It has no current market, not even a prescription price. Its makers stopped commercial production years ago, because demand was so low.
But an antibiotic long abandoned as a weak, low-dose treatment for tuberculosis (TB) may have found renewed purpose, this time as a potent, high-dose fighter against the most common and actively contagious form of the lung disease.
“Rifapentine is back,” says Johns Hopkins infectious disease specialist Eric Nuermberger, M.D., whose studies in mice, to be published in the Public Library of Science journal PLoS Medicine online Dec. 17, have found it so promising as an initial treatment for active TB that clinical trials are scheduled to begin next year in at least eight countries.
The mouse studies showed that substituting higher and daily doses of rifapentine for another antibiotic, rifampin, cured mice two to three times faster than the much older, standard regimen of drugs that includes rifampin. Researchers say if tests in people confirm the findings in mice, the average time to clear the potentially fatal bacterial infection could be reduced from six months to three or less.
“People infected with TB are desperate for better therapies to combat the infection, therapies that can work more quickly and thus limit its chances to spread,” says Nuermberger, who headed the team of researchers from Hopkins and elsewhere. “And having the ability to more effectively treat the most common form of the disease, so-called drug-susceptible TB, is a key step in holding off multidrug-resistant strains from developing, too.”
“It's a huge advantage to have a drug that's already government approved and an equally great surprise to know that it was there all the while,” says Nuermberger, an assistant professor at The Johns Hopkins University School of Medicine. He says that phase II clinical trials will begin as quickly as possible by mid-2008 to gauge the effectiveness of rifapentine as a key component to daily, anti-TB drug regimens.
The nonprofit Global Alliance for TB Drug Development (GATB) estimates that worldwide, more than 9 million people are infected with the highly contagious and active form of TB, caused by Mycobacterium tuberculosis; experts say another 424,000 are infected with the more dangerous, multidrug-resistant form of the disease.
Most of the antibiotics currently used to treat TB, Nuermberger notes, were developed in the 1950s or 1960s, and few new medications have appeared since.
Rifapentine, approved by the U.S. Food and Drug Administration in 1998 for treating widespread, drug-susceptible TB, was initially developed as a less cumbersome, once-weekly tablet. But the drug “was never really considered effective in low doses when compared to the gold standard, daily, high-dose regimens with rifampin,” says Nuermberger. Rifampin (sold as Rifadin and Rimactane) was F.D.A. approved in 1968.
The potential for shortened treatment times follows an advance by the team's top scientist, Richard Chaisson, M.D., director of Hopkins' Center for TB Research, in October. Chaisson and his group showed that moxifloxacin (Avelox), another antibiotic, when substituted for ethambutol (Myambutol), may cut treatment times from six months to four.
Nuermberger and his team investigated the high-dose potential of rifapentine because the drug was in the same class of drugs as rifampin, which is part of the standard antibiotic cocktail of rifampin, pyrazinamide, and isoniazid, a triple drug combo sold as Rifater, or with moxifloxacin in place of isoniazid.