MSF and TB experts call for new approach to test TB drugs - Donors and developers need to respond to the strategy

Johannesburg - Drug developers can speed up the development of urgently needed new tuberculosis drugs by adopting a different strategy, the medical humanitarian organisation Médecins Sans Frontières (MSF) joins international experts in stating today.

According to a report published today in the open-source medical journal PLoS Medicine, mimicking the approach used to test AIDS drugs would accelerate the research process, and get drugs to patients who most need them faster.

The authors call for testing new TB drugs in patients whose TB is resistant to standard treatment, making it easier to detect the anti-TB activity of new drugs. This strategy, adopted with success during the AIDS pandemic in the 1990s, means that clinical trials could be done quicker and in fewer patients, and ultimately newer and better drugs could be developed faster.

"This is quite simply the best hope we have of getting improved medicines to patients with multidrug-resistant TB faster," said Dr. Eric Goemaere, MSF Head of Mission,in South Africa. "We cannot afford to wait. MDR-TB is spreading rapidly, particularly in areas like South Africa where HIV is high. And with the current drugs, many patients on MDR-TB treatment give up half-way and the majority of patients co-infected with HIV will die before the end of treatment."

The important long-term goal is to develop a complete new treatment that works for both drug resistant and drug-susceptible TB. But until this is achieved, which will take over a decade, the urgency is to improve treatment of drug-resistant TB.

Globally there are almost five hundred thousand new cases of multidrug-resistant TB every year. The current treatment relies on weak drugs with harsh side effects and lasts up to two years. Even in the best treatment conditions, some patients develop extensively drug-resistant TB (XDR) simply because the drugs are so ineffective.

"There is an imperative to speed up TB drug development and one way to do this is through innovative trials," said Dr. Carole Mitnick, Harvard Medical School. "All new, promising compounds should be tested in patients with drug-resistant and drug-susceptible TB to accelerate access to improved treatments for those in need now. In light of recent improvements in the TB drug pipeline and growing evidence about the magnitude of the MDR problem, it is frustrating that this approach to improving treatment outcomes for all TB patients has not been widely adopted."

Introducing a different strategy and testing new drugs in drug-resistant patients would not compete with trials in drug-susceptible patients as they could be done in parallel. Countries with high burden of TB need to actively support the set up of these trials to address the TB crisis. In addition, the overall number of compounds that are in the pharmaceutical pipeline needs to be increased dramatically.

"I don't understand why this is not taken up by all drug developers," said Dr. Tido von Schoen-Angerer, director of MSF's Access to Essential Medicines Campaign. "On the one hand we have world-renowned experts and leading regulatory authorities such as the US FDA advising that clinical studies in multidrug-resistant patients would hasten加速the approval of new drugs. On the other hand we have key funders such as the Gates Foundation, sticking to a one track traditional approach. Funders and drug developers need to respond to this challenge."

The article "Randomized trials to optimize treatment of multi-drug resistant TB" appears in the current issue of PLoS Medicine and was authored by Carole D. Mitnick (Harvard Medical School), Kenneth G. Castro (Division of TB Elimination, US Centers for Disease Prevention and Control), Mark Harrington (Treatment Action Group) Leonard Sacks (US Food and Drug Administration), and William Burman (Denver Public Health and the University of Colorado Health Sciences Center). PloS can be accessed at: www.plosmedicine.org.