If Successful, Moxifloxacin Could Be First New Treatment For TB In More Than 40 Years

"Defeating the spread of tuberculosis in the United States and thedeveloping world will require scientists to take bold and creative newapproaches because there has not been a new therapy for tuberculosis inmore than 40 years," says tuberculosis expert Richard Chaisson, M.D., aprofessor of medicine, epidemiology and international health at TheJohns Hopkins University School of Medicine.

Chaisson will conduct the research as part of a series ofstudies on moxifloxacin that are being coordinated by the nonprofitGlobal Alliance for TB Drug Development (GATB) in collaboration withBayer Healthcare AG, the drug's maker. His research will assess theability of moxifloxacin to shorten the treatment period required tocure the disease.

One of Chaisson's studies will take place in Brazil, with support fromthe U.S. Food and Drug Administration's Office of Orphan ProductDevelopment. He will co-direct the second study with Susan Dorman,M.D., an assistant professor at Hopkins, and John Johnson, M.D., ofCase Western Reserve University. The study will take place in fivecountries - the United States, Canada, Brazil, Spain, South Africa andUganda - with funding support from the U.S. Centers for Disease Controland Prevention's TB Trials Consortium. (Maryland is one of the 10 U.S.states where the second study will take place.)

The overall research program, expected to last two to three years andenroll close to 2,500 patients worldwide, was to be announced today ata news conference during the 36th annual World Conference on LungHealth in Paris, France. Other related studies of moxifloxacin will beled by Stephen Gillespie, M.D., of the University College-London, andAndrew Nunn, M.D., of the British Medical Research Council.

The GATB estimates that 1 billion people worldwide will beinfected with tuberculosis by the year 2020, of whom 200 million willfall ill and 35 million will die. The group is developing moxifloxacinand other drugs in an effort to cure more patients by shortening thelength of time it takes to treat the disease.

"Shortening the time required to cure the disease could save millions of lives in the coming years," Chaisson says.

Chaisson has more than two decades of experience researching thetuberculosis epidemic, especially its impact on the health of people indeveloping countries, where most of the 9 million new cases of thedisease occur each year. Current treatments for tuberculosis, Chaissonsays, consist of a regimen of four antibiotic drugs usually, but notalways, given in view of a caregiver. Called Directly Observed TherapyShort-Course, or DOTS, the drugs must be taken several times daily forsix to eight months. Although DOTS cures 95 percent of those treated,the lengthy treatment period has proven a problem for patients, whosometimes miss taking their drugs on time, minimizing the therapy'seffectiveness.

Chaisson notes that multidrug-resistant strains of the tuberclebacillus, formally known as Mycobacterium tuberculosis, are spreadingat a rate of 300,000 newly diagnosed cases each year that cannot betreated by current drugs. "New options are needed, and they need to beboth effective and easier for patients to tolerate," he adds.

Chaisson says that substituting moxifloxacin for one of the keyingredients in DOTS could shorten the treatment period by nearly twomonths, to three to four months, making the form far less costlyoverall.

As part of the research program, Bayer has agreed to donate supplies ofmoxifloxacin for all of the trial sites, including those in Tanzaniaand Zambia that are part of a third study not involving Hopkins. The TBAlliance will coordinate the trial and cover study costs, withadditional support from the European and Developing Countries ClinicalTrials Partnership.

In addition to the moxifloxacin study, Chaisson directs theHopkins-based Consortium to Respond Effectively to the AIDS/TBEpidemic, called CREATE, an international effort to control the spreadof tuberculosis and treat the disease in countries hit most hard by theduel epidemics. CREATE, which is sponsored by the Bill and MelindaGates Foundation, has three community-based studies under way in Africaand Brazil.