Two new TB drugs advance to clinic

Two new drugs for tuberculosis are being tested in humans, an important step in addressing the dearth of treatments for the deadly infection. The nonprofit TB Alliance says Phase I studies have started for both TBA-7371, part of a new class of antimicrobials called DprE1 inhibitors, and the oxazolidinone sutezolid.

TBA-7371 blocks an enzyme critical for synthesizing the polysaccharides that compose the TB bacteria’s cell wall. Development of DprE1 inhibitors began as part of a research collaboration between TB Alliance and AstraZeneca. In 2014, AstraZeneca shut down the R&D site in Bangalore, India, where TB work was conducted, and the nonprofit continued to pursue the compound class.

Sutezolid, meanwhile, has been around since the late 1990s. The compound is an analog of the approved antibiotic linezolid, but with fewer side effects and better potency.

The trials are “definitely a step forward,” says Sean Ekins, who is CEO of Collaborations Pharmaceuticals and is on the advisory board of the TB-focused nonprofit MM4TB. Ekins points out that most combination treatments in clinical studies rely on drugs that were invented in the 1940s and ’50s. “The pipeline is so sparse that anything going into a clinical trial is huge.”

Indeed, just two other new TB drugs have been approved in recent years, and both—Johnson & Johnson’s bedaquiline and Otsuka Pharmaceutical’s delamanid—are intended only to treat multi-drug-resistant TB.

Yet the need for new TB treatments is great. The World Health Organization estimates that 2 billion people are infected with the bacteria that cause TB and that the infection kills some 1.8 million people each year. The threat has become particularly worrisome for those with compromised immune systems; in 2015, 400,000 people coinfected with TB and HIV died.