Trial tests new combination of drugs to treat tuberculosis

BMJ 2012; 344 doi: (Published 20 March 2012) Cite this as: BMJ 2012;344:e2216
  1. Bob Roehr
  1. 1Washington, DC

The Global Alliance for TB Drug Development (TB Alliance) has launched a first of its kind clinical trial of a new drug combination that is enrolling patients with drug sensitive or multidrug resistant tuberculosis.

The trial is a milestone in the process of revitalising all phases of tuberculosis research—from basic pathology to diagnostics, new drugs, and vaccines—that began a decade ago, said Mel Spigelman, president of the TB Alliance, at a forum in Washington, DC, in advance of world TB day on 24 March. The alliance is a collaboration of drug companies, government agencies, and charities.

To elicit a response in people with drug resistant tuberculosis, doctors have often added a new drug to a failing regimen, said Dr Spigelman. But this has often led to resistance to the new drug. The alliance has helped to bring about a conceptual shift that focuses on a regimen rather than an individual drug.

This trial is the fruit of that shift in thinking. It uses a combination of a new drug candidate (PA 824), the antibiotic moxifloxacin, which is not approved to treat tuberculosis, and pyrazinamide, a key component of existing regimens to treat the disease. Safety has already been shown in a two week study of the combination.

“If the preclinical data bears out,” Dr Spigelman said, “this shows promise to reduce treatment conservatively to four months, which for drug resistant TB would be an amazing advance.” The once daily oral regimen would eliminate the need for an injectable drug and would “reduce the treatment time by about 80% and the cost by about 90%,” he said.

Importantly the regimen does not have any known interactions with currently approved antiretrovirals so would allow simultaneous treatment of both diseases, which are the top two leading causes of death in sub-Saharan Africa.

Current regimens to treat tuberculosis have significant interactions with many of the drugs used to treat HIV. Anthony Fauci, director of the US National Institute of Allergy and Infectious Diseases, said that among coinfected patients “you actually need a computer to figure out what drugs you can use because so many of the drugs are contraindicated when used in combination.”

Because tuberculosis “practically disappeared” in developed countries during the 20th century, widespread complacency resulted, he said. That began to change with HIV and the emergence of drug resistant tuberculosis in that population.

“If we had 1.4 million deaths [a year] from tuberculosis in the developed world, do you really think that we wouldn’t have a vaccine right now that works? I don’t think so,” said Dr Fauci.

As a sign of this renewed concern, he pointed to the US National Institutes of Health budget for tuberculosis research, which has grown from $665 000 (£420 000; €505 000) in 1985 to $210m in the current fiscal year. It continues to grow even while the overall NIH budget does not.

Two other important developments are the opening up of the vast clinical trials infrastructure network for HIV research in Africa to tuberculosis research and the creation of a biobank of frozen specimens. Fauci hopes the biobank will facilitate a better understanding of the underlying pathogenesis of tuberculosis and the immune response to infection. He said that better biomarkers of the disease and of response to drugs are very much needed to speed development of drugs.


Cite this as: BMJ 2012;344:e2216

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