E-DRUG: Economist: One World Health and neglected diseases
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[Article from the Apr 14th 2005 edition of The Economist on One World
Health's recent work on leishmaniasis, and their future research plans.]
Hale and healthy
Andy Berry, Orange Photography
A new way of developing drugs for neglected diseases of the poor world
THIS week, scientists from the Institute for OneWorld Health, the first
not-for-profit pharmaceutical company in America, presented the results of
a large clinical trial at the Third World Congress on Leishmaniasis in
Palermo, Italy. Leishmaniasis is a parasitic infection transmitted by the
bite of a sand fly. The trial shows that an antibiotic called paromomycin
is effective for treating the most dangerous version of the disease,
visceral leishmaniasis, which affects 1.5m people around the world and
kills 200,000 of them every year. Those data are obviously important for
medical reasons. But they are also important as a demonstration that the
institute's novel approach to drug development is working.
About 90% of the planet's disease burden falls on the developing world. Yet
only 3% of the research and development expenditure of the pharmaceutical
industry is directed toward those ailments. The rest goes towards treating
diseases of the rich. In 2000, Victoria Hale (pictured above), founded the
institute to help tackle that discrepancy. She knew from her work as a
scientist in the pharmaceutical and biotechnology industries, and
subsequently as an official at America's Food and Drug Administration, that
numerous promising drug-development projectsparticularly for diseases of
the poorare dropped for lack of funding. She reasoned that there was a gap
in the market, between academically inclined university departments and
fully fledged pharmaceutical firms, for an organisation that would identify
such orphans, get their owners to donate the intellectual property if they
were still in patent, raise development funding from non-commercial
sources, and arm-twist researchers to contribute their expertise to the
development process pro bono.
So far, the donation side seems to have worked. In 2002 Celera Genomics
gave the institute a promising compound for the treatment of Chagas
disease, which infects 12m people in Latin America and is an important
cause of heart failure in the region. Yale University has also licensed a
potential drug for Chagas to the institute. And the University of
California, Santa Barbara, gave it a compound intended for the treatment of
schistosomiasis, which affects 200m people, mostly in sub-Saharan Africa.
The compound the institute has pushed furthest, though, is paromomycin. In
this case no donation was needed, as the drug's patent has expired. Indeed,
it is currently used for the treatment of a variety of parasites. But it
has never been properly road-tested for leishmaniasis.
Trials and tribulations
Visceral leishmaniasis occurs predominantly in Bangladesh, Brazil, India,
Nepal and Sudan. Its symptoms include fever, weight loss, enlargement of
the spleen and liver, and anaemia. Several drugs to treat it are available,
but their usefulness is limited either because the parasites have evolved
resistance to them, or because they are too expensive.
In the mid-1990s, the World Health Organisation (WHO) started testing an
injectable form of paromomycin as a treatment for visceral leishmaniasis.
Its researchers completed small-scale trials which demonstrated that the
drug was safe for use against the disease and seemed to cure the infection.
But development stalled at that point because the WHO was unable to find a
sponsor for a large-scale trial that would have compared paromomycin with
existing treatments.
In 2001, Dr Hale approached the WHO about taking over the trials. The WHO
agreed, the Bill and Melinda Gates Foundation stumped up the money, and the
institute teamed up with four health-care centres in the Indian state of
Bihar in order to test the drug against amphotericin B, an established but
expensive treatment.
The trial showed that the two drugs worked more or less equally well. In
both cases, 99% of patients responded within four weeksand though slightly
fewer of those on paromomycin remained uninfected after six months, all
those relapses proved treatable by other drugs. Given that a course of
amphotericin B costs $120, while the institute reckons a course of
paromomycin will come in at around $10, this seems a reasonable trade-off.
The institute, supported by a further donation from the Gates foundation,
plans to submit an application for regulatory approval to the Indian health
ministry by the end of the year. If that is granted, the manufacturing will
be done by Gland Pharma, a drug company based in Hyderabad.
Having shown its approach can work, the institute's next target is
diarrhoea, which kills 2m people a year, most of them children, by
dehydrating them. In this case, the Lehman Brothers Foundation is providing
the money.
Diarrhoea is a symptom, rather than a disease. Indeed, it has eight common
causes in the tropics (four bacteria, three viruses and a protozoan).
Instead of scattering its efforts among these causes, the institute's
researchers are sifting through orphan compounds that might attack
dehydration directly, by stopping the secretion of water into the gut. Such
a drug would augment oral rehydration therapya combination of salt and
sugars mixed into water that is the standard regimen used in the developing
world. Diarrhoea is hardly the most glamorous condition it is possible to
work on. But if Dr Hale and her institute can find a treatment for it among
other people's discards, they will truly have turned base metal into gold.