Tom Beal Arizona Daily Star | Posted: Friday, March 26, 2010 12:00 am

The independent, nonprofit Critical Path Institute was established in Tucson in 2005 by the University of Arizona and the U.S. Food and Drug Administration to address the problem of lagging drug development.

A worldwide effort to find new TB drugs is being coordinated by the Tucson-based Critical Path Institute, a nonprofit agency formed five years ago to bring promising drugs and devices onto the market quickly without sacrificing safety.

The new initiative – Critical Path to TB Drug Regimens – was created by the Critical Path Institute, the Bill & Melinda Gates Foundation and the Global Alliance for TB Drug Development.

Tuberculosis, one of the world’s deadliest infectious diseases, is increasingly resistant to the nearly 50-year-old, four-drug regimen developed to treat it. Researchers hope to find a combination of drugs that will work faster and better.

The groups hope to duplicate the success of the 1990s push for better treatments for AIDS, cutting development time from decades to a handful of years.

Joining the effort is a big step for the Critical Path Institute, or C-Path, said Dr. Raymond Woosley, the institute’s president and chief executive officer.

“It’s a big deal. We’re pretty excited about it. We never imagined it would happen this quickly,” Woosley said.

Critical Path will play the role of “honest broker” among the participants in the initiative, which includes the U.S. Food and Drug Administration and its European counterpart, and at least 10 international drug companies.

“This is really a first,” said Dr. Mel Spigelman, president and CEO of the TB Alliance, “all the major players being willing to work together, to put the public health agenda ahead of their own concerns.”

“TB is an age-old scourge but is still killing as many people as it ever did,” Spigelman said. “A third of the world – 2 billion – is infected with the bug.”

It hasn’t been a problem in the United States for decades, Spigelman said, because “this is the epitome of the disease of poverty.”

There are about 12,000 active cases in the United States, Spigelman said.

Worldwide, TB sickens 9.4 million people each year and kills 1.8 million.

Woosley said TB-drug development lagged after the disease was tamed in the developed world. Now, governments and charitable organizations such as the Gates Foundation are pushing for better therapies.

TB germs spontaneously mutate and require four different medicines for effective treatment. Each additional drug adds effectiveness but also piles on side effects – nausea, vomiting, bellyaches, and even liver toxicity.

When people stop taking the drugs prematurely, which happens often in the impoverished settings in which they are administered, resistance develops.

Spigelman said the threat to wealthier nations is real. Doctors can effectively treat ordinary strains and cure 90 percent of the cases of drug-resistant TB. But “extensively resistant” TB eludes most treatment.

The initiative proposes to pool information from the various drug companies and to undertake simultaneous trials of new combinations of medicines, instead of seeking approval from the FDA singly. That could cut development from 20 years to five, Spigelman said. Some combinations already have been identified in laboratories and in animal tests, Spigelman said.

The goal is to find a combination of three or fewer compounds that can cure in two months instead of six.

Spigelman said he is confident that Critical Path has the organizational skills to coordinate the effort, based on work it has done in other fields.

The big barrier, he said, will be financing.

The clinical trials require a large number of subjects who will need to be treated and followed for a long period of time. One trial already under way will cost about $50 million, he said.

The Gates Foundation alone can’t underwrite such an effort. Spigelman expects government involvement and help from other nonprofit organizations.

The initiative comes as the Critical Path Institute’s underwriting from the Arizona Science Foundation and local governments is increasingly tenuous.

Woosley said the institute has managed to leverage that local support six times over with outside funding.

The FDA has promised $2 million each year for the next five years for other programs it is running, Woosley said. The institute will apply for additional funds from the FDA for the TB initiative, he said.

It continues to refuse any funding from drug companies, he said.

“To a be a partner in something this big validates our model of being a neutral third party,” he said.

Currently, Woosley said, Critical Path employs 32 people who coordinate the work of more than 600 scientists across the globe.