A FEW YEARS AGO a passenger on a flight from Paris to New York infected 13 others with multi-drug-resistant tuberculosis. Sensational cases like this are rare, but they are helping draw attention to a disease many in the West had thought was no longer a threat. TB -- which infects one-third of the world's population -- never went away; this year it is expected to kill more people than ever.
About 60% of the world's TB victims live in Asia. In February the World Health Organization warned that millions more in the region could become infected with the disease in the next five years due to a lack of funding for anti-TB programmes.
TB's ability to migrate across borders is spreading it to developed countries, too. It is transmitted through the air like the common cold; when infected people cough, sneeze, talk or spit, they fill the air with the deadly bacteria. People who become infected may not even know it. The hardy bugs can hide out or lie dormant in the body for years -- even decades -- until they flare up from stress, age or weakened immune systems. Global efforts to stamp out tuberculosis have been a failure on many fronts.
Governments lack the political will to tackle the problem and have not done enough to ensure existing treatments are carried out properly. Funds for basic research are close to zero. Drug firms have shown little interest in spending money on TB because most of the need is in the developing world -- where people can't afford costly medicine. The last TB drug was developed more than 30 years ago. "We haven't got the disease under control," says Colin Ratledge, a professor of microbial biochemistry at the University of Hull in Britain.
But this dismal picture may be changing. A new partnership between the public and private sectors aims to get promising compounds off laboratory shelves and into the most needy markets at prices people can afford. The Global Alliance for TB Drug Development, a not-for-profit organization comprising non-governmental organizations, public-research institutes, a few pharmaceutical companies and the WHO, was set up less than two years ago.
To date, it has raised $40 million from charitable organizations like The Rockefeller Foundation and The Bill and Melinda Gates Foundation. With the funds, it buys the worldwide rights to promising drugs and outsources research and development to public laboratories or industry. It aims to have at least one effective new drug by 2010. In February, it licensed a potential new drug candidate called PA-824 from Chiron Corp., a United States-based biotech company. Now the Global Alliance is negotiating to acquire several more compounds -- one from a public research institute in Asia. The compounds are in the early stages of development, the deals are modest and success is by no means guaranteed; such is the risky nature of all drug development. But without the Global Alliance, leads like these may never get the chance to be developed. Research institutes, universities and biotech firms typically lack the experience and funds to develop promising compounds they discover into drugs for sale.
Pharmaceutical companies, meanwhile, are more interested in developing lucrative drugs for heart disease, cancer, impotence, obesity and baldness. When they do work on new antibiotics, they prefer to develop them for bacterial diseases that plague wealthy countries, such as ear infections in children, bronchitis and pneumonia. Critics call that inexcusable. "We're not talking enormous sums to develop a new TB drug," says Peter Davies, a TB expert at Liverpool University and co-founder of a London based NGO called TB Alert. "It would cost about $300 million-400 million to develop a new drug."
The need for collaboration to share the cost and risk of developing drugs to treat diseases like TB couldn't be clearer. Pharmaceutical companies -- responsible to their shareholders -- need to make profits and a return on capital investment like any other industry. So another model is needed to chase diseases that are uneconomical for drug companies to solve alone. "You can't rely on the private sector that is rooted in profit motives," notes the University of Hull's Ratledge.
The Global Alliance controls the development process, shouldering much of the development risk. Companies like Chiron are given the option to license back their drugs to sell in wealthier countries. If they exercise the option, they have to repay the Global Alliance all fees and R&D investments, plus royalties. The Global Alliance retains all rights to the rest of the world and Chiron receives no royalties for any products in these countries. This is how the alliance will ensure people in developing countries will have access to new TB drugs.
"This unique public-private agreement provides the necessary support to move forward with clinical trials for PA-824 and offers the best possibility for developing a drug that would meet an important public-health need," says John Gallagher, a Chiron spokesman. "It's absolutely incredible," adds Lee Reichman, an American TB expert and author of Timebomb: The Global Epidemic of Multi-Drug- Resistant Tuberculosis. "Nothing like this has ever happened before."
The problem with existing TB treatments is that they are lengthy and complicated. It takes six to nine months and a cocktail of drugs to cure a patient. In developing countries, most patients receive irregular doses of TB drugs or stop taking their medicine as soon as they start to feel better -- leading to multi-drug-resistant strains that are harder and more expensive to treat.
Curing a multi-drug-resistant case can take up to two years, cost 100 times more than a conventional case and cause severe side effects. Some cases are incurable. Drug resistance is such a worry that standard treatment involves directly observed therapy: A health-care worker watches a patient swallow each pill. That's why the Global Alliance is looking for drugs that cut the duration of treatment to two months, as well as ones that treat multi-drug-resistant TB and latent infections.
To stimulate interest in TB, the Global Alliance published a study in November 2001 on the economics of TB drug development. It found the global market for anti-TB drugs is worth $470 million. By 2010, the market is projected to reach $ 670 million. Moreover, the report notes a drug can be developed for between $150 million and $240 million-lower than the $300 million-800 million figure frequently quoted by multinationals. While these numbers won't cause a stampede into TB research, they may convince companies it's possible to make a modest return of between 15% and 30% for bringing a lead compound to market.
Eventually, the Global Alliance may even sign licensing deals with multinational drug companies, a handful of which have been investing in basic TB research in recent years. The timing couldn't be better. The sequencing of the TB genome in 1998 offers new opportunities to companies prepared to take a stab at a cure. So far the sums pledged still represent 1% or less of their R&D budgets -- but even small initiatives may lead to breakthroughs.
In June 2001, British-Swedish drug giant AstraZeneca unveiled plans to set up a research centre focusing on new treatments for the disease in the southern Indian city of Bangalore. The drug giant is spending $11 million to construct a research building, $15 million on equipment and at least $5 million annually over the next five years to support research activities. "Can we make a profit in TB?" asks AstraZeneca's chief scientist, Barry Furr. "The answer is probably no. But we saw it as part of our corporate social responsibility."
Britain's GlaxoSmithKline is also working on the disease. It has invested 20 million since 1993 into the Action TB initiative -- a collaboration between academia and industry for basic research. GSK's funding initiatives have helped Action TB to identify a number of promising compounds. Novartis AG, headquartered in Switzerland, is also looking for answers. In November last year, it committed to setting up a research centre for tropical diseases in Singapore costing S$220 million ($12 million). The centre will focus on TB and dengue fever.
Still, it will be at least eight years before a new drug comes to market and even longer before research yields a new vaccine. In the meantime, governments need to provide funds to ensure existing treatments are properly administered. Only 23% of TB patients are being properly treated, according to the Global Alliance. With numbers like that multi-drug resistance is going to get worse. Says Reichman: "To control TB anywhere, you have to control it everywhere."