[Ip-health] PLoS Medicine: New approaches to filling the gap in TB drug discovery

[James ARKINSTALL]

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In this week's magazine section, PLoS Medicine publishes three policy=0D
papers arising from a recent M=C3=A9decins Sans Fronti=C3=A8res/Doctors Wit=
hout=0D
Borders (MSF) symposium on the urgent need to develop new drugs for=0D
tuberculosis.=0D
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The first concerns "New approaches to filling the gap in TB drug=0D
discovery", and sees promise in this week=E2=80=99s talks at the WHO=0D
Intergovernmental Working Group on a global R&D framework treaty.=0D
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http://medicine.plosjournals.org/perlserv/?request=3Dget-document&doi=3D10.=
1371/journal.pmed.0040293=0D
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The second article =E2=80=9CRandomized trials to Optimize Treatment of=0D
MultiDrug-Resistant Tuberculosis=E2=80=9D calls for clinical trials of new =
regimens=0D
for treating MDR-TB.=0D
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http://medicine.plosjournals.org/perlserv/?request=3Dget-document&doi=3D10.=
1371/journal.pmed.0040292=0D
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A third article highlights the need  for an urgent and massive expansion of=
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clinical trials capacity to accelerate the development and evaluation of=0D
new TB drugs.=0D
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http://medicine.plosjournals.org/perlserv/?request=3Dget-document&doi=3D10.=
1371/journal.pmed.0040302=0D
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Please find below a press release from PLoS.=0D
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FROM THE PLOS MEDICINE MAGAZINE SECTION=0D
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In this week's magazine section, PLoS Medicine publishes three policy=0D
papers arising from a recent M=C3=A9decins Sans Fronti=C3=A8res/Doctors Wit=
hout=0D
Borders (MSF) symposium on the urgent need to develop new drugs for=0D
tuberculosis:=0D
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A new approach to overcoming the bottlenecks in the search for TB drugs=0D
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Early stage drug discovery is a key bottleneck in the pipeline to find=0D
novel drugs for tuberculosis, say Martina Casenghi (MSF) and colleagues.=0D
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The lack of candidate compounds is "cause for alarm," they say, given the=
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global emergence of strains of TB that are resistant to current TB drugs.=
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The authors argue that the few drug companies engaged in TB drug=0D
development are risk averse, generally embarking on drug development only=
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when given evidence of rigorously validated targets and lead compounds that=
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inhibit them. As a result, it has fallen largely to academia to undertake=
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early stage drug discovery.=0D
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Alternative approaches are needed, say Casenghi and colleagues, to=0D
stimulate research and development of TB drugs. They lay out one such=0D
approach, which they call "open-access drug discovery entities," in which=
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academia and industry collaborate and share their results at the earliest=
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opportunity. "One way to ensure that priority medical needs are met while=
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providing economic incentives," say the authors, "is to register resulting=
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patents under a patent track that rewards products based on the impact they=
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have in reducing the global burden of disease."=0D
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Massive expansion of clinical trials capacity is urgently needed=0D
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An urgent and massive expansion of clinical trials capacity is needed to=0D
carry out vital research to accelerate the development and evaluation of=0D
new TB drugs, say Unni Karunakara (MSF) and colleagues.=0D
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"Trials are urgently needed,=E2=80=9D they say, =E2=80=9Cto find regimens t=
hat are shorter,=0D
less toxic, and effective against multidrug-resistant TB (MDR-TB) and=0D
extensively drug-resistant TB (XDRTB)." Trials are also needed, they argue,=
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to find new TB treatment regimens for children, for those with TB and HIV=
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co-infection, and those with TB occurring outside the lungs=0D
(extra-pulmonary TB).=0D
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Unfortunately, say the authors, only about US $20-30 million was spent in=
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2005 around the world for TB clinical trials. The authors call for funding=
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of at least US $300-500 million annually for a TB trials agenda. Direct=0D
investment is also needed, they say, in the infrastructure required to=0D
conduct trials.=0D
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The time is right for trials of multidrug-resistant TB therapy=0D
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Drug-resistant TB strains may account for 10% of the 8 million new cases of=
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TB that occur each year, say Carole Mitnick (Harvard Medical School,=0D
Boston, USA) and colleagues. Increasing concern about resistance has=0D
redoubled interest in strategies to control drug-resistant TB, they say,=0D
especially in settings of high HIV prevalence.=0D
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Current treatments for MDR-TB last between 18 and 24 months, adverse=0D
effects are common, and many patients cannot be cured.=0D
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However, the time is now right, say Mitnick and colleagues, to conduct=0D
randomized clinical trials of new regimens for treating MDR-TB. For a=0D
start, MDR-TB treatment programs have expanded dramatically: 40 programs in=
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resource-limited settings are managing treatment for nearly 30,000=0D
patients. These treatment programs provide the settings in which trails can=
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be implemented. In addition, for the first time in 30 years, several new=0D
drug classes hold promise for MDR-TB treatment.=0D
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"Four elements are needed," say the authors, "to make MDR-TB treatment=0D
trials a reality: money; additional work on the drug pipeline; rigorous,=0D
interdisciplinary preclinical work on individual agents and regimens; and=
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an understanding that TB clinical trials need not be a zero=E2=80=93sum end=
eavor."