KEYSTONE, COLO. — New drugs are desperately needed to address the growing problem of extensively drug-resistant tuberculosis—and help appears to be on the way.
Indeed, the drug development pipeline for anti-TB medications is remarkably full as a result of recent, greatly increased global attention to what had long been a seriously neglected disease.
“These investigational drugs are very exciting,” Dr. Charles L. Daley said at a meeting on allergy and respiratory disease sponsored by the National Jewish Medical and Research Center, Denver.
Five new drugs are in or soon to enter phase II clinical trials, including several that are already slated for phase III. And more than a dozen other drugs in preclinical testing or the discovery phase are being developed by the National Institute of Allergy and Infectious Diseases, various universities in the United States and abroad, the TB Alliance, and pharmaceutical companies both large and small, according to Dr. Daley, head of the division of mycobacterial and respiratory infections at the center and professor of medicine at the University of Colorado.
The drugs now in clinical trials are diarylquinoline TMC207, a Johnson and Johnson molecule with greater activity against Mycobacterium tuberculosis than treatment mainstays isoniazid and rifampin; the widely prescribed Bayer antibiotic moxifloxacin; nitroimidazole PA-824, being developed through a collaboration between Chiron Corp. and the TB Alliance; nitroimidazole-oxazole OPC-67683, an Otsuka drug slated to go into phase II trials this summer; and the Lupin Ltd. drug pyrrole LL-3858, which is “probably a couple years behind the others,” he said.
These are drugs with novel mechanisms of action against M. tuberculosis. Resistance won't immediately be an issue.
Dr. Daley forecasted favorable long-term prospects for an effective TB vaccine, the key words being “long term.”
At least 10 new TB vaccines are now in phase I or II trials around the world. But because no surrogate markers for immunity exist, the only way to learn if a TB vaccine is effective is to vaccinate people, follow them for 10 years or so, and see how many get TB.
“That means that even the vaccines that show promise are still way, way off in terms of routine use. But they're coming,” he predicted.
Dr. Daley had no financial conflicts to disclose.