Promising New TB Drug Enters Trials

Mycobacterium tuberculosis, the bacteria that cause tuberculosis, up closeJanice Carr, Centers for Disease Control and Prevention.

The need for new drugs against tuberculosis (TB) has never been more urgent. Although many people think TB is a disease of the past, it's still one of the world's leading killers. About two billion people — a third of the world's population — are thought to be infected. Each year, eight million people worldwide develop active TB and nearly two million die, according to World Health Organization estimates. The incidence of extensive drug-resistant TB, a virtually untreatable form of the disease, is also rising. Now, a new TB drug candidate called SQ109 has received clearance from the Food and Drug Administration to enter Phase I clinical trials.

TB is caused by a chronic infection of bacteria called Mycobacterium tuberculosis. They spread through the air and usually infect the lungs, but other organs and parts of the body can also be involved. Most people who are infected harbor the bacteria without symptoms, but about one in ten develop active TB, often many years later.

The new drug began with an established anti-TB drug called ethambutol. A research team led by Dr. Clifton Barry, III, of NIH's National Institute of Allergy and Infectious Diseases (NIAID) developed a way to easily create thousands of compounds that slightly differ from ethambutol. Dr. Barry's team searched through more than 100,000 compounds looking for those that might be more active than the original. Indeed, several hundred deserved a closer look, and NIAID entered into a public-private partnership with Sequella, Inc. to continue winnowing down the promising candidates.

In animal studies, one candidate, code named SQ-109, quickly traveled to the lungs, where most TB bugs reside, and killed the bacteria instead of merely stopping their growth, as some other TB drugs do. SQ-109 also appeared to be highly effective against multidrug-resistant TB in animal testing. Sequella's findings from mouse studies showed that combining SQ-109 and the first-line TB drug rifampicin produced an enhanced anti-TB activity that continued to work for some time after the drug therapy ended.

Sequella announced in March that it had received a worldwide license from NIH to continue developing SQ-109. It recently received clearance from the Food and Drug Administration to enter SQ-109 into Phase I human clinical trials. This successful transition from the laboratory to clinical testing represents a major milestone for TB research, and also illustrates the successes that public-private partnerships can yield.