Researchers call for urgent TB drug development

Researchers have revealed that early stage drug discovery is a key bottleneck in the pipeline to find novel drugs for tuberculosis and have therefore called for a new approach to overcome it.

Washington, Nov 6 : Researchers have revealed that early stage drug discovery is a key bottleneck in the pipeline to find novel drugs for tuberculosis and have therefore called for a new approach to overcome it.

Martina Casenghi from Médecins Sans Frontières (MSF) and colleagues said that the lack of candidate compounds is "cause for alarm," given the global emergence of strains of TB that are resistant to current TB drugs.

The researchers argue that the few drug companies engaged in TB drug development are risk averse, generally embarking on drug development only when given evidence of rigorously validated targets and lead compounds that inhibit them.

As a result, it has fallen largely to academia to undertake early stage drug discovery, they said.

The researchers added that alternative approaches are needed to stimulate research and development of TB drugs.

They lay out one such approach, which they call "open-access drug discovery entities," in which academia and industry collaborate and share their results at the earliest opportunity.

"One way to ensure that priority medical needs are met while providing economic incentives is to register resulting patents under a patent track that rewards products based on the impact they have in reducing the global burden of disease," the authors said.

Unni Karunakara (MSF) and colleagues said that an urgent and massive expansion of clinical trials capacity is needed to carry out vital research to accelerate the development and evaluation of new TB drugs.

"Trials are urgently needed to find regimens that are shorter, less toxic, and effective against multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDRTB)," they said.

They argue that trials are also needed to find new TB treatment regimens for kids, for those with TB and HIV co-infection, and those with TB occurring outside the lungs (extra-pulmonary TB).

The authors said that unfortunately only about 20-30 million dollars was spent in 2005 around the world for TB clinical trials. Therefore, they call for funding of at least 300-500 million dollars annually for a TB trials agenda. hey said that direct investment is also needed in the infrastructure required to conduct trials.

Carole Mitnick (Harvard Medical School, Boston, USA) and colleagues said that drug-resistant TB strains might account for 10 percent of the 8 million new cases of TB that occur each year.

They said that increasing concern about resistance has redoubled interest in strategies to control drug-resistant TB especially in settings of high HIV prevalence.

However, Mitnick and colleagues said that the time is now right to conduct randomized clinical trials of new regimens for treating MDR-TB.

For a start, MDR-TB treatment programs have expanded dramatically: 40 programs in resource-limited settings are managing treatment for nearly 30,000 patients. These treatment programs provide the settings in which trials can be implemented.

In addition, for the first time in 30 years, several new drug classes hold promise for MDR-TB treatment.

"Four elements are needed to make MDR-TB treatment trials a reality: money; additional work on the drug pipeline; rigorous, interdisciplinary preclinical work on individual agents and regimens; and an understanding that TB clinical trials need not be a zero-sum endeavour," the authors said.

The study is published in the journal of PLoS Medicine.

ANI