/ 15 December 2004

Drug-resistant TB may have hit its sell-by date

The first promising tuberculosis (TB) drug in almost 40 years could be the best yet, according to the Science and Development Network. This is good news for Southern Africa, which is home to large numbers of people suffering from TB as a result of HIV/Aids.

Animal tests indicate that the drug could also treat the disease faster, reducing costs, according to research published online by Science Express.

The research team found that the new drug R207910 works by blocking an enzyme the bacterium uses to acquire energy. Because earlier drugs did not target this specific enzyme, the researchers say the new drug could even be used against strains of TB that are resistant to existing drugs.

About two million people die from the disease every year, according to the World Health Organisation (WHO).

“The neglect in TB drug development is due partly to the fact that TB was thought in the Western world to be a disease of the past,” says Chris Dye at the Stop TB Partnership run by the WHO.

“Investment in drug discovery has also been low because the market is in the poorest parts of the world,” says Dye. “TB patients are mostly poor people who cannot afford to pay for costly treatments developed by major drug companies.”

But recently the profile of TB has been raised dramatically because of the growing problem of TB and HIV co-infection, says Mel Spigelman, director of research and development at the Global Alliance for Tuberculosis Drug Development.

According to the organisation — created in 2000 to push for more research into TB drugs — 12-million people worldwide have both TB and HIV. Most of them live in Southern Africa. About two-thirds of people with TB do not have access to effective treatment. Even when they receive treatment, says Dye, the drugs fail to work against resistant strains.

WHO’s recommended strategy to fight TB, the directly observed treatment, short course (Dots) has come under criticism because it requires a long course of treatment (six to eight months) and constant monitoring and assessment.

Marcos Espinal, one of Dye’s colleagues, told SciDev.Net that speed — both in treatment and in developing new drugs — is crucial.

“A faster and simpler therapy for TB is critical to accelerate current TB control efforts and ultimately eliminate this major killer.”

Dye agrees that the ability to shorten the duration of treatment to about two months would be “a big step forward for TB control, with benefits both for patients and health services”.

A new drug would also need to be low-cost to compete with current anti-TB drugs priced at about $10 per treatment course, adds Dye.

The new drug would probably be used in combination because the use of one drug on its own has in the past quickly led to drug resistance. When the researchers replaced one of the drugs that make up the current cocktail of TB therapy with the new drug, they found that it boosted the effectiveness of existing combination treatments. The effectiveness of the new drug has been tested only in mice so far.

The drug passed safety tests in healthy people, but the next step will be to investigate how effective it is when used to treat people with full-blown TB. Several other TB drugs are in development, says Spigelman. But, he adds, whether R207910 is used together with other novel drugs or in a mix of old and new drugs will probably depend on how the different combinations work when tested in clinical trials in people.

In more good news, two major organisations last month announced their collaboration on a research programme to develop new drugs for the treatment of tuberculosis — and to make sure poor people have access to the new drugs.

The first candidate drug, known as PA-824, is scheduled to enter its first clinical trials on people in early 2005.

“New drugs are initially expensive and that is understandable because of the research investment involved,” Charles Yu, the newly elected president of the TB Alliance’s stakeholders’ association told SciDev.Net.

“The TB Alliance is unique in its asking of companies to make TB drugs available, affordable and accessible.”

The Novartis Institute for Tropical Diseases and the Global Alliance for Tuberculosis Drug Development are investigating potential drugs from a class of chemical compounds called nitroimidazopyrans. These chemicals have stirred the drug development scene since 2000, when one particular compound in the class showed potent activity against the bacterium responsible for TB. This particular chemical compound is effective in both active and latent TB infections.

More importantly, it is effective against TB infections that are resistant to many existing drugs. There have been no new drugs against TB for more than three decades. This is partly because drug companies have tended to focus their research and development efforts away from developing countries, where patients cannot afford expensive drugs.

The partnership has committed the Novartis Group to make the resulting drugs available to patients without a profit in developing countries where TB is endemic.

Now the aim of the joint research programme is to identify the next generation of nitroimidazopyran compounds. A modified form of the compound could result in a drug whose required dosage is easier to comply with than current TB drug regimes, which require patients to take medication for as many as six to nine months.

And Indian researchers have discovered a new molecule that they say could lead to a faster cure for TB. They have applied for clearance to perform human clinical trials on the potential drug after animal tests in rats and in guinea pigs slashed the normal treatment time to just two months.

In addition, it was found to be effective against all known drug-resistant strains of the bacterium that causes TB.

Almost one-third of the world’s human population is infected with TB. But that may change.

This article compiled from reports from New Delhi, London and Singapore by Christina Scott in Cape Town on behalf of the Science and Development Network, a global source of news from Africa and other parts of the third world, online at www.scidev.net