TB: Battling an Old Foe's Resurgence

December 3, 2003

Foundations and drug companies are finding fresh ways to fight tuberculosis, a deadly disease given new life by the AIDS epidemic

In the latest tally of the ravages of AIDS, the figures aren't good. In the U.N.'s just-released annual update on the epidemic, it estimates the disease will kill 3.1 million people around the world in 2003.

Less well-known, though, is an insidious AIDS side effect: The incidence of tuberculosis has soared. Effective treatment had set this respiratory infection, known in the past as "consumption," on a decline for decades. But it has found fresh legs following HIV's relentless path. Some 2 million people around the world die of TB each year, the World Health Organization figures, at an annual cost to the world economy of $16 billion. Only AIDS and diarrheal diseases kill more people.

FAST-WORKING DRUGS. Lately, however, an innovative effort by private foundations and big pharmaceutical companies may finally be making the progress needed to get TB back under control. Key players are such heavyweights as the Bill & Melinda Gates Foundation and drug giants Novartis (NVS ) and GlaxoSmithKline (GSK ).

A major goal is to find drugs that attack the disease far faster. "While we want to expand on the things that exist now, new drugs with better and less-complex regimens could improve cure rates," said Helene Gayle, director of HIV, TB, and Reproductive Health at the Gates Foundation, during a recent press briefing on the subject.

Unlike AIDS, which is kept at bay at best, TB can often be cured with a battery of antibiotics and other drugs. But tragically, incidence of the disease continues to spiral because compliance with six- to nine-month treatment regimens has proved difficult for patients in the developing world. New, drug-resistant TB strains also have appeared.

"ACCELERATED LETHAL PATH." Moreover, research into improved treatments has been practically nil over the last 40 years, says Mel Spigelman, director of research and development at the Global Alliance for Tuberculosis Drug Development, because the market for TB drugs is large but hardly profitable. "There really isn't the financial incentive to develop drugs. Clearly, if you look around at what companies have been working on, it hasn't been TB."

Much like HIV, TB flourishes in conditions common in many of the world's fast-growing developing countries, where overcrowding and poverty are common. TB spreads easily, and millions of people carry the bacteria without knowing it. A healthy person can live with a latent TB infection and be perfectly fine -- but it's much more likely to turn active in someone compromised by HIV.

"[HIV patients] infected with latent TB are on an accelerated lethal path," says Joelle Tanguy, head of public policy and resource development at the Global Alliance. Some 90% of AIDS victims who contract TB die within two months of infection.

ROYALTY-FREE. Under prodding from the foundations, the few anti-TB drug-research efforts already under way are gathering steam. The Global Alliance itself, whose largest backers are the Gates and Rockefeller Foundations, has perhaps the most advanced drug in development. Called PA-824, it has been shown in the lab and in animals to fight both drug-sensitive and multi-drug-resistant strains of TB. Phase I trials should start in the next two years. Chiron (CHIR ) licensed PA-824 and related compounds to the nonprofit group in 2002, with the understanding that the biotech outfit would receive royalties only on drugs marketed in developed economies.

Another positive development: Potential anti-TB drugs discovered by Novartis may be managed together with the Global Alliance and made available without royalties in developing countries.

Spigelman sees some hopeful signs that pharmaceutical concerns -- large and small -- may soon add to the number of TB drugs in the pipeline. Astra-Zeneca (AZN ) opened a TB-research facility in Bangalore, India, in June, 2003. Novartis opened a facility in Singapore for research in TB and dengue fever in January. GlaxoSmithKline researchers in Spain are focused primarily on finding potential TB and malaria drugs. Spigelman says the group is also discussing licensing deals with small companies like Lupin and Ranbaxy in India and Active Biotics in Massachusetts.

CORPORATE MODEL. Improved vaccines also may be in the offing. The Aeras Global TB Vaccine Foundation was reorganized this fall to focus solely on making TB vaccines more effective. At the same time, Aeras hired Jerald Sadoff, former clinical director for vaccine development at Merck (MRK ), as its chief executive. The nonprofit, also supported by the Gates Foundation, will begin human studies early next year of a traditional TB vaccine that has been genetically engineered to deliver higher levels of an important antigen that helps combat TB. Sadoff says Aeras aims to work with companies like GlaxoSmithKline and biotech company Corixa (CRXA ) on future generations of TB vaccines.

Eventually, these efforts could significantly improve TB treatments' availability and effectiveness. Increased political interest and businesslike discipline should also help. "Our model is to act like a biotech," says Sadoff. "If we miss our deadline by a year, that's 2 million lives lost." That kind of attitude -- and continued financial help from groups like the Gates Foundation -- will be critical in finding new products that can curb TB's death toll.