J&J reveals potential of novel TB drug
promising Tuberculosis (TB) drug in 40 years, may lead to a shorter
and more effective treatment.
Antibiotic-resistant strains of TB have made current treatments less effective. In addition, the HIV-AIDS epidemic sweeping across many parts of the world is making matters worse since the killer disease often triggers the latent TB, which is carried by an estimated one in three of the world's population.
Luc Van Hijfte, research director at Johnson and Johnson Pharmaceutical Research Department told DrugResearcher.com: "Tuberculosis (TB) is a disease that has made a comeback due to the emergence of resistant strains of the bacterium and the spread of AIDS."
"When the drug was combined with some of the existing TB drugs, TB in mice was cured in a time period 50 per cent shorter than with regular combination of drugs used by patients right now," said Van Hijfte.
Previous animal studies have also showed that the compound enters the bloodstream and concentrates itself in lung cells, which harbour the TB bacilli, killing the bacilli soon after they entered the body. R207910 lingers in the body for days continuing to kill bacilli even when administered only once a week in mice, suggesting that it might kill M. tuberculosis with fewer doses.
Speaking at the recent BioVision conference in Lyon, France, Van Hijfte added: "The compound belongs to a new family of anti-TB agents called diarylquinolines (DARQ). Its novel mechanism of action attacks an enzyme called ATP synthase, depleting the energy source for the bacterium."
Diarylquinolines are related to the existing quinolone class of antibiotics, but are structurally distinct, suggesting a different mode of action. Indeed, previous research revealed that genetic mutations in resistant TB strains pointed to a gene that codes for ATP synthase - the first identification of this as a drug target for TB.
TB is currently treated with a cocktail of antibiotics, including rifampin, isoniazid and pyrazinamide, which must be taken for six to nine months. The TB symptoms disappear after several weeks, and patients begin to feel healthy. To completely clear the infection, they must continue therapy at least four more months. However there have been a host of factors, which have contributed to the lack of success of these six-month regimens.
In the developing world, with poor infrastructure like roads and communications, even six months may be too long for the people out there. Another factor has been the HIV pandemic, which has increased the problem of TB in addition to HIV itself.
Like the rest of the pharmaceutical industry, J&J has little financial incentive to develop treatments for TB, a disease that mainly afflicts the poor. However, with 2 million deaths worldwide every year, mainly in third world countries, an effective yet cost-effective treatment is desperately needed.
R207910 is about to enter Phase II clinical trials, one of a number of several novel agents now entering or nearing human trials. Bayer currently has its TB drug Moxifloxacin in early clinical trials, as does an alliance between the European Commission and the WHO. Their drug Gatifloxacin has also shown early promise too.
Drug candidates in the pre-clinical stage include The TB Alliance and Chiron's Nitroimidazole and PA-824TB, Lupin's Pyrrole and LL-3858, Procter & Gamble's nonfluorinated quinolone and Sequella's Ethambutol analog.
The Global Alliance for TB development estimates the TB market size will grow from around $440 million (€343 million) in 2000, to almost $700 million by 2010, and although this represents a comparatively small market size, careful product placement and market strategies could drive a more significant growth in the market.
