An experimental treatment from Johnson & Johnson's Tibotec unit was effective in almost half of patients with drug-resistant forms of tuberculosis, a disease that has seen no new therapies in decades.

An eight-week study found that J&J's TMC207, given in combination with standard treatment, helped clear TB germs from the lungs of 48 percent of patients compared with 9 percent who took a placebo, researchers said. Those in the 47-patient study were newly diagnosed with a form of TB that is resistant to initial treatment, according to an article published today in the New England Journal of Medicine.

An estimated 110,000 people worldwide die each year from a form of TB that isn't responsive to standard therapy, the researchers said. Overall, about 9 million people are infected and 2 million die annually from all kinds of TB, a disease most prevalent in India, China and Indonesia, and patients typically undergo treatment with toxic medications, said David McNeeley, the study's lead author.

The study results represent "an important advance in the chemotherapy of tuberculosis," Clifton Barry, a TB researcher at the National Institutes of Health, in Bethesda, Maryland, wrote in an accompanying editorial. "It is perhaps most amazing because of the defiantly unconventional nature of the effort."

McNeeley, director of global clinical development for Mechelen, Belgium-based Tibotec BVBA, said there is "a great need" for alternatives to the drugs available now. "There have been no new medications with new mechanisms of action for over 40 years," he said in a telephone interview.

New Target

New Brunswick, New Jersey-based J&J's drug is in the second of three stages of testing typically required for U.S. approval. The J&J drug is the first TB therapy to target ATP synthase, an enzyme involved in creating the energy that TB bacteria need to thrive. Overall, 10 of 21 patients, or 48 percent, who took the drug showed no signs of the TB bacteria in their lungs, compared with two of 23, or 9 percent, of those given a placebo.

The only "significant" side effect reported in the study was nausea, which was reported by 6 patients, compared with one patient in the placebo group, the study found. "When you interrupt the formation of ATP, you starve the mycobacterium to death," McNeeley said.

‘Cornerstone'

The findings are "extremely impressive" for a "small population of patients," said Melvin Spigelman, chief executive officer of TB Alliance, a New York-based nonprofit drug- development organization, in an interview. "I would hope that TMC-207 will really be the cornerstone of future combination regimens" for treating TB, he said.

There now are at least eight medications being developed for forms of TB and undergoing tests in humans, Spigelman said. The TB Alliance is developing a drug, PA-824, under a license from Swiss drugmaker Novartis AG, that is also in mid- stage studies, Spigelman said. Bayer Healthcare AG is testing the drug moxifloxacin, in partnership with the TB Alliance, in a late-stage study. Otsuka Pharmaceutical Co. of Japan has a TB drug, OPC-67683, in the second phase of trials, he said.

Patients with drug-resistant forms of TB typically undergo treatment, with multiple medications, that can last as long as two years. Roughly 95 percent of those patients in developed countries, such as the U.S., are cured.

Treatment Discontinued

In developing nations where most TB occurs, the cure rates range from 60 percent to 70 percent among people who complete treatment, McNeeley said. Many patients discontinue treatment because of side effects and inadequacy of medical services, he said.

After years of not making TB a priority, health officials and drugmakers are paying more attention to the malady, McNeeley said. Cases of disease-resistant TB in the U.S. in the early 90s "probably made people much more aware of the problem with drug resistance," he said.

TB is a bacterium that usually attacks the lungs and can also strike the kidneys, spine and brain. In the U.S., about 14,000 cases were reported in 2006, according the Centers for Disease Control and Prevention, based in Atlanta. The standard four-drug combination for treating drug- resistant TB costs about $20 for six months in poorer nations, Spigelman said.

Not Lucrative

"This is not a lucrative market," Spigelman said. "No for-profit companies have really invested in TB the way they invest in diabetes, cancer or neurological disease. That's why we haven't had a new drug in 40 to 50 years." Spigelman credits philanthropies such as the Seattle-based Bill & Melinda Gates Foundation, which has provided $129 million in grants to the TB Alliance since 2000, for helping to focus attention on the need for new treatments.

A second phase of the J&J study will follow 150 patients for six months, researchers said. The study was funded by J&J's Tibotec, and McNeely reported that he holds shares in J&J.