Laboratory tests of a new type of antibiotic suggest it might revolutionize the treatment of tuberculosis, a global killer disease that has become increasingly resistant to current drugs and which is now claiming more than 2 million lives a year.
Scientists at Johnson & Johnson say experiments in mice show the new compound works better and faster and may reduce by months the time required to cure TB using the current therapy. Early clinical trials show the new drug is safe and further human testing already is under way.
If the drug fulfills its promise and is developed for therapeutic use, it will be the first new anti-TB agent put into clinical practice in more than 40 years. The last major new drug, rifampin, was introduced in 1963.
New group of anti-TB compounds
The new drug, called R207910, is part of a new group of anti-TB compounds called diarylquinolines, or DARQ. It attacks tuberculosis by neutralizing an enzyme which the TB bacillus uses to make energy. This mechanism of action is different from that of rifampin, isoniazid and pyrazinamide, the cocktail of drugs now standard treatment for TB.
Dr. Koen Andries, lead author of a study on the drug appearing this week in the journal Science, said studies with a laboratory mouse species commonly used to test TB drugs show the new compound concentrates in the lungs and other organs which are the major targets of tuberculosis.
Andries said R207910 shows in mouse tests to be as active against TB as the drugs in the standard cocktail. And when combined with isoniazid and pyrazinamide to form a new combination therapy, he said, “it achieves the same result after one month as is being obtained in two months by the standard care therapy.
“That is why we are quite optimistic that we would be able to shorten treatment duration substantially, by about 50 percent,” said Andries.
In one study using a combination including R207910RQ, the TB bacilli disappeared completely from the lungs of laboratory mice in just two months.
Human studies under way
The DARQ compound to be safe and well tolerated when tested on healthy adults, said Andries. The compound is now being tested in humans with active TB of the lung. However, he said it may be five years before the drug will be ready for general use.
“This is dynamite stuff,” said Dr. Lee Reichman, executive director of the New Jersey Medical School National Tuberculosis Center. “They’ve shown convincingly that it kills the (TB) organism. It seems to exceed rifampin which is the best drug we have.”
Reichman said he was impressed by the results reported by Andries and his colleagues even though the promise of R207910 is based on laboratory mouse studies.
“This mouse model is a very good portend for what will happen in humans,” he said. “The mouse model has been used successfully for virtually all TB research.”
Interviewed by Science, Dr. Denis Mitchison of St. George’s Hospital Medical School in London, called the Johnson & Johnson study “an astonishing set of results.”
He said the drug combination that included the DARQ compound sterilized organs in the mice within two months. “That’s never been done before,” Mitchison said in Science.
Shortening treatment times is key
Shortening the treatment time for TB is particularly important, said Reichman. Curing TB using the current drug cocktail, he said, takes six to nine months. This long treatment makes it more likely that patients will interrupt therapy or use the drug inappropriately. He said this can result in a patient developing a strain of TB that is resistant to the drugs.
Drug resistant tuberculosis has become a worldwide problem, with an estimated 300,000 new resistant cases developing annually. The World Health Organization said that TB, usually in a latent form, infects about a third of the Earth’s human population. Each year, about 9 million active cases of TB develop, killing about 2 million patients.
In 2002, 15,075 cases of TB were reported by the federal Centers for Disease Control and Prevention, and of those, 802 people died from the disease.
Reichman said that TB and HIV (AIDS) have become a worldwide plague. Among AIDS patients outside the U.S., he said, tuberculosis is the most common cause of death.
Andries said that patients infected with both HIV and TB would be able to take a combination of R207910, isoniazid and pyrazinamide along with HIV drugs. The current standard TB cocktail is not compatible with some HIV drugs because of an interaction with rifampin, he said.