pipeline. That may not be too far off, given
the way companies are more actively participating in developing drugs for neglected diseases. Before 2000, companies that
conducted R&D in this area largely did so alone, forcing them to carry out large, late-stage clinical trials in the developing
world. However, the cost and the risk of these types of ventures made it unsustainable.
In the last five years, however, pharma has developed new ways of partnering and has shifted its focus to discovery and early-stage
research. Today, it is far more likely that a company working in neglected diseases will hand off the late-stage R&D to a
non-profit or NGO partner. This strategy is working: While only 13 new neglected-disease drugs were introduced from 1975 to
1999, there are now 63 active projects in development, which should yield eight or nine new therapies by 2010, according to
a report by Wellcome Trust, an independent UK-based charity funding biomedical research. A third of these active projects
are being conducted by three Big Pharma companies: AstraZeneca, GlaxoSmithKline, and Novartis.
"Mind you, this is a double-edged sword, because they don't want to carry the cost of clinical trials," says Freire. "But
I'm very excited because at last we have a discovery pipeline."
These companies have taken different approaches to setting up their TB units. Novartis, for instance, has created the Novartis
Institute for Tropical Diseases (NITD), a public/private partnership between the company and the government of Singapore.
GlaxoSmithKline, on the other hand, has teamed up with the TB Alliance to create a shared research program out of GSK's Tres
Cantos site in Spain. And AstraZeneca converted its Bangalore-based R&D site into a center of excellence for TB research in
2001. Novartis pays for its own research; GSK leans on its partner for half of its employees; while AstraZeneca has kept the
unit within its ordinary drug-development structure and, some say, sees it as a basis for a potential commercial operation.
Despite their differences, these operations benefit from their relationships with the companies that started them, and they
are positioned to also partner with outside organizations.
Commercial libraries Perhaps the greatest advantage pharma's neglected-disease research groups have is access to the commercial libraries of their
companies. "That's the starting point for finding new leads," says Paul Herrling, Novartis' head of corporate research and
chairman of NITD "We can't give general access to our libraries because that's also the basis of our commercial success. Instead,
NITD can screen the entire Novartis library, and just pick out those compounds that work—and make them available at no profit."
Existing infrastructure These groups can also draw on existing infrastructure at the companies for experience, tools, and manpower. For example,
in addition to pursuing its own drug discovery, the AstraZeneca site in Bangalore can call on the company's genomics and infection-research
operations in Boston, among other sites.