TB advocates complain that there have been no new TB drugs for 40 years. Certainly, pharma never had it easy in TB—and it
won't get better soon. New science must harvest innovative therapies; new partnerships must develop treatment for patients
and entire countries without the resources to pay market prices. And new programs must deliver those treatments on the ground.
The Search for Basic Science
The first anti-TB drug, streptomycin, was discovered in 1944 by Selman Waksman at Rutgers University—funded by a grant from
Merck—which made the disease treatable for the first time in its long history. Following streptomycin, other TB agents were
introduced, including isoniazid (1952), pyrazinamide (1954), ethambutol (1962), and rifampicin (1963). Researchers soon demonstrated
that TB therapy was more efficient, and less likely to end in drug resistance, when they switched from single-drug regimens
to combination therapies using multiple drugs.
In 1969, following the discovery of these and other antibacterial drugs, US Surgeon General William Stewart proclaimed it
was "time to close the book on infectious diseases." And indeed, the book closed—though not quite in the way Stewart meant.
The disease continued largely unabated outside the United States, and the evolution of treatment stood still.
The result is that today's therapies are good—they work—but they have their problems. "Rifampacin is the best of drugs and
the worst of drugs," says Balganesh Tanjore, head of research at AstraZeneca's TB-focused site in Bangalore, India. He says
that rifampacin is powerful against the disease, but the toxicity of the drug can outweigh the benefits.
Add poverty to the mix, and the margin for error grows tighter: "Most of the people are very poor," says Ali Hamisi, MD, from
Tanzania's Bagamoyo District Hospital, where TB is a top killer. "If they are not well-fed, toxicity is very high." What's
more, rifampacin is contraindicated with several AIDS therapies, and pyrazinamide is unsafe for pregnant women.
The biggest challenge of TB treatment, however, is maintaining compliance during the long course of therapy. "Why can't TB
have a standard 10-day treatment, just like any ordinary antibiotic?" asks Marie Freire, who heads the Global Alliance for
TB Drug Development, an organization working to increase industry participation in TB R&D. According to WHO's recently published
"Global Plan to Fight TB, 2006-2015," that's unlikely to happen before 2050. The basic science of the disease is not yet there.
"When you talk to various communities, you realize the understanding of how a TB bacillus behaves in humans is virtually non-existent,"
says Ken Duncan, consultant to the Bill and Melinda Gates Foundation, and former GlaxoSmithKline executive.
TB researchers also lack some important research tools, such as targets, biomarkers, and predictive models to tell scientists
if what works in cell cultures will work in man. "Most drugs so far are developed against TB in test tubes," says Douglas
Young, a professor of medical microbiology at the Imperial College London, and a recipient of a Gates Grand Challenge grant
to develop new treatments for latent TB infection. "We want to choose a defined target—a protein or enzyme that if inhibited,
has a good chance of killing the disease—based on an understanding of the physiology of the bacteria as it exists inside our
body. If we choose targets that way, then the drugs will be more effective."