[procaare] The Road to a New Tb Drug May be Longer than Some People Hope

["Economist" <procaare@healthnet.org>]

News: The road to a new drug for tuberculosis may be longer than some
people hope 
The Economist 3 March 2006
************

"AFTER YEARS IN THE WILDERNESS, OVERSHADOWED BY THE MORE FASHIONABLE
DISEASES OF AIDS AND MALARIA, THERE SEEMS TO BE A RESURGENCE OF INTEREST
IN DEALING WITH TB"

Tuberculosis is the disease that will not go away. For about a century
after 1882, the year that Robert Koch identified the bacterium which
causes TB, infection rates dropped as drugs were developed and
vaccination programmes rolled out. But once TB was eliminated from the
rich world, interest waned. No new drug has been developed in the past
40 years, and the existing treatment regime takes six to nine months to
clear the bacteria from a patient's body. Indeed, the past two decades
have seen TB's resurgence in poor countries - in particular as an
opportunistic infection in those whose immune systems have been damaged
by HIV. Some 2m people a year now die of the infection.

New drugs, it is widely agreed, are needed. And many are now being
shepherded through the tedious process of research and development by
the Global Alliance for TB Drug Development, a six-year-old venture
based in New York which acts as a dating agency for companies,
governments and academic institutions that would like to collaborate in
developing such drugs.

On the face of it, the alliance is a success. Partly under its aegis, 27
potential anti-TB drugs are at various points along the pipeline that
leads from a promising molecule to a medicine that doctors can
prescribe. The aim is to have at least one of these molecules complete
the journey by 2010. But a group of medical economists led by Kevin
Schulman, of Duke University in North Carolina, doubts the feasibility
of this goal. And they explain the reasons for their disbelief in a
paper in this week's Science.

Public-private partnerships of the sort the alliance encourages are
supposed to bring, among other advantages, a realistic appraisal of the
chance of success. Dr Schulman and his colleagues have taken this idea
at face value, and treated the TB-drug programme-which is, admittedly,
being run by several different groups-as though it were the project of a
single drug company. They have then applied a test called a portfolio
model to the process.

Such models, which are widely used in the pharmaceutical industry, take
inputs such as the costs of clinical trials, the length of each stage of
drug development and the probability of success at each stage. They
convert these into the expected number of successful molecules, the
expected costs at each stage of development, and the total cost of the
process taking into account both successful and rejected molecules. Add
in the effects of chance (what is known as the Monte Carlo simulation
method), and you end up with what should be a plausible range of
timescales and costs.

Applied to the TB portfolio, the result does not look good. Even
extending the timescale to 2019, the model suggests there is only a 73%
chance that a successful drug will emerge. By the 2010 deadline the
alliance has set itself, the chance of success is estimated at less than
5%.

Dr Schulman and his colleagues then started tinkering with the inputs to
try to find out how easily this state of affairs could be improved.
Clinical trials on people are conventionally divided into three phases,
each more rigorous and wide-ranging than its predecessor. The real state
of the world is that five anti-TB molecules are in phase I trials and
two are in phase II. The researchers magically doubled these numbers and
found that the chance of success by 2019 went up to 93%, but success by
2010 remained less than 5% probable.

This is, of course, only a model. And the alliance counters its specific
criticism - that its 2010 target is unrealistic - by pointing to a
particular drug that it hopes might enable it to meet that target. This
drug is moxifloxacin. It is made by Bayer and its advantage is that it
is already widely used against bronchitis, so it is known to be safe.
Tests on mice suggest it will also work against TB, and might reduce the
length of treatment by two to three months, which would be a useful
gain.

Whether moxifloxacin will fulfil its promise remains to be seen. Dr
Schulman's model, though, has cost as a second element, which should
certainly help the alliance with its planning. The upshot, according to
the model's calculations, is that to have a reasonable chance of
producing a successful drug, about $400m will have to be committed to
the research.

Raising that sum is by no means out of the question. The Bill & Melinda
Gates Foundation, for example, plans to make $900m available for TB
eradication over the next ten years, and some of that will surely come
the alliance's way. Moreover, after years in the wilderness,
overshadowed by the more fashionable diseases of AIDS and malaria, there
seems to be a resurgence of interest in dealing with TB. A realistic
appraisal of the task ahead is therefore timely, and a businesslike
approach is the one most likely to succeed.

Online at:
http://www.economist.com/science/displaystory.cfm?story_id=5572481
(subscription may be required)

Cross-posted from Stop-TB
March 07, 2006
Stop-TB eForum 2006: stop-tb@eforums.healthdev.org